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Sample records for cholesterol constrains glycolipid

  1. How cholesterol constrains glycolipid conformation for optimal recognition of Alzheimer's beta amyloid peptide (Abeta1-40).

    Science.gov (United States)

    Yahi, Nouara; Aulas, Anaïs; Fantini, Jacques

    2010-02-05

    Membrane lipids play a pivotal role in the pathogenesis of Alzheimer's disease, which is associated with conformational changes, oligomerization and/or aggregation of Alzheimer's beta-amyloid (Abeta) peptides. Yet conflicting data have been reported on the respective effect of cholesterol and glycosphingolipids (GSLs) on the supramolecular assembly of Abeta peptides. The aim of the present study was to unravel the molecular mechanisms by which cholesterol modulates the interaction between Abeta(1-40) and chemically defined GSLs (GalCer, LacCer, GM1, GM3). Using the Langmuir monolayer technique, we show that Abeta(1-40) selectively binds to GSLs containing a 2-OH group in the acyl chain of the ceramide backbone (HFA-GSLs). In contrast, Abeta(1-40) did not interact with GSLs containing a nonhydroxylated fatty acid (NFA-GSLs). Cholesterol inhibited the interaction of Abeta(1-40) with HFA-GSLs, through dilution of the GSL in the monolayer, but rendered the initially inactive NFA-GSLs competent for Abeta(1-40) binding. Both crystallographic data and molecular dynamics simulations suggested that the active conformation of HFA-GSL involves a H-bond network that restricts the orientation of the sugar group of GSLs in a parallel orientation with respect to the membrane. This particular conformation is stabilized by the 2-OH group of the GSL. Correspondingly, the interaction of Abeta(1-40) with HFA-GSLs is strongly inhibited by NaF, an efficient competitor of H-bond formation. For NFA-GSLs, this is the OH group of cholesterol that constrains the glycolipid to adopt the active L-shape conformation compatible with sugar-aromatic CH-pi stacking interactions involving residue Y10 of Abeta(1-40). We conclude that cholesterol can either inhibit or facilitate membrane-Abeta interactions through fine tuning of glycosphingolipid conformation. These data shed some light on the complex molecular interplay between cell surface GSLs, cholesterol and Abeta peptides, and on the influence

  2. How cholesterol constrains glycolipid conformation for optimal recognition of Alzheimer's beta amyloid peptide (Abeta1-40.

    Directory of Open Access Journals (Sweden)

    Nouara Yahi

    Full Text Available Membrane lipids play a pivotal role in the pathogenesis of Alzheimer's disease, which is associated with conformational changes, oligomerization and/or aggregation of Alzheimer's beta-amyloid (Abeta peptides. Yet conflicting data have been reported on the respective effect of cholesterol and glycosphingolipids (GSLs on the supramolecular assembly of Abeta peptides. The aim of the present study was to unravel the molecular mechanisms by which cholesterol modulates the interaction between Abeta(1-40 and chemically defined GSLs (GalCer, LacCer, GM1, GM3. Using the Langmuir monolayer technique, we show that Abeta(1-40 selectively binds to GSLs containing a 2-OH group in the acyl chain of the ceramide backbone (HFA-GSLs. In contrast, Abeta(1-40 did not interact with GSLs containing a nonhydroxylated fatty acid (NFA-GSLs. Cholesterol inhibited the interaction of Abeta(1-40 with HFA-GSLs, through dilution of the GSL in the monolayer, but rendered the initially inactive NFA-GSLs competent for Abeta(1-40 binding. Both crystallographic data and molecular dynamics simulations suggested that the active conformation of HFA-GSL involves a H-bond network that restricts the orientation of the sugar group of GSLs in a parallel orientation with respect to the membrane. This particular conformation is stabilized by the 2-OH group of the GSL. Correspondingly, the interaction of Abeta(1-40 with HFA-GSLs is strongly inhibited by NaF, an efficient competitor of H-bond formation. For NFA-GSLs, this is the OH group of cholesterol that constrains the glycolipid to adopt the active L-shape conformation compatible with sugar-aromatic CH-pi stacking interactions involving residue Y10 of Abeta(1-40. We conclude that cholesterol can either inhibit or facilitate membrane-Abeta interactions through fine tuning of glycosphingolipid conformation. These data shed some light on the complex molecular interplay between cell surface GSLs, cholesterol and Abeta peptides, and on the

  3. A fluorescent glycolipid-binding peptide probe traces cholesterol dependent microdomain-derived trafficking pathways.

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    Steffen Steinert

    Full Text Available BACKGROUND: The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order to address this problem, we have developed an exogenous, non-toxic probe consisting of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid peptide Abeta, and conjugated by a neutral linker with an organic fluorophore. The current work presents the characterization of the sphingolipid binding and live cell trafficking of this novel probe, the SBD peptide. SBD was the name given to a motif originally recognized by Fantini et al in a number of glycolipid-associated proteins, and was proposed to interact with sphingolipids in membrane microdomains. METHODOLOGY/PRINCIPAL FINDINGS: In accordance with Fantini's model, optimal SBD binding to membranes depends on the presence of sphingolipids and cholesterol. In synthetic membrane binding assays, SBD interacts preferentially with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex gangliosides in a pH-dependent manner, but is less glycolipid-specific than Cholera toxin B (CtxB. Using quantitative time-course colocalization in live cells, we show that the uptake and intracellular trafficking route of SBD is unlike that of either the non-raft marker Transferrin or the raft markers CtxB and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially intersects with raft-associated pathways, with a major portion being diverted at a late time point to rab11-positive recycling endosomes. Trafficking of SBD to acidified compartments is strongly disrupted by cholesterol perturbations, consistent with the regulation of sphingolipid trafficking by cholesterol

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

    DEFF Research Database (Denmark)

    Rog, T.; Vattulainen, I.

    2014-01-01

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

  5. The assembly of GM1 glycolipid- and cholesterol-enriched raft-like membrane microdomains is important for giardial encystation.

    Science.gov (United States)

    De Chatterjee, Atasi; Mendez, Tavis L; Roychowdhury, Sukla; Das, Siddhartha

    2015-05-01

    Although encystation (or cyst formation) is an important step of the life cycle of Giardia, the cellular events that trigger encystation are poorly understood. Because membrane microdomains are involved in inducing growth and differentiation in many eukaryotes, we wondered if these raft-like domains are assembled by this parasite and participate in the encystation process. Since the GM1 ganglioside is a major constituent of mammalian lipid rafts (LRs) and known to react with cholera toxin B (CTXB), we used Alexa Fluor-conjugated CTXB and GM1 antibodies to detect giardial LRs. Raft-like structures in trophozoites are located in the plasma membranes and on the periphery of ventral discs. In cysts, however, they are localized in the membranes beneath the cyst wall. Nystatin and filipin III, two cholesterol-binding agents, and oseltamivir (Tamiflu), a viral neuraminidase inhibitor, disassembled the microdomains, as evidenced by reduced staining of trophozoites with CTXB and GM1 antibodies. GM1- and cholesterol-enriched LRs were isolated from Giardia by density gradient centrifugation and found to be sensitive to nystatin and oseltamivir. The involvement of LRs in encystation could be supported by the observation that raft inhibitors interrupted the biogenesis of encystation-specific vesicles and cyst production. Furthermore, culturing of trophozoites in dialyzed medium containing fetal bovine serum (which is low in cholesterol) reduced raft assembly and encystation, which could be rescued by adding cholesterol from the outside. Our results suggest that Giardia is able to form GM1- and cholesterol-enriched lipid rafts and these raft domains are important for encystation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Yeast glycolipid biosurfactants.

    Science.gov (United States)

    Jezierska, Sylwia; Claus, Silke; Van Bogaert, Inge

    2017-10-25

    Various yeasts, both conventional and exotic ones, are known to produce compounds useful to mankind. Ethanol is the most known of these compounds, but more complex molecules such as amphiphilic biosurfactants can also be derived from eukaryotic microorganisms at an industrially and commercially relevant scale. Among them, glycolipids are the most promising, due to their attractive properties and high product titers. Many of these compounds can be considered as secondary metabolites with a specific function for the host. Hence, a dedicated biosynthetic process enables regulation and combines pathways delivering the lipidic moiety and the hydrophilic carbohydrate part of the glycolipid. In this Review, we will discuss the biosynthetic and regulatory aspects of the yeast-derived sophorolipids, mannosylerythritol lipids, and cellobiose lipids, with special emphasis on the relation between glycolipid synthesis and the general lipid metabolism. © 2017 Federation of European Biochemical Societies.

  7. MICROBIAL SURFACTANTS. I. GLYCOLIPIDS

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    Pirog T. Р.

    2014-02-01

    Full Text Available The review is devoted to surface-active glycolipids. The general characteristics, the physiological role of the rhamnolipids, trehalose lipids, sophorolipids, mannosylerythritol lipids and their traditional producers — the representatives of the genera Pseudozyma, Pseudomonas, Rhodococcus and Candida are given. The detailed analysis of the chemical structure, the stages of the biosynthesis and the regulation of some low molecular glycolipids are done. The own experimental data concerning the synthesis intensification, the physiological role and the practical use of Rhodococcus erythropolis IMV Ac-5017, Acinetobacter calcoaceticus IMV B-7241 and Nocardia vaccinii IMV B-7405 surfactants, which are a complex of the glyco-, phospho-, amino- and neutral lipids (glycolipids of all strains are presented by trehalose mycolates are summarized. It was found that R. erythropolis IMV Ac-5017, A. calcoaceticus IMV B-7241 and N. vaccinii IMV B-7405 surfactants have protective, antimicrobial and antiadhesive properties. It was shown that R. erythropolis IMV Ac-5017, A. calcoaceticus IMV B-7241 and N. vaccinii IMV B-7405 surfactants preparation of cultural liquid intensified the degradation of oil in water due to the activation of the natural petroleum-oxidizing microflora.

  8. Glycolipid biosynthesis in cyanobacteria

    International Nuclear Information System (INIS)

    Van Dusen, W.J.; Jaworski, J.G.

    1987-01-01

    The biosynthesis of monogalactosyldiacyl-glycerol (MGDG) was studied in five different cyanobacteria. Previous work has shown Anabaena variabilis to synthesize both MGDG and monoglucosyl-diacylglycerol (MG1cDG) with MG1cDG being the precursor of MGDG. They have examined four other cyanobacteria to determine if a similar relationship exists. The cyanobacteria studied were Anabaena variabilis, Chlorogloeopsis sp., Schizothrix calcicola, Anacystis nidulans, and Anacystis marina. Each were grown in liquid culture and lipids were labeled with 14 C]CO 2 for 20 min., 1.0 hr, 1.0 hr + 10 hr chase. Glycolipids were analyzed by initial separation of MGDG and MG1cDG by TLC followed by further analysis by HPLC. Complete separation of molecular species was obtained isocratically on an ODS column. All of the cyanobacteria labeled 16-C and 18-C fatty acids except for A. marina which labeled only 14-C and 16-C fatty acids. Desaturation of the fatty acids could be observed in the 1.0 hr and chase experiments. All were capable of labeling both MG1cDG and MGDG with the precursor-product relationship being observed. There does not appear to be a direct relationship between the epimerization of the sugar moiety and fatty acid desaturation

  9. Martini Force Field Parameters for Glycolipids

    NARCIS (Netherlands)

    Lopez, Cesar A.; Sovova, Zofie; van Eerden, Floris J.; de Vries, Alex H.; Marrink, Siewert J.

    We present an extension of the Martini coarse-grained force field to glycolipids. The glycolipids considered here are the glycoglycerolipids monogalactosyldiacylglycerol (MGDG), sulfoquinovosyldiacylglycerol (SQDG), digalactosyldiacylglycerol (DGDG), and phosphatidylinositol (PI) and its

  10. Membranes and mammalian glycolipid transferring proteins.

    Science.gov (United States)

    Tuuf, Jessica; Mattjus, Peter

    2014-02-01

    Glycolipids are synthesized in and on various organelles throughout the cell. Their trafficking inside the cell is complex and involves both vesicular and protein-mediated machineries. Most important for the bulk lipid transport is the vesicular system, however, lipids moved by transfer proteins are also becoming more characterized. Here we review the latest advances in the glycolipid transfer protein (GLTP) and the phosphoinositol 4-phosphate adaptor protein-2 (FAPP2) field, from a membrane point of view. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Production and antimicrobial property of glycolipid biosurfactants

    Science.gov (United States)

    Microbial glycolipids such as rhamnolipid (RL) and sophorolipid (SL) are an important class of biosurfactants with excellent surface tension-lowering activity. Besides their surfactant- and environment-friendly properties, however, additional value-added property such as bacteriocidal activity is n...

  12. What's Cholesterol?

    Science.gov (United States)

    ... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

  13. Stimulation of Natural Killer T Cells by Glycolipids

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    Brian L. Anderson

    2013-12-01

    Full Text Available Natural killer T (NKT cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d protein. The initial discovery of immunostimulatory glycolipids from a marine sponge and the T cells that respond to the compounds has led to extensive research by chemists and immunologists to understand how glycolipids are recognized, possible responses by NKT cells, and the structural features of glycolipids necessary for stimulatory activity. The presence of this cell type in humans and most mammals suggests that it plays critical roles in antigen recognition and the interface between innate and adaptive immunity. Both endogenous and exogenous natural antigens for NKT cells have been identified, and it is likely that glycolipid antigens remain to be discovered. Multiple series of structurally varied glycolipids have been synthesized and tested for stimulatory activity. The structural features of glycolipids necessary for NKT cell stimulation are moderately well understood, and designed compounds have proven to be much more potent antigens than their natural counterparts. Nevertheless, control over NKT cell responses by designed glycolipids has not been optimized, and further research will be required to fully reveal the therapeutic potential of this cell type.

  14. Murine cell glycolipids customization by modular expression of glycosyltransferases.

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    Cid, Emili; Yamamoto, Miyako; Buschbeck, Marcus; Yamamoto, Fumiichiro

    2013-01-01

    Functional analysis of glycolipids has been hampered by their complex nature and combinatorial expression in cells and tissues. We report an efficient and easy method to generate cells with specific glycolipids. In our proof of principle experiments we have demonstrated the customized expression of two relevant glycosphingolipids on murine fibroblasts, stage-specific embryonic antigen 3 (SSEA-3), a marker for stem cells, and Forssman glycolipid, a xenoantigen. Sets of genes encoding glycosyltansferases were transduced by viral infection followed by multi-color cell sorting based on coupled expression of fluorescent proteins.

  15. Ultrastructural study of chromoplast components rich in glycolipids

    OpenAIRE

    Wrischer, Mercedes; Prebeg, Tatjana; Magnus, Volker; Ljubešić, Nikola

    2001-01-01

    A cytochemical method for the ultrastructural localization of glycolipids, performed on thin sections, was used in the study of tubular chromoplasts. The method gave clear pictures of structures that contained glycolipids, while other chemical constituents were not stained. The method was tested on two flowers (Impatients noli-tangere L. and Thunbergia alata Boj. ex Sims) containing different types of tubular chromoplasts. The ultrastructure and mode of development of the two types of tubu...

  16. Oligosaccharides and glycolipids addition in charged lamellar phases

    International Nuclear Information System (INIS)

    Ricoul, F.

    1997-01-01

    The aim of this work is to study the addition of oligosaccharides and glycolipids in lamellar phases of the cationic surfactant DDAB (di-dodecyl-dimethyl-ammonium bromide). Two steps have been followed: the determination of phases prisms and the thermodynamic interpretation in terms of molecular interactions. In order to characterize these systems, two new experimental small angle scattering methods have been perfected: 1) a neutron scattering contrast variation method which allows to study the adsorption of aqueous solution in bilayers and 2) a capillary concentration gradient method to establish directly and quantitatively the phases diagrams of ternary systems by X rays scattering. It has been pointed out that the oligosaccharides induce a depletion attractive force on the lamellar-lamellar equilibrium of the DDAB when they are excluded of the most concentrated phase. For the two studied glycolipids: 2-O lauroyl-saccharose and N-lauroyl N-nonyl lactitol, the ternary phase diagrams water-DDAB-glycolipid have been established in terms of temperature. Critical points at ambient temperature have been given. The osmotic pressure in concentrated lamellar phases has been measured. It has been shown that glycolipids increase the hydration repulsion at short distance and that the electrostatic repulsion is outstanding and unchanged at high distance if there is at less 1 mole percent of ionic surfactant. In a dilute solution, glycolipids decrease the maximum swelling of lamellar phases, with a competition between the lamellar phase and the micellae dilute phase for water. (O.M.)

  17. Cholesterol (image)

    Science.gov (United States)

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  18. Cholesterol Test

    Science.gov (United States)

    ... artery disease. Other names for a cholesterol test: Lipid profile, Lipid panel What is it used for? If you ... Clinic [Internet]. Mayo Foundation for Medical Education and Research; c1998-2017.Cholesterol Test: Overview; 2016 Jan 12 [ ...

  19. Oligosaccharides and glycolipids addition in charged lamellar phases; Addition d`oligosaccharides et de glycolipides dans des phases lamellaires chargees

    Energy Technology Data Exchange (ETDEWEB)

    Ricoul, F

    1997-09-26

    The aim of this work is to study the addition of oligosaccharides and glycolipids in lamellar phases of the cationic surfactant DDAB (di-dodecyl-dimethyl-ammonium bromide). Two steps have been followed: the determination of phases prisms and the thermodynamic interpretation in terms of molecular interactions. In order to characterize these systems, two new experimental small angle scattering methods have been perfected: 1) a neutron scattering contrast variation method which allows to study the adsorption of aqueous solution in bilayers and 2) a capillary concentration gradient method to establish directly and quantitatively the phases diagrams of ternary systems by X rays scattering. It has been pointed out that the oligosaccharides induce a depletion attractive force on the lamellar-lamellar equilibrium of the DDAB when they are excluded of the most concentrated phase. For the two studied glycolipids: 2-O lauroyl-saccharose and N-lauroyl N-nonyl lactitol, the ternary phase diagrams water-DDAB-glycolipid have been established in terms of temperature. Critical points at ambient temperature have been given. The osmotic pressure in concentrated lamellar phases has been measured. It has been shown that glycolipids increase the hydration repulsion at short distance and that the electrostatic repulsion is outstanding and unchanged at high distance if there is at less 1 mole percent of ionic surfactant. In a dilute solution, glycolipids decrease the maximum swelling of lamellar phases, with a competition between the lamellar phase and the micellae dilute phase for water. (O.M.). 165 refs.

  20. Current status in biotechnological production and applications of glycolipid biosurfactants.

    Science.gov (United States)

    Paulino, Bruno Nicolau; Pessôa, Marina Gabriel; Mano, Mario Cezar Rodrigues; Molina, Gustavo; Neri-Numa, Iramaia Angélica; Pastore, Glaucia Maria

    2016-12-01

    Biosurfactants are natural compounds with surface activity and emulsifying properties produced by several types of microorganisms and have been considered an interesting alternative to synthetic surfactants. Glycolipids are promising biosurfactants, due to low toxicity, biodegradability, and chemical stability in different conditions and also because they have many biological activities, allowing wide applications in different fields. In this review, we addressed general information about families of glycolipids, rhamnolipids, sophorolipids, mannosylerythritol lipids, and trehalose lipids, describing their chemical and surface characteristics, recent studies using alternative substrates, and new strategies to improve of production, beyond their specificities. We focus in providing recent developments and trends in biotechnological process and medical and industrial applications.

  1. Improved Method for the Isolation of Biosurfactant Glycolipids from Rhodococcus sp. Strain H13A

    OpenAIRE

    Bryant, Frank O.

    1990-01-01

    An improved method for the isolation of the biosurfactant glycolipids from Rhodococcus sp. strain H13A by using XM 50 diafiltration and isopropanol precipitation was devised. This procedure was advantageous since it removes protein coisolated when the glycolipids are obtained by organic extraction and silicic acid chromatography. The protein apparently does not contribute any biosurfactant characteristics to the glycolipids. The deacylated glycolipid backbone included only a disaccharide.

  2. Production of microbial glycolipid biosurfactants and their antimicrobial activity

    Science.gov (United States)

    Microbial glycolipids produced by bacteria or yeast as secondary metabolites, such as sophorolipids (SLs), rhamnolipids (RLs) and mannosylerythritol lipids (MELs) are “green” biosurfactants desirable in a bioeconomy. High cost of production is a major hurdle toward widespread commercial use of bios...

  3. Isolation and screening of glycolipid biosurfactant producers from sugarcane.

    Science.gov (United States)

    Morita, Tomotake; Fukuoka, Tokuma; Imura, Tomohiro; Hirose, Naoto; Kitamoto, Dai

    2012-01-01

    Forty-three fungal producers for glycolipid biosurfactants, mannosylerythritol lipids (MELs), were isolated from leaves and smuts of sugarcane plants. These isolates produced MELs with sugarcane juice as nutrient source. The strains were taxonomically categorized into the genera Pseudozyma and Ustilago on the basis of partial sequences of the ribosomal RNA gene.

  4. Temperature induced changes in the heterocyst glycolipid composition of N

    NARCIS (Netherlands)

    Bauersachs, T.; Stal, L.J.; Grego, M.; Schwark, L.; Schwark, L.

    2014-01-01

    We investigated the effect of temperature on the heterocyst glycolipid (HG) composition of the diazotrophic heterocystous cyanobacteria Anabaena sp. strain CCY9613 and Nostoc sp. strain CCY9926 grown at 9, 12, 16, 20 and 24 degrees C. Both strains contained an overall similar composition of

  5. High blood cholesterol levels

    Science.gov (United States)

    Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

  6. Analysis of glycolipids in vegetable lecithin with HPLC-ELSD

    OpenAIRE

    Nguyen Tuyet, Mai; De Vrieze, Mike; Van de Walle, Davy; Van Hoed, Vera; Lynen, Frederic; Dewettinck, Koen

    2014-01-01

    Vegetable lecithins play an important role in the microstructural and macroscopic properties of food and cosmetic products. They are widely used as a natural emulsifier. As lecithin is a by-product of the vegetable oil refining industry, its composition is quite variable and rather complex. Therefore, a more complete view on the chemical composition of lecithin would assist in elucidating its functionality. This study focused on the separation and quantification of several glycolipid...

  7. Biofilm disruption potential of a glycolipid biosurfactant from marine Brevibacterium casei.

    Science.gov (United States)

    Kiran, George Seghal; Sabarathnam, Balu; Selvin, Joseph

    2010-08-01

    The antibiofilm activity of a glycolipid biosurfactant isolated from the marine actinobacterium Brevibacterium casei MSA19 was evaluated against pathogenic biofilms in vitro. The isolate B. casei MSA19 was a potential biosurfactant producer among the 57 stable strains isolated from the marine sponge Dendrilla nigra. The biosurfactant production was optimized under submerged fermentation. The purified glycolipid showed a broad spectrum of antimicrobial activity. Based on the minimum inhibitory concentration/minimum bactericidal concentration ratio, the glycolipid was determined as bacteriostatic. The glycolipid biosurfactant disrupted the biofilm formation under dynamic conditions. The disruption of the biofilm by the MSA19 glycolipid was consistent against mixed pathogenic biofilm bacteria. Therefore, the glycolipid biosurfactant can be used as a lead compound for the development of novel antibiofilm agents.

  8. Cholesterol testing and results

    Science.gov (United States)

    ... your cholesterol is in this normal range. LDL (Bad) Cholesterol LDL cholesterol is sometimes called "bad" cholesterol. ... to 3.3 mmol/l) are desired. VLDL (Bad) Cholesterol VLDL contains the highest amount of triglycerides. ...

  9. What Is Cholesterol?

    Science.gov (United States)

    ... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

  10. Cholesterol Facts and Statistics

    Science.gov (United States)

    ... Managing High Cholesterol Cholesterol-lowering Medicine High Cholesterol Statistics and Maps High Cholesterol Facts High Cholesterol Maps ... Deo R, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart ...

  11. Adjuvant effect in aquaculture fish of cell-wall glycolipids isolated from acid-fast bacteria.

    Science.gov (United States)

    Matsumoto, Megumi; Araki, Kyosuke; Nishimura, Sayaka; Kuriyama, Hideki; Nakanishi, Teruyuki; Shiozaki, Kazuhiro; Takeuchi, Yutaka; Yamamoto, Atsushi

    2018-08-01

    Mycobacteriosis and nocardiosis in cultured fish caused by infections with acid-fast bacteria, are responsible for large economic losses globally. In this study, we suggest a novel adjuvant using glycolipids that activates host immune systems. The immune response to glycolipids stimulation was investigated using ginbuna crucian carp. Ginbuna vaccinated with FKC (formalin-killed cells) + glycolipids isolated from Mycobacterium sp., upregulated inflammatory- and Th1-related cytokines, and a DTH (delayed-type hypersensitivity) response was confirmed only in ginbuna vaccinated with FKC + glycolipids. These observations suggest that glycolipids activated host innate and cell-mediated immunity. Subsequently, we evaluated the adjuvant effect of glycolipids against amberjack nocardiosis. In a challenge test, a higher survival rate was observed in amberjack vaccinated with FKC + glycolipids emulsified with conventional oil adjuvant than in fish vaccinated with FKC + oil adjuvant without glycolipids. Therefore, glycolipids potentially could be used as a practical, economical and safe adjuvant for aquaculture fish. Copyright © 2018. Published by Elsevier Ltd.

  12. [Characterization of an extracellular glycolipid from Lentinus edodes (Berk.) Sing [Lentinula edodes (Berk.) Pegler

    Science.gov (United States)

    Tsivileva, O M; Nikitina, V E; Makarov, O E

    2008-01-01

    Submerged mycelium of a xylotrophic basidiomycete Lentinus edodes produces an extracellular glycolipid, S3, associated with a lectin. Galactose glycan residue, as well as the lipid pool composition, which includes nonhydroxylated short-chain fatty acids, is uncommon for basidiomycetes. The glycolipid consists of D-galactopyranose (15% of S3 contains galactose sulfate) acylated by octadecanoic and nonadecanoic fatty acid residues (28 and 72%, respectively). The glycolipid structure and composition are confirmed by physicochemical analysis. The glycolipid is assumed to be a regulator of lectin activity.

  13. Recognition of microbial glycolipids by Natural Killer T cells

    Directory of Open Access Journals (Sweden)

    Dirk Michael Zajonc

    2015-08-01

    Full Text Available T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the Major Histocompatibility (MHC family (MHC I and II, lipids, glycolipids and lipopeptides can be presented by the non-classical MHC member CD1. The best studied subset of lipid-reactive T cells are Type I Natural killer T (iNKT cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi the causative agents of Lyme disease and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry microbial glycolipids that can trigger the T cell antigen receptor (TCR, leading to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha chain, yet retain the ability to recognize structurally diverse glycolipids. They do so using a conserved recognition mode, in which the TCR enforces a conserved binding orientation on CD1d. TCR binding is accompanied by structural changes within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In addition to direct recognition of microbial antigens, iNKT cells can also be activated by a combination of cytokines (IL-12/IL-18 and TCR stimulation. Many microbes carry TLR antigens and microbial infections can lead to TLR activation. The subsequent cytokine response in turn lower the threshold of TCR mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here we will review the molecular basis of iNKT cell

  14. Effects of Chimonanthus nitens Oliv. Leaf Extract on Glycolipid Metabolism and Antioxidant Capacity in Diabetic Model Mice

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2017-01-01

    Full Text Available The paper investigated the antihyperglycemic and antihyperlipidemic efficacy and antioxidant capacity of Chimonanthus nitens Oliv. leaf extract (COE in combination of high-glucose-fat diet-fed and streptozotocin-induced diabetic model mice. Various physiological indexes in diabetic model mice were well improved especially by oral administration of high dose of COE; the results were listed as follows. Fast blood glucose (FBG level and serum triglyceride (TC, total cholesterol (TG, low-density lipoprotein cholesterol (LDLC, and malondialdehyde (MDA as well as MDA in liver were significantly reduced; fasting serum insulin (FINS and insulin sensitivity index (ISI were both increased; high-density lipoprotein cholesterol (HDLC in serum was significantly increased; total antioxidant capacity (T-AOC, activities of superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, and catalase (CAT in serum and liver were apparently enhanced; liver coefficient (LC, liver transaminase, and alkaline phosphatase (ALP were decreased. Furthermore, pancreas islets and liver in diabetic model mice showed some extend of improvement in morphology and function after 4 weeks of COE treatment. In consequence, COE was advantageous to regulate glycolipid metabolism and elevate antioxidant capacity in diabetic model mice. Thus, the present study will provide a scientific evidence for the use of COE in the management of diabetes and its related complications.

  15. NKT-cell glycolipid agonist as adjuvant in synthetic vaccine.

    Science.gov (United States)

    Liu, Zheng; Guo, Jun

    2017-11-27

    NKT cells are CD1d-restricted, glycolipid antigen-reactive, immunoregulatory T lymphocytes that can serve as a bridge between the innate and adaptive immunities. NKT cells have a wide range of therapeutic application in autoimmunity, transplant biology, infectious disease, cancer, and vaccinology. Rather than triggering "danger signal" and eliciting an innate immune response, αGalCer-based NKT-cell agonist act via a unique mechanism, recruiting NKT cells which play a T helper-like role even without peptide as Th epitope. Importantly, the non-polymorphism of CD1d render glycolipid a universal helper epitope, offering the potential to simplify the vaccine construct capable of eliciting consistent immune response in different individuals. This review details recent advances in the design of synthetic vaccines using NKT-cell agonist as adjuvant, highlighting the role of organic synthesis and conjugation technique to enhance the immunological actives and to simplify the vaccine constructs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. LDL: The "Bad" Cholesterol

    Science.gov (United States)

    ... There are two main types of cholesterol: LDL (bad) cholesterol and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because a high LDL level leads to ...

  17. Glycolipids from spinach suppress LPS-induced vascular inflammation through eNOS and NK-κB signaling.

    Science.gov (United States)

    Ishii, Masakazu; Nakahara, Tatsuo; Araho, Daisuke; Murakami, Juri; Nishimura, Masahiro

    2017-07-01

    Glycolipids are the major constituent of the thylakoid membrane of higher plants and have a variety of biological and pharmacological activities. However, anti-inflammatory effects of glycolipids on vascular endothelial cells have not been elucidated. Here, we investigated the effect of glycolipids extracted from spinach on lipopolysaccharides (LPS)-induced endothelial inflammation and evaluated the underlying molecular mechanisms. Treatment with glycolipids from spinach had no cytotoxic effects on cultured human umbilical vein endothelial cells (HUVECs) and significantly blocked the expression of LPS-induced interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) in them. Glycolipids treatment also effectively suppressed monocyte adhesion to HUVECs. Treatment with glycolipids inhibited LPS-induced NF-κB phosphorylation and nuclear translocation. In addition, glycolipids treatment significantly promoted endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production in HUVECs. Furthermore, glycolipids treatment blocked LPS-induced inducible NOS (iNOS) expression in HUVECs. Pretreatment with a NOS inhibitor attenuated glycolipids-induced suppression of NF-κB activation and adhesion molecule expression, and abolished the glycolipids-mediated suppression of monocyte adhesion to HUVECs. These results indicate that glycolipids suppress LPS-induced vascular inflammation through attenuation of the NF-κB pathway by increasing NO production in endothelial cells. These findings suggest that glycolipids from spinach may have a potential therapeutic use for inflammatory vascular diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammad Abdel-Mawgoud

    2018-03-01

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

  19. Glycolipid biosurfactants: main properties and potential applications in agriculture and food industry.

    Science.gov (United States)

    Mnif, Inès; Ghribi, Dhouha

    2016-10-01

    Glycolipids, consisting of a carbohydrate moiety linked to fatty acids, are microbial surface active compounds produced by various microorganisms. They are characterized by high structural diversity and have the ability to decrease the surface and interfacial tension at the surface and interface, respectively. Rhamnolipids, trehalolipids, mannosylerythritol lipids and cellobiose lipids are among the most popular glycolipids. They have received much practical attention as biopesticides for controlling plant diseases and protecting stored products. As a result of their antifungal activity towards phytopathogenic fungi and larvicidal and mosquitocidal potencies, glycolipid biosurfactants permit the preservation of plants and plant crops from pest invasion. Also, as a result of their emulsifying and antibacterial activities, glycolipids have great potential as food additives and food preservatives. Furthermore, the valorization of food byproducts via the production of glycolipid biosurfactant has received much attention because it permits the bioconversion of byproducts on valuable compounds and decreases the cost of production. Generally, the use of glycolipids in many fields requires their retention from fermentation media. Accordingly, different strategies have been developed to extract and purify glycolipids. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  20. Characterization of glycolipid galactosyltransferases from embryonic chicken brain

    International Nuclear Information System (INIS)

    Kyle, J.W.

    1985-01-01

    Glycolipid galactosyltransferases (GalT-3 and GalT-4) were solubilized from a membrane fraction isolated from embryonic chicken brain. The profiles of specific activity and total units per brain of GalT-3 and GalT-4 varied with embryonic age. GalT-4 had the highest specific activity at 9 days of embryonic development and showed a steady decrease until hatching. GalT-3 showed a gradual increase in specific activity. Both GalT3 and GalT-4 showed a steady increase in total units per brain throughout embryonic development. The solubilized enzymes could be separated using gel filtration, ion exchange chromatography or affinity chromatography on α-lactalbumin-agarose. Data obtained in the study imply that GalT-4 is involved in both glycoprotein and glycolipid biosynthesis. Glycosphingolipid products from GalT-3 and GalT-4 catalyzed reactions labeled with [ 14 C]galactose comigrated with authentic GMI and nLcOse 4 Cer, when examined by thin layer chromatography and autoradiography. Studies with galactosidases revealed that all of the enzyme products formed by GalT-3 and GalT-4 contained a [ 14 C]-galactose in a β anomeric linkage. Periodate oxidation studies of Gal-[ 14 C]GlcNAc, formed by purified GalT-4 using [ 14 C]GlcNAc as the acceptor, demonstrated that approximately 70% of the linkage formed was Galβ1-4GlcNAc and 30% was Galβ1-3GlcNAc. Studies on the susceptibility of [ 14 C]Gal-GlcNAc to base catalyzed β-elimination also suggested the presence of approximately 30% Galβ1-3GlcNAc

  1. Cholesterol IQ Quiz

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Jul 5,2017 Begin the quiz ... What Your Cholesterol Levels Mean Common Misconceptions Cholesterol IQ Quiz • HDL, LDL, and Triglycerides • Causes of High ...

  2. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Jan 29,2018 How much do you ... are some common misconceptions — and the truth. High cholesterol isn’t a concern for children. High cholesterol ...

  3. Synthesis and physicochemical properties of glycolipids bearing oligosaccharide headgroups; Origoto wo shinsuiki tosuru toshishitsu no gose to butsusei

    Energy Technology Data Exchange (ETDEWEB)

    Minamikawa, H [National Institute of Materials and Chemical Research, Tsukuba (Japan)

    1999-12-22

    Glycolipids, amphiphiles that bear oligosaccharides their hydrophilic, are of importance both scientifically and technically. This review describes recent advances in our understanding of the molecular correlations in phase behavior of aqueous glycolipids. In the first part, we discuss how headgroup stereochemistry affects the phase behavior of glycolipids both two- and three- dimensional systems. In the second part, we discuss effects of alkyl chain structure behavior of phytanyl-chained glycolipid/water systems Physical properties of glycolipid/water systems strongly depend on the inter-headgroup interactions that is related to factors such as stereochemistry (conformation) and size of headgroups, type of sugar residues involved, alkyl chain structure, etc. Thus. apart from the conventional concept like [hydrophilic/lipophilic balance], explicit accounts of headgroup interactions are crucial to control a particular glycolipid/water system concerned. This makes contrast to the conventional amphiphile/water systems where the inter-headgroup interaction are in most cases simply repulsive. (author)

  4. Comparison of micelle structure of glycolipids with different head groups by small angle neutron scattering

    International Nuclear Information System (INIS)

    He, Lizhong; Middelberg, Anton; Hartmann, Thorsten; Niemeyer, Bernd; Garamus, V.M.; Willumeit, Regine

    2005-01-01

    Full text: Glycolipids such as n-alkyl- beta-D-glucopyranoside and n-alkyl- beta-D-maltopyranoside can self-assemble into different structures depending on solution conditions. Their amphiphilic properties enable them to serve as biosurfactants in biology and biotechnology, especially for solubilizing membrane proteins. The physicochemical properties of glycolipids have attracted attentions from several research groups, aiming to better understand their application in biological and environmental processes. For example, small angle neutron and X-ray scattering have been used to study micelle structures formed by glycolipids. Our previous work has shown that n-octyl-beta- D-glucopyranoside and n-octyl- beta-D-maltopyranoside form micelles with different structure, suggesting an important role of the sugar head group in micelle formation. In the present work, we further compare micelle structures of n-octyl- beta-Dglucopyranoside and n-octyl- beta-D-galactopyranoside. These two glycolipids have the same hydrophobic tail and their head sugar groups differ only in the conformation with one hydroxyl group pointing to different direction. Our SANS data together with phase behaviours reported by other group have suggested that a slight alteration of head group conformation can significantly affect self-assembly of glycolipids. (authors)

  5. Disassembly of Bacterial Biofilms by the Self-Assembled Glycolipids Derived from Renewable Resources.

    Science.gov (United States)

    Prasad, Yadavali Siva; Miryala, Sandeep; Lalitha, Krishnamoorthy; Ranjitha, K; Barbhaiwala, Shehnaz; Sridharan, Vellaisamy; Maheswari, C Uma; Srinandan, C S; Nagarajan, Subbiah

    2017-11-22

    More than 80% of chronic infections of bacteria are caused by biofilms. It is also a long-term survival strategy of the pathogens in a nonhost environment. Several amphiphilic molecules have been used in the past to potentially disrupt biofilms; however, the involvement of multistep synthesis, complicated purification and poor yield still remains a major problem. Herein, we report a facile synthesis of glycolipid based surfactant from renewable feedstocks in good yield. The nature of carbohydrate unit present in glycolipid influence the ring chain tautomerism, which resulted in the existence of either cyclic structure or both cyclic and acyclic structures. Interestingly, these glycolipids self-assemble into gel in highly hydrophobic solvents and vegetable oils, and displayed foam formation in water. The potential application of these self-assembled glycolipids to disrupt preformed biofilm was examined against various pathogens. It was observed that glycolipid 6a disrupts Staphylococcus aureus and Listeria monocytogenes biofilm, while the compound 6c was effective in disassembling uropathogenic E. coli and Salmonella enterica Typhimurium biofilms. Altogether, the supramolecular self-assembled materials, either as gel or as surfactant solution could be potentially used for surface cleansing in hospital environments or the food processing industries to effectively reduce pathogenic biofilms.

  6. Constrained consequence

    CSIR Research Space (South Africa)

    Britz, K

    2011-09-01

    Full Text Available their basic properties and relationship. In Section 3 we present a modal instance of these constructions which also illustrates with an example how to reason abductively with constrained entailment in a causal or action oriented context. In Section 4 we... of models with the former approach, whereas in Section 3.3 we give an example illustrating ways in which C can be de ned with both. Here we employ the following versions of local consequence: De nition 3.4. Given a model M = hW;R;Vi and formulas...

  7. The challenges of understanding glycolipid functions: An open outlook based on molecular simulations

    DEFF Research Database (Denmark)

    Manna, M.; Rog, T.; Vattulainen, I.

    2014-01-01

    and molecular simulations can be used to shed light on the role of glycolipids in membrane structure and dynamics, receptor function, and other phenomena related to emergence of diseases such as Parkinson's. The cases we discuss highlight the challenge to understand how glycolipids function in cell membranes......, and the significant added value that one would gain by bridging molecular simulations with experiments. This article is part of a Special Issue entitled Tools to study lipid functions. (C) 2014 Elsevier B.V. All rights reserved.......Glycolipids are the most complex lipid type in cell membranes, characterized by a great diversity of different structures and functions. The underlying atomistic/molecular interactions and mechanisms associated with these functions are not well understood. Here we discuss how atomistic...

  8. Phase sensitive molecular dynamics of self-assembly glycolipid thin films: A dielectric spectroscopy investigation

    Science.gov (United States)

    Velayutham, T. S.; Ng, B. K.; Gan, W. C.; Majid, W. H. Abd.; Hashim, R.; Zahid, N. I.; Chaiprapa, Jitrin

    2014-08-01

    Glycolipid, found commonly in membranes, is also a liquid crystal material which can self-assemble without the presence of a solvent. Here, the dielectric and conductivity properties of three synthetic glycolipid thin films in different thermotropic liquid crystal phases were investigated over a frequency and temperature range of (10-2-106 Hz) and (303-463 K), respectively. The observed relaxation processes distinguish between the different phases (smectic A, columnar/hexagonal, and bicontinuous cubic Q) and the glycolipid molecular structures. Large dielectric responses were observed in the columnar and bicontinuous cubic phases of the longer branched alkyl chain glycolipids. Glycolipids with the shortest branched alkyl chain experience the most restricted self-assembly dynamic process over the broad temperature range studied compared to the longer ones. A high frequency dielectric absorption (Process I) was observed in all samples. This is related to the dynamics of the hydrogen bond network from the sugar group. An additional low-frequency mechanism (Process II) with a large dielectric strength was observed due to the internal dynamics of the self-assembly organization. Phase sensitive domain heterogeneity in the bicontinuous cubic phase was related to the diffusion of charge carriers. The microscopic features of charge hopping were modelled using the random walk scheme, and two charge carrier hopping lengths were estimated for two glycolipid systems. For Process I, the hopping length is comparable to the hydrogen bond and is related to the dynamics of the hydrogen bond network. Additionally, that for Process II is comparable to the bilayer spacing, hence confirming that this low-frequency mechanism is associated with the internal dynamics within the phase.

  9. Controlling Cholesterol with Statins

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

  10. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  11. Home-Use Tests - Cholesterol

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

  12. Biosynthesis and derivatization of microbial glycolipids and their potential application in tribology

    Science.gov (United States)

    Microbial-produced glycolipids are biobased products with immense potential for commercial applications. Advances in the production process have led to the lowering of production cost and the appearance of commercial products in niche markets. The ability to manipulate the molecular structure by f...

  13. Endosymbiotic heterocystous cyanobacteria synthesize different heterocyst glycolipids than free-living heterocystous cyanobacteria

    NARCIS (Netherlands)

    Schouten, S.; Villareal, T.A.; Hopmans, E.C.; Mets, A.; Swanson, K.M.; Sinninghe Damsté, J.S.

    2013-01-01

    The heterocysts of limnetic nitrogen-fixing filamentous cyanobacteria contain unique glycolipids in their cell wall that create the distinctive gas impermeability of the heterocyst cell wall as well as serve as biomarker lipids for these microbes. It has been assumed that marine free-living and

  14. Temperature induced changes in the heterocyst glycolipid composition of N2-fixing heterocystous cyanobacteria

    NARCIS (Netherlands)

    Bauersachs, T.; Stal, L.J.; Grego, M.; Schwark, L.

    2014-01-01

    We investigated the effect of temperature on the heterocyst glycolipid (HG) composition of the diazotrophic heterocystous cyanobacteria Anabaena sp. strain CCY9613 and Nostoc sp. strain CCY9926 grown at 9, 12, 16, 20 and 24 °C. Both strains contained an overall similar composition of heterocyst

  15. Self-glycolipids modulate dendritic cells changing the cytokine profiles of committed autoreactive T cells.

    Directory of Open Access Journals (Sweden)

    Karsten Buschard

    Full Text Available The impact of glycolipids of non-mammalian origin on autoimmune inflammation has become widely recognized. Here we report that the naturally occurring mammalian glycolipids, sulfatide and β-GalCer, affect the differentiation and the quality of antigen presentation by monocyte-derived dendritic cells (DCs. In response to sulfatide and β-GalCer, monocytes develop into immature DCs with higher expression of HLA-DR and CD86 but lower expression of CD80, CD40 and CD1a and lower production of IL-12 compared to non-modulated DCs. Self-glycolipid-modulated DCs responded to lipopolysaccharide (LPS by changing phenotype but preserved low IL-12 production. Sulfatide, in particular, reduced the capacity of DCs to stimulate autoreactive Glutamic Acid Decarboxylase (GAD65 - specific T cell response and promoted IL-10 production by the GAD65-specific clone. Since sulfatide and β-GalCer induced toll-like receptor (TLR-mediated signaling, we hypothesize that self-glycolipids deliver a (tolerogenic polarizing signal to differentiating DCs, facilitating the maintenance of self-tolerance under proinflammatory conditions.

  16. Monitoring glycolipid transfer protein activity and membrane interaction with the surface plasmon resonance technique.

    Science.gov (United States)

    Ohvo-Rekilä, Henna; Mattjus, Peter

    2011-01-01

    The glycolipid transfer protein (GLTP) is a protein capable of binding and transferring glycolipids. GLTP is cytosolic and it can interact through its FFAT-like (two phenylalanines in an acidic tract) motif with proteins localized on the surface of the endoplasmic reticulum. Previous in vitro work with GLTP has focused mainly on the complete transfer reaction of the protein, that is, binding and subsequent removal of the glycolipid from the donor membrane, transfer through the aqueous environment, and the final release of the glycolipid to an acceptor membrane. Using bilayer vesicles and surface plasmon resonance spectroscopy, we have now, for the first time, analyzed the binding and lipid removal capacity of GLTP with a completely label-free technique. This technique is focused on the initial steps in GLTP-mediated transfer and the parameters affecting these steps can be more precisely determined. We used the new approach for detailed structure-function studies of GLTP by examining the glycolipid transfer capacity of specific GLTP tryptophan mutants. Tryptophan 96 is crucial for the transfer activity of the protein and tryptophan 142 is an important part of the proteins membrane interacting domain. Further, we varied the composition of the used lipid vesicles and gained information on the effect of membrane properties on GLTP activity. GLTP prefers to interact with more tightly packed membranes, although GLTP-mediated transfer is faster from more fluid membranes. This technique is very useful for the study of membrane-protein interactions and lipid-transfer rates and it can easily be adapted to other membrane-interacting proteins. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Novel Polyoxyethylene-Containing Glycolipids Are Synthesized in Corynebacterium matruchotii and Mycobacterium smegmatis Cultured in the Presence of Tween 80

    Directory of Open Access Journals (Sweden)

    Cindy Wang

    2011-01-01

    Full Text Available The addition of polyoxyethylene sorbitan monooleate (Tween 80 to a culture of mycobacteria greatly influences cell permeability and sensitivity to antibiotics but very little is known regarding the underlying mechanism. Here we show that Corynebacterium matruchotii (surrogate of mycobacteria converts Tween 80 to a structural series of polyoxyethylenic acids which are then used to form novel series-2A and series-2B glycolipids. Minor series-3 glycolipids were also synthesized. The polyoxyethylenic acids replaced corynomycolic acids in the cell wall. Correspondingly the trehalose dicorynomycolate content was reduced. MALDI mass spectrometry, MS-MS, 1H-NMR, and 13C-NMR were used to characterize the series-2 glycolipids. Series-2A glycolipid is trehalose 6-C36:2-corynomycolate-6′-polyoxyethylenate and series-2B glycolipid is trehalose 6-C36:2-corynomycolate-6′-furan ring-containing polyoxyethylenate. Mycobacterium smegmatis grown in the presence of Tween 80 also synthesizes series-2 type glycolipids. The synthesis of these novel glycolipids in corynebacteria and mycobacteria should result in gross changes in the cell wall permeability and drug sensitivity.

  18. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  19. Cholesterol - what to ask your doctor

    Science.gov (United States)

    ... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

  20. Topical Application of Glycolipids from Isochrysis galbana Prevents Epidermal Hyperplasia in Mice

    Directory of Open Access Journals (Sweden)

    Azahara Rodríguez-Luna

    2017-12-01

    Full Text Available Chronic inflammatory skin diseases such as psoriasis have a significant impact on society. Currently, the major topical treatments have many side effects, making their continued use in patients difficult. Microalgae have emerged as a source of bio-active molecules such as glycolipids with potent anti-inflammatory properties. We aimed to investigate the effects of a glycolipid (MGMG-A and a glycolipid fraction (MGDG obtained from the microalga Isochrysis galbana on a TPA-induced epidermal hyperplasia murine model. In a first set of experiments, we examined the preventive effects of MGMG-A and MGDG dissolved in acetone on TPA-induced hyperplasia model in mice. In a second step, we performed an in vivo permeability study by using rhodamine-containing cream, ointment, or gel to determinate the formulation that preserves the skin architecture and reaches deeper. The selected formulation was assayed to ensure the stability and enhanced permeation properties of the samples in an ex vivo experiment. Finally, MGDG-containing cream was assessed in the hyperplasia murine model. The results showed that pre-treatment with acetone-dissolved glycolipids reduced skin edema, epidermal thickness, and pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6, IL-17 in epidermal tissue. The in vivo and ex vivo permeation studies showed that the cream formulation had the best permeability profile. In the same way, MGDG-cream formulation showed better permeation than acetone-dissolved preparation. MGDG-cream application attenuated TPA-induced skin edema, improved histopathological features, and showed a reduction of the inflammatory cell infiltrate. In addition, this formulation inhibited epidermal expression of COX-2 in a similar way to dexamethasone. Our results suggest that an MGDG-containing cream could be an emerging therapeutic strategy for the treatment of inflammatory skin pathologies such as psoriasis.

  1. Decay accelerating factor (DAF) is anchored to membranes by a C-terminal glycolipid

    International Nuclear Information System (INIS)

    Medof, M.E.; Haas, R.; Walter, E.I.; Rosenberry, T.L.

    1986-01-01

    Purified 70 kDa membrane (m) DAF incorporates into cells when added in vitro. A 2 kDa smaller DAF form which functions extrinsically like C4bp but is unable to incorporate can be isolated from urine (u). Because of common deficits of mDAF and acetylcholinesterase (AChE) in erythrocytes (E) of patients with paroxysmal nocturnal hemoglobinuria (PNH), mDAF was analyzed for a O-terminal glycolipid membrane anchor similar to that in E AChE. Incubation of E with phosphatidylinositol-specific phospholipase C, an enzyme which cleaves a similar glycolipid anchor in trypanosome variant surface glycoproteins (mfVSGs), released 20% of the DAF antigen. The released DAF species resembled uDAF in size, extrinsic model of C4b2a decay, and lack of hydrophobicity. Reductive radiomethylation of mDAF with [ 14 C]HCHO and NaCNBH 3 revealed ethanolamine and glucosamine in proportions similar to those in the E AChE glycolipid anchor. Papain cleavage of radiomethylated mDAF released the labeled ethanolamine and glucosamine in small O-terminal fragments from the residual DAF that retained N-terminal Asp. Following labeling of the anchors of mDAF and E AChE with the lipophilic photoreagent 3-trifluoromethyl-3-(m-[ 125 I]iodophenyl)diazirine, cleavage at the glucosamine residue by deamination quantitatively released the label from both proteins. Biosynthetic labeling of Hela cells with [ 3 H]ethanolamine resulted in rapid 3 H incorporation into both 48 kDa proDAF and 70 kDa mDAF. These data indicate that mDAF is anchored by a glycolipid similar to that in E AChE, mfVSGs and Thy-1 antigen and raise the possibility that a defect in the assembly or attachment of this structure could account for the deficits of mDAF and E AChE in PNH

  2. Fossilized glycolipids reveal past oceanic N2 fixation by heterocystous cyanobacteria

    Science.gov (United States)

    Bauersachs, Thorsten; Speelman, Eveline N.; Hopmans, Ellen C.; Reichart, Gert-Jan; Schouten, Stefan; Damsté, Jaap S. Sinninghe

    2010-01-01

    N2-fixing cyanobacteria play an essential role in sustaining primary productivity in contemporary oceans and freshwater systems. However, the significance of N2-fixing cyanobacteria in past nitrogen cycling is difficult to establish as their preservation potential is relatively poor and specific biological markers are presently lacking. Heterocystous N2-fixing cyanobacteria synthesize unique long-chain glycolipids in the cell envelope covering the heterocyst cell to protect the oxygen-sensitive nitrogenase enzyme. We found that these heterocyst glycolipids are remarkably well preserved in (ancient) lacustrine and marine sediments, unambiguously indicating the (past) presence of N2-fixing heterocystous cyanobacteria. Analysis of Pleistocene sediments of the eastern Mediterranean Sea showed that heterocystous cyanobacteria, likely as epiphytes in symbiosis with planktonic diatoms, were particularly abundant during deposition of sapropels. Eocene Arctic Ocean sediments deposited at a time of large Azolla blooms contained glycolipids typical for heterocystous cyanobacteria presently living in symbiosis with the freshwater fern Azolla, indicating that this symbiosis already existed in that time. Our study thus suggests that heterocystous cyanobacteria played a major role in adding “new” fixed nitrogen to surface waters in past stratified oceans. PMID:20966349

  3. Biosynthesis and structure-activity relationships of the lipid a family of glycolipids.

    Science.gov (United States)

    Xiao, Xirui; Sankaranarayanan, Karthik; Khosla, Chaitan

    2017-10-01

    Lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, is a potent elicitor of innate immune responses in mammals. A typical LPS molecule is composed of three different structural domains: a polysaccharide called the O-antigen, a core oligosaccharide, and Lipid A. Lipid A is the amphipathic glycolipid moiety of LPS. It stimulates the immune system by tightly binding to Toll-like receptor 4. More recently, Lipid A has also been shown to activate intracellular caspase-4 and caspase-5. An impressive diversity is observed in Lipid A structures from different Gram-negative bacteria, and it is well established that subtle changes in chemical structure can result in dramatically different immune activities. For example, Lipid A from Escherichia coli is highly toxic to humans, whereas a biosynthetic precursor called Lipid IV A blocks this toxic activity, and monophosphoryl Lipid A from Salmonella minnesota is a vaccine adjuvant. Thus, an understanding of structure-activity relationships in this glycolipid family could be used to design useful immunomodulatory agents. Here we review the biosynthesis, modification, and structure-activity relationships of Lipid A. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  5. How to Lower Cholesterol

    Science.gov (United States)

    ... includes high triglyceride levels, low HDL (good) cholesterol levels, and being overweight with a large waist measurement (more than 40 inches for men and more than 35 inches for women). Physical Activity. Everyone should get regular physical activity (30 minutes ...

  6. Cholesterol and Health

    Indian Academy of Sciences (India)

    fats and oil in the diet on the other hand. Gallstones result from ... such factors as high levels of estrogens, multiple pregnancies, obesity, genetic factors and certain ... protein with an inner core of cholesterol and triglycerides. Lipoproteins are ...

  7. Reference intervals for serum total cholesterol, HDL cholesterol and ...

    African Journals Online (AJOL)

    Reference intervals of total cholesterol, HDL cholesterol and non-HDL cholesterol concentrations were determined on 309 blood donors from an urban and peri-urban population of Botswana. Using non-parametric methods to establish 2.5th and 97.5th percentiles of the distribution, the intervals were: total cholesterol 2.16 ...

  8. Cholesterol in unusual places

    International Nuclear Information System (INIS)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J

    2010-01-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  9. Cholesterol in unusual places

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

    2010-11-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  10. Glycolipid precursors for the membrane anchor of Trypanosoma brucei variant surface glycoproteins. II. Lipid structures of phosphatidylinositol-specific phospholipase C sensitive and resistant glycolipids

    International Nuclear Information System (INIS)

    Mayor, S.; Menon, A.K.; Cross, G.A.

    1990-01-01

    A common diagnostic feature of glycosylinositol phospholipid (GPI)-anchored proteins is their release from the membrane by a phosphatidylinositol-specific phospholipase C (PI-PLC). However, some GPI-anchored proteins are resistant to this enzyme. The best characterized example of this subclass is the human erythrocyte acetylcholinesterase, where the structural basis of PI-PLC resistance has been shown to be the acylation of an inositol hydroxyl group(s). Both PI-PLC-sensitive and resistant GPI-anchor precursors (P2 and P3, respectively) have been found in Trypanosoma brucei, where the major surface glycoprotein is anchored by a PI-PLC-sensitive glycolipid anchor. The accompanying paper shows that P2 and P3 have identical glycans, indistinguishable from the common core glycan found on all the characterized GPI protein anchors. This paper shows that the single difference between P2 and P3, and the basis for the PI-PLC insusceptibility of P3, is a fatty acid, ester-linked to the inositol residue in P3. The inositol-linked fatty acid can be removed by treatment with mild base to restore PI-PLC sensitivity. Biosynthetic labeling experiments with [3H]palmitic acid and [3H]myristic acid show that [3H]palmitic acid specifically labels the inositol residue in P3 while [3H]myristic acid labels the diacylglycerol portion. Possible models to account for the simultaneous presence of PI-PLC-resistant and sensitive glycolipids are discussed in the context of available information on the biosynthesis of GPI-anchors

  11. The effect of the head group on branched-alkyl chain surfactants in glycolipid/n-octane/water ternary system.

    Science.gov (United States)

    Nainggolan, Irwana; Radiman, Shahidan; Hamzah, Ahmad Sazali; Hashim, Rauzah

    2009-10-01

    Two novel glycolipids have been synthesized and their phase behaviour studied. They have been characterized using FT-IR, FAB and 13C NMR and 1H NMR to ensure the purity of novel glycolipids. The two glycolipids are distinguished based on the head group of glycolipids (monosaccharide/glucose and disaccharide/maltose). These two novel glycolipids have been used as surfactant to perform two phase diagrams. Phase behaviours that have been investigated are 2-hexyldecyl-beta-D-glucopyranoside (2-HDG)/n-octane/water ternary system and 2-hexyldecyl-beta-D-maltoside (2-HDM)/n-octane/water ternary system. SAXS and polarizing optical microscope have been used to study the phase behaviours of these two surfactants in ternary phase diagram. Study of effect of the head group on branched-alkyl chain surfactants in ternary system is a strategy to derive the structure-property relationship. For comparison, 2-HDM and 2-HDG have been used as surfactant in the same ternary system. The phase diagram of 2-hexyldecyl-beta-D-maltoside/n-octane/water ternary system exhibited a Lalpha phase at a higher concentration regime, followed with two phases and a micellar solution region in a lower concentration regime. The phase diagram of 2-HDG/water/n-octane ternary system shows hexagonal phase, cubic phase, rectangular ribbon phase, lamellar phase, cubic phase as the surfactant concentration increase.

  12. Ancient rice cultivar extensively replaces phospholipids with non-phosphorus glycolipid under phosphorus deficiency.

    Science.gov (United States)

    Tawaraya, Keitaro; Honda, Soichiro; Cheng, Weiguo; Chuba, Masaru; Okazaki, Yozo; Saito, Kazuki; Oikawa, Akira; Maruyama, Hayato; Wasaki, Jun; Wagatsuma, Tadao

    2018-02-07

    Recycling of phosphorus (P) from P-containing metabolites is an adaptive strategy of plants to overcome soil P deficiency. This study was aimed at demonstrating differences in lipid remodelling between low-P-tolerant and -sensitive rice cultivars using lipidome profiling. The rice cultivars Akamai (low-P-tolerant) and Koshihikari (low-P-sensitive) were grown in a culture solution with [2 mg l -1 (+P)] or without (-P) phosphate for 21 and 28 days after transplantation. Upper and lower leaves were collected. Lipids were extracted from the leaves and their composition was analysed by liquid chromatography/mass spectrometry (LC-MS). Phospholipids, namely phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and phosphatidylinositol (PI), lysophosphatidylcholine (lysoPC), diacylglycerol (DAG), triacylglycerol (TAG) and glycolipids, namely sulfoquinovosyl diacylglycerol (SQDG), digalactosyldiacylglycerol (DGDG), monogalactosyldiacylglycerol (MGDG) and 1,2-diacyl-3-O-alpha-glucuronosyl glycerol (GlcADG), were detected. GlcADG level was higher in both cultivars grown in -P than in +P and the increase was larger in Akamai than in Koshihikari. DGDG, MGDG and SQDG levels were higher in Akamai grown in -P than in +P and the increase was larger in the upper leaves than in the lower leaves. PC, PE, PG and PI levels were lower in both cultivars grown in -P than in +P and the decrease was larger in the lower leaves than in the upper leaves and in Akamai than in Koshihikari. Akamai catabolised more phospholipids in older leaves and synthesised glycolipids in younger leaves. These results suggested that extensive phospholipid replacement with non-phosphorus glycolipids is a mechanism underlying low-P-tolerance in rice cultivars. © 2018 Scandinavian Plant Physiology Society.

  13. Tritium labelling of a cholesterol amphiphile designed for cell membrane anchoring of proteins.

    Science.gov (United States)

    Schäfer, Balázs; Orbán, Erika; Kele, Zoltán; Tömböly, Csaba

    2015-01-01

    Cell membrane association of proteins can be achieved by the addition of lipid moieties to the polypeptide chain, and such lipid-modified proteins have important biological functions. A class of cell surface proteins contains a complex glycosylphosphatidylinositol (GPI) glycolipid at the C-terminus, and they are accumulated in cholesterol-rich membrane microdomains, that is, lipid rafts. Semisynthetic lipoproteins prepared from recombinant proteins and designed lipids are valuable probes and model systems of the membrane-associated proteins. Because GPI-anchored proteins can be reinserted into the cell membrane with the retention of the biological function, they are appropriate candidates for preparing models via reduction of the structural complexity. A synthetic headgroup was added to the 3β-hydroxyl group of cholesterol, an essential lipid component of rafts, and the resulting cholesterol derivative was used as a simplified GPI mimetic. In order to quantitate the membrane integrated GPI mimetic after the exogenous addition to live cells, a tritium labelled cholesterol anchor was prepared. The radioactive label was introduced into the headgroup, and the radiolabelled GPI mimetic anchor was obtained with a specific activity of 1.37 TBq/mmol. The headgroup labelled cholesterol derivative was applied to demonstrate the sensitive detection of the cell membrane association of the anchor under in vivo conditions. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Cholesterol and myelin biogenesis.

    Science.gov (United States)

    Saher, Gesine; Simons, Mikael

    2010-01-01

    Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

  15. Biogenesis of plasma membrane cholesterol

    International Nuclear Information System (INIS)

    Lange, Y.

    1986-01-01

    A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular cholesterol pools untouched. With this technique, the plasma membrane was shown to contain 95% of the unesterified cholesterol of cultured human fibroblasts. Cholesterol synthesized from [ 3 H] acetate moved to the plasma membrane with a half-time of 1 h at 37 0 C. They used equilibrium gradient centrifugation of homogenates of biosynthetically labeled, cholesterol oxidase treated cells to examine the distribution of newly synthesized sterols among intracellular pools. Surprisingly, lanosterol, a major precursor of cholesterol, and intracellular cholesterol both peaked at much lower buoyant density than did 3-hydroxy-3-methylglutaryl-CoA reductase. This suggests that cholesterol biosynthesis is not taken to completion in the endoplasmic reticulum. The cholesterol in the buoyant fraction eventually moved to the plasma membrane. Digitonin treatment increased the density of the newly synthesized cholesterol fractions, indicating that nascent cholesterol in transit is associated with cholesterol-rich membranes. The authors are testing the hypothesis that the pathway of cholesterol biosynthesis is spatially organized in various intracellular membranes such that the sequence of biosynthetic steps both concentrates the sterol and conveys it to the plasma membrane

  16. Inhibition of glycolipid biosynthesis by N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin protects against the inflammatory response in hapten-induced colitis

    NARCIS (Netherlands)

    Shen, Chong; Bullens, Dominique; Kasran, Ahmad; Maerten, Philippe; Boon, Louis; Aerts, Johannes M. F. G.; van Assche, Gert; Geboes, Karel; Rutgeerts, Paul; Ceuppens, Jan L.

    2004-01-01

    Since glycolipid biosynthesis is potentially involved in immunological and inflammatory responses, we tested the effect of a novel inhibitor of intracellular glycolipid biosynthesis N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) in two hapten-induced colitis models: trinitrobenzene

  17. Nanodiscs for immobilization of lipid bilayers and membrane receptors: kinetic analysis of cholera toxin binding to a glycolipid receptor

    DEFF Research Database (Denmark)

    Borch, Jonas; Torta, Federico; Sligar, Stephen G

    2008-01-01

    nanodiscs and their incorporated membrane receptors can be attached to surface plasmon resonance sensorchips and used to measure the kinetics of the interaction between soluble molecules and membrane receptors inserted in the bilayer of nanodiscs. Cholera toxin and its glycolipid receptor G(M1) constitute...... a system that can be considered a paradigm for interactions of soluble proteins with membrane receptors. In this work, we have investigated different technologies for capturing nanodiscs containing the glycolipid receptor G(M1) in lipid bilayers, enabling measurements of binding of its soluble interaction...

  18. Proteomic analysis of the metabolic adaptation of the biocontrol agent Pseudozyma flocculosa leading to glycolipid production

    Directory of Open Access Journals (Sweden)

    Bélanger Richard R

    2010-02-01

    Full Text Available Abstract The yeast-like epiphytic fungus Pseudozyma flocculosa is known to antagonize powdery mildew fungi through proliferation on colonies presumably preceded by the release of an antifungal glycolipid (flocculosin. In culture conditions, P. flocculosa can be induced to produce or not flocculosin through manipulation of the culture medium nutrients. In order to characterize and understand the metabolic changes in P. flocculosa linked to glycolipid production, we conducted a 2-DE proteomic analysis and compared the proteomic profile of P. flocculosa growing under conditions favoring the development of the fungus (control or conducive to flocculosin synthesis (stress. A large number of protein spots (771 were detected in protein extracts of the control treatment compared to only 435 matched protein spots in extracts of the stress cultures, which clearly suggests an important metabolic reorganization in slow-growing cells producing flocculosin. From the latter treatment, we were able to identify 21 protein spots that were either specific to the treatment or up-regulated significantly (2-fold increase. All of them were identified based on similarity between predicted ORF of the newly sequenced genome of P. flocculosa with Ustilago maydis' available annotated sequences. These proteins were associated with the carbon and fatty acid metabolism, and also with the filamentous change of the fungus leading to flocculosin production. This first look into the proteome of P. flocculosa suggests that flocculosin synthesis is elicited in response to specific stress or limiting conditions.

  19. The moisturizing effects of glycolipid biosurfactants, mannosylerythritol lipids, on human skin.

    Science.gov (United States)

    Yamamoto, Shuhei; Morita, Tomotake; Fukuoka, Tokuma; Imura, Tomohiro; Yanagidani, Shusaku; Sogabe, Atsushi; Kitamoto, Dai; Kitagawa, Masaru

    2012-01-01

    Glycolipid biosurfactants, such as mannosylerythritol lipids (MELs), are produced by different yeasts belonging to the genus Pseudozyma and have been attracting much attention as new cosmetic ingredients owing to their unique liquid-crystal-forming and moisturizing properties. In this study, the effects of different MEL derivatives on the skin were evaluated in detail using a three-dimensional cultured human skin model and an in vivo human study. The skin cells were cultured and treated with sodium dodecyl sulfate (SDS), and the effects of different lipids on the SDS-damaged cells were evaluated on the basis of cell viability. Most MEL derivatives efficiently recovered the viability of the cells and showed high recovery rates (over 80%) comparable with that of natural ceramide. It is interesting that the recovery rate with MEL-A prepared from olive oil was significantly higher than that of MEL-A prepared from soybean oil. The water retention properties of MEL-B were further investigated on human forearm skin in a preliminary study. Compared with the control, the aqueous solution of MEL-B (5 wt%) was estimated to considerably increase the stratum corneum water content in the skin. Moreover, perspiration on the skin surface was clearly suppressed by treatment with the MEL-B solution. These results suggest that MELs are likely to exhibit a high moisturizing action, by assisting the barrier function of the skin. Accordingly, the yeast glycolipids have a strong potential as a new ingredient for skin care products.

  20. Estrogen influences dolichyl phosphate distribution among glycolipid pools in mouse uteri

    Energy Technology Data Exchange (ETDEWEB)

    Carson, D.D.; Tang, J.; Hu, G.

    1987-03-24

    To determine the role that dolichyl phosphate availability plays in this induction, the authors studied the effects of estrogen priming on the content of dolichyl phosphate and the distribution of dolichyl phosphate among various glycolipids in uteri. Dolichol-linked saccharides were metabolically labeled to equilibrium with either (/sup 3/H)glucosamine or (/sup 3/H)mannose and extracted from primary explants of uterine tissue. The amount of dolichol-linked saccharide was calculated from the specific radioactivity determined for the corresponding sugar nucleotides extracted from the tissues. The major dolichol-linked saccharides identified were mannosylphosphoryldolichol (MPD), oligosaccharylpyrophosphorydolichol (OSL), and N,N'-diacetylchitobiosylpyrophosphoryldolichol (CBL). Estrogen increased the levels of MPD and OSL 4-fold; however, CBL levels did not change. After 3 days of treatment, the levels of these glycolipids were very similar to those in uteri from pregnant mice. The specific activity of GPD synthase was similar under all conditions studied. These studies provide the first determination of the levels of dolichol-linked saccharides in tissues and how these levels change during hormonal induction of glycoprotein assembly. Coupled with earlier studies, the present work demonstrates that among a number of key points of N-linked oligosaccharide assembly and transfer only synthesis of MPD increases coordinately with the increase observed in lipid- and protein-linked oligosaccharide assembly that occurs in vivo in response to estrogen. They suggest that control of MPD levels is an important regulatory aspect of N-linked glycoprotein assembly in this system.

  1. Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

    NARCIS (Netherlands)

    Jakulj, L.

    2013-01-01

    Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible

  2. Transintestinal cholesterol excretion in humans

    NARCIS (Netherlands)

    Reeskamp, Laurens F.; Meessen, Emma C. E.; Groen, Albert K.

    2018-01-01

    Purpose of review To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. Recent findings TICE is the net effect of cholesterol excretion by

  3. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Daisuke; Miyamoto, Ayumi; Hattori, Yuki; Komori, Takaya [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Nakamura, Takashi [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Igarashi, Tatsuhiko [Laboratory of Primate Model, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Harashima, Hideyoshi [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Sugita, Masahiko [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)

    2013-11-08

    Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection.

  4. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques

    International Nuclear Information System (INIS)

    Morita, Daisuke; Miyamoto, Ayumi; Hattori, Yuki; Komori, Takaya; Nakamura, Takashi; Igarashi, Tatsuhiko; Harashima, Hideyoshi; Sugita, Masahiko

    2013-01-01

    Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection

  5. Decay accelerating factor of complement is anchored to cells by a C-terminal glycolipid

    International Nuclear Information System (INIS)

    Medof, M.E.; Walter, E.I.; Roberts, W.L.; Haas, R.; Rosenberry, T.L.

    1986-01-01

    Membrane-associated decay accelerating factor (DAF) of human erythrocytes (E/sup hu/) was analyzed for a C-terminal glycolipid anchoring structure. Automated amino acid analysis of DAF following reductive radiomethylation revealed ethanolamine and glucosamine residues in proportions identical with those present in the E/sup hu/ acetylcholinesterase (AChE) anchor. Cleavage of radiomethylated 70-kilodalton (kDa) DAF with papain released the labeled ethanolamine and glucosamine and generated 61- and 55-kDa DAF products that retained all labeled Lys and labeled N-terminal Asp. Incubation of intact E/sup hu/ with phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves the anchors in trypanosome membrane form variant surface glycoproteins (mfVSGs) and murine thymocyte Thy-1 antigen, released 15% of the cell-associated DAF antigen. The released 67-kDa PI-PLC DAF derivative retained its ability to decay the classical C3 convertase C4b2a but was unable to membrane-incorporate and displayed physicochemical properties similar to urine DAF, a hydrophilic DAF form that can be isolated for urine. Nitrous acid deamination cleavage of E/sup hu/ DAF at glucosamine following labeling with the lipophilic photoreagent 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)diazirine ([ 125 I]TID) released the [ 125 I]TID label in a parallel fashion as from [ 125 I]TID-labeled AChE. Biosynthetic labeling of HeLa cells with [ 3 H] ethanolamine resulted in rapid 3 H incorporation into both 48-kDa pro-DAF and 72-kDa mature epithelial cell DAF. The findings indicate that DAF and AChE are anchored in E/sup hu/ by the same or a similar glycolipid structure and that, like VSGs, this structure is incorporated into DAF early in DAF biosynthesis prior to processing of pro-DAF in the Golgi

  6. Evolutionary constrained optimization

    CERN Document Server

    Deb, Kalyanmoy

    2015-01-01

    This book makes available a self-contained collection of modern research addressing the general constrained optimization problems using evolutionary algorithms. Broadly the topics covered include constraint handling for single and multi-objective optimizations; penalty function based methodology; multi-objective based methodology; new constraint handling mechanism; hybrid methodology; scaling issues in constrained optimization; design of scalable test problems; parameter adaptation in constrained optimization; handling of integer, discrete and mix variables in addition to continuous variables; application of constraint handling techniques to real-world problems; and constrained optimization in dynamic environment. There is also a separate chapter on hybrid optimization, which is gaining lots of popularity nowadays due to its capability of bridging the gap between evolutionary and classical optimization. The material in the book is useful to researchers, novice, and experts alike. The book will also be useful...

  7. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

    2008-01-01

    Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  8. Transcytosis of immunoglobulin A in the mouse enterocyte occurs through glycolipid raft- and rab17-containing compartments

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, L L; Immerdal, Lissi

    1999-01-01

    BACKGROUND & AIMS: Glycolipid "rafts" have been shown to play a role in apical membrane trafficking in the enterocyte. The present study characterized the membrane compartments of the enterocyte involved in transepithelial transport of small intestinal immunoglobulin A (IgA). Methods: Immunogold...... electron microscopy and radioactive labeling of mouse small intestinal explants were performed. RESULTS: IgA and the polymeric immunoglobulin receptor/secretory component were present in a raft compartment. Raft association occurred posttranslationally within 30 minutes, preceding secretion...... and were also frequently seen associated with the same vesicular profiles of glycolipid rafts. Colocalization of IgA and rab17, a small guanosine triphosphatase involved in transcytosis, was seen mainly along the basolateral plasma membrane and over basolateral endosomes and vesicles, but also...

  9. Correlation of bacterial viability with uptake of (14C) acetate into phenolic glycolipid-1 of Mycobacterium leprae within Schwannoma cells

    International Nuclear Information System (INIS)

    Mistry, Y.; Antia, N.H.; Mukherjee, R.

    1989-01-01

    The viability of Mycobacterium leprae, maintained within 33B Schwannoma cells, was estimated in terms of incorporation of ( 14 C) acetate into its specific phenolic glycolipid-1. This measure of viability was correlated with two other assays, viz., fluorescein diacetate/ethidium bromide staining and mouse footpad growth. Observation of a 2-fold increase in the number of intracellular Mycobacterium leprae over an experimental period of 12 days also corroborated this contention. Furthermore, on addition of anti-leprosy drugs to these intracellular Mycobacterium leprae there was significant decrease in phenolic glycolipid-1 synthesis indicative of loss of viability of the organisms. This study also established the importance of the host cell for active bacillary metabolism, as Mycobacterium leprae maintained in cell-free conditions showed no incorporation into phenolic glycolipid-1. Moreover, compromising the host's protein synthesis capacity with cycloheximide, also led to reduction in bacillary metabolism. As this system measures the metabolic synthesis of a unique Mycobacterium leprae component, it would be useful for development and screening of compounds acting against specific bacillary targets. (author). 19 refs., 5 tabs

  10. Exploring Constrained Creative Communication

    DEFF Research Database (Denmark)

    Sørensen, Jannick Kirk

    2017-01-01

    Creative collaboration via online tools offers a less ‘media rich’ exchange of information between participants than face-to-face collaboration. The participants’ freedom to communicate is restricted in means of communication, and rectified in terms of possibilities offered in the interface. How do...... these constrains influence the creative process and the outcome? In order to isolate the communication problem from the interface- and technology problem, we examine via a design game the creative communication on an open-ended task in a highly constrained setting, a design game. Via an experiment the relation...... between communicative constrains and participants’ perception of dialogue and creativity is examined. Four batches of students preparing for forming semester project groups were conducted and documented. Students were asked to create an unspecified object without any exchange of communication except...

  11. Choosing health, constrained choices.

    Science.gov (United States)

    Chee Khoon Chan

    2009-12-01

    In parallel with the neo-liberal retrenchment of the welfarist state, an increasing emphasis on the responsibility of individuals in managing their own affairs and their well-being has been evident. In the health arena for instance, this was a major theme permeating the UK government's White Paper Choosing Health: Making Healthy Choices Easier (2004), which appealed to an ethos of autonomy and self-actualization through activity and consumption which merited esteem. As a counterpoint to this growing trend of informed responsibilization, constrained choices (constrained agency) provides a useful framework for a judicious balance and sense of proportion between an individual behavioural focus and a focus on societal, systemic, and structural determinants of health and well-being. Constrained choices is also a conceptual bridge between responsibilization and population health which could be further developed within an integrative biosocial perspective one might refer to as the social ecology of health and disease.

  12. HDL cholesterol: atherosclerosis and beyond

    NARCIS (Netherlands)

    Bochem, A.E.

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western world. Myocardial infarction and stroke are the result of a compromised blood flow which may result from cholesterol accumulation in the vessel wall due to high plasma levels of LDL cholesterol. High plasma levels of HDL

  13. Evidence that a glycolipid tail anchors antigen 117 to the plasma membrane of Dictyostelium discoideum cells

    International Nuclear Information System (INIS)

    Sadeghi, H.; Da Silva, A.M.; Klein, C.

    1988-01-01

    The authors describe the biochemical features of the putative cell cohesion molecule antigen 117, indicating that it is anchored to the plasma membrane by a glycolipid tail. Antigen 117 can be radiolabeled with [ 3 H]myristate, [ 3 H]palmitate, and [ 14 C]ethanolamine. The fatty acid label is removed by periodate oxidation and nitrous acid deamination, indicating that the fatty acid is attached to the protein by a structure containing carbohydrate and an unsubstituted glucosamine. As cells develop aggregation competence, the antigen is released from the cell surface in a soluble form that can still be radiolabeled with [ 14 C]ethanolamine but not with [ 3 H]myristate of [ 3 H]-palmitate. The molecular weight of the released antigen is similar to that found in the plasma membrane, but it preferentially partitions in Triton X-114 as a hydrophilic, as opposed to a hydrophobic, protein. Plasma membranes contain the enzyme activity responsible for the release of the antigen in a soluble form

  14. Accelerated in vivo wound healing evaluation of microbial glycolipid containing ointment as a transdermal substitute.

    Science.gov (United States)

    Gupta, Sonam; Raghuwanshi, Navdeep; Varshney, Ritu; Banat, I M; Srivastava, Amit Kumar; Pruthi, Parul A; Pruthi, Vikas

    2017-10-01

    A potent biosurfactant (BS) producing Bacillus licheniformis SV1 (NCBI GenBank Accession No. KX130852) was isolated from oil contaminated soil sample. Physicochemical investigations (TLC, HPLC, FTIR, GC-MS and NMR) revealed it to be glycolipid in nature. Fibroblast culture assay showed cytocompatibility and increased cell proliferation of 3T3/NIH fibroblast cells treated with this biosurfactant when checked using MTT assay and DAPI fluorescent staining. To evaluate the wound healing potential, BS ointment was formulated and checked for its spreadability and viscosity consistency. In vivo wound healing examination of full thickness skin excision wound rat model demonstrated the prompt re-epithelialization and fibroblast cell proliferation in the early phase while quicker collagen deposition in later phases of wound healing when BS ointment was used. These results validated the potential usage of BS ointment as a transdermal substitute for faster healing of impaired skin wound. Biochemical evaluation also substantiated the highest concentration of hydroxyproline (32.18±0.46, ptreated animal tissue samples compared to the control. Hematoxylin-Eosin (H&E) and Masson's Trichrome staining validated the presence of increased amount of collagen fibers and blood vessels in the test animals treated with BS ointment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Glycolipid Biosurfactants Activate, Dimerize, and Stabilize Thermomyces lanuginosus Lipase in a pH-Dependent Fashion.

    Science.gov (United States)

    Madsen, Jens Kvist; Kaspersen, Jørn Døvling; Andersen, Camilla Bertel; Nedergaard Pedersen, Jannik; Andersen, Kell Kleiner; Pedersen, Jan Skov; Otzen, Daniel E

    2017-08-15

    We present a study of the interactions between the lipase from Thermomyces lanuginosus (TlL) and the two microbially produced biosurfactants (BSs), rhamnolipid (RL) and sophorolipid (SL). Both RL and SL are glycolipids; however, RL is anionic, while SL is a mixture of anionic and non-ionic species. We investigate the interactions of RL and SL with TlL at pH 6 and 8 and observe different effects at the two pH values. At pH 8, neither RL nor SL had any major effect on TlL stability or activity. At pH 6, in contrast, both surfactants increase TlL's thermal stability and fluorescence and activity measurements indicate interfacial activation of TlL, resulting in 3- and 6-fold improved activity in SL and RL, respectively. Nevertheless, isothermal titration calorimetry reveals binding of only a few BS molecules per lipase. Size-exclusion chromatography and small-angle X-ray scattering suggest formation of TlL dimers with binding of small amounts of either RL or SL at the dimeric interface, forming an elongated complex. We conclude that RL and SL are compatible with TlL and constitute promising green alternatives to traditional surfactants.

  16. Lipidomic Approaches towards Deciphering Glycolipids from Microalgae as a Reservoir of Bioactive Lipids

    Directory of Open Access Journals (Sweden)

    Elisabete da Costa

    2016-05-01

    Full Text Available In recent years, noteworthy research has been performed around lipids from microalgae. Among lipids, glycolipids (GLs are quite abundant in microalgae and are considered an important source of fatty acids (FAs. GLs are rich in 16- and 18-carbon saturated and unsaturated fatty acids and often contain polyunsaturated fatty acids (PUFAs like n-3 α-linolenic (ALA 18:3, eicosapentaenoic (EPA, 20:5 and docosahexaenoic (DHA, 22:6. GLs comprise three major classes: monogalactosyldiacyl glycerolipids (MGDGs, digalactosyl diacylglycerolipids (DGDGs and sulfoquinovosyl diacylglycerolipids (SQDGs, whose composition in FA directly depends on the growth conditions. Some of these lipids are high value-added compounds with antitumoral, antimicrobial and anti-inflammatory activities and also with important nutritional significance. To fully explore GLs’ bioactive properties it is necessary to fully characterize their structure and to understand the relation between the structure and their biological properties, which can be addressed using modern mass spectrometry (MS-based lipidomic approaches. This review will focus on the up-to-date FA composition of GLs identified by MS-based lipidomics and their potential as phytochemicals.

  17. Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Kawahito, Yutaka; Ichinose, Sizuko; Sano, Hajime; Tsubouchi, Yasunori; Kohno, Masataka; Yoshikawa, Toshikazu; Tokunaga, Daisaku; Hojo, Tatsuya; Harasawa, Ryo; Nakano, Teruaki; Matsuda, Kazuhiro

    2008-01-01

    Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in osteoarthritis (OA) and normal synovial tissues. Immunoelectron microscopy revealed that a part of GGPL-III antigens are located at endoplasmic reticulum. GGPL-III significantly induced TNF-α and IL-6 production from peripheral blood mononulear cells, and also proliferation of synovial fibroblasts. Further study is necessary to prove that M. fermentans is a causative microorganism of RA; however, the new mechanisms of disease pathogenesis provides hope for the development of effective and safe immunotherapeutic strategies based on the lipid-antigen, GGPL-III, in the near future

  18. Mycobacterial Phenolic Glycolipids Selectively Disable TRIF-Dependent TLR4 Signaling in Macrophages

    Directory of Open Access Journals (Sweden)

    Reid Oldenburg

    2018-01-01

    Full Text Available Phenolic glycolipids (PGLs are cell wall components of a subset of pathogenic mycobacteria, with immunomodulatory properties. Here, we show that in addition, PGLs exert antibactericidal activity by limiting the production of nitric oxide synthase (iNOS in mycobacteria-infected macrophages. PGL-mediated downregulation of iNOS was complement receptor 3-dependent and comparably induced by bacterial and purified PGLs. Using Mycobacterium leprae PGL-1 as a model, we found that PGLs dampen the toll-like receptor (TLR4 signaling pathway, with macrophage exposure to PGLs leading to significant reduction in TIR-domain-containing adapter-inducing interferon-β (TRIF protein level. PGL-driven decrease in TRIF operated posttranscriptionally and independently of Src-family tyrosine kinases, lysosomal and proteasomal degradation. It resulted in the defective production of TRIF-dependent IFN-β and CXCL10 in TLR4-stimulated macrophages, in addition to iNOS. Our results unravel a mechanism by which PGLs hijack both the bactericidal and inflammatory responses of host macrophages. Moreover, they identify TRIF as a critical node in the crosstalk between CR3 and TLR4.

  19. Differential Interaction of Synthetic Glycolipids with Biomimetic Plasma Membrane Lipids Correlates with the Plant Biological Response.

    Science.gov (United States)

    Nasir, Mehmet Nail; Lins, Laurence; Crowet, Jean-Marc; Ongena, Marc; Dorey, Stephan; Dhondt-Cordelier, Sandrine; Clément, Christophe; Bouquillon, Sandrine; Haudrechy, Arnaud; Sarazin, Catherine; Fauconnier, Marie-Laure; Nott, Katherine; Deleu, Magali

    2017-09-26

    Natural and synthetic amphiphilic molecules including lipopeptides, lipopolysaccharides, and glycolipids are able to induce defense mechanisms in plants. In the present work, the perception of two synthetic C14 rhamnolipids, namely, Alk-RL and Ac-RL, differing only at the level of the lipid tail terminal group have been investigated using biological and biophysical approaches. We showed that Alk-RL induces a stronger early signaling response in tobacco cell suspensions than does Ac-RL. The interactions of both synthetic RLs with simplified biomimetic membranes were further analyzed using experimental and in silico approaches. Our results indicate that the interactions of Alk-RL and Ac-RL with lipids were different in terms of insertion and molecular responses and were dependent on the lipid composition of model membranes. A more favorable insertion of Alk-RL than Ac-RL into lipid membranes is observed. Alk-RL forms more stable molecular assemblies than Ac-RL with phospholipids and sterols. At the molecular level, the presence of sterols tends to increase the RLs' interaction with lipid bilayers, with a fluidizing effect on the alkyl chains. Taken together, our findings suggest that the perception of these synthetic RLs at the membrane level could be related to a lipid-driven process depending on the organization of the membrane and the orientation of the RLs within the membrane and is correlated with the induction of early signaling responses in tobacco cells.

  20. A Macrophage Response to Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage in Leprosy.

    Science.gov (United States)

    Madigan, Cressida A; Cambier, C J; Kelly-Scumpia, Kindra M; Scumpia, Philip O; Cheng, Tan-Yun; Zailaa, Joseph; Bloom, Barry R; Moody, D Branch; Smale, Stephen T; Sagasti, Alvaro; Modlin, Robert L; Ramakrishnan, Lalita

    2017-08-24

    Mycobacterium leprae causes leprosy and is unique among mycobacterial diseases in producing peripheral neuropathy. This debilitating morbidity is attributed to axon demyelination resulting from direct interaction of the M. leprae-specific phenolic glycolipid 1 (PGL-1) with myelinating glia and their subsequent infection. Here, we use transparent zebrafish larvae to visualize the earliest events of M. leprae-induced nerve damage. We find that demyelination and axonal damage are not directly initiated by M. leprae but by infected macrophages that patrol axons; demyelination occurs in areas of intimate contact. PGL-1 confers this neurotoxic response on macrophages: macrophages infected with M. marinum-expressing PGL-1 also damage axons. PGL-1 induces nitric oxide synthase in infected macrophages, and the resultant increase in reactive nitrogen species damages axons by injuring their mitochondria and inducing demyelination. Our findings implicate the response of innate macrophages to M. leprae PGL-1 in initiating nerve damage in leprosy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Constrained superfields in supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Dall’Agata, Gianguido; Farakos, Fotis [Dipartimento di Fisica ed Astronomia “Galileo Galilei”, Università di Padova,Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova,Via Marzolo 8, 35131 Padova (Italy)

    2016-02-16

    We analyze constrained superfields in supergravity. We investigate the consistency and solve all known constraints, presenting a new class that may have interesting applications in the construction of inflationary models. We provide the superspace Lagrangians for minimal supergravity models based on them and write the corresponding theories in component form using a simplifying gauge for the goldstino couplings.

  2. Minimal constrained supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Cribiori, N. [Dipartimento di Fisica e Astronomia “Galileo Galilei”, Università di Padova, Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova, Via Marzolo 8, 35131 Padova (Italy); Dall' Agata, G., E-mail: dallagat@pd.infn.it [Dipartimento di Fisica e Astronomia “Galileo Galilei”, Università di Padova, Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova, Via Marzolo 8, 35131 Padova (Italy); Farakos, F. [Dipartimento di Fisica e Astronomia “Galileo Galilei”, Università di Padova, Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova, Via Marzolo 8, 35131 Padova (Italy); Porrati, M. [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States)

    2017-01-10

    We describe minimal supergravity models where supersymmetry is non-linearly realized via constrained superfields. We show that the resulting actions differ from the so called “de Sitter” supergravities because we consider constraints eliminating directly the auxiliary fields of the gravity multiplet.

  3. Minimal constrained supergravity

    Directory of Open Access Journals (Sweden)

    N. Cribiori

    2017-01-01

    Full Text Available We describe minimal supergravity models where supersymmetry is non-linearly realized via constrained superfields. We show that the resulting actions differ from the so called “de Sitter” supergravities because we consider constraints eliminating directly the auxiliary fields of the gravity multiplet.

  4. Minimal constrained supergravity

    International Nuclear Information System (INIS)

    Cribiori, N.; Dall'Agata, G.; Farakos, F.; Porrati, M.

    2017-01-01

    We describe minimal supergravity models where supersymmetry is non-linearly realized via constrained superfields. We show that the resulting actions differ from the so called “de Sitter” supergravities because we consider constraints eliminating directly the auxiliary fields of the gravity multiplet.

  5. What Are High Blood Cholesterol and Triglycerides?

    Science.gov (United States)

    ... Reduction Cholesterol What Are High Blood Cholesterol and Triglycerides? Cholesterol travels to the body’s cells through the ... doctor about medicines that can help. What are triglycerides? Triglycerides are the most common type of fat ...

  6. Cholesterol Perturbs Lipid Bilayers Nonuniversally

    International Nuclear Information System (INIS)

    Pan Jianjun; Mills, Thalia T.; Tristram-Nagle, Stephanie; Nagle, John F.

    2008-01-01

    Cholesterol is well known to modulate the physical properties of biomembranes. Using modern x-ray scattering methods, we have studied the effects of cholesterol on the bending modulus K C , the thickness D HH , and the orientational order parameter S xray of lipid bilayers. We find that the effects are different for at least three classes of phospholipids characterized by different numbers of saturated hydrocarbon chains. Most strikingly, cholesterol strongly increases K C when both chains of the phospholipid are fully saturated but not at all when there are two monounsaturated chains

  7. Dietary and biliary cholesterol absorption in rats. Effect of dietary cholesterol level and cholesterol saturation of bile

    International Nuclear Information System (INIS)

    Wilson, M.D.

    1985-01-01

    The principal objective of this research was to determine if cholesterol introduced into the duodenum of rats in a micellar form as occurs with bile, is absorbed more efficiently than cholesterol presented in a nonmicellar form, as occurs with dietary cholesterol. Cholesterol absorption was measured during the constant intraduodenal infusion of liquid diets ([ 14 C] cholesterol) and artificial biles ([ 3 H] cholesterol) in thoracic lymph duct cannulated rats. Percentage absorption was calculated by dividing the rate of appearance of radiolabeled cholesterol in lymph by its rate of infusion when lymph cholesterol specific activity was constant. Results provide strong evidence that under certain conditions biliary cholesterol is more efficiently absorbed than is dietary cholesterol, and that this differential must be considered when evaluating the influence of diet or drug therapy on cholesterol absorption

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

    Directory of Open Access Journals (Sweden)

    Helio K. Takahashi

    2009-09-01

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

  9. Animal ice-binding (antifreeze) proteins and glycolipids: an overview with emphasis on physiological function.

    Science.gov (United States)

    Duman, John G

    2015-06-01

    Ice-binding proteins (IBPs) assist in subzero tolerance of multiple cold-tolerant organisms: animals, plants, fungi, bacteria etc. IBPs include: (1) antifreeze proteins (AFPs) with high thermal hysteresis antifreeze activity; (2) low thermal hysteresis IBPs; and (3) ice-nucleating proteins (INPs). Several structurally different IBPs have evolved, even within related taxa. Proteins that produce thermal hysteresis inhibit freezing by a non-colligative mechanism, whereby they adsorb onto ice crystals or ice-nucleating surfaces and prevent further growth. This lowers the so-called hysteretic freezing point below the normal equilibrium freezing/melting point, producing a difference between the two, termed thermal hysteresis. True AFPs with high thermal hysteresis are found in freeze-avoiding animals (those that must prevent freezing, as they die if frozen) especially marine fish, insects and other terrestrial arthropods where they function to prevent freezing at temperatures below those commonly experienced by the organism. Low thermal hysteresis IBPs are found in freeze-tolerant organisms (those able to survive extracellular freezing), and function to inhibit recrystallization - a potentially damaging process whereby larger ice crystals grow at the expense of smaller ones - and in some cases, prevent lethal propagation of extracellular ice into the cytoplasm. Ice-nucleator proteins inhibit supercooling and induce freezing in the extracellular fluid at high subzero temperatures in many freeze-tolerant species, thereby allowing them to control the location and temperature of ice nucleation, and the rate of ice growth. Numerous nuances to these functions have evolved. Antifreeze glycolipids with significant thermal hysteresis activity were recently identified in insects, frogs and plants. © 2015. Published by The Company of Biologists Ltd.

  10. Biosynthesis of fucose containing lacto-series glycolipids in human colonic adenocarcinoma Colo 205 cells.

    Science.gov (United States)

    Holmes, E H; Levery, S B

    1989-11-01

    Biosynthesis of fucose containing lacto-series glycolipids has been studied in human colonic adenocarcinoma Colo 205 cells. Transfer of fucose in both alpha 1----3 linkage to type 2 chain acceptors and alpha 1----4 linkage to type 1 chain acceptors was demonstrated with a Triton X-100 solubilized membrane fraction. The enzyme was found to be highly active over a broad pH range between 6.0 and 7.5. Kinetics of the transfer reactions were studied and indicated that the enzyme had an apparent Km for GDPfucose of 53 and 49 microM with acceptors nLc4 and Lc4, respectively. The apparent Km values for acceptors Lc4, nLc4, and IV3NeuAcnLc4 were determined to be 42, 18, and 26 microM, respectively. Transfer of fucose to the type 1 chain acceptor Lc4 alone and in the presence of increasing concentrations of the type 2 chain acceptor IV3NeuAcnLc4 or Gb3 suggested that both type 1 and 2 acceptors were alternate acceptors for a single enzyme. This was further established by the finding that IV3NeuAcnLc4 behaved as a competitive inhibitor of fucose transfer with respect to Lc4. Conditions were defined for preparative scale in vitro synthesis of fucosylated products of nLc6 catalyzed by the Colo 205 cell enzyme. Yields of the monofucosyl derivative of 2.5 mg (46%) and 1 mg (17%) of the difucosyl derivative were obtained from 5 mg of original nLc6. The structures of these biosynthetic products were carefully studied by 1H NMR, +FAB-MS, and methylation analysis. These studies revealed extremely high purity products composed of III3FucnLc6 and III3V3Fuc2nLc6. The significance of the nature of these products and enzymatic properties is discussed.

  11. Constrained Vapor Bubble Experiment

    Science.gov (United States)

    Gokhale, Shripad; Plawsky, Joel; Wayner, Peter C., Jr.; Zheng, Ling; Wang, Ying-Xi

    2002-11-01

    Microgravity experiments on the Constrained Vapor Bubble Heat Exchanger, CVB, are being developed for the International Space Station. In particular, we present results of a precursory experimental and theoretical study of the vertical Constrained Vapor Bubble in the Earth's environment. A novel non-isothermal experimental setup was designed and built to study the transport processes in an ethanol/quartz vertical CVB system. Temperature profiles were measured using an in situ PC (personal computer)-based LabView data acquisition system via thermocouples. Film thickness profiles were measured using interferometry. A theoretical model was developed to predict the curvature profile of the stable film in the evaporator. The concept of the total amount of evaporation, which can be obtained directly by integrating the experimental temperature profile, was introduced. Experimentally measured curvature profiles are in good agreement with modeling results. For microgravity conditions, an analytical expression, which reveals an inherent relation between temperature and curvature profiles, was derived.

  12. Constrained noninformative priors

    International Nuclear Information System (INIS)

    Atwood, C.L.

    1994-10-01

    The Jeffreys noninformative prior distribution for a single unknown parameter is the distribution corresponding to a uniform distribution in the transformed model where the unknown parameter is approximately a location parameter. To obtain a prior distribution with a specified mean but with diffusion reflecting great uncertainty, a natural generalization of the noninformative prior is the distribution corresponding to the constrained maximum entropy distribution in the transformed model. Examples are given

  13. Imaging appearances of cholesterol pneumonia

    International Nuclear Information System (INIS)

    Miao Yanwei; Zhang Jingwen; Wu Jianlin; Zhou Yong; Li Mingwu; Lei Zhen; Shi Lifu

    2006-01-01

    Objection: To analyze the imaging appearances of cholesterol pneumonia. Methods We retrospectively analyzed the X-ray and CT findings of 3 patients with cholesterol pneumonia confirmed pathologically and reviewed correlative literature. Results: Lesions similar to mass were found in X-ray and CT imaging of three cases. Two of them appeared cavity with fluid-level and one showed multiple ring enhancement after CT contrast. The course of disease was very. long and it had no respond to antibiotic therapy. Amounts of foam cells rich in cholesterol crystal were detected in pathological examination. Conclusions: Cholesterol pneumonia is a rare chronic pulmonary idiopathic disease, and the radiological findings can do some help to its diagnosis. (authors)

  14. Beta-glucans and cholesterol

    Czech Academy of Sciences Publication Activity Database

    Šíma, Petr; Vannucci, Luca; Větvička, V.

    2017-01-01

    Roč. 41, č. 4 (2017), s. 1799-1808 ISSN 1107-3756 Institutional support: RVO:61388971 Keywords : cholesterol * beta-glucans * diet Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.341, year: 2016

  15. to HDL-cholesterol functionality

    Directory of Open Access Journals (Sweden)

    Malara Marzena

    2016-05-01

    Full Text Available The purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol bring about atherosclerosis and an increased risk of cardiovascular disease (CVD which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C and increasing the HDL-cholesterol (HDL-C. However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1 and myeloperoxidase (MPO – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

  16. Cholesterol and related sterols autoxidation.

    Science.gov (United States)

    Zerbinati, Chiara; Iuliano, Luigi

    2017-10-01

    Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

  17. Production of glycolipidic bio surfactants by environment bacteria: diversity and physiological part; Production de biosurfactants glycolipidiques par les bacteries de l`environnement: diversite et role physiologique

    Energy Technology Data Exchange (ETDEWEB)

    Arino, S

    1996-10-09

    About a hundred bacterial strains, isolated from soils, polluted or not by hydrocarbons, were tested for their capacity to excrete glycosides. The biggest productions were obtained for a soluble carbon source (glycerol) in a culture medium limited in the nitrogen source. In these conditions, 18 g/l of rhamnose lipids were produced by train Pseudomonas aeruginosa GL1 in a 200 h culture. Pseudomonas aeruginosa GL1, Cellulomonas celulans SA43 and Rhodococcus erythropolis DSM 43060 were studied in detail. The bio-surfactants produced were identified respectively as rhamnose lipids, oligosaccharide lipids and trehalose lipids, using various original analytical methods. Sugars and fatty acids composing these glycolipids had been shown to be usual components of the outer part of the cell wall in these microbial species. Moreover, cell hydrophobicity of the producing bacteria varied in time during culture. These results showed that both the cell wall and the extracellular glycolipids take part in the process of hydrocarbon uptake in the polluted environments. As other bacteria of the same species from different origins present the same characteristics, it may be concluded that glycolipid excretion does not constitute a specific response for hydrocarbon assimilation. In fact, a more general physiological role of glycolipids, concerning modifications of hydrophobic interfaces between the producing bacteria and their surrounding environment, could explain the production of glycolipids, and could also be utilized in hydrocarbon uptake. (author)

  18. Modulation in the activity of purified tonoplast H+-ATPase by tonoplast glycolipids prepared from cultured rice (Oryza sativa L. var. Boro) cells.

    Science.gov (United States)

    Yamaguchi, M; Kasamo, K

    2001-05-01

    Glycolipids, phospholipids, and neutral lipids were extracted from the tonoplast fraction of cultured rice cells (Oryza sativa L. var. Boro). Acyl steryl glucoside (ASG) and glucocerebroside (GlcCer) were also prepared from this fraction. We determined the effects of these tonoplast lipids on the activity of H+-ATPase which was delipidated and purified from the tonoplast fraction. Exogenously added tonoplast phospholipids stimulated the activity of purified tonoplast H+-ATPase, but tonoplast glycolipids did not. When tonoplast glycolipids or tonoplast ASG was added in the presence of tonoplast phospholipids, they decreased the phospholipid-induced activation of the tonoplast H+-ATPase; tonoplast GlcCer only caused a small decrease. Steryl glucoside (SG) did not cause any decrease in this activation. Phospholipids, ASG, and GlcCer made up 35 mol%, 20 mol% and 7 mol% of the total lipids of the tonoplast fraction of cultured rice cells, respectively, and these glycolipid levels were enough to depress the phospholipid-induced activation of the tonoplast H+-ATPASE: These results revealed that H+-ATPase activity in the tonoplast may be modulated toward activation and depression by tonoplast phospholipids and glycolipids, respectively. The acylation of SG would be responsible for the depression in the phospholipid-induced H+-ATPase activity.

  19. Colonization of olive trees (Olea europaea L.) with the arbuscular mycorrhizal fungus Glomus sp. modified the glycolipids biosynthesis and resulted in accumulation of unsaturated fatty acids.

    Science.gov (United States)

    Mechri, Beligh; Attia, Faouzi; Tekaya, Meriem; Cheheb, Hechmi; Hammami, Mohamed

    2014-09-01

    The influence of arbuscular mycorrhizal (AM) fungi colonization on photosynthesis, mineral nutrition, the amount of phospholipids and glycolipids in the leaves of olive (Olea europaea L.) trees was investigated. After six months of growth, the rate of photosynthesis, carboxylation efficiency, transpiration and stomatal conductance in mycorrhizal (M) plants was significantly higher than that of non-mycorrhizal (NM) plants. The inoculation treatment increased the foliar P and Mg but not N. The amount of glycolipids in the leaves of M plants was significantly higher than that of NM plants. However, the amount of phospholipids in the leaves of M plants was not significantly different to that in the leaves of NM plants. Also, we observed a significant increase in the level of α-linolenic acid (C18:3ω3) in glycolipids of M plants. This work supports the view that increased glycolipids level in the leaves of M plants could be involved, at least in part, in the beneficial effects of mycorrhizal colonization on photosynthesis performance of olive trees. To our knowledge, this is the first report on the effect of AM fungi on the amount of glycolipids in the leaves of mycorrhizal plants. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Production of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall in aerosol murine models of tuberculosis.

    Science.gov (United States)

    Cardona, P J; Julián, E; Vallès, X; Gordillo, S; Muñoz, M; Luquin, M; Ausina, V

    2002-06-01

    Evolution of antibodies against glycolipids from the Mycobacterium tuberculosis cell wall has been studied for the first time in experimental murine models of tuberculosis induced by aerosol, in which infection, reinfection, reactivation, prophylaxis and treatment with antibiotics have been assayed. Results show a significant humoral response against these antigens, where diacyltrehaloses (DAT) and sulpholipid I (SL-I) elicited higher antibody levels than protein antigens like antigen 85 protein complex (Ag85), culture filtrate proteins (CFP) and purified protein derivative (PPD). Only immunoglobulin M (IgM) antibodies have been detected against DAT and SL-I. Their evolution has a positive correlation with bacillary concentration in tissues.

  1. Palmitoylated claudin7 captured in glycolipid-enriched membrane microdomains promotes metastasis via associated transmembrane and cytosolic molecules

    OpenAIRE

    Thuma, Florian; Heiler, Sarah; Schn?lzer, Martina; Z?ller, Margot

    2016-01-01

    In epithelial cells claudin7 (cld7) is a major component of tight junctions, but is also recovered from glycolipid-enriched membrane microdomains (GEM). In tumor cells, too, cld7 exists in two stages. Only GEM-located cld7, which is palmitoylated, promotes metastasis. Searching for the underlying mechanism(s) revealed the following. The metastatic capacity of the rat pancreatic adenocarcinoma cell line ASML is lost by a knockdown (kd) of cld7 and is not regained by rescuing cld7 with a mutate...

  2. High Cholesterol in Children and Teens

    Science.gov (United States)

    ... dairy products. The body needs some cholesterol to work properly. But if your child or teen has high cholesterol (too much cholesterol in the blood), he or she has a higher risk of coronary artery disease and other heart diseases. What causes high cholesterol in children and teens? Three main ...

  3. Cholesterol Medicines: MedlinePlus Health Topic

    Science.gov (United States)

    ... heart diseases . There are two main types of cholesterol. LDL is the "bad" cholesterol. A high LDL level leads to a buildup of cholesterol in ... 75 years old, you have diabetes, and your LDL cholesterol level is 70 mg/dL or higher You ...

  4. Niacin to Boost Your HDL "Good" Cholesterol

    Science.gov (United States)

    Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

  5. Ring-constrained Join

    DEFF Research Database (Denmark)

    Yiu, Man Lung; Karras, Panagiotis; Mamoulis, Nikos

    2008-01-01

    . This new operation has important applications in decision support, e.g., placing recycling stations at fair locations between restaurants and residential complexes. Clearly, RCJ is defined based on a geometric constraint but not on distances between points. Thus, our operation is fundamentally different......We introduce a novel spatial join operator, the ring-constrained join (RCJ). Given two sets P and Q of spatial points, the result of RCJ consists of pairs (p, q) (where p ε P, q ε Q) satisfying an intuitive geometric constraint: the smallest circle enclosing p and q contains no other points in P, Q...

  6. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  7. Seasonal lake surface water temperature trends reflected by heterocyst glycolipid-based molecular thermometers

    Science.gov (United States)

    Bauersachs, T.; Rochelmeier, J.; Schwark, L.

    2015-06-01

    It has been demonstrated that the relative distribution of heterocyst glycolipids (HGs) in cultures of N2-fixing heterocystous cyanobacteria is largely controlled by growth temperature, suggesting a potential use of these components in paleoenvironmental studies. Here, we investigated the effect of environmental parameters (e.g., surface water temperatures, oxygen concentrations and pH) on the distribution of HGs in a natural system using water column filtrates collected from Lake Schreventeich (Kiel, Germany) from late July to the end of October 2013. HPLC-ESI/MS (high-performance liquid chromatography coupled to electrospray ionization-mass spectrometry) analysis revealed a dominance of 1-(O-hexose)-3,25-hexacosanediols (HG26 diols) and 1-(O-hexose)-3-keto-25-hexacosanol (HG26 keto-ol) in the solvent-extracted water column filtrates, which were accompanied by minor abundances of 1-(O-hexose)-3,27-octacosanediol (HG28 diol) and 1-(O-hexose)-3-keto-27-octacosanol (HG28 keto-ol) as well as 1-(O-hexose)-3,25,27-octacosanetriol (HG28 triol) and 1-(O-hexose)-3-keto-25,27-octacosanediol (HG28 keto-diol). Fractional abundances of alcoholic and ketonic HGs generally showed strong linear correlations with surface water temperatures and no or only weak linear correlations with both oxygen concentrations and pH. Changes in the distribution of the most abundant diol and keto-ol (e.g., HG26 diol and HG26 keto-ol) were quantitatively expressed as the HDI26 (heterocyst diol index of 26 carbon atoms) with values of this index ranging from 0.89 in mid-August to 0.66 in mid-October. An average HDI26 value of 0.79, which translates into a calculated surface water temperature of 15.8 ± 0.3 °C, was obtained from surface sediments collected from Lake Schreventeich. This temperature - and temperatures obtained from other HG indices (e.g., HDI28 and HTI28) - is similar to the one measured during maximum cyanobacterial productivity in early to mid-September and suggests that HGs

  8. Detecting Protein-Glycolipid Interactions Using Glycomicelles and CaR-ESI-MS.

    Science.gov (United States)

    Han, Ling; Kitova, Elena N; Klassen, John S

    2016-11-01

    This study reports on the use of the catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) assay, combined with glycomicelles, as a method for detecting specific interactions between water-soluble proteins and glycolipids (GLs) in aqueous solution. The B subunit homopentamers of cholera toxin (CTB 5 ) and Shiga toxin type 1 B (Stx1B 5 ) and the gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, and GD2 served as model systems for this study. The CTB 5 exhibits broad specificity for gangliosides and binds to GM1, GM2, GM3, GD1a, GD1b, and GT1b; Stx1B 5 does not recognize gangliosides. The CaR-ESI-MS assay was used to analyze solutions of CTB 5 or Stx1B 5 and individual gangliosides (GM1, GM2, GM3, GD1a, GD1b, GT1b, and GD2) or mixtures thereof. The high affinity interaction of CTB 5 with GM1 was successfully detected. However, the apparent affinity, as determined from the mass spectra, is significantly lower than that of the corresponding pentasaccharide or when GM1 is presented in model membranes such as nanodiscs. Interactions between CTB 5 and the low affinity gangliosides GD1a, GD1b, and GT1b, as well as GD2, which served as a negative control, were detected; no binding of CTB 5 to GM2 or GM3 was observed. The CaR-ESI-MS results obtained for Stx1B 5 reveal that nonspecific protein-ganglioside binding can occur during the ESI process, although the extent of binding varies between gangliosides. Consequently, interactions detected for CTB 5 with GD1a, GD1b, and GT1b are likely nonspecific in origin. Taken together, these results reveal that the CaR-ESI-MS/glycomicelle approach for detecting protein-GL interactions is prone to false positives and false negatives and must be used with caution. Graphical Abstract GRAPHICAL ABSTRACT TEXT HERE] -->.

  9. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam; Noutsi, Bakiza Kamal; Chaieb, Saharoui

    2016-01-01

    to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration

  10. Detecting Protein-Glycolipid Interactions Using CaR-ESI-MS and Model Membranes: Comparison of Pre-loaded and Passively Loaded Picodiscs

    Science.gov (United States)

    Li, Jun; Han, Ling; Li, Jianing; Kitova, Elena N.; Xiong, Zi Jian; Privé, Gilbert G.; Klassen, John S.

    2018-04-01

    Catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS), implemented using model membranes (MMs), is a promising approach for the discovery of glycolipid ligands of glycan-binding proteins (GBPs). Picodiscs (PDs), which are lipid-transporting complexes composed of the human sphingolipid activator protein saposin A and phospholipids, have proven to be useful MMs for such studies. The present work compares the use of conventional (pre-loaded) PDs with passively loaded PDs (PLPDs) for CaR-ESI-MS screening of glycolipids against cholera toxin B subunit homopentamer (CTB5). The pre-loaded PDs were prepared from a mixture of purified glycolipid and phospholipid or a mixture of lipids extracted from tissue, while the PLPDs were prepared by incubating PDs containing only phospholipid with glycolipid-containing lipid mixtures in aqueous solution. Time-dependent changes in the composition of the PLPDs produced by incubation with glycomicelles of the ganglioside GM1 were monitored using collision-induced dissociation of the gaseous PD ions and from the extent of ganglioside binding to CTB5 measured by ESI-MS. GM1 incorporation into PDs was evident within a few hours of incubation. At incubation times ≥ 10 days, GM1 binding to CTB5 was indistinguishable from that observed with pre-loaded PDs produced directly from GM1 at the same concentration. Comparison of ganglioside binding to CTB5 measured for pre-loaded PDs and PLPDs prepared from glycolipids extracted from pig and mouse brain revealed that the PLPDs allow for the detection of a greater number of ganglioside ligands. Together, the results of this study suggest PLPDs may have advantages over conventionally prepared PDs for screening glycolipids against GBPs using CaR-ESI-MS. [Figure not available: see fulltext.

  11. Binding of fluorescently labeled cholera toxin subunit B to glycolipids in the human submandibular gland and inhibition of binding by periodate oxidation and by galactose

    DEFF Research Database (Denmark)

    Kirkeby, S

    2016-01-01

    FITC-labeled cholera toxin subunit B (CTB) stained the surfaces of cells of mucous acini in the submandibular gland. CTB, also called choleragenoid, binds to the GM1 glycolipid in the cell membrane. The binding in most acini was inhibited by periodic acid oxidation of the sections, while some acini...... to the internal galactose residue linked to GalNAc, as in the GM1 glycolipid. Inhibition of the GM1 receptor binding to cholera toxin has potential for protection of humans against cholera. Galactose and agents that modify sialic acid inhibit the accessibility of the toxin to the GM1 carbohydrate receptor. Human...

  12. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

    Energy Technology Data Exchange (ETDEWEB)

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.; Rapson, N.; Dudley, H.A.

    1987-10-01

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and /sup 75/selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.

  13. Multiplatform Mass Spectrometry-Based Approach Identifies Extracellular Glycolipids of the Yeast Rhodotorula babjevae UCDFST 04-877.

    Science.gov (United States)

    Cajka, Tomas; Garay, Luis A; Sitepu, Irnayuli R; Boundy-Mills, Kyria L; Fiehn, Oliver

    2016-10-28

    A multiplatform mass spectrometry-based approach was used for elucidating extracellular lipids with biosurfactant properties produced by the oleaginous yeast Rhodotorula babjevae UCDFST 04-877. This strain secreted 8.6 ± 0.1 g/L extracellular lipids when grown in a benchtop bioreactor fed with 100 g/L glucose in medium without addition of hydrophobic substrate, such as oleic acid. Untargeted reversed-phase liquid chromatography-quadrupole/time-of-flight mass spectrometry (QTOFMS) detected native glycolipid molecules with masses of 574-716 Da. After hydrolysis into the fatty acid and sugar components and hydrophilic interaction chromatography-QTOFMS analysis, the extracellular lipids were found to consist of hydroxy fatty acids and sugar alcohols. Derivatization and chiral separation gas chromatography-mass spectrometry (GC-MS) identified these components as d-arabitol, d-mannitol, (R)-3-hydroxymyristate, (R)-3-hydroxypalmitate, and (R)-3-hydroxystearate. In order to assemble these substructures back into intact glycolipids that were detected in the initial screen, potential structures were in-silico acetylated to match the observed molar masses and subsequently characterized by matching predicted and observed MS/MS fragmentation using the Mass Frontier software program. Eleven species of acetylated sugar alcohol esters of hydroxy fatty acids were characterized for this yeast strain.

  14. Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

    International Nuclear Information System (INIS)

    Aldridge, M.C.; Chadwick, S.J.; Cheslyn-Curtis, S.; Rapson, N.; Dudley, H.A.

    1987-01-01

    To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and 75 selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES

  15. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne

    2016-01-01

    According to the World Health Organization the number one cause of death throughout the world is cardiovascular disease. Therefore, there is an urgent need for new therapeutic strategies to prevent and treat cardiovascular disease. One possible way is to target the HDL-driven reverse cholesterol

  16. Cholesterol Levels: What You Need to Know: MedlinePlus Health Topic

    Science.gov (United States)

    ... lipoprotein ( LDL ) cholesterol and high-density lipoprotein ( HDL ) cholesterol. LDL (bad) cholesterol - the main source of cholesterol buildup ... Teens How to Lower Cholesterol How to Lower Cholesterol with Diet LDL: The "Bad" Cholesterol Nutrition Statins Triglycerides VLDL Cholesterol ...

  17. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

  18. Sharp spatially constrained inversion

    DEFF Research Database (Denmark)

    Vignoli, Giulio G.; Fiandaca, Gianluca G.; Christiansen, Anders Vest C A.V.C.

    2013-01-01

    We present sharp reconstruction of multi-layer models using a spatially constrained inversion with minimum gradient support regularization. In particular, its application to airborne electromagnetic data is discussed. Airborne surveys produce extremely large datasets, traditionally inverted...... by using smoothly varying 1D models. Smoothness is a result of the regularization constraints applied to address the inversion ill-posedness. The standard Occam-type regularized multi-layer inversion produces results where boundaries between layers are smeared. The sharp regularization overcomes...... inversions are compared against classical smooth results and available boreholes. With the focusing approach, the obtained blocky results agree with the underlying geology and allow for easier interpretation by the end-user....

  19. The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

    OpenAIRE

    Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.

    2009-01-01

    Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-choleste...

  20. Lecithin intake and serum cholesterol.

    NARCIS (Netherlands)

    Knuiman, J.T.; Beynen, A.C.; Katan, M.B.

    1989-01-01

    To find out whether the consumption of lecithin has a more beneficial effect on serum cholesterol than does the consumption of equivalent amounts of polyunsaturated oils, we scrutinized 24 studies on the effect of supplementary lecithin intakes ranging from 1 to 54 mg/d. Most of the studies lacked

  1. The ABC of cholesterol transport

    NARCIS (Netherlands)

    Plösch, Torsten

    2004-01-01

    Cholesterol fulfills an indispensable role in mammalian physiology. It is an important constituent of all cell membranes. Furthermore, it is the precursor of steroid hormones, which regulate a variety of physiological functions, and of bile salts, which are necessary for the generation of bile flow

  2. Membrane Cholesterol Modulates Superwarfarin Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

  3. Cholesterol autoxidation in phospholipid membrane bilayers

    International Nuclear Information System (INIS)

    Sevanian, A.; McLeod, L.L.

    1987-01-01

    Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation

  4. Hyperreactive malarial splenomegaly is associated with low levels of antibodies against red blood cell and Plasmodium falciparum derived glycolipids in Yanomami Amerindians from Venezuela.

    Science.gov (United States)

    Vivas, Livia; O'Dea, Kieran P; Noya, Oscar; Pabon, Rosalba; Magris, Magda; Botto, Carlos; Holder, Anthony A; Brown, K Neil

    2008-03-01

    The immunological basis of the aberrant immune response in hyperreactive malarial splenomegaly (HMS) is poorly understood, but believed to be associated with polyclonal B cell activation by an unidentified malaria mitogen, leading to unregulated immunoglobulin and autoantibody production. HMS has been previously reported in Yanomami communities in the Upper Orinoco region of the Venezuelan Amazon. To investigate a possible association between antibody responses against Plasmodium falciparum and uninfected red blood cell (URBC) glycolipids and splenomegaly, a direct comparison of the parasite versus host anti-glycolipid antibody responses was made in an isolated community of this area. The anti-P. falciparum glycolipid (Pfglp) response was IgG3 dominated, whereas the uninfected red blood cell glycolipid (URBCglp) response showed a predominance of IgG1. The levels of IgG1 against Pfglp, and of IgG4 and IgM against URBCglp were significantly higher in women, while the anti-Pfglp or URBCglp IgM levels were inversely correlated with the degree of splenomegaly. Overall, these results suggest differential regulation of anti-parasite and autoreactive responses and that these responses may be linked to the development and evolution of HMS in this population exposed to endemic malaria. The high mortality rates associated with HMS point out that its early diagnosis together with the implementation of malaria control measures in these isolated Amerindian communities are a priority.

  5. Early cosmology constrained

    Energy Technology Data Exchange (ETDEWEB)

    Verde, Licia; Jimenez, Raul [Institute of Cosmos Sciences, University of Barcelona, IEEC-UB, Martí Franquès, 1, E08028 Barcelona (Spain); Bellini, Emilio [University of Oxford, Denys Wilkinson Building, Keble Road, Oxford, OX1 3RH (United Kingdom); Pigozzo, Cassio [Instituto de Física, Universidade Federal da Bahia, Salvador, BA (Brazil); Heavens, Alan F., E-mail: liciaverde@icc.ub.edu, E-mail: emilio.bellini@physics.ox.ac.uk, E-mail: cpigozzo@ufba.br, E-mail: a.heavens@imperial.ac.uk, E-mail: raul.jimenez@icc.ub.edu [Imperial Centre for Inference and Cosmology (ICIC), Imperial College, Blackett Laboratory, Prince Consort Road, London SW7 2AZ (United Kingdom)

    2017-04-01

    We investigate our knowledge of early universe cosmology by exploring how much additional energy density can be placed in different components beyond those in the ΛCDM model. To do this we use a method to separate early- and late-universe information enclosed in observational data, thus markedly reducing the model-dependency of the conclusions. We find that the 95% credibility regions for extra energy components of the early universe at recombination are: non-accelerating additional fluid density parameter Ω{sub MR} < 0.006 and extra radiation parameterised as extra effective neutrino species 2.3 < N {sub eff} < 3.2 when imposing flatness. Our constraints thus show that even when analyzing the data in this largely model-independent way, the possibility of hiding extra energy components beyond ΛCDM in the early universe is seriously constrained by current observations. We also find that the standard ruler, the sound horizon at radiation drag, can be well determined in a way that does not depend on late-time Universe assumptions, but depends strongly on early-time physics and in particular on additional components that behave like radiation. We find that the standard ruler length determined in this way is r {sub s} = 147.4 ± 0.7 Mpc if the radiation and neutrino components are standard, but the uncertainty increases by an order of magnitude when non-standard dark radiation components are allowed, to r {sub s} = 150 ± 5 Mpc.

  6. Covalent immobilization of cholesterol esterase and cholesterol oxidase on polyaniline films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Solanki, Pratima R. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Pandey, M.K. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India)]. E-mail: bansi@mail.nplindia.ernet.in

    2006-05-24

    Cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) have been covalently immobilized on electrochemically prepared polyaniline (PANI) films. These PANI/ChEt/ChOx enzyme films have been characterized using UV-visible, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Electrochemical behavior of these films has been studied using cyclic voltammetry (CV) and amperometric techniques, respectively. The PANI/ChEt/ChOx enzyme films show broad oxidation peak from 0.2 to 0.5 V. These PANI/ChEt/ChOx biosensing electrodes have a response time of about 40 s, linearity from 50 to 500 mg/dl of cholesterol oleate concentration. These PANI/ChEt/ChOx films are thermally stable up to 46 deg. C. This polyaniline based cholesterol biosensor has optimum pH in the range of 6.5-7.5, sensitivity as 7.5 x 10{sup -4} nA/mg dl and a lifetime of about 6 weeks.

  7. Nanoscale Membrane Domain Formation Driven by Cholesterol

    DEFF Research Database (Denmark)

    Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

    2017-01-01

    Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

  8. Cholesterol, bile acid and triglyceride metabolism intertwined

    NARCIS (Netherlands)

    Schonewille, Marleen

    2016-01-01

    Hyperlipidemie wordt gekarakteriseerd door verhoogd plasma cholesterol en/of triglyceriden en sterk geassocieerd met het risico op cardiovasculaire aandoeningen. Dit proefschrift beschrijft onderzoek naar de regulatie van plasma cholesterol en triglyceriden concentraties en de achterliggende

  9. Cholesterol Level: Can It Be Too Low?

    Science.gov (United States)

    ... total cholesterol level has been associated with some health problems. Doctors are still trying to find out more about the connection between low cholesterol and health risks. There is no consensus on how to ...

  10. Cholesterol: the debate should be terminated.

    Science.gov (United States)

    Nathan, David G

    2017-07-01

    Here, I offer personal perspectives on cholesterol homeostasis that reflect my belief that certain aspects of the debate have been overstated.-Nathan, D. G. Cholesterol: the debate should be terminated. © FASEB.

  11. Phytosterol glycosides reduce cholesterol absorption in humans

    OpenAIRE

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series ...

  12. Anti-phenolic glycolipid-I (PGL-I determination using blood collection on filter paper in leprosy patients

    Directory of Open Access Journals (Sweden)

    TOMIMORI-YAMASHITA Jane

    1999-01-01

    Full Text Available The authors studied 70 leprosy patients and 20 normal individuals, comparing the traditional sera collection method and the finger prick blood with the conservation on filter paper for specific antibodies against the native phenolic glycolipid-I (PGL-I from Mycobacterium leprae. The finger prick blood dried on filter paper was eluated in phosphate buffer saline (PBS containing 0.5% gelatin. The classical method for native PGL-I was performed for these eluates, and compared with the antibody determination for sera. It was observed that there is a straight correlation comparing these two methods; although the titles found for the eluates were lower than those obtained for serology. This blood collection method could be useful for investigation of new leprosy cases in field, specially in contacts individuals.

  13. Constraining neutrinoless double beta decay

    International Nuclear Information System (INIS)

    Dorame, L.; Meloni, D.; Morisi, S.; Peinado, E.; Valle, J.W.F.

    2012-01-01

    A class of discrete flavor-symmetry-based models predicts constrained neutrino mass matrix schemes that lead to specific neutrino mass sum-rules (MSR). We show how these theories may constrain the absolute scale of neutrino mass, leading in most of the cases to a lower bound on the neutrinoless double beta decay effective amplitude.

  14. Intestinal cholesterol secretion: future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  15. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  16. Isolation of Cholesterol from an Egg Yolk

    Science.gov (United States)

    Taber, Douglass F.; Li, Rui; Anson, Cory M.

    2011-01-01

    A simple procedure for the isolation of the cholesterol, by hydrolysis and extraction followed by column chromatography, is described. The cholesterol can be further purified by complexation with oxalic acid. It can also be oxidized and conjugated to cholestenone. The source of the cholesterol is one egg yolk, which contains about 200 mg of…

  17. Topical cholesterol in clofazimine induced ichthyosis

    Directory of Open Access Journals (Sweden)

    Pandey S

    1994-01-01

    Full Text Available Topical application of 10% cholesterol in petrolatum significantly (P< 0.05 controlled the development of ichthyosis in 62 patients taking 100 mg clofazimine daily for a period of 3 months. However, topical cholesterol application did not affect the lowering of serum cholesterol induced by oral clofazimine. Probable mechanism of action is being discussed.

  18. Production of a new glycolipid biosurfactant from marine Nocardiopsis lucentensis MSA04 in solid-state cultivation.

    Science.gov (United States)

    Kiran, G Seghal; Thomas, T Anto; Selvin, Joseph

    2010-06-15

    Considering the need of potential biosurfactant producers and economic production processes using industrial waste, the present study aims to develop solid-state culture (SSC) of a marine actinobacterium for biosurfactant production. A potential biosurfactant producer Nocardiopsis lucentensis MSA04 was isolated from the marine sponge Dendrilla nigra. Among the substrates screened, wheat bran increased the production significantly (E(24) 25%) followed by oil seed cake and industrial waste such as tannery pretreated sludge, treated molasses (distillery waste) and pretreated molasses. Enhanced biosurfactant production was achieved under SSC conditions using kerosene as carbon source, beef extract as nitrogen source and wheat bran as substrate. The maximum production of biosurfactant by MSA04 occurred at a C/N ratio of 0.5 envisaging that a higher amount of nitrogen source is required by the strain compared to that of the carbon source. The kerosene and beef extract interactively increase the production and a stable production was attained with the influence of both factors independently. A significant interactive influence of secondary control factors such as copper sulfate and inoculum size was validated in response surface methods-based experiments. The surface active compound produced by MSA04 was characterized as glycolipid with a hydrophobic non-polar hydrocarbon chain (nonanoic acid methyl ester) and hydrophilic sugar, 3-acetyl 2,5 dimethyl furan. In conclusion, the strain N. lucentensis MSA04 was a potential source of glycolipid biosurfactant, could be used for the development of bioremediation processes in the marine environment. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Distributions of Heterocyst Glycolipids in Settling Particulate Matter Record Ecological and Environmental Parameters in a Tropical Lake

    Science.gov (United States)

    Meegan Kumar, D.; Hopmans, E.; S Sinninghe Damsté, J.; Schouten, S.; Bauersachs, T.; Werne, J. P.

    2017-12-01

    Temperature is a critical component of paleoenvironmental reconstructions, yet it is notoriously difficult to measure in terrestrial archives. Presented here is an investigation of unique glycolipids produced by heterocystous cyanobacteria, so-called heterocyst glycolipids (HGs), in the water column of Lake Malawi (East Africa). The goal of the study is to evaluate the potential of HGs to function as a paleotemperature proxy in tropical lacustrine environments. HGs in Lake Malawi were extracted from settling particulate matter (SPM) collected at bi-monthly intervals from 2011 - 2013. Sediment traps were moored in the metalimnion of both the north and south basins of the lake in order to evaluate the spatial and the temporal trends in lipid production and export. This study is the first to analyze HGs in SPM and contains the longest time-series of HG production in a natural environment to date. HGs are consistently present throughout the three-year study period, but maximum fluxes occur annually in December, coincident with the timing of cyanobacterial blooms in the lake. HGs in SPM appear to be sourced from living cyanobacteria populations, indicating rapid export of the lipids through the water column. Temperatures reconstructed with published HG-based indices, which are derived from the relative abundances of HG diols and triols to HG keto-(di)ols, do not accurately reflect the seasonal variability in measured surface water temperatures. Rather, the production of C28 HG keto-ols appears to be related to the timing of heterocyst differentiation. Heterocystous cyanobacteria in Lake Malawi may instead respond to growth temperatures by elongating the alkyl side chain of HG diols, as indicated by increases in the abundance of the C28 HG diol relative to the C26 HG diol with warmer surface water temperatures. Distributions of HGs thus may indeed provide a novel tool for paleotemperature reconstructions in tropical lakes.

  20. C5 glycolipids of heterocystous cyanobacteria track symbiont abundance in the diatom Hemiaulus hauckii across the tropical North Atlantic

    Science.gov (United States)

    Bale, Nicole J.; Villareal, Tracy A.; Hopmans, Ellen C.; Brussaard, Corina P. D.; Besseling, Marc; Dorhout, Denise; Sinninghe Damsté, Jaap S.; Schouten, Stefan

    2018-03-01

    Diatom-diazotroph associations (DDAs) include marine heterocystous cyanobacteria found as exosymbionts and endosymbionts in multiple diatom species. Heterocysts are the site of N2 fixation and have thickened cell walls containing unique heterocyst glycolipids which maintain a low oxygen environment within the heterocyst. The endosymbiotic cyanobacterium Richelia intracellularis found in species of the diatom genus Hemiaulus and Rhizosolenia makes heterocyst glycolipids (HGs) which are composed of C30 and C32 diols and triols with pentose (C5) moieties that are distinct from limnetic cyanobacterial HGs with predominantly hexose (C6) moieties. Here we applied a method for analysis of intact polar lipids to the study of HGs in suspended particulate matter (SPM) and surface sediment from across the tropical North Atlantic. The study focused on the Amazon plume region, where DDAs are documented to form extensive surface blooms, in order to examine the utility of C5 HGs as markers for DDAs as well as their transportation to underlying sediments. C30 and C32 triols with C5 pentose moieties were detected in both marine SPM and surface sediments. We found a significant correlation between the water column concentration of these long-chain C5 HGs and DDA symbiont counts. In particular, the concentrations of both the C5 HGs (1-(O-ribose)-3,27,29-triacontanetriol (C5 HG30 triol) and 1-(O-ribose)-3,29,31-dotriacontanetriol (C5 HG32 triol)) in SPM exhibited a significant correlation with the number of Hemiaulus hauckii symbionts. This result strengthens the idea that long-chain C5 HGs can be applied as biomarkers for marine endosymbiotic heterocystous cyanobacteria. The presence of the same C5 HGs in surface sediment provides evidence that they are effectively transported to the sediment and hence have potential as biomarkers for studies of the contribution of DDAs to the paleo-marine N cycle.

  1. Peptide mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K.; Johansson, Jan

    2013-04-09

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  2. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam

    2016-06-01

    Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

  3. Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

    International Nuclear Information System (INIS)

    Dallongeville, J.; Davignon, J.; Lussier-Cacan, S.

    1990-01-01

    The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with [ 14 C]sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans

  4. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel

    2012-01-01

    Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport...... that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy...... and by multiphoton microscopy are described. Some label-free methods for imaging cholesterol itself are also discussed briefly....

  5. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol

  6. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

    NARCIS (Netherlands)

    Boer, J.F. de; Schonewille, M.; Boesjes, M.; Wolters, H.; Bloks, V.W.; Bos, T.; Dijk, T.H. van; Jurdzinski, A.; Boverhof, R.; Wolters, J.C.; Kuivenhoven, J.A.; Deursen, J.M.A. van; Elferink, R.P.; Moschetta, A.; Kremoser, C.; Verkade, H.J.; Kuipers, F.; Groen, A.K.

    2017-01-01

    BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE)

  7. Constrained evolution in numerical relativity

    Science.gov (United States)

    Anderson, Matthew William

    The strongest potential source of gravitational radiation for current and future detectors is the merger of binary black holes. Full numerical simulation of such mergers can provide realistic signal predictions and enhance the probability of detection. Numerical simulation of the Einstein equations, however, is fraught with difficulty. Stability even in static test cases of single black holes has proven elusive. Common to unstable simulations is the growth of constraint violations. This work examines the effect of controlling the growth of constraint violations by solving the constraints periodically during a simulation, an approach called constrained evolution. The effects of constrained evolution are contrasted with the results of unconstrained evolution, evolution where the constraints are not solved during the course of a simulation. Two different formulations of the Einstein equations are examined: the standard ADM formulation and the generalized Frittelli-Reula formulation. In most cases constrained evolution vastly improves the stability of a simulation at minimal computational cost when compared with unconstrained evolution. However, in the more demanding test cases examined, constrained evolution fails to produce simulations with long-term stability in spite of producing improvements in simulation lifetime when compared with unconstrained evolution. Constrained evolution is also examined in conjunction with a wide variety of promising numerical techniques, including mesh refinement and overlapping Cartesian and spherical computational grids. Constrained evolution in boosted black hole spacetimes is investigated using overlapping grids. Constrained evolution proves to be central to the host of innovations required in carrying out such intensive simulations.

  8. Intracellular transport of cholesterol in mammalian cells

    International Nuclear Information System (INIS)

    Brasaemle, D.L.

    1989-01-01

    The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of [ 3 H]cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth

  9. Cholesterol

    Science.gov (United States)

    ... eating habits, such as eating lots of bad fats. One type, saturated fat, is found in some meats, dairy products, chocolate, ... goods, and deep-fried and processed foods. Another type, trans fat, is in some fried and processed foods. Eating ...

  10. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers......, at least initially, an intralayer cholesterol rearrangement in a single-crystal-to-single-crystal transition. The preferred nucleation of the monoclinic phase of cholesterol . H2O followed by transformation to the stable monohydrate phase may be associated with an energetically more stable cholesterol...... bilayer arrangement of the former and a more favorable hydrogen-bonding arrangement of the latter. The relevance of this nucleation process of cholesterol monohydrate to pathological crystallization of cholesterol from cell biomembranes is discussed....

  11. Lightweight cryptography for constrained devices

    DEFF Research Database (Denmark)

    Alippi, Cesare; Bogdanov, Andrey; Regazzoni, Francesco

    2014-01-01

    Lightweight cryptography is a rapidly evolving research field that responds to the request for security in resource constrained devices. This need arises from crucial pervasive IT applications, such as those based on RFID tags where cost and energy constraints drastically limit the solution...... complexity, with the consequence that traditional cryptography solutions become too costly to be implemented. In this paper, we survey design strategies and techniques suitable for implementing security primitives in constrained devices....

  12. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  13. The cholesterol space of the rat

    International Nuclear Information System (INIS)

    Chevallier, F.

    1959-01-01

    The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [fr

  14. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  15. Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

    Science.gov (United States)

    Venkataswamy, Manjunatha M; Ng, Tony W; Kharkwal, Shalu S; Carreño, Leandro J; Johnson, Alison J; Kunnath-Velayudhan, Shajo; Liu, Zheng; Bittman, Robert; Jervis, Peter J; Cox, Liam R; Besra, Gurdyal S; Wen, Xiangshu; Yuan, Weiming; Tsuji, Moriya; Li, Xiangming; Ho, David D; Chan, John; Lee, Sunhee; Frothingham, Richard; Haynes, Barton F; Panas, Michael W; Gillard, Geoffrey O; Sixsmith, Jaimie D; Korioth-Schmitz, Birgit; Schmitz, Joern E; Larsen, Michelle H; Jacobs, William R; Porcelli, Steven A

    2014-01-01

    Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

  16. Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

    Directory of Open Access Journals (Sweden)

    Manjunatha M Venkataswamy

    Full Text Available Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag. We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

  17. Analysis of NMR spectra of sugar chains of glycolipids by multiple relayed COSY and 2D homonuclear Hartman-Hahn spectroscopy

    International Nuclear Information System (INIS)

    Inagaki, F.; Kohda, D.; Kodama, C.; Suzuki, A.

    1987-01-01

    The authors applied multiple relayed COSY and 2D homonuclear Hartman-Hahn spectroscopy to globoside, a glycolipid purified from human red blood cells. The subspectra corresponding to individual sugar components were extracted even from overlapping proton resonances by taking the cross sections of 2D spectra parallel to the F 2 axis at anomeric proton resonances, so that unambiguous assignments of sugar proton resonances were accomplished. (Auth.)

  18. Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

    Science.gov (United States)

    Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

    2014-04-27

    The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol

  19. Cholesterol oxidation products and their biological importance

    DEFF Research Database (Denmark)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr

    2016-01-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low...... and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have...

  20. Isolation of basidiomycetous yeast Pseudozyma tsukubaensis and production of glycolipid biosurfactant, a diastereomer type of mannosylerythritol lipid-B.

    Science.gov (United States)

    Morita, Tomotake; Takashima, Masako; Fukuoka, Tokuma; Konishi, Masaaki; Imura, Tomohiro; Kitamoto, Dai

    2010-10-01

    The producers of glycolipid biosurfactant, mannosylerythritol lipid-B (MEL-B), were isolated from leaves of Perilla frutescens on Ibaraki in Japan. Four isolates, 1D9, 1D10, 1D11, and 1E5, were identified as basidiomycetous yeast Pseudozyma tsukubaensis by rDNA sequence and biochemical properties. The structure of MEL-B produced by these strains was analyzed by (1)H nuclear magnetic resonance and gas chromatography-mass spectrometry methods, and was determined to be the same as the diastereomer MEL-B produced by P. tsukubaensis NBRC 1940. Of these isolates, P. tsukubaensis 1E5 (JCM 16987) is capable of producing the largest amount of the diastereomer MEL-B from vegetable oils. In order to progress the diastereomer MEL-B production by strain 1E5, factors affecting the production, such as carbon and organic nutrient sources, were further examined. Olive oil and yeast extract were the best carbon and nutrient sources, respectively. Under the optimal conditions, a maximum yield, productivity, and yield coefficient of 73.1 g/L, 10.4 g L(-1) day(-1), and 43.5 g/g were achieved by feeding of olive oil in a 5-L jar-fermenter culture using strain 1E5.

  1. Playing hide-and-seek with host macrophages through the use of mycobacterial cell envelope phthiocerol dimycocerosates and phenolic glycolipids

    Directory of Open Access Journals (Sweden)

    Ainhoa eARBUES

    2014-12-01

    Full Text Available Mycobacterial pathogens, including Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB, have evolved a remarkable ability to evade the immune system in order to survive and to colonize the host. Among the most important evasion strategies is the capacity of these bacilli to parasitize host macrophages, since these are major effector cells against intracellular pathogens that can be used as long-term cellular reservoirs. Mycobacterial pathogens employ an array of virulence factors that manipulate macrophage function to survive and establish infection. Until recently, however, the role of mycobacterial cell envelope lipids as virulence factors in macrophage subversion has remained elusive. Here, we will address exclusively the proposed role for phthiocerol dimycocerosates (DIM in the modulation of the resident macrophage response and that of phenolic glycolipids (PGL in the regulation of the recruitment and phenotype of incoming macrophage precursors to the site of infection. We will provide a unique perspective of potential additional functions for these lipids, and highlight obstacles and opportunities to further understand their role in the pathogenesis of TB and other mycobacterial diseases.

  2. Production and characterisation of glycolipid biosurfactant by Halomonas sp. MB-30 for potential application in enhanced oil recovery.

    Science.gov (United States)

    Dhasayan, Asha; Kiran, G Seghal; Selvin, Joseph

    2014-12-01

    Biosurfactant-producing Halomonas sp. MB-30 was isolated from a marine sponge Callyspongia diffusa, and its potency in crude oil recovery from sand pack column was investigated. The biosurfactant produced by the strain MB-30 reduced the surface tension to 30 mN m(-1) in both glucose and hydrocarbon-supplemented minimal media. The critical micelle concentration of biosurfactant obtained from glucose-based medium was at 0.25 mg ml(-1) at critical micelle dilution 1:10. The chemical structure of glycolipid biosurfactant was characterised by infrared spectroscopy and proton magnetic resonance spectroscopy. The emulsification activity of MB-30 biosurfactant was tested with different hydrocarbons, and 93.1 % emulsification activity was exhibited with crude oil followed by kerosene (86.6 %). The formed emulsion was stable for up to 1 month. To identify the effectiveness of biosurfactant for enhanced oil recovery in extreme environments, the interactive effect of pH, temperature and salinity on emulsion stability with crude oil and kerosene was evaluated. The stable emulsion was formed at and above pH 7, temperature >80 °C and NaCl concentration up to 10 % in response surface central composite orthogonal design model. The partially purified biosurfactant recovered 62 % of residual crude oil from sand pack column. Thus, the stable emulsifying biosurfactant produced by Halomonas sp. MB-30 could be used for in situ biosurfactant-mediated enhanced oil recovery process and hydrocarbon bioremediation in extreme environments.

  3. Bioactivity of a Novel Glycolipid Produced by a Halophilic Buttiauxella sp. and Improving Submerged Fermentation Using a Response Surface Method

    Directory of Open Access Journals (Sweden)

    Abdolrazagh Marzban

    2016-09-01

    Full Text Available An antimicrobial glycolipid biosurfactant (GBS, extracted and identified from a marine bacterium, was studied to inhibit pathogenic microorganisms. Production of the GBS was optimized using a statistical method, a response surface method (RSM with a central composite design (CCD for obtaining maximum yields on a cost-effective substrate, molasses. The GBS-producing bacterium was identified as Buttiauxella Species in terms of biochemical and molecular characteristics. This compound showed a desirable antimicrobial activity against some pathogens such as E. coli, Bacillus subtilis, Bacillus cereus, Candida albicans, Aspergilus niger, Salmonella enterica. The rheological studies described the stability of the GBS at high values in a range of pH (7–8, temperature (20–60 and salinity (0%–3%. The statistical optimization of GBS fermentation was found to be pH 7, temperature 33 °C, Peptone 1%, NaCl 1% and molasses 1%. The potency of the GBS as an effective antimicrobial agent provides evidence for its use against food and human pathogens. Moreover, favorable production of the GBS in the presence of molasses as a cheap substrate and the feasibility of pilot scale fermentation using an RSM method could expand its uses in food, pharmaceutical products and oil industries.

  4. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  5. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  6. Dietary cholesterol and fats at a young age : do they influence cholesterol metabolism in adult life?

    NARCIS (Netherlands)

    Temmerman, A.M.; Vonk, R.J.; Niezen-Koning, K.; Berger, R.; Fernandes, J.

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the

  7. From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol lowering therapies By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body For a long time this removal via

  8. Cholesterol Transport Revisited : A New Turbo Mechanism to Drive Cholesterol Excretion

    NARCIS (Netherlands)

    de Boer, Jan Freark; Kuipers, Folkert; Groen, Albert K.

    A fine-tuned balance between cholesterol uptake and excretion by the body is pivotal to maintain health and to remain free from the deleterious consequences of cholesterol accumulation such as cardiovascular disease. The pathways involved in intracellular and extracellular cholesterol transport are

  9. Co-localization of a CD1d-binding glycolipid with a radiation-attenuated sporozoite vaccine in LN-resident DCs for a robust adjuvant effect

    Science.gov (United States)

    Li, Xiangming; Kawamura, Akira; Andrews, Chasity D.; Miller, Jessica L.; Wu, Douglass; Tsao, Tiffany; Zhang, Min; Oren, Deena; Padte, Neal N.; Porcelli, Steven A.; Wong, Chi-Huey; Kappe, Stefan H. I.; Ho, David D.; Tsuji, Moriya

    2015-01-01

    A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant natural killer T (iNKT) cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the present study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer for a vaccine based on radiation-attenuated sporozoites (RAS) of a rodent malaria parasite, Plasmodium yoelii, also referred to as irradiated P. yoelii sporozoites (IrPySpz). 7DW8-5 had a superb adjuvant effect only when the glycolipid and IrPySpz were conjointly administered intramuscularly (i.m.). Therefore, we evaluated the impact of distinctly different biodistribution patterns of αGalCer and 7DW8-5 on their respective adjuvant activities. While both glycolipids induce a similar cytokine response in sera of mice injected intravenously, after i.m. injection, αGalCer induces a systemic cytokine response, whereas 7DW8-5 is locally trapped by CD1d expressed by dendritic cells (DCs) in draining lymph nodes (dLNs). Moreover, the i.m. co-administration of 7DW8-5 with IrPySpz results in the recruitment of DCs to dLNs and the activation and maturation of DCs. These events cause the potent adjuvant effect of 7DW8-5, resulting in the enhancement of the CD8+ T-cell response induced by IrPySpz, and, ultimately, improved protection against malaria. Our study is the first to show that the co-localization of a CD1d-binding iNKT-cell stimulatory glycolipid and a vaccine, like RAS, in dLN-resident DCs upon i.m. conjoin administration governs the potency of the adjuvant effect of the glycolipid. PMID:26254338

  10. Colocalization of a CD1d-Binding Glycolipid with a Radiation-Attenuated Sporozoite Vaccine in Lymph Node-Resident Dendritic Cells for a Robust Adjuvant Effect.

    Science.gov (United States)

    Li, Xiangming; Kawamura, Akira; Andrews, Chasity D; Miller, Jessica L; Wu, Douglass; Tsao, Tiffany; Zhang, Min; Oren, Deena; Padte, Neal N; Porcelli, Steven A; Wong, Chi-Huey; Kappe, Stefan H I; Ho, David D; Tsuji, Moriya

    2015-09-15

    A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant NK T cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the current study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer for a vaccine based on radiation-attenuated sporozoites of a rodent malaria parasite, Plasmodium yoelii, also referred to as irradiated P. yoelii sporozoites (IrPySpz). 7DW8-5 had a superb adjuvant effect only when the glycolipid and IrPySpz were conjointly administered i.m. Therefore, we evaluated the effect of distinctly different biodistribution patterns of αGalCer and 7DW8-5 on their respective adjuvant activities. Although both glycolipids induce a similar cytokine response in sera of mice injected i.v., after i.m. injection, αGalCer induces a systemic cytokine response, whereas 7DW8-5 is locally trapped by CD1d expressed by dendritic cells (DCs) in draining lymph nodes (dLNs). Moreover, the i.m. coadministration of 7DW8-5 with IrPySpz results in the recruitment of DCs to dLNs and the activation and maturation of DCs. These events cause the potent adjuvant effect of 7DW8-5, resulting in the enhancement of the CD8(+) T cell response induced by IrPySpz and, ultimately, improved protection against malaria. Our study is the first to show that the colocalization of a CD1d-binding invariant NK T cell-stimulatory glycolipid and a vaccine, like radiation-attenuated sporozoites, in dLN-resident DCs upon i.m. conjoint administration governs the potency of the adjuvant effect of the glycolipid. Copyright © 2015 by The American Association of Immunologists, Inc.

  11. The cholesterol space of the rat; L'espace cholesterol du rat

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1959-07-01

    The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [French] Les experiences ont consiste a faire ingerer quotidiennement une meme masse de cholesterol radioactif a des rats, durant des laps de temps variables. L'evolution de la radioactivite specifique du carbone-14 du cholesterol des organes en fonction du temps permet d'obtenir des renseignements relatifs au transport du cholesterol dans l'organisme. 1) L'espace cholesterol defini comme l'ensemble des molecules susceptibles d'etre transferees des organes dans le serum, et vice-versa, represente au plus 50 pour cent du cholesterol total du rat adulte. 2) Le va et vient incessant entre le cholesterol tissulaire et le cholesterol serique renouvelle en totalite ou en

  12. Phytosterol glycosides reduce cholesterol absorption in humans

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received ∼300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4–5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6 ± 4.8% (P lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content. PMID:19246636

  13. Phytosterol glycosides reduce cholesterol absorption in humans.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Anderson Spearie, Catherine L; Ostlund, Richard E

    2009-04-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (Pphytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

  14. Nuclear receptors in control of cholesterol transport

    NARCIS (Netherlands)

    van der Veen, Jelske Nynke

    2007-01-01

    Cholesterol is een structurele component van celmembranen en een grondstof voor de aanmaak van steroïde hormonen en galzouten en vervult dus een aantal essentiële fysiologische functies. Een goede balans van cholesterol opname, synthese, afbraak en uitscheiding is noodzakelijk, omdat verhoogde

  15. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    Science.gov (United States)

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  16. Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

    Science.gov (United States)

    Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

    2018-03-01

    Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Cholesterol in myelin biogenesis and hypomyelinating disorders.

    Science.gov (United States)

    Saher, Gesine; Stumpf, Sina Kristin

    2015-08-01

    The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Constraining walking and custodial technicolor

    DEFF Research Database (Denmark)

    Foadi, Roshan; Frandsen, Mads Toudal; Sannino, Francesco

    2008-01-01

    We show how to constrain the physical spectrum of walking technicolor models via precision measurements and modified Weinberg sum rules. We also study models possessing a custodial symmetry for the S parameter at the effective Lagrangian level-custodial technicolor-and argue that these models...

  19. Mucins and calcium phosphate precipitates additively stimulate cholesterol crystallization

    NARCIS (Netherlands)

    van den Berg, A. A.; van Buul, J. D.; Tytgat, G. N.; Groen, A. K.; Ostrow, J. D.

    1998-01-01

    Human biliary mucin and calcium binding protein (CBP) influence formation of both calcium salt precipitates and cholesterol crystals and colocalize in the center of cholesterol gallstones. We investigated how physiological concentrations of these proteins regulate cholesterol crystallization in

  20. Tuberculosis treatment raises total cholesterol level and restores ...

    African Journals Online (AJOL)

    aghomotsegin

    2013-10-09

    Oct 9, 2013 ... and restores high density lipoprotein cholesterol (HDL- ... cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were determined .... However, we found a strong negative correlation (r = - 0.96,.

  1. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Gent, van C.M.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and

  2. Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties.

    Science.gov (United States)

    Thomann, Jean-Sébastien; Monneaux, Fanny; Creusat, Gaëlle; Spanedda, Maria Vittoria; Heurtault, Béatrice; Habermacher, Chloé; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

    2012-05-01

    A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratio>9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  3. Interaction of pathogens with host cholesterol metabolism.

    Science.gov (United States)

    Sviridov, Dmitri; Bukrinsky, Michael

    2014-10-01

    Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance their own development and to impair host immune responses, but also causing metabolic complications, for example, atherosclerosis. This review describes recent findings of how pathogens do it. A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward-looking molecules that can be used as receptors. At the same time, disruption of the rafts' functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesize cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and microRNAs secreted by infected cells affect lipid metabolism systemically. Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections, as well as metabolic complications of the infections.

  4. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    Ponz de Leon, M.; Carubbi, F.; Di Donato, P.; Carulli, N.

    1985-01-01

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14 C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  5. Cholesterol asymmetry in synaptic plasma membranes.

    Science.gov (United States)

    Wood, W Gibson; Igbavboa, Urule; Müller, Walter E; Eckert, Gunter P

    2011-03-01

    Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  6. [Cholesterol reducing food certainly is useful].

    Science.gov (United States)

    Stalenhoef, A F

    1997-12-27

    The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease.

  7. HYPOLIPEMIC THERAPY AND LOW SERUM CHOLESTEROL CONCENTRATION

    Directory of Open Access Journals (Sweden)

    Vladmila Bojanic

    2004-01-01

    Full Text Available Low concentration of plasma lipoproteins (hypolipoproteinemia presents decreasing concentrations of all or particular lipids components. Classification of hypolipoproteinemia (hypoLP divides them into: primary (hereditary and secondary. Primary hipoLP are rare diseases and their main characteristic is disorder of apolipoproteins synthesis, which leads to low serum cholesterol concentration. Secondary hipoLP are presented in many diseases. They have diagnostic, prognostic significance and present good therapeutic marker. However, modern therapeutic approaches for aggressive lipid lowering pointed out many questions about physiological limits for cholesterol lowering. These approaches, also, open many questions about consequences of low serum concentration of total cholesterol and triglicerides.

  8. Trends in PDE constrained optimization

    CERN Document Server

    Benner, Peter; Engell, Sebastian; Griewank, Andreas; Harbrecht, Helmut; Hinze, Michael; Rannacher, Rolf; Ulbrich, Stefan

    2014-01-01

    Optimization problems subject to constraints governed by partial differential equations (PDEs) are among the most challenging problems in the context of industrial, economical and medical applications. Almost the entire range of problems in this field of research was studied and further explored as part of the Deutsche Forschungsgemeinschaft (DFG) priority program 1253 on “Optimization with Partial Differential Equations” from 2006 to 2013. The investigations were motivated by the fascinating potential applications and challenging mathematical problems that arise in the field of PDE constrained optimization. New analytic and algorithmic paradigms have been developed, implemented and validated in the context of real-world applications. In this special volume, contributions from more than fifteen German universities combine the results of this interdisciplinary program with a focus on applied mathematics.   The book is divided into five sections on “Constrained Optimization, Identification and Control”...

  9. Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

    Science.gov (United States)

    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-01-01

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

  10. Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

    Science.gov (United States)

    Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

    2011-06-01

    Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

  11. HDL (Good), LDL (Bad) Cholesterol and Triglycerides

    Science.gov (United States)

    ... Are Cholesterol-Lowering Medications? How Statins Work Medication Tracker Personal ... or Sudden Cardiac Arrest: How Are They Different? 7 Warning Signs of a Heart Attack 8 Low Blood Pressure - ...

  12. Overview of Cholesterol and Lipid Disorders

    Science.gov (United States)

    ... Professor of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version ... Cholesterol and triglycerides are important ...

  13. Co-localization of a CD1d-binding glycolipid with a radiation-attenuated sporozoite vaccine in LN-resident DCs for a robust adjuvant effect

    OpenAIRE

    Li, Xiangming; Kawamura, Akira; Andrews, Chasity D.; Miller, Jessica L.; Wu, Douglass; Tsao, Tiffany; Zhang, Min; Oren, Deena; Padte, Neal N.; Porcelli, Steven A.; Wong, Chi-Huey; Kappe, Stefan H. I.; Ho, David D.; Tsuji, Moriya

    2015-01-01

    A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant natural killer T (iNKT) cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the present study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer for a vaccine based on radiation-attenuated sporozoites (RAS) of a rodent malaria parasite, Plasmodium yoelii, also referred to a...

  14. Biochemical characterization of cholesterol-reducing Eubacterium.

    OpenAIRE

    Mott, G E; Brinkley, A W; Mersinger, C L

    1980-01-01

    We characterized two isolates of cholesterol-reducing Eubacterium by conducting conventional biochemical tests and by testing various sterols and glycerolipids as potential growth factors. In media containing cholesterol and plasmenylethanolamine, the tests for nitrate reduction, indole production, and gelatin and starch hydrolyses were negative, and no acid was produced from any of 22 carbohydrates. Both isolates hydrolyzed esculin to esculetin, indicating beta-glycosidase activity. In addit...

  15. Impact of a public cholesterol screening program.

    Science.gov (United States)

    Fischer, P M; Guinan, K H; Burke, J J; Karp, W B; Richards, J W

    1990-12-01

    The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L [9 mg/dL]) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease.

  16. Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

    Science.gov (United States)

    Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

    2012-05-01

    In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol

  17. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  18. Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant

    International Nuclear Information System (INIS)

    Patel, S.C.; Suresh, S.; Weintroub, H.; Brady, R.O.; Pentchev, P.G.

    1987-01-01

    Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3 H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture

  19. Nested Sampling with Constrained Hamiltonian Monte Carlo

    OpenAIRE

    Betancourt, M. J.

    2010-01-01

    Nested sampling is a powerful approach to Bayesian inference ultimately limited by the computationally demanding task of sampling from a heavily constrained probability distribution. An effective algorithm in its own right, Hamiltonian Monte Carlo is readily adapted to efficiently sample from any smooth, constrained distribution. Utilizing this constrained Hamiltonian Monte Carlo, I introduce a general implementation of the nested sampling algorithm.

  20. Constrained minimization in C ++ environment

    International Nuclear Information System (INIS)

    Dymov, S.N.; Kurbatov, V.S.; Silin, I.N.; Yashchenko, S.V.

    1998-01-01

    Based on the ideas, proposed by one of the authors (I.N.Silin), the suitable software was developed for constrained data fitting. Constraints may be of the arbitrary type: equalities and inequalities. The simplest of possible ways was used. Widely known program FUMILI was realized to the C ++ language. Constraints in the form of inequalities φ (θ i ) ≥ a were taken into account by change into equalities φ (θ i ) = t and simple inequalities of type t ≥ a. The equalities were taken into account by means of quadratic penalty functions. The suitable software was tested on the model data of the ANKE setup (COSY accelerator, Forschungszentrum Juelich, Germany)

  1. Coherent states in constrained systems

    International Nuclear Information System (INIS)

    Nakamura, M.; Kojima, K.

    2001-01-01

    When quantizing the constrained systems, there often arise the quantum corrections due to the non-commutativity in the re-ordering of constraint operators in the products of operators. In the bosonic second-class constraints, furthermore, the quantum corrections caused by the uncertainty principle should be taken into account. In order to treat these corrections simultaneously, the alternative projection technique of operators is proposed by introducing the available minimal uncertainty states of the constraint operators. Using this projection technique together with the projection operator method (POM), these two kinds of quantum corrections were investigated

  2. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  3. Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

    Directory of Open Access Journals (Sweden)

    Fourgeux Cynthia

    2015-03-01

    Full Text Available The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch’s membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch’s membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.

  4. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

    Science.gov (United States)

    Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2012-04-15

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null

  5. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  6. The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

    Directory of Open Access Journals (Sweden)

    Se-Jin Jeong

    2017-03-01

    Full Text Available Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

  7. Cd1b-Mediated T Cell Recognition of a Glycolipid Antigen Generated from Mycobacterial Lipid and Host Carbohydrate during Infection

    Science.gov (United States)

    Moody, D. Branch; Guy, Mark R.; Grant, Ethan; Cheng, Tan-Yun; Brenner, Michael B.; Besra, Gurdyal S.; Porcelli, Steven A.

    2000-01-01

    T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) α and β chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria. PMID:11015438

  8. Influence of length and conformation of saccharide head groups on the mechanics of glycolipid membranes: Unraveled by off-specular neutron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Akihisa, E-mail: ayamamoto@icems.kyoto-u.ac.jp, E-mail: tanaka@uni-heidelberg.de; Tanaka, Motomu, E-mail: ayamamoto@icems.kyoto-u.ac.jp, E-mail: tanaka@uni-heidelberg.de [Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg (Germany); Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501 (Japan); Abuillan, Wasim; Körner, Alexander [Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg (Germany); Burk, Alexandra S. [Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg (Germany); Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76021 Karlsruhe (Germany); Ries, Annika [Institute of Organic and Biomolecular Chemistry, University of Göttingen, 37077 Göttingen (Germany); Werz, Daniel B. [Institute of Organic Chemistry, Technische Universität Braunschweig, 38106 Braunschweig (Germany); Demé, Bruno [Institut Laue-Langevin, 38042 Grenoble Cedex 9, Grenoble (France)

    2015-04-21

    The mechanical properties of multilayer stacks of Gb3 glycolipid that play key roles in metabolic disorders (Fabry disease) were determined quantitatively by using specular and off-specular neutron scattering. Because of the geometry of membrane stacks deposited on planar substrates, the scattered intensity profile was analyzed in a 2D reciprocal space map as a function of in-plane and out-of-plane scattering vector components. The two principal mechanical parameters of the membranes, namely, bending rigidity and compression modulus, can be quantified by full calculation of scattering functions with the aid of an effective cut-off radius that takes the finite sample size into consideration. The bulkier “bent” Gb3 trisaccharide group makes the membrane mechanics distinctly different from cylindrical disaccharide (lactose) head groups and shorter “bent” disaccharide (gentiobiose) head groups. The mechanical characterization of membranes enriched with complex glycolipids has high importance in understanding the mechanisms of diseases such as sphingolipidoses caused by the accumulation of non-degenerated glycosphingolipids in lysosomes or inhibition of protein synthesis triggered by the specific binding of Shiga toxin to Gb3.

  9. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events

    NARCIS (Netherlands)

    Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera; Fruchart, Jean-Charles

    2007-01-01

    BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol. METHODS: A post hoc analysis of the recently

  10. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice

    NARCIS (Netherlands)

    Bura, Kanwardeep S.; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A.; Sawyer, Janet K.; Shah, Ramesh; Wilson, Martha D.; Dikkers, Arne; Tietge, Uwe J. F.; Collet, Xavier; Rudel, Lawrence L.; Temel, Ryan E.; Brown, J. Mark

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the non-biliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI

  11. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    OpenAIRE

    Matthias Orth; Stefano Bellosta

    2012-01-01

    Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein...

  12. Melanocortin signaling in the CNS directly regulates circulating cholesterol

    OpenAIRE

    Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

    2010-01-01

    Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

  13. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases. © 2014 médecine/sciences – Inserm.

  14. Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

    Science.gov (United States)

    Feillet, F; Feillet-Coudray, C; Bard, J M; Parra, H J; Favre, E; Kabuth, B; Fruchart, J C; Vidailhet, M

    2000-04-01

    Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

  15. Free cholesterol and cholesterol esters in bovine oocytes: Implications in survival and membrane raft organization after cryopreservation.

    Directory of Open Access Journals (Sweden)

    Jorgelina Buschiazzo

    Full Text Available Part of the damage caused by cryopreservation of mammalian oocytes occurs at the plasma membrane. The addition of cholesterol to cell membranes as a strategy to make it more tolerant to cryopreservation has been little addressed in oocytes. In order to increase the survival of bovine oocytes after cryopreservation, we proposed not only to increase cholesterol level of oocyte membranes before vitrification but also to remove the added cholesterol after warming, thus recovering its original level. Results from our study showed that modulation of membrane cholesterol by methyl-β-cyclodextrin (MβCD did not affect the apoptotic status of oocytes and improved viability after vitrification yielding levels of apoptosis closer to those of fresh oocytes. Fluorometric measurements based on an enzyme-coupled reaction that detects both free cholesterol (membrane and cholesteryl esters (stored in lipid droplets, revealed that oocytes and cumulus cells present different levels of cholesterol depending on the seasonal period. Variations at membrane cholesterol level of oocytes were enough to account for the differences found in total cholesterol. Differences found in total cholesterol of cumulus cells were explained by the differences found in both the content of membrane cholesterol and of cholesterol esters. Cholesterol was incorporated into the oocyte plasma membrane as evidenced by comparative labeling of a fluorescent cholesterol. Oocytes and cumulus cells increased membrane cholesterol after incubation with MβCD/cholesterol and recovered their original level after cholesterol removal, regardless of the season. Finally, we evaluated the effect of vitrification on the putative raft molecule GM1. Cholesterol modulation also preserved membrane organization by maintaining ganglioside level at the plasma membrane. Results suggest a distinctive cholesterol metabolic status of cumulus-oocyte complexes (COCs among seasons and a dynamic organizational structure

  16. Ordering effects of cholesterol and its analogues

    DEFF Research Database (Denmark)

    Róg, Tomasz; Pasenkiewicz-Gierula, Marta; Vattulainen, Ilpo

    2009-01-01

    Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins....... In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid...... rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches....

  17. Characteristics of human hypo- and hyperresponders to dietary cholesterol.

    Science.gov (United States)

    Katan, M B; Beynen, A C

    1987-03-01

    The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

  18. Formal language constrained path problems

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, C.; Jacob, R.; Marathe, M.

    1997-07-08

    In many path finding problems arising in practice, certain patterns of edge/vertex labels in the labeled graph being traversed are allowed/preferred, while others are disallowed. Motivated by such applications as intermodal transportation planning, the authors investigate the complexity of finding feasible paths in a labeled network, where the mode choice for each traveler is specified by a formal language. The main contributions of this paper include the following: (1) the authors show that the problem of finding a shortest path between a source and destination for a traveler whose mode choice is specified as a context free language is solvable efficiently in polynomial time, when the mode choice is specified as a regular language they provide algorithms with improved space and time bounds; (2) in contrast, they show that the problem of finding simple paths between a source and a given destination is NP-hard, even when restricted to very simple regular expressions and/or very simple graphs; (3) for the class of treewidth bounded graphs, they show that (i) the problem of finding a regular language constrained simple path between source and a destination is solvable in polynomial time and (ii) the extension to finding context free language constrained simple paths is NP-complete. Several extensions of these results are presented in the context of finding shortest paths with additional constraints. These results significantly extend the results in [MW95]. As a corollary of the results, they obtain a polynomial time algorithm for the BEST k-SIMILAR PATH problem studied in [SJB97]. The previous best algorithm was given by [SJB97] and takes exponential time in the worst case.

  19. [Screening and optimization of cholesterol conversion strain].

    Science.gov (United States)

    Fan, Dan; Xiong, Bingjian; Pang, Cuiping; Zhu, Xiangdong

    2014-10-04

    Bacterial strain SE-1 capable of transforming cholesterol was isolated from soil and characterized. The transformation products were identified. Fermentation conditions were optimized for conversion. Cholesterol was used as sole carbon source to isolate strain SE-1. Morphology, physiological and biochemical characteristics of strain SE-1 were studied. 16S rRNA gene was sequenced and subjected to phylogenetic analysis. Fermentation supernatants were extracted with chloroform, the transformation products were analyzed by silica gel thin layer chromatography and Sephadex LH20. Their structures were identified by 1H-NMR and 13C-NMR. Fermentation medium including carbon and nitrogen, methods of adding substrates and fermentation conditions for Strain SE-1 were optimized. Strain SE-1 was a Gram-negative bacterium, exhibiting the highest homologs to Burkholderia cepacia based on the physiological analysis. The sequence analysis of 16S rRNA gene of SE-1 strain and comparison with related Burkholderia show that SE-1 strain was very close to B. cepacia (Genbank No. U96927). The similarity was 99%. The result of silica gel thin layer chromatography shows that strain SE-1 transformed cholesterol to two products, 7beta-hydroxycholesterol and the minor product was 7-oxocholesterol. The optimum culture conditions were: molasses 5%, (NH4 )2SO4 0.3%, 4% of inoculation, pH 7.5 and 36 degrees C. Under the optimum culture condition, the conversion rate reached 34.4% when concentration of cholesterol-Tween 80 was 1 g/L. Cholesterol 7beta-hydroxylation conversion rate under optimal conditions was improved by 20.8%. Strain SE-1 isolated from soil is capable of converting cholesterol at lab-scale.

  20. Tympanomastoid cholesterol granulomas: Immunohistochemical evaluation of angiogenesis.

    Science.gov (United States)

    Iannella, Giannicola; Di Gioia, Cira; Carletti, Raffaella; Magliulo, Giuseppe

    2017-08-01

    This study investigates the immunohistochemical expression of vascular endothelial growth factor (VEGF) and CD34 in patients treated for middle ear and mastoid cholesterol granulomas to evaluate the angiogenesis and vascularization of this type of lesion. A correlation between the immunohistochemical data and the radiological and intraoperative evidence of temporal bone marrow invasion and blood source connection was performed to validate this hypothesis. Retrospective study. Immunohistochemical expression of VEGF and CD34 in a group of 16 patients surgically treated for cholesterol granuloma was examined. Middle ear cholesteatomas with normal middle ear mucosa and external auditory canal skin were used as the control groups. The radiological and intraoperative features of cholesterol granulomas were also examined. In endothelial cells, there was an increased expression of angiogenetic growth factor receptors in all the cholesterol granulomas in this study. The quantitative analysis of VEGF showed a mean value of 37.5, whereas the CD34 quantitative analysis gave a mean value of 6.8. Seven patients presented radiological or intraoperative evidence of bone marrow invasion, hematopoietic potentialities, or blood source connections that might support the bleeding theory. In all of these cases there was computed tomography or intraoperative evidence of bone erosion of the middle ear and/or temporal bone structures. The mean values of VEGF and CD34 were 41.1 and 7.7, respectively. High values of VEGF and CD34 are present in patients with cholesterol granulomas. Upregulation of VEGF and CD34 is indicative of a remarkable angiogenesis and a widespread vascular concentration in cholesterol granulomas. 3b. Laryngoscope, 127:E283-E290, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  1. The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

    Directory of Open Access Journals (Sweden)

    Frans Stellaard

    2017-01-01

    Full Text Available The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1 The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2 The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3 The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

  2. Lack of Abcg1 results in decreased plasma HDL cholesterol levels and increased biliary cholesterol secretion in mice fed a high cholesterol diet

    NARCIS (Netherlands)

    Wiersma, Harmen; Nijstad, Niels; de Boer, Jan Freark; Out, Ruud; Hogewerf, Wytse; Van Berkel, Theo J.; Kuipers, Folkert; Tietge, Uwe J. F.

    Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1

  3. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol

  4. The cholesterol system of the swine

    International Nuclear Information System (INIS)

    Aigueperse, Jocelyne

    1979-01-01

    The purpose of this work was to characterize the dynamic system of adult female Large White swine. The content of this system and its relationships with both the external environment and between the different parts of the system were explained. The analysis of these results in terms of compared physiology showed that the structure of the cholesterol system was the same in man and in the swine. Consequently, the swine constitutes a good biological tool to study human cholesterol indirectly and to foresee the changes that might be induced in various physio-pathological cases. (author) [fr

  5. 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis?

    NARCIS (Netherlands)

    Bangalore, Sripal; Fayyad, Rana; Kastelein, John J.; Laskey, Rachel; Amarenco, Pierre; Demicco, David A.; Waters, David D.

    2016-01-01

    The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether

  6. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  7. Survival of adult neurons lacking cholesterol synthesis in vivo.

    Science.gov (United States)

    Fünfschilling, Ursula; Saher, Gesine; Xiao, Le; Möbius, Wiebke; Nave, Klaus-Armin

    2007-01-02

    Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  8. Survival of adult neurons lacking cholesterol synthesis in vivo

    Directory of Open Access Journals (Sweden)

    Möbius Wiebke

    2007-01-01

    Full Text Available Abstract Background Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Results Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1, which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. Conclusion We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  9. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  10. Effect of Processing Methods on Cholesterol Contents and Cholesterol Oxides Formation in Some Dairy Products

    International Nuclear Information System (INIS)

    AlRowaily, Meshref A

    2008-01-01

    The effects of pasteurization, boiling, microwaving, processing and storage of milk and some locally produced dairy products on cholesterol contents and cholesterol oxides formation were studied and evaluated. The 7-ketocholesterol were not detected (ND) in all raw milk samples. On the contrary, heating of milk led to formation of cholesterol oxidation products (COPs), mostly, 7- ketocholesterol in different quantities. No significant effect of heating of milk on cholesterol level was observed with the exception of the ultra-high temperature (UHT) milk prepared from milk powder heated at 140 + - 1.0 degree C for 4 sec showed the highest value of 7-ketocholesterol (80.97 mgg-1), followed by microwave heated milk for 5 min (31.29 mgg-1), whereas the lowest value was in milk pasteurized at 85 + - 1.0 degree C for 16 sec (3.125 mgg-1). Commercial storage showed no significant effect on cholesterol and 7-ketocholestrol but lowered cholesterol concentration and increased 7-ketocholestrol level of UHT reconstituted milk. Cholesterol content of both yogurt and labaneh strained by centrifugal separator showed significant decrease while 7-ketochostrol level was increased significantly with refrigerated storage. The findings are discussed in the context with the results of previous similar studies. (author)

  11. A New Glucocerebrosidase Chaperone Reduces α-Synuclein and Glycolipid Levels in iPSC-Derived Dopaminergic Neurons from Patients with Gaucher Disease and Parkinsonism.

    Science.gov (United States)

    Aflaki, Elma; Borger, Daniel K; Moaven, Nima; Stubblefield, Barbara K; Rogers, Steven A; Patnaik, Samarjit; Schoenen, Frank J; Westbroek, Wendy; Zheng, Wei; Sullivan, Patricia; Fujiwara, Hideji; Sidhu, Rohini; Khaliq, Zayd M; Lopez, Grisel J; Goldstein, David S; Ory, Daniel S; Marugan, Juan; Sidransky, Ellen

    2016-07-13

    Among the known genetic risk factors for Parkinson disease, mutations in GBA1, the gene responsible for the lysosomal disorder Gaucher disease, are the most common. This genetic link has directed attention to the role of the lysosome in the pathogenesis of parkinsonism. To study how glucocerebrosidase impacts parkinsonism and to evaluate new therapeutics, we generated induced human pluripotent stem cells from four patients with Type 1 (non-neuronopathic) Gaucher disease, two with and two without parkinsonism, and one patient with Type 2 (acute neuronopathic) Gaucher disease, and differentiated them into macrophages and dopaminergic neurons. These cells exhibited decreased glucocerebrosidase activity and stored the glycolipid substrates glucosylceramide and glucosylsphingosine, demonstrating their similarity to patients with Gaucher disease. Dopaminergic neurons from patients with Type 2 and Type 1 Gaucher disease with parkinsonism had reduced dopamine storage and dopamine transporter reuptake. Levels of α-synuclein, a protein present as aggregates in Parkinson disease and related synucleinopathies, were selectively elevated in neurons from the patients with parkinsonism or Type 2 Gaucher disease. The cells were then treated with NCGC607, a small-molecule noninhibitory chaperone of glucocerebrosidase identified by high-throughput screening and medicinal chemistry structure optimization. This compound successfully chaperoned the mutant enzyme, restored glucocerebrosidase activity and protein levels, and reduced glycolipid storage in both iPSC-derived macrophages and dopaminergic neurons, indicating its potential for treating neuronopathic Gaucher disease. In addition, NCGC607 reduced α-synuclein levels in dopaminergic neurons from the patients with parkinsonism, suggesting that noninhibitory small-molecule chaperones of glucocerebrosidase may prove useful for the treatment of Parkinson disease. Because GBA1 mutations are the most common genetic risk factor for

  12. High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.

    Science.gov (United States)

    Subczynski, Witold K; Pasenkiewicz-Gierula, Marta; Widomska, Justyna; Mainali, Laxman; Raguz, Marija

    2017-12-01

    Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability, as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

  13. Cholesterol metabolism in blood cells of irradiated rats

    International Nuclear Information System (INIS)

    Novoselova, E.G.; Kulagina, T.P.; Potekhina, N.I.

    1985-01-01

    Cholesterol metabolism in blood erythrocytes and lymphocytes of irradiated rats has been investigated. It has been found that at all terms and doses of irradiation, a suppression of the synthesis of erythrocyte cholesterol is observed. The increase of cholesterol quantiy in erythrocytes upon total gamma irradiation in the 10 Gr dose possibly is the result of growth of cholesterol transfer from plasma into erythrocyte cells. The study of the cholesterol synthesis in suspension of lymphocytes elminated from peripheral blood of control and irradiated rats has shown that at irradiation doses of 4 and 10 Gr in an hour acivation of cholesterol synthesis in vitro takes places

  14. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

    Directory of Open Access Journals (Sweden)

    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  15. Blood cholesterol : a public health perspective

    NARCIS (Netherlands)

    Verschuren, W.M.M.

    1995-01-01

    Changes in total cholesterol levels (TC) were studied using data from three epidemiological studies: about 30,000 men and women aged 37-43 were examined between 1974 and 1980 (CB Project), about 80,000 men aged 33-37 between 1981 and 1986 (RIFOH Project) and 42,000 men and women aged 20-59 from 1987

  16. The Success Story of LDL Cholesterol Lowering.

    Science.gov (United States)

    Pedersen, Terje R

    2016-02-19

    We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. © 2016 American Heart Association, Inc.

  17. Cholesterol oxidation products and their biological importance

    Czech Academy of Sciences Publication Activity Database

    Kulig, W.; Cwiklik, Lukasz; Jurkiewicz, P.; Rog, T.; Vattulainen, I.

    2016-01-01

    Roč. 199, Sep (2016), s. 144-160 ISSN 0009-3084 R&D Projects: GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388963 Keywords : cholesterol * oxidation * oxysterols * biological membranes * biophysical properties Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.361, year: 2016

  18. Resveratrol protects rabbits against cholesterol diet- induced ...

    African Journals Online (AJOL)

    ... groups compared to HFD group only. In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrations and might be beneficial in treatment of hyperlipidemia and atherosclerosis. Keywords: Cholesterol diet, Lipidaemia, Rabbit; Resveratrol, LDL-c, HDL-c, TC, TG ...

  19. Biochemical characterization of cholesterol-reducing Eubacterium.

    Science.gov (United States)

    Mott, G E; Brinkley, A W; Mersinger, C L

    1980-12-01

    We characterized two isolates of cholesterol-reducing Eubacterium by conducting conventional biochemical tests and by testing various sterols and glycerolipids as potential growth factors. In media containing cholesterol and plasmenylethanolamine, the tests for nitrate reduction, indole production, and gelatin and starch hydrolyses were negative, and no acid was produced from any of 22 carbohydrates. Both isolates hydrolyzed esculin to esculetin, indicating beta-glycosidase activity. In addition to plasmenylethanolamine, five other lipids which contain an alkenyl ether residue supported growth of Eubacterium strain 403 in a lecithin-cholesterol base medium. Of six steroids tested, cholesterol, cholest-4-en-3-one, cholest-4-en-3 beta-ol (allocholesterol), and androst-5-en-3 beta-ol-17-one supported growth of Eubacterium strain 403. All four steroids were reduced to the 3 beta-ol, 5 beta-H products. The delta 5 steroids cholest-5-en-3 alpha-ol (epicholesterol) and 22,23-bisnor-5-cholenic acid-3-beta-ol were not reduced and did not support growth of the Eubacterium strain.

  20. Stroke secondary to multiple spontaneous cholesterol emboli.

    Science.gov (United States)

    Pascual, M; Baumgartner, J M; Bounameaux, H

    1991-01-01

    We describe one male, 49-year-old diabetic patient in whom regressive stroke with aphasia and right-sided hemiparesia was related to multiple small emboli in the left paraventricular cortex. Simultaneous presence of several cholesterol emboli in the left eye ground and detection of an atheromatous plaque at the homolateral carotid bifurcation let assume that the cerebral emboli originated from that plaque and also consisted of cholesterol crystals. The patient was discharged on low-dose aspirin (100 mg/day) after neurologic improvement. Follow-up at one year revealed clinical stability, recurrence of the cholesterol emboli at the eye ground examination and no change of the carotid plaque. Cholesterol embolization with renal failure, hypertension and peripheral arterial occlusions causing skin ulcerations is classical in case of atheromatous aortic disease but stroke has rarely been reported in this syndrome. However, more frequent use of invasive procedures (arteriography, transluminal angioplasty, vascular surgery) or thrombolytic treatment might increase its incidence in the near future.

  1. Cholesterol oxidation products and their biological importance

    Czech Academy of Sciences Publication Activity Database

    Kulig, W.; Cwiklik, Lukasz; Jurkiewicz, Piotr; Rog, T.; Vattulainen, I.

    2016-01-01

    Roč. 199, SI (2016), s. 144-160 ISSN 0009-3084 R&D Projects: GA ČR(CZ) GBP208/12/G016; GA ČR GA15-14292S Institutional support: RVO:61388955 Keywords : cholesterol * oxidation * oxysterols Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.361, year: 2016

  2. estimations of cholesterol, triglycerides and fractionation

    African Journals Online (AJOL)

    Preferred Customer

    *Corresponding author. E-mail: eiadeyeye@yahoo.com. ESTIMATIONS OF CHOLESTEROL, TRIGLYCERIDES AND FRACTIONATION OF. LIPOPROTEINS IN SERUM SAMPLES OF SOME NIGERIAN FEMALE SUBJECTS. E.I. Adeyeye1* and I. Oluwadare2. 1Department of Chemistry, University of Ado Ekiti, P.M.B. 5363, ...

  3. Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

    Science.gov (United States)

    Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

    2017-01-01

    Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

  4. Wavelet library for constrained devices

    Science.gov (United States)

    Ehlers, Johan Hendrik; Jassim, Sabah A.

    2007-04-01

    The wavelet transform is a powerful tool for image and video processing, useful in a range of applications. This paper is concerned with the efficiency of a certain fast-wavelet-transform (FWT) implementation and several wavelet filters, more suitable for constrained devices. Such constraints are typically found on mobile (cell) phones or personal digital assistants (PDA). These constraints can be a combination of; limited memory, slow floating point operations (compared to integer operations, most often as a result of no hardware support) and limited local storage. Yet these devices are burdened with demanding tasks such as processing a live video or audio signal through on-board capturing sensors. In this paper we present a new wavelet software library, HeatWave, that can be used efficiently for image/video processing/analysis tasks on mobile phones and PDA's. We will demonstrate that HeatWave is suitable for realtime applications with fine control and range to suit transform demands. We shall present experimental results to substantiate these claims. Finally this library is intended to be of real use and applied, hence we considered several well known and common embedded operating system platform differences; such as a lack of common routines or functions, stack limitations, etc. This makes HeatWave suitable for a range of applications and research projects.

  5. Fluorimetric determination of cholesterol in hypercholesterolemia serum

    Science.gov (United States)

    Lan, Xiufeng; Liu, Jiangang; Liu, Ying; Luo, Xiaosen; Lu, Jian; Ni, Xiaowu

    2005-01-01

    With the increase of people"s living standard and the changes of living form, the number of people who suffer from hypercholesterolemia is increasing. It is not only harmful to heart and blood vessel, but also leading to obstruction of cognition. The conventional blood detection technology has weakness such as complex operation, long detecting period, and bad visibility. In order to develop a new detection method that can checkout hypercholesterolemia conveniently, spectroscopy of cholesterol in hypercholesterolemia serum is obtained by the multifunctional grating spectrograph. The experiment results indicate that, under the excitation of light-emitting diode (LED) with the wavelength at 407 nm, the serum from normal human and the hypercholesterolemia serum emit different fluorescence spectra. The former can emit one fluorescence region with the peak locating at 516 nm while the latter can emit two more regions with peaks locating at 560 nm and 588 nm. Moreover, the fluorescence intensity of serum is non-linear increasing with the concentration of cholesterol increases when the concentration of cholesterol is lower than 13.8 mmol/L, and then, with the concentration of cholesterol increase, the fluorescence intensity decreases. However, the fluorescence intensity is still much higher than that of serum from normal human. Conclusions can be educed from the experiments: the intensity and the shape of fluorescence spectra of hypercholesterolemia serum are different of those of normal serum, from which the cholesterol abnormal in blood can be judged. The consequences in this paper may offer an experimental reference for the diagnosis of the hypercholesterolemia.

  6. Cholesterol transfer at endosomal-organelle membrane contact sites.

    Science.gov (United States)

    Ridgway, Neale D; Zhao, Kexin

    2018-06-01

    Cholesterol is delivered to the limiting membrane of late endosomes by Niemann-Pick Type C1 and C2 proteins. This review summarizes recent evidence that cholesterol transfer from endosomes to the endoplasmic reticulum and other organelles is mediated by lipid-binding proteins that localize to membrane contact sites (MCS). LDL-cholesterol in the late endosomal/lysosomes is exported to the plasma membrane, where most cholesterol resides, and the endoplasmic reticulum, which harbors the regulatory complexes and enzymes that control the synthesis and esterification of cholesterol. A major advance in dissecting these cholesterol transport pathways was identification of frequent and dynamic MCS between endosomes and the endoplasmic reticulum, peroxisomes and plasma membrane. Positioned at these MCS are members of the oxysterol-binding protein (OSBP) and steroidogenic acute regulatory protein-related lipid-transfer family of lipid transfer proteins that bridge the opposing membranes and directly or indirectly mediate cholesterol transfer. OSBP-related protein 1L (ORP1L), ORP5 and ORP6 mediate cholesterol transfer to the endoplasmic reticulum that regulates cholesterol homeostasis. ORP1L and STARD3 also move cholesterol from the endoplasmic reticulum-to-late endosomal/lysosomes under low-cholesterol conditions to facilitate intraluminal vesicle formation. Cholesterol transport also occurs at MCS with peroxisomes and possibly the plasma membrane. Frequent contacts between organelles and the endo-lysosomal vesicles are sites for bidirectional transfer of cholesterol.

  7. 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

  8. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof

    1992-01-01

    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  9. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  10. Statins: Are These Cholesterol-Lowering Drugs Right for You?

    Science.gov (United States)

    Statins: Are these cholesterol-lowering drugs right for you? Find out whether your risk factors for heart disease make you a ... risk prediction. In addition to your cholesterol numbers, these risk calculators also ask about your age, race, ...

  11. Dietary Rhus coriaria L. powder reduces the blood cholesterol ...

    African Journals Online (AJOL)

    Dietary Rhus coriaria L. powder reduces the blood cholesterol, VLDL-c and ... of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-c), low ... birds had higher feed conversion ratio compared with birds in the other treatments.

  12. Membrane cholesterol mediates the cellular effects of monolayer graphene substrates.

    Science.gov (United States)

    Kitko, Kristina E; Hong, Tu; Lazarenko, Roman M; Ying, Da; Xu, Ya-Qiong; Zhang, Qi

    2018-02-23

    Graphene possesses extraordinary properties that promise great potential in biomedicine. However, fully leveraging these properties requires close contact with the cell surface, raising the concern of unexpected biological consequences. Computational models have demonstrated that graphene preferentially interacts with cholesterol, a multifunctional lipid unique to eukaryotic membranes. Here we demonstrate an interaction between graphene and cholesterol. We find that graphene increases cell membrane cholesterol and potentiates neurotransmission, which is mediated by increases in the number, release probability, and recycling rate of synaptic vesicles. In fibroblasts grown on graphene, we also find an increase in cholesterol, which promotes the activation of P2Y receptors, a family of receptor regulated by cholesterol. In both cases, direct manipulation of cholesterol levels elucidates that a graphene-induced cholesterol increase underlies the observed potentiation of each cell signaling pathway. These findings identify cholesterol as a mediator of graphene's cellular effects, providing insight into the biological impact of graphene.

  13. An update on the measurement and management of cholesterol with ...

    African Journals Online (AJOL)

    ... and management of cholesterol with specific reference to secondary prevention of ... Serum-cholesterol has emerged as the dominant risk factor for coronary ... reduce the incidence of secondary myocardial infarctions, strokes and death ...

  14. High cholesterol level is essential for myelin membrane growth.

    Science.gov (United States)

    Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

    2005-04-01

    Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

  15. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  16. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    International Nuclear Information System (INIS)

    Singh, Suman; Singhal, Rahul; Malhotra, B.D.

    2007-01-01

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL -1 (12 mM), shelf life of 1 month, detection limit of 12 mg dL -1 and sensitivity as 5.4 x 10 -5 Abs. mg -1 dL -1

  17. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Central Mechanical Engineering Research Institute, G. Avenue, Durgapur 713209, West Bengal (India); Singhal, Rahul [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India)]. E-mail: bansi.malhotra@gmail.com

    2007-01-23

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL{sup -1} (12 mM), shelf life of 1 month, detection limit of 12 mg dL{sup -1} and sensitivity as 5.4 x 10{sup -5} Abs. mg{sup -1} dL{sup -1}.

  18. Order-constrained linear optimization.

    Science.gov (United States)

    Tidwell, Joe W; Dougherty, Michael R; Chrabaszcz, Jeffrey S; Thomas, Rick P

    2017-11-01

    Despite the fact that data and theories in the social, behavioural, and health sciences are often represented on an ordinal scale, there has been relatively little emphasis on modelling ordinal properties. The most common analytic framework used in psychological science is the general linear model, whose variants include ANOVA, MANOVA, and ordinary linear regression. While these methods are designed to provide the best fit to the metric properties of the data, they are not designed to maximally model ordinal properties. In this paper, we develop an order-constrained linear least-squares (OCLO) optimization algorithm that maximizes the linear least-squares fit to the data conditional on maximizing the ordinal fit based on Kendall's τ. The algorithm builds on the maximum rank correlation estimator (Han, 1987, Journal of Econometrics, 35, 303) and the general monotone model (Dougherty & Thomas, 2012, Psychological Review, 119, 321). Analyses of simulated data indicate that when modelling data that adhere to the assumptions of ordinary least squares, OCLO shows minimal bias, little increase in variance, and almost no loss in out-of-sample predictive accuracy. In contrast, under conditions in which data include a small number of extreme scores (fat-tailed distributions), OCLO shows less bias and variance, and substantially better out-of-sample predictive accuracy, even when the outliers are removed. We show that the advantages of OCLO over ordinary least squares in predicting new observations hold across a variety of scenarios in which researchers must decide to retain or eliminate extreme scores when fitting data. © 2017 The British Psychological Society.

  19. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine-K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor

  20. Regulation of direct transintestinal cholesterol excretion in mice

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Vrins, Carlos L. J.; van den Oever, Karin; Seemann, Ingar; Elferink, Ronald P. J. Oude; van Eck, Miranda; Kuipers, Folkert; Groen, Albert K.

    2008-01-01

    Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux ( TICE) contributes significantly to cholesterol removal in mice. Our aim

  1. Regulation of direct transintestinal cholesterol excretion in mice

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Vrins, Carlos L. J.; van den Oever, Karin; Seemann, Ingar; Oude Elferink, Ronald P. J.; van Eck, Miranda; Kuipers, Folkert; Groen, Albert K.

    2008-01-01

    Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux (TICE) contributes significantly to cholesterol removal in mice. Our aim

  2. Hypercholesterolemia: The Role of Schools in Cholesterol Screening.

    Science.gov (United States)

    Price, James H.; Casler, Suzanne M.

    1997-01-01

    Examines the prevalence of cardiovascular disease risk factors among children and adolescents, the pros and cons of cholesterol screening among youth, cholesterol assessments of at-risk youth, and the role of schools in cholesterol education and screening (focusing on comprehensive school health education and services). (SM)

  3. Plasma cholesterol and related lipid levels of seemingly healthy ...

    African Journals Online (AJOL)

    The purpose of this study was achieved through analysis of fasting plasma samples for the following: Total cholesterol (TC), Triacylglycerols (TG), High density lipoprotein cholesterol (HDL), Low density lipoprotein cholesterol (LDL), and molar ratios of LDL/HDL, TC/ HDL, and TC/TG. Methods: One hundred and seventy four ...

  4. Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

    Directory of Open Access Journals (Sweden)

    Ingemar Björkhem

    2013-09-01

    Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

  5. Critical time window of neuronal cholesterol synthesis during neurite outgrowth.

    Science.gov (United States)

    Fünfschilling, Ursula; Jockusch, Wolf J; Sivakumar, Nandhini; Möbius, Wiebke; Corthals, Kristina; Li, Sai; Quintes, Susanne; Kim, Younghoon; Schaap, Iwan A T; Rhee, Jeong-Seop; Nave, Klaus-Armin; Saher, Gesine

    2012-05-30

    Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to brain cholesterol metabolism is unknown. To investigate whether cortical projection neurons in vivo essentially require cholesterol biosynthesis and which cell types support neurons, we have conditionally ablated the cholesterol biosynthesis in these neurons in mice either embryonically or postnatally. We found that cortical projection neurons synthesize cholesterol during their entire lifetime. At all stages, they can also benefit from glial support. Adult neurons that lack cholesterol biosynthesis are mainly supported by astrocytes such that their functional integrity is preserved. In contrast, microglial cells support young neurons. However, compensatory efforts of microglia are only transient leading to layer-specific neuronal death and the reduction of cortical projections. Hence, during the phase of maximal membrane growth and maximal cholesterol demand, neuronal cholesterol biosynthesis is indispensable. Analysis of primary neurons revealed that neurons tolerate only slight alteration in the cholesterol content and plasma membrane tension. This quality control allows neurons to differentiate normally and adjusts the extent of neurite outgrowth, the number of functional growth cones and synapses to the available cholesterol. This study highlights both the flexibility and the limits of horizontal cholesterol transfer in vivo and may have implications for the understanding of neurodegenerative diseases.

  6. Alcohol consumption stimulates early stemps in reverse cholesterol transport

    NARCIS (Netherlands)

    Gaag, van der M.S.; Tol, van A.; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

    2001-01-01

    Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol

  7. Alcohol consumption stimulates early steps in reverse cholesterol transport

    NARCIS (Netherlands)

    Gaag, M.S. van der; Tol, A. van; Vermunt, S.H.F.; Scheek, L.M.; Schaafsma, G.; Hendriks, H.F.J.

    2001-01-01

    Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol

  8. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    OpenAIRE

    Tomaro-Duchesneau, Catherine; Jones, Mitchell L.; Shah, Divya; Jain, Poonam; Saha, Shyamali; Prakash, Satya

    2014-01-01

    Excess cholesterol is associated with cardiovascular diseases (CVD), an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and ch...

  9. Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1

    NARCIS (Netherlands)

    Beulens, J.W.J.; Sierksma, A.; Tol, A. van; Fournier, N.; Gent, T. van; Paul, J.L.; Hendriks, H.F.J.

    2004-01-01

    Moderate alcohol consumption increases HDL cholesterol, which is involved in reverse cholesterol transport (RCT). The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux, using J774 mouse macrophages and Fu5AH cells, and on other parameters in the

  10. HDL Cholesterol and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2015-01-01

    Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally as...

  11. Cholesterol Crystal Embolism and Chronic Kidney Disease.

    Science.gov (United States)

    Li, Xuezhu; Bayliss, George; Zhuang, Shougang

    2017-05-24

    Renal disease caused by cholesterol crystal embolism (CCE) occurs when cholesterol crystals become lodged in small renal arteries after small pieces of atheromatous plaques break off from the aorta or renal arteries and shower the downstream vascular bed. CCE is a multisystemic disease but kidneys are particularly vulnerable to atheroembolic disease, which can cause an acute, subacute, or chronic decline in renal function. This life-threatening disease may be underdiagnosed and overlooked as a cause of chronic kidney disease (CKD) among patients with advanced atherosclerosis. CCE can result from vascular surgery, angiography, or administration of anticoagulants. Atheroembolic renal disease has various clinical features that resemble those found in other kidney disorders and systemic diseases. It is commonly misdiagnosed in clinic, but confirmed by characteristic renal biopsy findings. Therapeutic options are limited, and prognosis is considered to be poor. Expanding knowledge of atheroembolic renal disease due to CCE opens perspectives for recognition, diagnosis, and treatment of this cause of progressive renal insufficiency.

  12. Cytosolic cholesterol ester hydrolase in adrenal cortex

    OpenAIRE

    Tocher, Douglas R.

    1983-01-01

    Cholesterol ester hydrolase (CEH) in adrenocortical cytosol was known to be phosphorylated and activated, in response to ACTH in a cAMPdependent protein kinase mediated process. The purification of CEH from bovine adrenocortical cytosol was attempted. The use of detergents to solubilise the enzyme from lipid-rich aggregates was investigated and sodium cholate was found to be effective. A purification procedure using cholate solubilised enzyme was developed. The detergent int...

  13. Structure of cholesterol/ceramide monolayer mixtures

    DEFF Research Database (Denmark)

    Scheffer, L.; Solomonov, I.; Weygand, M.J.

    2005-01-01

    The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two....... As ceramide incorporates the lipid backbone common to all sphingolipids, this arrangement may be relevant to the understanding of the molecular organization of lipid rafts....

  14. Potent and selective mediators of cholesterol efflux

    Energy Technology Data Exchange (ETDEWEB)

    Bielicki, John K; Johansson, Jan

    2015-03-24

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  15. Human plasma lecithin-cholesterol acyltransferase

    International Nuclear Information System (INIS)

    Jauhiainen, M.; Stevenson, K.J.; Dolphin, P.J.

    1988-01-01

    Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme which catalyzes the transacylation of the fatty acid at the sn-2 position of lecithin to cholesterol forming lysolecithin and cholesteryl ester. The substrates for and products of this reaction are present within the plasma lipoproteins upon which the enzyme acts to form the majority of cholesteryl ester in human plasma. The authors proposed a covalent catalytic mechanism of action for LCAT in which serine and histidine residues mediate lecithin cleavage and two cysteine residues cholesterol esterification. With the aid of sulfhydryl reactive trivalent organoarsenical compounds which are specific for vicinal thiols they have probed the geometry of the catalytic site. They conclude that the two catalytic cysteine residues of LCAT (Cys 31 and Cys 184 ) are vicinal with a calculated distance between their sulfur atoms of 3.50-3.62 A. The additional residue alkylated by teh bifunctional reagent is within the catalytic site and may represent a previously identified catalytic serine or histidine residue

  16. Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone

    International Nuclear Information System (INIS)

    Hu, Z.Y.; Bourreau, E.; Jung-Testas, I.; Robel, P.; Baulieu, E.E.

    1987-01-01

    Oligodendrocyte mitochondria from 21-day-old Sprague-Dawley male rats were incubated with 100 nM [ 3 H]cholesterol. It yielded [ 3 H]pregnenolone at a rate of 2.5 +/- 0.7 and 5-[ 3 H]pregnene-3β,20α-diol at a rate of 2.5 +/- 1.1 pmol per mg of protein per hr. Cultures of glial cells from 19- to 21-day-old fetuses (a mixed population of astrocytes and oligodendrocytes) were incubated for 24 hr with [ 3 H]mevalonolactone. [ 3 H]Cholesterol, [ 3 H]pregnenolone, and 5-[ 3 H]pregnene-3β,20α-diol were characterized in cellular extracts. The formation of the 3 H-labeled steroids was increased by dibutyryl cAMP (0.2 mM) added to the culture medium. The active cholesterol side-chain cleavage mechanism, recently suggested immunohistochemically and already observed in cultures of C6 glioma cells, reinforces the concept of neurosteroids applied to Δ 5 -3β-hydroxysteroids previously isolated from brain

  17. Cholesterol impairment contributes to neuroserpin aggregation

    Science.gov (United States)

    Giampietro, Costanza; Lionetti, Maria Chiara; Costantini, Giulio; Mutti, Federico; Zapperi, Stefano; La Porta, Caterina A. M.

    2017-03-01

    Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer’s and Parkinson’s diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol reg-ulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.

  18. Steady-state oxidation of cholesterol catalyzed by cholesterol oxidase in lipid bilayer membranes on platinum electrodes

    International Nuclear Information System (INIS)

    Bokoch, Michael P.; Devadoss, Anando; Palencsar, Mariela S.; Burgess, James D.

    2004-01-01

    Cholesterol oxidase is immobilized in electrode-supported lipid bilayer membranes. Platinum electrodes are initially modified with a self-assembled monolayer of thiolipid. A vesicle fusion method is used to deposit an outer leaflet of phospholipids onto the thiolipid monolayer forming a thiolipid/lipid bilayer membrane on the electrode surface. Cholesterol oxidase spontaneously inserts into the electrode-supported lipid bilayer membrane from solution and is consequently immobilized to the electrode surface. Cholesterol partitions into the membrane from buffer solutions containing cyclodextrin. Cholesterol oxidase catalyzes the oxidation of cholesterol by molecular oxygen, forming hydrogen peroxide as a product. Amperometric detection of hydrogen peroxide for continuous solution flow experiments are presented, where flow was alternated between cholesterol solution and buffer containing no cholesterol. Steady-state anodic currents were observed during exposures of cholesterol solutions ranging in concentration from 10 to 1000 μM. These data are consistent with the Michaelis-Menten kinetic model for oxidation of cholesterol as catalyzed by cholesterol oxidase immobilized in the lipid bilayer membrane. The cholesterol detection limit is below 1 μM for cholesterol solution prepared in buffered cyclodextrin. The response of the electrodes to low density lipoprotein solutions is increased upon addition of cyclodextrin. Evidence for adsorption of low density lipoprotein to the electrode surface is presented

  19. Modeling the microstructural evolution during constrained sintering

    DEFF Research Database (Denmark)

    Bjørk, Rasmus; Frandsen, Henrik Lund; Tikare, V.

    A numerical model able to simulate solid state constrained sintering of a powder compact is presented. The model couples an existing kinetic Monte Carlo (kMC) model for free sintering with a finite element (FE) method for calculating stresses on a microstructural level. The microstructural response...... to the stress field as well as the FE calculation of the stress field from the microstructural evolution is discussed. The sintering behavior of two powder compacts constrained by a rigid substrate is simulated and compared to free sintering of the same samples. Constrained sintering result in a larger number...

  20. Biochemical and Bioimaging Evidence of Cholesterol in Acquired Cholesteatoma

    DEFF Research Database (Denmark)

    Thorsted, Bjarne; Bloksgaard, Maria; Groza, Alexandra

    2016-01-01

    : The results show that the total lipid content of the cholesteatoma matrix is similar to that of stratum corneum from skin and that the cholesteatoma matrix unquestionably contains cholesterol. The cholesterol content in the cholesteatoma matrix is increased by over 30% (w/w dry weight) compared to the control....... The cholesterol sulfate content is below 1% of the total lipids in both the cholesteatoma and the control. Cholesterol ester was reduced by over 30% when compared to the control. CONCLUSIONS: The content of cholesterol in the cholesteatoma matrix is significantly different from that in stratum corneum from skin...

  1. Endoscopic Transnasal Approach for Cholesterol Granuloma of the Petrous Apex

    Directory of Open Access Journals (Sweden)

    Mohammad Samadian

    2015-01-01

    Full Text Available Cholesterol granulomas are rare round or ovoid cysts. They contain cholesterol crystals surrounded by foreign bodies of giant cells and are characterized by chronic inflammation. Large cholesterol granuloma can compress surrounding tissue especially cranial nerves. There are several types of surgery for the resection of cholesterol granuloma. We describe 4 cases of cholesterol granuloma operated on via transnasal endoscopic approach. In this report, we describe radiologic and pathologic features of this lesion and explain the advantages and disadvantages of transsphenoidal endoscopic approach for these rare lesions.

  2. The influence of saponins on cell membrane cholesterol.

    Science.gov (United States)

    Böttger, Stefan; Melzig, Matthias F

    2013-11-15

    We studied the influence of structurally different saponins on the cholesterol content of cellular membranes. Therefore a cell culture model using ECV-304 urinary bladder carcinoma cells was developed. To measure the cholesterol content we used radiolabeled (3)H-cholesterol which is chemically and physiologically identical to natural cholesterol. The cells were pre-incubated with (3)H-cholesterol and after a medium change, they were treated with saponins to assess a saponin-induced cholesterol liberation from the cell membrane. In another experiment the cells were pre-incubated with saponins and after a medium change, they were treated with (3)H-cholesterol to assess a saponin-induced inhibition of cholesterol uptake into the cell membrane. Furthermore, the membrane toxicity of all applied saponins was analyzed using extracellular LDH quantification and the general cytotoxicity was analyzed using a colorimetric MTT-assay and DNA quantification. Our results revealed a correlation between membrane toxicity and general cytotoxicity. We also compared the results from the experiments on the saponin-induced cholesterol liberation as well as the saponin-induced inhibition of cholesterol uptake with the membrane toxicity. A significant reduction in the cell membrane cholesterol content was noted for those saponins who showed membrane toxicity (IC50 saponins either liberated (3)H-cholesterol from intact cell membranes or blocked the integration of supplemented (3)H-cholesterol into the cell membrane. Saponins with little influence on the cell membrane (IC50 >100 μM) insignificantly altered the cell membrane cholesterol content. The results suggested that the general cytotoxicity of saponins is mainly dependent on their membrane toxicity and that the membrane toxicity might be caused by the loss of cholesterol from the cell membrane. We also analyzed the influence of a significantly membrane toxic saponin on the cholesterol content of intracellular membranes such as those

  3. Association between cholesterol plasma levels and craving among heroin users.

    Science.gov (United States)

    Lin, Shih-Hsien; Yang, Yen Kuang; Lee, Sheng-Yu; Hsieh, Pei Chun; Chen, Po See; Lu, Ru-Band; Chen, Kao Chin

    2012-12-01

    Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

  4. Cholesterol: a novel regulatory role in myelin formation.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

    2011-02-01

    Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

  5. Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study

    NARCIS (Netherlands)

    van de Heijning, B. J.; Stolk, M. F.; van Erpecum, K. J.; Renooij, W.; Groen, A. K.; vanBerge-Henegouwen, G. P.

    1994-01-01

    Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid

  6. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S., E-mail: pundircs@rediffmail.com [M. D. University, Department of Biochemistry (India)

    2013-09-15

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 Degree-Sign C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5-700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 Degree-Sign C.

  7. THE REDUCTION OF CHOLESTEROL WITH CUPPING THERAPY ON CHOLESTEROL REDUCTION IN PATIENTS WITH HYPERCHOLESTEROLEMIA

    Directory of Open Access Journals (Sweden)

    Zahid Fikri

    2017-04-01

    Full Text Available Introduction: Hypercholesterolemia is a risk factor causes of death at younger ages. Hypercholesterolemia may increase the risk of atherosclerosis, coronary heart disease, pancreatitis (pancreas inflammation in organs, diabetes mellitus, thyroid disorders, liver disease and kidney disease. Many patients with hypercholesterolemia using cupping therapy. Cupping therapy is alternative treatment process of throwing dirty blood from the body through the skin surface. The objective of this study was to determine the effect of cupping therapy to decrease cholesterol levels in patients with hypercholesterolemia. Method: Design used in this study was quasy experimental design. The population is all patients with hypercholesterolemia in the health center plaza Gresik. The total sample is 18 respondents, taken according to inclusion criteria. Independent variable is the cupping therapy. The dependent variable was the decrease in cholesterol levels. Data were collected using a questionnaire and observation of cholesterol. Data were analyzed using independent t-test and paired t tests with signi fi cance level α < 0.05. Result: The results show that cholesterol levels in patients with hypercholesterolemia treated groups decreased majority. Independent statistical analysis using t-test showed p = 0.001 and with the Paired t-test p value = 0.003. Discussion: This result means that there are significant effects of cupping therapy on cholesterol reduction in patients with hypercholesterolemia aged 45 years and over. Further research needs to be done in control diet, lifestyle and daily activities for the success of cupping therapy.

  8. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    International Nuclear Information System (INIS)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S.

    2013-01-01

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 °C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5–700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 °C

  9. Microwave assisted direct saponification for the simultaneous determination of cholesterol and cholesterol oxides in shrimp.

    Science.gov (United States)

    Souza, Hugo A L; Mariutti, Lilian R B; Bragagnolo, Neura

    2017-05-01

    A novel microwave-assisted direct saponification method for the simultaneous determination of cholesterol and cholesterol oxides in shrimp was developed and validated. Optimal saponification conditions, determined by means of an experimental design, were achieved using 500mg of sample and 20mL of 1mol/L KOH ethanol solution for 16min at 45°C at maximum power at 200W and magnetic stirring at 120rpm. Higher extraction of cholesterol oxides in a reduced saponification time (∼75 times) was achieved in comparison with the direct cold saponification method. The new method showed low detection (≤0.57μg/mL) and quantification (≤1.73μg/mL) limits, good repeatability (≤10.50% intraday and ≤8.56% interday) and low artifact formation (evaluated by using a deuterated cholesterol-D6 standard). Raw, salted and dried-salted shrimps were successfully analyzed by the validated method. The content of cholesterol oxides increased after salting and decreased after drying. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Dietary cholesterol, heart disease risk and cognitive dissonance.

    Science.gov (United States)

    McNamara, Donald J

    2014-05-01

    In the 1960s, the thesis that dietary cholesterol contributes to blood cholesterol and heart disease risk was a rational conclusion based on the available science at that time. Fifty years later the research evidence no longer supports this hypothesis yet changing the dietary recommendation to limit dietary cholesterol has been a slow and at times contentious process. The preponderance of the clinical and epidemiological data accumulated since the original dietary cholesterol restrictions were formulated indicate that: (1) dietary cholesterol has a small effect on the plasma cholesterol levels with an increase in the cholesterol content of the LDL particle and an increase in HDL cholesterol, with little effect on the LDL:HDL ratio, a significant indicator of heart disease risk, and (2) the lack of a significant relationship between cholesterol intake and heart disease incidence reported from numerous epidemiological surveys. Over the last decade, many countries and health promotion groups have modified their dietary recommendations to reflect the current evidence and to address a now recognised negative consequence of ineffective dietary cholesterol restrictions (such as inadequate choline intake). In contrast, health promotion groups in some countries appear to suffer from cognitive dissonance and continue to promote an outdated and potentially hazardous dietary recommendation based on an invalidated hypothesis. This review evaluates the evidence for and against dietary cholesterol restrictions and the potential consequences of such restrictions.

  11. Cholesterol in the retina: the best is yet to come

    Science.gov (United States)

    Pikuleva, Irina A.; Curcio, Christine A.

    2014-01-01

    Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes’ roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. PMID:24704580

  12. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  13. The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

    Science.gov (United States)

    Miettinen, T A; Gylling, H; Nissinen, M J

    2011-10-01

    To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Asymptotic Likelihood Distribution for Correlated & Constrained Systems

    CERN Document Server

    Agarwal, Ujjwal

    2016-01-01

    It describes my work as summer student at CERN. The report discusses the asymptotic distribution of the likelihood ratio for total no. of parameters being h and 2 out of these being are constrained and correlated.

  15. Constrained bidirectional propagation and stroke segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Mori, S; Gillespie, W; Suen, C Y

    1983-03-01

    A new method for decomposing a complex figure into its constituent strokes is described. This method, based on constrained bidirectional propagation, is suitable for parallel processing. Examples of its application to the segmentation of Chinese characters are presented. 9 references.

  16. Mathematical Modeling of Constrained Hamiltonian Systems

    NARCIS (Netherlands)

    Schaft, A.J. van der; Maschke, B.M.

    1995-01-01

    Network modelling of unconstrained energy conserving physical systems leads to an intrinsic generalized Hamiltonian formulation of the dynamics. Constrained energy conserving physical systems are directly modelled as implicit Hamiltonian systems with regard to a generalized Dirac structure on the

  17. Client's Constraining Factors to Construction Project Management

    African Journals Online (AJOL)

    factors as a significant system that constrains project management success of public and ... finance for the project and prompt payment for work executed; clients .... consideration of the loading patterns of these variables, the major factor is ...

  18. On the origin of constrained superfields

    Energy Technology Data Exchange (ETDEWEB)

    Dall’Agata, G. [Dipartimento di Fisica “Galileo Galilei”, Università di Padova,Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova,Via Marzolo 8, 35131 Padova (Italy); Dudas, E. [Centre de Physique Théorique, École Polytechnique, CNRS, Université Paris-Saclay,F-91128 Palaiseau (France); Farakos, F. [Dipartimento di Fisica “Galileo Galilei”, Università di Padova,Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova,Via Marzolo 8, 35131 Padova (Italy)

    2016-05-06

    In this work we analyze constrained superfields in supersymmetry and supergravity. We propose a constraint that, in combination with the constrained goldstino multiplet, consistently removes any selected component from a generic superfield. We also describe its origin, providing the operators whose equations of motion lead to the decoupling of such components. We illustrate our proposal by means of various examples and show how known constraints can be reproduced by our method.

  19. The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

    Science.gov (United States)

    Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C

    2015-02-27

    ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

  20. Cold labelled substrate and estimation of cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay

    International Nuclear Information System (INIS)

    Dobiasova, M.; Schuetzova, M.

    1986-01-01

    A new method is described of cold labelling of blood serum, plasma and body fluids containing lecithin cholesterol acyltransferase (LCAT) and/or lipoproteins for radioassay to assess the cholesterol esterification rate. The method uses the principle of transfer, in refrigeration conditions, of 14 C-cholesterol from filter paper discs to the fluids. The preparation of the disc guarantees homogeneous labelling and high stability. The use of the labelling disc was shown to be reliable, easy and fast and suitable for accurate assessment of LCAT reaction, applicable in the widest possible enzyme concentration range. It was also, found suited for the measurement of the esterification rate of rabbit intraocular fluid which is a medium with the lowest contents of the substrate and LCAT. (L.O.)

  1. Isotope dilution/mass spectrometry of serum cholesterol with [3,4-13C]cholesterol: proposed definitive method

    International Nuclear Information System (INIS)

    Pelletier, O.; Wright, L.A.; Breckenridge, W.C.

    1987-01-01

    We describe a new gas-chromatographic/mass-spectrometric (GC/MS) isotope-dilution method for determination of serum cholesterol. The method has been fully optimized and documented to provide the high accuracy and precision expected for a Definitive Method. In the presence of [3,4- 13 C]cholesterol, cholesteryl esters in serum are hydrolyzed under optimum conditions and the entire cholesterol pool is extracted and derivatized to silyl ethers. The cholesterol derivatives are resolved from other sterols by gas-liquid chromatography on a fused silica column, and selected ions characteristic of cholesterol and the [3,4- 13 C]cholesterol are monitored with a GC/MS quandrupole system. We estimated the cholesterol content of samples by bracketing each sample with standards of comparable cholesterol concentration that also contained the [3,4- 13 C]cholesterol. The procedure was highly reproducible (CV less than 0.5%), better accuracy and precision being obtained with [3,4- 13 C]cholesterol than with heptadeuterated cholesterol. Mean values per gram of dry serum for one serum pool assayed by this method and that of the National Bureau of Standards differed by 0.5%. We conclude that the method satisfies the criteria for a Definitive Method

  2. Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

    International Nuclear Information System (INIS)

    Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

    1986-01-01

    EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

  3. Voluntary exercise increases cholesterol efflux but not macrophage reverse cholesterol transport in vivo in mice

    Directory of Open Access Journals (Sweden)

    Kuipers Folkert

    2010-07-01

    Full Text Available Abstract Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT. After two weeks of voluntary wheel running (average 10.1 ± 1.4 km/day plasma triglycerides were lower (p

  4. Ricinus communis agglutinin-mediated agglutination and fusion of glycolipid-containing phospholipid vesicles: effect of carbohydrate head group size, calcium ions, and spermine.

    Science.gov (United States)

    Hoekstra, D; Düzgüneş, N

    1986-03-25

    The glycolipids galactosylcerebroside (GalCer), lactosylceramide (LacCer), and trihexosylceramide (Gb3) were inserted into phospholipid vesicles, consisting of phosphatidylethanolamine and phosphatidic acid. The extent to which their carbohydrate head groups protruded beyond the vesicle surface and their interference with membrane approach were examined by determining vesicle susceptibility toward type I Ricinus communis agglutinin (RCA1) induced agglutination and Ca2+- and spermine-induced aggregation and fusion either in the presence or in the absence of the lectin. The initial agglutination rates increased in the order GalCer much less than LacCer less than Gb3, while a reversed order was obtained for Ca2+- and spermine-induced aggregation and fusion, indicating an enhanced steric interference on close approach of bilayers with increasing head group size. The lectin-mediated agglutination rates for LacCer- and Gb3-containing vesicles increased by an order of magnitude when Ca2+ was also included in the medium, at a concentration that did not induce aggregation per se. Charge neutralization could not account for this observation as the polyvalent cation spermine did not display this synergistic effect with RCA1. Addition of Ca2+ to preagglutinated vesicles substantially reduced the threshold cation concentration for fusion (micromolar vs. millimolar). Quantitatively, this concentration decreased with decreasing carbohydrate head group size, indicating that the head group protrusion determined the interbilayer distance within the vesicle aggregate. The distinct behavior of Ca2+ vs. spermine on RCA1-induced agglutination on the one hand and fusion on the other indicated that Ca2+ regulates the steric orientation of the carbohydrate head group, which appears to be related to its ability to dehydrate the bilayer. As a result, lectin agglutinability becomes enhanced while fusion will be interrupted as the interbilayer distance increases, the threshold head group size

  5. Immunohistological Analysis of In Situ Expression of Mycobacterial Antigens in Skin Lesions of Leprosy Patients Across the Histopathological Spectrum : Association of Mycobacterial Lipoarabinomannan (LAM) and Mycobacterium leprae Phenolic Glycolipid-I (PGL-I) with Leprosy Reactions

    OpenAIRE

    Verhagen, Claudia; Faber, William; Klatser, Paul; Buffing, Anita; Naafs, Ben; Das, Pranab

    1999-01-01

    The presence of mycobacterial antigens in leprosy skin lesions was studied by immunohistological methods using monoclonal antibodies (MAbs) to Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) and to cross-reactive mycobacterial antigens of 36 kd, 65 kd, and lipoarabinomannan (LAM). The staining patterns with MAb to 36 kd and 65 kd were heterogeneous and were also seen in the lesions of other skin diseases. The in situ staining of PGL-I and LAM was seen only in ...

  6. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Matthias Orth

    2012-01-01

    Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

  7. The effects of cholesterol on learning and memory.

    Science.gov (United States)

    Schreurs, Bernard G

    2010-07-01

    Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, pro-inflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer's disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore.

  8. Pitfalls in the detection of cholesterol in Huntington's disease models.

    Science.gov (United States)

    Marullo, Manuela; Valenza, Marta; Leoni, Valerio; Caccia, Claudio; Scarlatti, Chiara; De Mario, Agnese; Zuccato, Chiara; Di Donato, Stefano; Carafoli, Ernesto; Cattaneo, Elena

    2012-10-11

    Background Abnormalities in brain cholesterol homeostasis have been reported in Huntington's disease (HD), an adult-onset neurodegenerative disorder caused by an expansion in the number of CAG repeats in the huntingtin (HTT) gene. However, the results have been contradictory with respect to whether cholesterol levels increase or decrease in HD models. Biochemical and mass spectrometry methods show reduced levels of cholesterol precursors and cholesterol in HD cells and in the brains of several HD animal models. Abnormal brain cholesterol homeostasis was also inferred from studies in HD patients. In contrast, colorimetric and enzymatic methods indicate cholesterol accumulation in HD cells and tissues. Here we used several methods to investigate cholesterol levels in cultured cells in the presence or absence of mutant HTT protein. Results Colorimetric and enzymatic methods with low sensitivity gave variable results, whereas results from a sensitive analytical method, gas chromatography-mass spectrometry, were more reliable. Sample preparation, high cell density and cell clonality also influenced the detection of intracellular cholesterol. Conclusions Detection of cholesterol in HD samples by colorimetric and enzymatic assays should be supplemented by detection using more sensitive analytical methods. Care must be taken to prepare the sample appropriately. By evaluating lathosterol levels using isotopic dilution mass spectrometry, we confirmed reduced cholesterol biosynthesis in knock-in cells expressing the polyQ mutation in a constitutive or inducible manner. *Correspondence should be addressed to Elena Cattaneo: elena.cattaneo@unimi.it.

  9. Lack of P2Y(13) in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Lichtenstein, Laeticia; Serhan, Nizar; Annema, Wijtske; Combes, Guillaume; Robaye, Bernard; Boeynaems, Jean-Marie; Perret, Bertrand; Tietge, Uwe J. F.; Laffargue, Muriel; Martinez, Laurent O.

    2013-01-01

    Background: The protective effect of HDL is mostly attributed to their metabolic function in reverse cholesterol transport (RCT), a process whereby excess cellular cholesterol is taken up from peripheral cells, processed in HDL particles, and later delivered to the liver for further metabolism and

  10. Effect of cholesterol nucleation-promoting activity on cholesterol solubilization in model bile

    NARCIS (Netherlands)

    Groen, A. K.; Ottenhoff, R.; Jansen, P. L.; van Marle, J.; Tytgat, G. N.

    1989-01-01

    Human bile contains a factor with cholesterol nucleation-promoting activity that binds to concanavalin A-Sepharose. In this study we have investigated the effect of this activity on the dynamics of lipid solubilization in supersaturated model bile. A concanavalin A binding protein fraction of human

  11. Potassium-doped carbon nanotubes toward the direct electrochemistry of cholesterol oxidase and its application in highly sensitive cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaorong [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Xu Jingjuan, E-mail: xujj@nju.edu.cn [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Chen Hongyuan [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2011-10-30

    We demonstrate herein a newly developed serum total cholesterol biosensor by using the direct electron transfer of cholesterol oxidase (ChOx), which is based on the immobilization of cholesterol oxidase and cholesterol esterase (ChEt) on potassium-doped multi-walled carbon nanotubes (KMWNTs) modified electrodes. The KMWNTs accelerate the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx and maintaining its bioactivity. As a new platform in cholesterol analysis, the resulting electrode (ChOx/KMWNTs/GCE) exhibits a sensitive response to free cholesterol, with a linear range of 0.050-16.0 {mu}mol L{sup -1} and a detection limit of 5.0 nmol L{sup -1} (S/N = 3). Coimmobilization of ChEt and ChOx (ChEt/ChOx/KMWNTs/GCE) allows the determination of both free cholesterol and esterified cholesterol. The resulting biosensor shows the same linear range of 0.050-16.0 {mu}mol L{sup -1} for free cholesterol and cholesteryl oleate, with the detection limit of 10.0 and 12.0 nmol L{sup -1} (S/N = 3), respectively. The concentrations of total (free and esterified) cholesterol in human serum samples, determined by using the techniques developed in the present study, are in good agreement with those determined by the well-established techniques using the spectrophotometry.

  12. Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

    Science.gov (United States)

    Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

    1986-02-12

    Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase

  13. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  14. Specific Ion Effects in Cholesterol Monolayers

    Directory of Open Access Journals (Sweden)

    Teresa Del Castillo-Santaella

    2016-05-01

    Full Text Available The interaction of ions with interfaces and, in particular, the high specificity of these interactions to the particular ions considered, are central questions in the field of surface forces. Here we study the effect of different salts (NaI, NaCl, CaCl2 and MgCl2 on monolayers made of cholesterol molecules, both experimentally (surface area vs. lateral pressure isotherms measured by a Langmuir Film Balance and theoretically (molecular dynamics (MD all-atomic simulations. We found that surface isotherms depend, both quantitatively and qualitatively, on the nature of the ions by altering the shape and features of the isotherm. In line with the experiments, MD simulations show clear evidences of specific ionic effects and also provide molecular level details on ion specific interactions with cholesterol. More importantly, MD simulations show that the interaction of a particular ion with the surface depends strongly on its counterion, a feature ignored so far in most theories of specific ionic effects in surface forces.

  15. Pairing of cholesterol with oxidized phospholipid species in lipid bilayers

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Loubet, Bastien; Olzynska, Agnieszka

    2014-01-01

    We claim that (1) cholesterol protects bilayers from disruption caused by lipid oxidation by sequestering conical shaped oxidized lipid species such as 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PZPC) away from phospholipid, because cholesterol and the oxidized lipid have complementary...... shapes and (2) mixtures of cholesterol and oxidized lipids can self-assemble into bilayers much like lysolipid–cholesterol mixtures. The evidence for bilayer protection comes from molecular dynamics (MD) simulations and dynamic light scattering (DLS) measurements. Unimodal size distributions of extruded...... vesicles (LUVETs) made up of a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and PZPC containing high amounts of PZPC are only obtained when cholesterol is present in high concentrations. In simulations, bilayers containing high amounts of PZPC become porous, unless cholesterol is also present...

  16. Co-localization of a CD1d-binding glycolipid with an adenovirus-based malaria vaccine for a potent adjuvant effect.

    Science.gov (United States)

    Li, Xiangming; Huang, Jing; Kawamura, Akira; Funakoshi, Ryota; Porcelli, Steven A; Tsuji, Moriya

    2017-05-31

    A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, α-Galactosylceramide (αGalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than αGalCer. In the present study, 7DW8-5 co-administered intramuscularly (i.m.) with a recombinant adenovirus expressing a Plasmodium yoelii circumsporozoite protein (PyCSP), AdPyCS, has led to a co-localization of 7DW8-5 and a PyCSP in draining lymph nodes (dLNs), particularly in dendritic cells (DCs). This occurrence initiates a cascade of events, such as the recruitment of DCs to dLNs and their activation and maturation, and the enhancement of the ability of DCs to prime CD8+ T cells induced by AdPyCS and ultimately leading to a potent adjuvant effect and protection against malaria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor?

    OpenAIRE

    Rousset, Xavier; Shamburek, Robert; Vaisman, Boris; Amar, Marcelo; Remaley, Alan T.

    2011-01-01

    Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme that esterifies cholesterol and raises high-density lipoprotein cholesterol, but its role in atherosclerosis is not clearly established. Studies of various animal models have yielded conflicting results, but studies done in rabbits and non-human primates, which more closely simulate human lipoprotein metabolism, indicate that LCAT is likely atheroprotective. Although suggestive, there are also no biomarker studies that mechanisti...

  18. LDL cholesterol estimation in patients with the metabolic syndrome

    OpenAIRE

    Gazi, Irene; Tsimihodimos, Vasilis; Filippatos, Theodosios D; Saougos, Vasilios G; Bairaktari, Eleni T; Tselepis, Alexandros D; Elisaf, Moses

    2006-01-01

    Abstract Background The Friedewald formula (LDL-F) for the estimation of low-density lipoprotein (LDL) cholesterol concentrations is the most often used formula in clinical trials and clinical practice. However, much concern has been raised as to whether this formula is applicable in all patient populations such as the presence of chylomicronaemia and/or hypertriglyceridaemia. The aim of the present study was to evaluate various LDL cholesterol calculation formulas as well as LDL cholesterol ...

  19. A convenient method to synthesize specifically labelled cholesterol with tritium

    International Nuclear Information System (INIS)

    Malik, S.; Kenny, M.; Ahmad, S.; Washington Univ., Seattle, WA

    1992-01-01

    A simple method is described to label cholesterol with tritium. Cholesterol was first oxidized to 5-cholesten-3-one which was then purified by HPLC. Its structure was established by electron impact (EI) mass spectrometry and 1 H-NMR spectroscopy. The ketone was reduced with NaB 3 H 4 to give specifically labelled cholesterol (C-3 3 H) at low specific activity. (author)

  20. A Cholesterol-Sensitive Regulator of the Androgen Receptor

    Science.gov (United States)

    2010-07-01

    Oncogene (2010) 29, 3745–3747; doi:10.1038/onc.2010.132; published online 3 May 2010 Cholesterol is a sterol that serves as a metabolic precursor to other...bioactive sterols , such as nuclear receptor ligands, and also has a major role in plasma membrane structure. Cholesterol and long- chain...cholesterol synthesis (these drugs are generically termed ‘statins’), have been reported to inhibit cancer incidence or progres- sion in some studies. Although

  1. In vitro cholesterol uptake by Lactobacillus delbrueckii subsp. bulgaricus isolates

    OpenAIRE

    Małgorzata Ziarno

    2009-01-01

    Background. Some researchers have indicated that Lactobacillus delbrueckii subsp. bulgaricus may provide additional health benefits, reduce serum cholesterol level, for example. The aim of this study was to determine cholesterol uptake by Lb. delbrueckii subsp. bulgaricus commercial yoghurt starter isolates in artificial GIT fluids. Material and methods. Lb. delbrueckii subsp. bulgaricus isolates were cultured in MRS broth and in artificial GIT fluids contained cholesterol at initial con...

  2. Towards weakly constrained double field theory

    Directory of Open Access Journals (Sweden)

    Kanghoon Lee

    2016-08-01

    Full Text Available We show that it is possible to construct a well-defined effective field theory incorporating string winding modes without using strong constraint in double field theory. We show that X-ray (Radon transform on a torus is well-suited for describing weakly constrained double fields, and any weakly constrained fields are represented as a sum of strongly constrained fields. Using inverse X-ray transform we define a novel binary operation which is compatible with the level matching constraint. Based on this formalism, we construct a consistent gauge transform and gauge invariant action without using strong constraint. We then discuss the relation of our result to the closed string field theory. Our construction suggests that there exists an effective field theory description for massless sector of closed string field theory on a torus in an associative truncation.

  3. Continuation of Sets of Constrained Orbit Segments

    DEFF Research Database (Denmark)

    Schilder, Frank; Brøns, Morten; Chamoun, George Chaouki

    Sets of constrained orbit segments of time continuous flows are collections of trajectories that represent a whole or parts of an invariant set. A non-trivial but simple example is a homoclinic orbit. A typical representation of this set consists of an equilibrium point of the flow and a trajectory...... that starts close and returns close to this fixed point within finite time. More complicated examples are hybrid periodic orbits of piecewise smooth systems or quasi-periodic invariant tori. Even though it is possible to define generalised two-point boundary value problems for computing sets of constrained...... orbit segments, this is very disadvantageous in practice. In this talk we will present an algorithm that allows the efficient continuation of sets of constrained orbit segments together with the solution of the full variational problem....

  4. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

    Science.gov (United States)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

    2013-04-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

  5. Colorimetric detection of cholesterol based on enzyme modified gold nanoparticles

    Science.gov (United States)

    Nirala, Narsingh R.; Saxena, Preeti S.; Srivastava, Anchal

    2018-02-01

    We develop a simple colorimetric method for determination of free cholesterol in aqueous solution based on functionalized gold nanoparticles with cholesterol oxidase. Functionalized gold nanoparticles interact with free cholesterol to produce H2O2 in proportion to the level of cholesterol visually is being detected. The quenching in optical properties and agglomeration of functionalized gold nanoparticles play a key role in cholesterol sensing due to the electron accepting property of H2O2. While the lower ranges of cholesterol (lower detection limit i.e. 0.2 mg/dL) can be effectively detected using fluorescence study, the absorption study attests evident visual color change which becomes effective for detection of higher ranges of cholesterol (lower detection limit i.e. 19 mg/dL). The shades of red gradually change to blue/purple as the level of cholesterol detected (as evident at 100 mg/dL) using unaided eye without the use of expensive instruments. The potential of the proposed method to be applied in the field is shown by the proposed cholesterol measuring color wheel.

  6. The metabolic syndrome using the National Cholesterol Education ...

    African Journals Online (AJOL)

    The metabolic syndrome using the National Cholesterol Education Program and International Diabetes Federation definitions among urbanised black South Africans with established coronary artery disease.

  7. Effect of doxazosin on cholesterol synthesis in cell culture

    International Nuclear Information System (INIS)

    D'Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent

  8. Cholesterol monohydrate nucleation in ultrathin films on water

    DEFF Research Database (Denmark)

    Rapaport, H.; Kuzmenko, I.; Lafont, S.

    2001-01-01

    The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity to a tri......The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity...... in pathological lipid deposits....

  9. Cholesterol granuloma of the petrous apex: CT diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-12-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment.

  10. Cholesterol Assimilation by Lactobacillus Probiotic Bacteria: An In Vitro Investigation

    Directory of Open Access Journals (Sweden)

    Catherine Tomaro-Duchesneau

    2014-01-01

    Full Text Available Excess cholesterol is associated with cardiovascular diseases (CVD, an important cause of mortality worldwide. Current CVD therapeutic measures, lifestyle and dietary interventions, and pharmaceutical agents for regulating cholesterol levels are inadequate. Probiotic bacteria have demonstrated potential to lower cholesterol levels by different mechanisms, including bile salt hydrolase activity, production of compounds that inhibit enzymes such as 3-hydroxy-3-methylglutaryl coenzyme A, and cholesterol assimilation. This work investigates 11 Lactobacillus strains for cholesterol assimilation. Probiotic strains for investigation were selected from the literature: Lactobacillus reuteri NCIMB 11951, L. reuteri NCIMB 701359, L. reuteri NCIMB 702655, L. reuteri NCIMB 701089, L. reuteri NCIMB 702656, Lactobacillus fermentum NCIMB 5221, L. fermentum NCIMB 8829, L. fermentum NCIMB 2797, Lactobacillus rhamnosus ATCC 53103 GG, Lactobacillus acidophilus ATCC 314, and Lactobacillus plantarum ATCC 14917. Cholesterol assimilation was investigated in culture media and under simulated intestinal conditions. The best cholesterol assimilator was L. plantarum ATCC 14917 (15.18 ± 0.55 mg/1010 cfu in MRS broth. L. reuteri NCIMB 701089 assimilated over 67% (2254.70 ± 63.33 mg/1010 cfu of cholesterol, the most of all the strains, under intestinal conditions. This work demonstrates that probiotic bacteria can assimilate cholesterol under intestinal conditions, with L. reuteri NCIMB 701089 showing great potential as a CVD therapeutic.

  11. Cholesterol granuloma of the petrous apex: CT diagnosis

    International Nuclear Information System (INIS)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-01-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment

  12. Cholesterol turnover and metabolism in two patients with abetalipoproteinemia

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  13. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas

    2012-01-01

    , S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...... was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies......Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...

  14. The role of cholesterol metabolism and cholesterol transport in carcinogenesis; A review of scientific findings, relevant to future cancer therapeutics.

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Cruz

    2013-09-01

    Full Text Available While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins, area the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

  15. Recovery and purification of cholesterol from cholesterol-β-cyclodextrin inclusion complex using ultrasound-assisted extraction.

    Science.gov (United States)

    Li, Yong; Chen, Youliang; Li, Hua

    2017-01-01

    Response surface methodology was used to optimize ultrasound-assisted ethanol extraction (UAE) of cholesterol from cholesterol-β-cyclodextrin (C-β-CD) inclusion complex prepared from duck yolk oil. The best extraction conditions were solvent-solid ratio 10mL/g, ultrasonic power 251W, extraction temperature 56°C and sonication time 36min. Under these conditions, the highest cholesterol extraction yield and cholesterol content obtained 98.12±0.25% and 43.38±0.61mg/g inclusion complex, respectively. As compared with Reflux extraction and Soxhlet extraction, the UAE was more efficient and economical. To increase the purity of crude cholesterol extraction, silica gel column chromatography and crystallization were carried out. Finally, cholesterol was obtained at 95.1% purity, 71.7% recovery and 22.0% yield. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

    Fasting blood sample of 50 normal subjects (control) and 100 patients of breast cancer were investigated for serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein, high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio and total cholesterol:high density lipoprotein cholesterol ratio during breast cancer of women. Five cancer stages, types, age groups, parity and menopausal status were undertaken...

  17. Constrained principal component analysis and related techniques

    CERN Document Server

    Takane, Yoshio

    2013-01-01

    In multivariate data analysis, regression techniques predict one set of variables from another while principal component analysis (PCA) finds a subspace of minimal dimensionality that captures the largest variability in the data. How can regression analysis and PCA be combined in a beneficial way? Why and when is it a good idea to combine them? What kind of benefits are we getting from them? Addressing these questions, Constrained Principal Component Analysis and Related Techniques shows how constrained PCA (CPCA) offers a unified framework for these approaches.The book begins with four concre

  18. Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics.

    Science.gov (United States)

    Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling

    2017-08-01

    Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  19. The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol.

    Science.gov (United States)

    Trinidad, Trinidad P; Loyola, Anacleta S; Mallillin, Aida C; Valdez, Divinagracia H; Askali, Faridah C; Castillo, Joan C; Resaba, Rosario L; Masa, Dina B

    2004-01-01

    This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.

  20. Synthesis of cholesterol 26. C{sup 14} (1961); Synthese du cholesterol {sup 14}C-26 (1961)

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, M; Pichat, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1961-07-01

    Cholesterol 26 {sup 14}C is synthesized from methylmagnesium iodide {sup 14}C with a 48 per cent overall yield. Cholesterol is purified by chromatography on alumina. The various intermediates of the synthesis are characterized by thin-layer chromatography according to Stahl. (authors) [French] Le cholesterol {sup 14}C-26 est synthetise a partir d'iodure de methyl magnesium {sup 14}C, avec un rendement de 48 pour cent par rapport a l'iodure de methyl {sup 14}C mis en jeu. Le cholesterol est purifie par chromatographie sur alumine. Les intermediaires de la synthese sont caracterises par chromatographie en couche mince, selon Stahl. (auteurs)

  1. Whole body and tissue cholesterol turnover in the baboon

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  2. The hedgehog receptor patched is involved in cholesterol transport.

    Directory of Open Access Journals (Sweden)

    Michel Bidet

    Full Text Available Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.

  3. On Tree-Constrained Matchings and Generalizations

    NARCIS (Netherlands)

    S. Canzar (Stefan); K. Elbassioni; G.W. Klau (Gunnar); J. Mestre

    2011-01-01

    htmlabstractWe consider the following \\textsc{Tree-Constrained Bipartite Matching} problem: Given two rooted trees $T_1=(V_1,E_1)$, $T_2=(V_2,E_2)$ and a weight function $w: V_1\\times V_2 \\mapsto \\mathbb{R}_+$, find a maximum weight matching $\\mathcal{M}$ between nodes of the two trees, such that

  4. Constrained systems described by Nambu mechanics

    International Nuclear Information System (INIS)

    Lassig, C.C.; Joshi, G.C.

    1996-01-01

    Using the framework of Nambu's generalised mechanics, we obtain a new description of constrained Hamiltonian dynamics, involving the introduction of another degree of freedom in phase space, and the necessity of defining the action integral on a world sheet. We also discuss the problem of quantizing Nambu mechanics. (authors). 5 refs

  5. Client's constraining factors to construction project management ...

    African Journals Online (AJOL)

    This study analyzed client's related factors that constrain project management success of public and private sector construction in Nigeria. Issues that concern clients in any project can not be undermined as they are the owners and the initiators of project proposals. It is assumed that success, failure or abandonment of ...

  6. Hyperbolicity and constrained evolution in linearized gravity

    International Nuclear Information System (INIS)

    Matzner, Richard A.

    2005-01-01

    Solving the 4-d Einstein equations as evolution in time requires solving equations of two types: the four elliptic initial data (constraint) equations, followed by the six second order evolution equations. Analytically the constraint equations remain solved under the action of the evolution, and one approach is to simply monitor them (unconstrained evolution). Since computational solution of differential equations introduces almost inevitable errors, it is clearly 'more correct' to introduce a scheme which actively maintains the constraints by solution (constrained evolution). This has shown promise in computational settings, but the analysis of the resulting mixed elliptic hyperbolic method has not been completely carried out. We present such an analysis for one method of constrained evolution, applied to a simple vacuum system, linearized gravitational waves. We begin with a study of the hyperbolicity of the unconstrained Einstein equations. (Because the study of hyperbolicity deals only with the highest derivative order in the equations, linearization loses no essential details.) We then give explicit analytical construction of the effect of initial data setting and constrained evolution for linearized gravitational waves. While this is clearly a toy model with regard to constrained evolution, certain interesting features are found which have relevance to the full nonlinear Einstein equations

  7. A Dynamic Programming Approach to Constrained Portfolios

    DEFF Research Database (Denmark)

    Kraft, Holger; Steffensen, Mogens

    2013-01-01

    This paper studies constrained portfolio problems that may involve constraints on the probability or the expected size of a shortfall of wealth or consumption. Our first contribution is that we solve the problems by dynamic programming, which is in contrast to the existing literature that applies...

  8. A model for optimal constrained adaptive testing

    NARCIS (Netherlands)

    van der Linden, Willem J.; Reese, Lynda M.

    2001-01-01

    A model for constrained computerized adaptive testing is proposed in which the information on the test at the ability estimate is maximized subject to a large variety of possible constraints on the contents of the test. At each item-selection step, a full test is first assembled to have maximum

  9. A model for optimal constrained adaptive testing

    NARCIS (Netherlands)

    van der Linden, Willem J.; Reese, Lynda M.

    1997-01-01

    A model for constrained computerized adaptive testing is proposed in which the information in the test at the ability estimate is maximized subject to a large variety of possible constraints on the contents of the test. At each item-selection step, a full test is first assembled to have maximum

  10. Neutron Powder Diffraction and Constrained Refinement

    DEFF Research Database (Denmark)

    Pawley, G. S.; Mackenzie, Gordon A.; Dietrich, O. W.

    1977-01-01

    The first use of a new program, EDINP, is reported. This program allows the constrained refinement of molecules in a crystal structure with neutron diffraction powder data. The structures of p-C6F4Br2 and p-C6F4I2 are determined by packing considerations and then refined with EDINP. Refinement is...

  11. Terrestrial Sagnac delay constraining modified gravity models

    Science.gov (United States)

    Karimov, R. Kh.; Izmailov, R. N.; Potapov, A. A.; Nandi, K. K.

    2018-04-01

    Modified gravity theories include f(R)-gravity models that are usually constrained by the cosmological evolutionary scenario. However, it has been recently shown that they can also be constrained by the signatures of accretion disk around constant Ricci curvature Kerr-f(R0) stellar sized black holes. Our aim here is to use another experimental fact, viz., the terrestrial Sagnac delay to constrain the parameters of specific f(R)-gravity prescriptions. We shall assume that a Kerr-f(R0) solution asymptotically describes Earth's weak gravity near its surface. In this spacetime, we shall study oppositely directed light beams from source/observer moving on non-geodesic and geodesic circular trajectories and calculate the time gap, when the beams re-unite. We obtain the exact time gap called Sagnac delay in both cases and expand it to show how the flat space value is corrected by the Ricci curvature, the mass and the spin of the gravitating source. Under the assumption that the magnitude of corrections are of the order of residual uncertainties in the delay measurement, we derive the allowed intervals for Ricci curvature. We conclude that the terrestrial Sagnac delay can be used to constrain the parameters of specific f(R) prescriptions. Despite using the weak field gravity near Earth's surface, it turns out that the model parameter ranges still remain the same as those obtained from the strong field accretion disk phenomenon.

  12. Chance constrained uncertain classification via robust optimization

    NARCIS (Netherlands)

    Ben-Tal, A.; Bhadra, S.; Bhattacharayya, C.; Saketha Nat, J.

    2011-01-01

    This paper studies the problem of constructing robust classifiers when the training is plagued with uncertainty. The problem is posed as a Chance-Constrained Program (CCP) which ensures that the uncertain data points are classified correctly with high probability. Unfortunately such a CCP turns out

  13. Integrating job scheduling and constrained network routing

    DEFF Research Database (Denmark)

    Gamst, Mette

    2010-01-01

    This paper examines the NP-hard problem of scheduling jobs on resources such that the overall profit of executed jobs is maximized. Job demand must be sent through a constrained network to the resource before execution can begin. The problem has application in grid computing, where a number...

  14. Neuroevolutionary Constrained Optimization for Content Creation

    DEFF Research Database (Denmark)

    Liapis, Antonios; Yannakakis, Georgios N.; Togelius, Julian

    2011-01-01

    and thruster types and topologies) independently of game physics and steering strategies. According to the proposed framework, the designer picks a set of requirements for the spaceship that a constrained optimizer attempts to satisfy. The constraint satisfaction approach followed is based on neuroevolution...... and survival tasks and are also visually appealing....

  15. Models of Flux Tubes from Constrained Relaxation

    Indian Academy of Sciences (India)

    tribpo

    J. Astrophys. Astr. (2000) 21, 299 302. Models of Flux Tubes from Constrained Relaxation. Α. Mangalam* & V. Krishan†, Indian Institute of Astrophysics, Koramangala,. Bangalore 560 034, India. *e mail: mangalam @ iiap. ernet. in. † e mail: vinod@iiap.ernet.in. Abstract. We study the relaxation of a compressible plasma to ...

  16. LDL cholesterol still a problem in old age?

    DEFF Research Database (Denmark)

    Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz

    2015-01-01

    BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may...

  17. Cholesterol: Top Five Foods to Lower Your Numbers

    Science.gov (United States)

    ... enough trans fats in a day to be unhealthy and increase cholesterol. If a food label lists "partially hydrogenated oil," it has trans fat, and it's best to avoid it. In addition to changing your diet, making other heart-healthy lifestyle changes is key to improving your cholesterol. Exercising, ...

  18. Endoscopic transsphenoidal surgery for cholesterol granulomas involving the petrous apex

    NARCIS (Netherlands)

    Georgalas, C.; Kania, R.; Guichard, J.-P.; Sauvaget, E.; Tran Ba Huy, P.; Herman, P.

    2008-01-01

    Surgery for cholesterol granulomas involving the petrous apex has traditionally been performed via a lateral skull base approach. We present a case-series of four cholesterol granulomas treated through the endoscopic-transsphenoid approach over the last 10 years. Drainage was successful and

  19. [Phytosterols: another way to reduce LDL cholesterol levels].

    Science.gov (United States)

    Bitzur, Rafael; Cohen, Hofit; Kamari, Yehuda; Harats, Dror

    2013-12-01

    Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.

  20. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

    NARCIS (Netherlands)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M.; Gautier, Emmanuel L.; Westerterp, Marit; Bittman, Robert; Tall, Alan R.; Chen, Shu-Hsia; Thomas, Michael J.; Kreisel, Daniel; Swartz, Melody A.; Sorci-Thomas, Mary G.; Randolph, Gwendalyn J.

    2013-01-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic

  1. The structure of a cholesterol-trapping protein

    Science.gov (United States)

    cholesterol-trapping protein Contact: Dan Krotz, dakrotz@lbl.gov Berkeley Lab Science Beat Lab website index Institute researchers determined the three-dimensional structure of a protein that controls cholesterol level in the bloodstream. Knowing the structure of the protein, a cellular receptor that ensnares

  2. Lowering of cholesterol bioaccessibility and serum concentrations by saponins

    NARCIS (Netherlands)

    Vinarova, Liliya; Vinarov, Zahari; Atanasov, Vasil; Pantcheva, Ivayla; Tcholakova, Slavka; Denkov, Nikolai; Stoyanov, Simeon

    2015-01-01

    Using an in vitro digestion model, we studied the effect of six saponin extracts on the bioaccessibility of cholesterol and saturated fatty acids (SFAs). In the absence of saponins, around 78% of the available cholesterol was solubilized in the simulated intestinal fluids. The addition of two

  3. Nonlinear associations between plasma cholesterol levels and neuropsychological function.

    Science.gov (United States)

    Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

    2016-11-01

    Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  4. Serum cholesterol decline and depression in the postpartum period

    NARCIS (Netherlands)

    Dam, van R.M.; Schuit, A.J.; Schouten, E.G.; Vader, H.L.; Pop, V.J.M.

    1999-01-01

    We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for

  5. Serum cholesterol decline and depression in the postpartum period

    NARCIS (Netherlands)

    van Dam, R M; Schuit, A.J.; Schouten, E G; Vader, H L; Pop, V.J.

    We examined the relation between total serum cholesterol decline and depression in the postpartum period in a prospective study of 266 Dutch women, who were followed until 34 weeks after delivery. The decline in serum cholesterol between week 32 of pregnancy and week 10 postpartum was similar for

  6. Manipulation of Host Cholesterol by Obligate Intracellular Bacteria

    Directory of Open Access Journals (Sweden)

    Dhritiman Samanta

    2017-05-01

    Full Text Available Cholesterol is a multifunctional lipid that plays important metabolic and structural roles in the eukaryotic cell. Despite having diverse lifestyles, the obligate intracellular bacterial pathogens Chlamydia, Coxiella, Anaplasma, Ehrlichia, and Rickettsia all target cholesterol during host cell colonization as a potential source of membrane, as well as a means to manipulate host cell signaling and trafficking. To promote host cell entry, these pathogens utilize cholesterol-rich microdomains known as lipid rafts, which serve as organizational and functional platforms for host signaling pathways involved in phagocytosis. Once a pathogen gains entrance to the intracellular space, it can manipulate host cholesterol trafficking pathways to access nutrient-rich vesicles or acquire membrane components for the bacteria or bacteria-containing vacuole. To acquire cholesterol, these pathogens specifically target host cholesterol metabolism, uptake, efflux, and storage. In this review, we examine the strategies obligate intracellular bacterial pathogens employ to manipulate cholesterol during host cell colonization. Understanding how obligate intracellular pathogens target and use host cholesterol provides critical insight into the host-pathogen relationship.

  7. Low serum cholesterol, serotonin metabolism, and violent death

    NARCIS (Netherlands)

    P.H.A. Steegmans

    1995-01-01

    textabstractA high serum cholesterol level is a well documented risk factor for atherosclerotic cardiovascular disease. Consequently, a low serum cholesterol has in general been viewed as beneficial. However, since the early 70s, results from several cohort studies and randomized trials have

  8. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Peng, Shi-Kaung; Phillips, G.A.; Xia, Guang-Zhi; Morin, R.J.

    1987-01-01

    Radiolabeled pure [4- 14 C] cholesterol was kept at 60 0 C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  9. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Science.gov (United States)

    Hannaoui, Samia; Shim, Su Yeon; Cheng, Yo Ching; Corda, Erica; Gilch, Sabine

    2014-01-01

    Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. PMID:25419621

  10. Plasma cholesterol and sodium in some Nigerians | Ighoroje ...

    African Journals Online (AJOL)

    Cholesterol moderates the fluidity of cell membrane and this in turn controls the transmembrane movement of Na+. We have thus attempted to investigate the relationship of serum cholesterol and Na+ concentrations in some Nigerians. Blood samples were obtained from 122 healthy adult Nigerians and the plasma ...

  11. Rare cause of post-squalene disorder of cholesterol biosynthesis ...

    African Journals Online (AJOL)

    Errors of cholesterol biosynthesis represent a heterogeneous group of metabolic disorders. The aim of the authors of this article is to present a case of a patient with typical symptoms of a rare post-squalene disorder of cholesterol biosynthesis, its diagnostics and progress in neonatal period. The differential diagnosis of a ...

  12. Recognition of Odontogenic Cyst-Fluid Cholesterol Concentration ...

    African Journals Online (AJOL)

    Background: Hypercholesterolaemia is a risk factor for cardiovascular diseases. Serum cholesterol is usually determined to know if a subject is at a risk of heart diseases. This lipid is found in most fluids in the body including the odontogenic cyst-fluid. We investigated the concentration of cholesterol in the odontogenic ...

  13. Strategies for increasing house staff management of cholesterol with inpatients.

    Science.gov (United States)

    Boekeloo, B O; Becker, D M; Levine, D M; Belitsos, P C; Pearson, T A

    1990-01-01

    This study tested the effectiveness of two conceptually different chart audit-based approaches to modifying physicians' clinical practices to conform with quality-assurance standards. The objective was to increase intern utilization of cholesterol management opportunities in the inpatient setting. Using a clinical trial study design, 29 internal medicine interns were randomly assigned to four intervention groups identified by the intervention they received: control, reminder checklists (checklists), patient-specific feedback (feedback), or both interventions (combined). Over a nine-month period, intern management of high blood cholesterol levels in internal medicine inpatients (n = 459) was monitored by postdischarge chart audit. During both a baseline and subsequent intervention period, interns documented significantly more cholesterol management for inpatients with coronary artery disease (CAD) than without CAD. During baseline, 27.3%, 24.3%, 21.7%, 12.4%, 5.4%, and 2.7% of all inpatient charts had intern documentation concerning a low-fat hospital diet, cholesterol history, screening blood cholesterol level assessment, follow-up lipid profile, nutritionist consult, and preventive cardiology consult, respectively. The feedback intervention significantly increased overall intern-documented cholesterol management among inpatients with CAD. The checklists significantly decreased overall intern-documented cholesterol management. Feedback appears to be an effective approach to increasing intern cholesterol management in inpatients.

  14. Cholesterol Check (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Heart disease and stroke are among the leading causes of death in the U.S. One of the main risk factors is high blood cholesterol. In this podcast, Dr. Carla Mercado discusses the importance of a healthy diet and regular screening to prevent high blood cholesterol.

  15. Exercise Enhances Whole-Body Cholesterol Turnover in Mice

    NARCIS (Netherlands)

    Meissner, Maxi; Havinga, Rick; Boverhof, Renze; Kema, Ido; Groen, Albert K.; Kuipers, Folkert

    MEISSNER, M., R. HAVINGA, R. BOVERHOF, I. KEMA, A. K. GROEN, and F. KUIPERS. Exercise Enhances Whole-Body Cholesterol Turnover in Mice. Med. Sci. Sports Exerc., Vol. 42, No. 8, pp. 1460-1468, 2010. Purpose: Regular exercise reduces cardiovascular risk in humans by reducing cholesterol levels, but

  16. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Samia Hannaoui

    2014-11-01

    Full Text Available Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD: whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.

  17. Cholesterol Check (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    High blood cholesterol is a risk factor for cardiovascular disease. This podcast discusses the importance of a healthy diet and regular cholesterol screening.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  18. marital status and occupation versus serum total cholesterol and hdl

    African Journals Online (AJOL)

    DR. AMIN

    ABSTRACT. The influence of marital status and occupation on serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL – CH) concentrations was studied in sixty one (61) adult male and female Hausa subjects aged 20 – 50 years. Irrespective of marital status and occupation, female subjects had higher ...

  19. Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

    International Nuclear Information System (INIS)

    Carr, B.R.; Simpson, E.R.

    1984-01-01

    The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

  20. Immobilization of cholesterol oxidase in LbL films and detection of cholesterol using ac measurements

    International Nuclear Information System (INIS)

    Moraes, Marli L.; Souza, Nara C. de; Hayasaka, Caio O.; Ferreira, Marystela; Rodrigues Filho, Ubirajara P.; Riul, Antonio; Zucolotto, Valtencir; Oliveira, Osvaldo N.

    2009-01-01

    The preserved activity of immobilized biomolecules in layer-by-layer (LbL) films can be exploited in various applications, including biosensing. In this study, cholesterol oxidase (COX) layers were alternated with layers of poly(allylamine hydrochloride) (PAH) in LbL films whose morphology was investigated with atomic force microscopy (AFM). The adsorption kinetics of COX layers comprised two regimes, a fast, first-order kinetics process followed by a slow process fitted with a Johnson-Mehl-Avrami (JMA) function, with exponent ∼ 2 characteristic of aggregates growing as disks. The concept based on the use of sensor arrays to increase sensitivity, widely employed in electronic tongues, was extended to biosensing with impedance spectroscopy measurements. Using three sensing units, made of LbL films of PAH/COX and PAH/PVS (polyvinyl sulfonic acid) and a bare gold interdigitated electrode, we were able to detect cholesterol in aqueous solutions down to the 10 -6 M level. This high sensitivity is attributed to the molecular-recognition interaction between COX and cholesterol, and opens the way for clinical tests to be made with low cost, fast experimental procedures

  1. Enzymatic-fluorometric quantification of cholesterol in bovine milk

    DEFF Research Database (Denmark)

    Larsen, Torben

    2012-01-01

    The present paper describes an enzymatic–fluorometric method for the determination of cholesterol in milk and other opaque matrices. The initial step of the method is to liberate chemically and physically bound cholesterol from the milk fat globule membrane by enzymatic action. The method is able...... to discriminate between esterified and free cholesterol in milk. The analysis is cost effective and is developed to work directly on whole, fresh milk thereby eliminating time consuming and tedious pre-treatment procedures of the sample. More than 1000 milk samples were analysed on the day of sampling. The total...... concentration of milk cholesterol ranged from 80 to 756 μM (n = 1068; mean 351 μM). Milk cholesterol was significantly correlated to milk fat concentration as analysed by mid-infra red spectrometry (r = 0.630; n = 853) and by an enzymatic–fluorometric method (triacylglycerol) (r = 0.611; n = 842)....

  2. Effect of medicinal plants on the crystallization of cholesterol

    Science.gov (United States)

    Saraswathi, N. T.; Gnanam, F. D.

    1997-08-01

    One of the least desirable calcifications in the human body is the mineral deposition in atherosclerosis plaques. These plaques principally consist of lipids such as cholesterol, cholesteryl esters, phospholipids and triglycerides. Chemical analysis of advanced plaques have shown the presence of considerable amounts of free cholesterol identified as cholesterol monohydrate crystals. Cholesterol has been crystallized in vitro. The extracts of some of the Indian medicinal plants detailed below were used as additives to study their effect on the crystallization behaviour of cholesterol. It has been found that many of the herbs have inhibitory effect on the crystallization such as nucleation, crystal size and habit modification. The inhibitory effect of the plants are graded as Commiphora mughul > Aegle marmeleos > Cynoden dactylon > Musa paradisiaca > Polygala javana > Alphinia officinarum > Solanum trilobatum > Enicostemma lyssopifolium.

  3. Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

    International Nuclear Information System (INIS)

    Zaater, M.K.

    2011-01-01

    Cholesterol is the principal constituent of more than three quarters of gallstones. Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones. The risk of gallstones does not correlate with total serum cholesterol levels, but it does correlate with decreased high-density lipoprotein cholesterol and increased triglyceride levels. At least 10 percent of adults have gallstones where female: male ratio of about 2:1 in the younger age groups with increasing prevalence with age. Nine patients with gallstones (6 females and 3 males) were included in the study. Patients were treated with ursodeoxycholic acids tablets in two oral doses, one after breakfast, and the other after dinner for 9 months. Ultrasound examination was repeated every 3 months. Re-examination by abdominal ultrasonography revealed that gallstone 1 cm or less in diameter disappeared within 6 months, and the largest stone 3.06 cm in diameter disappeared within 9 months.

  4. Effect of ionizing radiation on cholesterol in aqueous dispersion

    International Nuclear Information System (INIS)

    Lakritz, L.; Maerker, G.

    1989-01-01

    Aqueous sodium stearate dispersions of cholesterol were irradiated at 0-2 degrees C with absorbed doses ranging from 2.5 to 50 kGy. The resulting mixture of cholesterol derivatives was isolated and examined for 7-ketocholesterol and cholesterol 5 alpha, 6 alpha-epoxide and 5 beta, 6 beta-epoxide content. Concentrations of all three compounds increased with dose, while the ratio of 7-ketocholesterol to total epoxides decreased with increasing dose. The ratio of 7-ketocholestrol to the epoxides was approximately 1 or below at all dose levels while the same ratio in autoxidations of cholesterol in dispersions was normally 6 or greater. The change in the keto/epoxide ratio may be a means for determining whether meat or other foods containing cholesterol have been subjected to ionizing radiation

  5. Cholesterol Protects the Oxidized Lipid Bilayer from Water Injury

    DEFF Research Database (Denmark)

    Owen, Michael C; Kulig, Waldemar; Rog, Tomasz

    2018-01-01

    In an effort to delineate how cholesterol protects membrane structure under oxidative stress conditions, we monitored the changes to the structure of lipid bilayers comprising 30 mol% cholesterol and an increasing concentration of Class B oxidized 1-palmitoyl-2-oleoylphosphatidylcholine (POPC...... in a characteristic reduction in bilayer thickness and increase in area per lipid, thereby increasing the exposure of the membrane hydrophobic region to water. However, cholesterol was observed to help reduce water injury by moving into the bilayer core and forming more hydrogen bonds with the oxPLs. Cholesterol also...... resists altering its tilt angle, helping to maintain membrane integrity. Water that enters the 1-nm-thick core region remains part of the bulk water on either side of the bilayer, with relatively few water molecules able to traverse through the bilayer. In cholesterol-rich membranes, the bilayer does...

  6. Cholesterol biosynthesis in polychlorinated biphenyl-treated rats

    International Nuclear Information System (INIS)

    Kling, D.; Gamble, W.

    1982-01-01

    After administration of polychlorinated biphenly (PCB) at 0.055 (w/w) of the diet to Wistar rats for 30 days, followed by intraperitioneal injection of tritiated water, [ 14 C]mevalonate, and [ 14 C]acetate, there was a decrease in cholesterol biosynthesis in rat liver. No significant change in cholesterol formation was observed when PCB was administered at 0.01% (w/w) of the diet. In vitro inhibition of cholesterol synthesis by rat liver microsomes was observed with PCB. Squalene 2,3-oxidocyclase activity of rat liver microsomes was not significantly altered. Desmosterol delta 24 reductase activity was inhibited only at relatively high concentrations of PCB. There was increased incorporation of radioactivity into squalene and lanosterol, in vitro, in the presence of PCB. The primary inhibition of cholesterol biosynthesis appears to be at the demethylation and rearrangement reactions between lanosterol and cholesterol in the biosynthetic pathway

  7. Bad cholesterol and good mood: exploring the link

    Directory of Open Access Journals (Sweden)

    Yashaswi Gupta

    2016-01-01

    Full Text Available It is a well-known fact that high cholesterol increases the risks of heart disease. Hence, physicians actively encourage cholesterol-lowering interventions using medications and lifestyle modifications. However, there is considerable evidence that aggressive lowering of cholesterol is associated with depression, bipolar disorders, violent behaviour, and suicidal ideation. It has been hypothesised that low cholesterol leads to low levels of serotonin, a chemical that is responsible for maintaining mood balance. South Korea and India have highest number of suicides in Asia. It is a significant challenge for physicians to search an alternative that will not only maintain healthy level of cholesterol, but also contribute to psychological well-being of the patient. Generally, the role of diet and physical activity is considered secondary to medications. However, dietary supplements like coenzyme Q10 (CoQ10, omega-3 fatty acids, niacin, and physical activity like Yoga are extremely beneficial for improving lipid profile and symptoms of depression.

  8. Effects of exogenous retinol and retinoic acid on the biosynthesis of 14C-mannose labelled glycolipids and glycoproteins in rat liver

    International Nuclear Information System (INIS)

    Sato, Mayumi; DeLuca, L.M.; Muto, Yasutoshi

    1978-01-01

    The in vivo and in vitro effects of retinol and retionic acid was investigated on the synthesis of mannolipids and mannopeptides in rat liver. Weanling male, Wister-strain rats (Japan Clea Inc., Tokyo), weighing 35 to 40g are housed in hanging wire bottom cages and maintained on a vitamin A-deficient diet. The incorporation of 14 C-mannose into glycolipids and glycoproteins showed a decrease in vitamin A-depleted rats as compared with vitamin A-fed rats. The mannose-containing lipids were separated into retinyl phosphate (MRP, R sub(f) 0.2) and dolichyl mannosyl phosphate (DMP, R sub(f) 0.4), respectively, by DEAE-cellulose, silicic acid and thin-layer chromatography. A rapid increase in the synthesis of labelled MPR was observed, exhibiting a peak between 25 and 60 minutes after intraperitoneal administration of retinol to vitamin A-depleted rats. Similarly, administration of retionic acid brought about elevation of 14 C-mannolipid (R sub(f) 0.2) synthesis with a peak at 60 minutes after injection. On the other hand, the incorporation of 14 C-mannose into DMP (R sub(f) 0.4) remained unchanged by such treatment. These results suggest that not only retinol but also retionic acid plays an important biological role in manosyl transfer reaction in rat liver. However, the molecular participation of a metabolite of retionic acid in the formation of manolipid and the structure of such a metabolite remain to be established. (Iwakiri, K.)

  9. The Holocene sedimentary record of cyanobacterial glycolipids in the Baltic Sea: an evaluation of their application as tracers of past nitrogen fixation

    Directory of Open Access Journals (Sweden)

    M. Sollai

    2017-12-01

    Full Text Available Heterocyst glycolipids (HGs are lipids exclusively produced by heterocystous dinitrogen-fixing cyanobacteria. The Baltic Sea is an ideal environment to study the distribution of HGs and test their potential as biomarkers because of its recurring summer phytoplankton blooms, dominated by a few heterocystous cyanobacterial species of the genera Nodularia and Aphanizomenon. A multi-core and a gravity core from the Gotland Basin were analyzed to determine the abundance and distribution of a suite of selected HGs at a high resolution to investigate the changes in past cyanobacterial communities during the Holocene. The HG distribution of the sediments deposited during the Modern Warm Period (MoWP was compared with those of cultivated heterocystous cyanobacteria, including those isolated from Baltic Sea waters, revealing high similarity. However, the abundance of HGs dropped substantially with depth, and this may be caused by either a decrease in the occurrence of the cyanobacterial blooms or diagenesis, resulting in partial destruction of the HGs. The record also shows that the HG distribution has remained stable since the Baltic turned into a brackish semi-enclosed basin ∼ 7200 cal. yr BP. This suggests that the heterocystous cyanobacterial species composition remained relatively stable as well. During the earlier freshwater phase of the Baltic (i.e., the Ancylus Lake and Yoldia Sea phases, the distribution of the HGs varied much more than in the subsequent brackish phase, and the absolute abundance of HGs was much lower than during the brackish phase. This suggests that the cyanobacterial community adjusted to the different environmental conditions in the basin. Our results confirm the potential of HGs as a specific biomarker of heterocystous cyanobacteria in paleo-environmental studies.

  10. Frequent Detection of Anti-Tubercular-Glycolipid-IgG and -IgA Antibodies in Healthcare Workers with Latent Tuberculosis Infection in the Philippines

    Directory of Open Access Journals (Sweden)

    Umme Ruman Siddiqi

    2012-01-01

    Full Text Available Anti-tubercular-glycolipid-IgG (TBGL-IgG and -IgA (TBGL-IgA antibodies, and the QuantiFERON-TB Gold test (QFT were compared in healthcare workers (HCWs, n=31 and asymptomatic human immunodeficiency virus-carriers (HIV-AC, n=56 in Manila. In HCWs, 48%, 51%, and 19% were positive in QFT, TBGL-IgG, and -IgA, respectively. The TBGL-IgG positivity was significantly higher (P=0.02 in QFT-positive than QFT-negative HCWs. Both TBGL-IgG- and -IgA-positive cases were only found in QFT-positive HCWs (27%. The plasma IFN-γ levels positively correlated with TBGL-IgA titers (r=0.74, P=0.005, but not TBGL-IgG titers in this group, indicating that mucosal immunity is involved in LTBI in immunocompetent individuals. The QFT positivity in HIV-AC was 31% in those with CD4+ cell counts >350/μL and 12.5% in low CD4 group (<350/μL. 59 % and 29% were positive for TBGL-IgG and -IgA, respectively, in HIV-AC, but no association was found between QFT and TBGL assays. TBGL-IgG-positive rates in QFT-positive and QFT-negative HIV-AC were 61% and 58%, and those of TBGL-IgA were 23% and 30%, respectively. The titers of TBGL-IgA were associated with serum IgA (P=0.02 in HIV-AC. Elevations of TBGL-IgG and -IgA were related to latent tuberculosis infection in HCWs, but careful interpretation is necessary in HIV-AC.

  11. Effect of cholesterol deposition on bacterial adhesion to contact lenses.

    Science.gov (United States)

    Babaei Omali, Negar; Zhu, Hua; Zhao, Zhenjun; Ozkan, Jerome; Xu, Banglao; Borazjani, Roya; Willcox, Mark D P

    2011-08-01

    To examine the effect of cholesterol on the adhesion of bacteria to silicone hydrogel contact lenses. Contact lenses, collected from subjects wearing Acuvue Oasys or PureVision lenses, were extracted in chloroform:methanol (1:1, v/v) and amount of cholesterol was estimated by thin-layer chromatography. Unworn lenses were soaked in cholesterol, and the numbers of Pseudomonas aeruginosa strains or Staphylococcus aureus strains that adhered to the lenses were measured. Cholesterol was tested for effects on bacterial growth by incubating bacteria in medium containing cholesterol. From ex vivo PureVision lenses, 3.4 ± 0.3 μg/lens cholesterol was recovered, and from Acuvue Oasys lenses, 2.4 ± 0.2 to 1.0 ± 0.1 μg/lens cholesterol was extracted. Cholesterol did not alter the total or viable adhesion of any strain of P. aeruginosa or S. aureus (p > 0.05). However, worn PureVision lenses reduced the numbers of viable cells of P. aeruginosa (5.8 ± 0.4 log units) compared with unworn lenses (6.4 ± 0.2 log units, p = 0.001). Similarly, there were fewer numbers of S. aureus 031 adherent to worn PureVision (3.05 ± 0.8 log units) compared with unworn PureVision (4.6 ± 0.3 log units, p = 0.0001). Worn Acuvue Oasys lenses did not affect bacterial adhesion. Cholesterol showed no effect on the growth of any test strain. Although cholesterol has been shown to adsorb to contact lenses during wear, this lipid does not appear to modulate bacterial adhesion to a lens surface.

  12. Changes to cholesterol trafficking in macrophages by Leishmania parasites infection.

    Science.gov (United States)

    Semini, Geo; Paape, Daniel; Paterou, Athina; Schroeder, Juliane; Barrios-Llerena, Martin; Aebischer, Toni

    2017-08-01

    Leishmania spp. are protozoan parasites that are transmitted by sandfly vectors during blood sucking to vertebrate hosts and cause a spectrum of diseases called leishmaniases. It has been demonstrated that host cholesterol plays an important role during Leishmania infection. Nevertheless, little is known about the intracellular distribution of this lipid early after internalization of the parasite. Here, pulse-chase experiments with radiolabeled cholesteryl esterified to fatty acids bound to low-density lipoproteins indicated that retention of this source of cholesterol is increased in parasite-containing subcellular fractions, while uptake is unaffected. This is correlated with a reduction or absence of detectable NPC1 (Niemann-Pick disease, type C1), a protein responsible for cholesterol efflux from endocytic compartments, in the Leishmania mexicana habitat and infected cells. Filipin staining revealed a halo around parasites within parasitophorous vacuoles (PV) likely representing free cholesterol accumulation. Labeling of host cell membranous cholesterol by fluorescent cholesterol species before infection revealed that this pool is also trafficked to the PV but becomes incorporated into the parasites' membranes and seems not to contribute to the halo detected by filipin. This cholesterol sequestration happened early after infection and was functionally significant as it correlated with the upregulation of mRNA-encoding proteins required for cholesterol biosynthesis. Thus, sequestration of cholesterol by Leishmania amastigotes early after infection provides a basis to understand perturbation of cholesterol-dependent processes in macrophages that were shown previously by others to be necessary for their proper function in innate and adaptive immune responses. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  13. What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

    DEFF Research Database (Denmark)

    Falkovich, Stanislav G.; Martinez-Seara, Hector; Nesterenko, Alexey M.

    2016-01-01

    Cholesterol is abundant in the plasma membranes of animal cells and is known to regulate a variety of membrane properties. Despite decades of research, the transmembrane distribution of cholesterol is still a matter of debate. Here we consider this outstanding issue through atomistic simulations ...

  14. Molecular interactions between bile salts, phospholipids and cholesterol : relevance to bile formation, cholesterol crystallization and bile salt toxicity

    NARCIS (Netherlands)

    Moschetta, Antonio

    2001-01-01

    Cholesterol is a nonpolar lipid dietary constituent, absorbed from the small intestine, transported in blood and taken up by the liver. In bile, the sterol is solubilized in mixed micelles by bile salts and phospholipids. In case of supersaturation, cholesterol is kept in vesicles with phospholipid

  15. Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Haan, W. de; Hoogt, C.C. van der; Westerterp, M.; Hoekstra, M.; Dallinga-Thie, G.M.; Princen, H.M.G.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

    2008-01-01

    Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP

  16. Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

    Science.gov (United States)

    Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

    2017-03-01

    Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

  17. Relevance of hereditary defects in lipid transport proteins for the pathogenesis of cholesterol gallstone disease

    NARCIS (Netherlands)

    vanBerge-Henegouwen, G. P.; Venneman, N. G.; Portincasa, P.; Kosters, A.; van Erpecum, K. J.; Groen, A. K.

    2004-01-01

    In the formation of cholesterol gallstones, cholesterol hypersecretion into bile causing cholesterol supersaturation and crystallization appears to be the primary factor, with disturbed gallbladder and intestinal motility as secondary factors. Although intestinal uptake mechanisms have not yet been

  18. Self-constrained inversion of potential fields

    Science.gov (United States)

    Paoletti, V.; Ialongo, S.; Florio, G.; Fedi, M.; Cella, F.

    2013-11-01

    We present a potential-field-constrained inversion procedure based on a priori information derived exclusively from the analysis of the gravity and magnetic data (self-constrained inversion). The procedure is designed to be applied to underdetermined problems and involves scenarios where the source distribution can be assumed to be of simple character. To set up effective constraints, we first estimate through the analysis of the gravity or magnetic field some or all of the following source parameters: the source depth-to-the-top, the structural index, the horizontal position of the source body edges and their dip. The second step is incorporating the information related to these constraints in the objective function as depth and spatial weighting functions. We show, through 2-D and 3-D synthetic and real data examples, that potential field-based constraints, for example, structural index, source boundaries and others, are usually enough to obtain substantial improvement in the density and magnetization models.

  19. Cosmogenic photons strongly constrain UHECR source models

    Directory of Open Access Journals (Sweden)

    van Vliet Arjen

    2017-01-01

    Full Text Available With the newest version of our Monte Carlo code for ultra-high-energy cosmic ray (UHECR propagation, CRPropa 3, the flux of neutrinos and photons due to interactions of UHECRs with extragalactic background light can be predicted. Together with the recently updated data for the isotropic diffuse gamma-ray background (IGRB by Fermi LAT, it is now possible to severely constrain UHECR source models. The evolution of the UHECR sources especially plays an important role in the determination of the expected secondary photon spectrum. Pure proton UHECR models are already strongly constrained, primarily by the highest energy bins of Fermi LAT’s IGRB, as long as their number density is not strongly peaked at recent times.

  20. A constrained supersymmetric left-right model

    Energy Technology Data Exchange (ETDEWEB)

    Hirsch, Martin [AHEP Group, Instituto de Física Corpuscular - C.S.I.C./Universitat de València, Edificio de Institutos de Paterna, Apartado 22085, E-46071 València (Spain); Krauss, Manuel E. [Bethe Center for Theoretical Physics & Physikalisches Institut der Universität Bonn, Nussallee 12, 53115 Bonn (Germany); Institut für Theoretische Physik und Astronomie, Universität Würzburg,Emil-Hilb-Weg 22, 97074 Wuerzburg (Germany); Opferkuch, Toby [Bethe Center for Theoretical Physics & Physikalisches Institut der Universität Bonn, Nussallee 12, 53115 Bonn (Germany); Porod, Werner [Institut für Theoretische Physik und Astronomie, Universität Würzburg,Emil-Hilb-Weg 22, 97074 Wuerzburg (Germany); Staub, Florian [Theory Division, CERN,1211 Geneva 23 (Switzerland)

    2016-03-02

    We present a supersymmetric left-right model which predicts gauge coupling unification close to the string scale and extra vector bosons at the TeV scale. The subtleties in constructing a model which is in agreement with the measured quark masses and mixing for such a low left-right breaking scale are discussed. It is shown that in the constrained version of this model radiative breaking of the gauge symmetries is possible and a SM-like Higgs is obtained. Additional CP-even scalars of a similar mass or even much lighter are possible. The expected mass hierarchies for the supersymmetric states differ clearly from those of the constrained MSSM. In particular, the lightest down-type squark, which is a mixture of the sbottom and extra vector-like states, is always lighter than the stop. We also comment on the model’s capability to explain current anomalies observed at the LHC.

  1. Coding for Two Dimensional Constrained Fields

    DEFF Research Database (Denmark)

    Laursen, Torben Vaarbye

    2006-01-01

    a first order model to model higher order constraints by the use of an alphabet extension. We present an iterative method that based on a set of conditional probabilities can help in choosing the large numbers of parameters of the model in order to obtain a stationary model. Explicit results are given...... for the No Isolated Bits constraint. Finally we present a variation of the encoding scheme of bit-stuffing that is applicable to the class of checkerboard constrained fields. It is possible to calculate the entropy of the coding scheme thus obtaining lower bounds on the entropy of the fields considered. These lower...... bounds are very tight for the Run-Length limited fields. Explicit bounds are given for the diamond constrained field as well....

  2. Communication Schemes with Constrained Reordering of Resources

    DEFF Research Database (Denmark)

    Popovski, Petar; Utkovski, Zoran; Trillingsgaard, Kasper Fløe

    2013-01-01

    This paper introduces a communication model inspired by two practical scenarios. The first scenario is related to the concept of protocol coding, where information is encoded in the actions taken by an existing communication protocol. We investigate strategies for protocol coding via combinatorial...... reordering of the labelled user resources (packets, channels) in an existing, primary system. However, the degrees of freedom of the reordering are constrained by the operation of the primary system. The second scenario is related to communication systems with energy harvesting, where the transmitted signals...... are constrained by the energy that is available through the harvesting process. We have introduced a communication model that covers both scenarios and elicits their key feature, namely the constraints of the primary system or the harvesting process. We have shown how to compute the capacity of the channels...

  3. Q-deformed systems and constrained dynamics

    International Nuclear Information System (INIS)

    Shabanov, S.V.

    1993-01-01

    It is shown that quantum theories of the q-deformed harmonic oscillator and one-dimensional free q-particle (a free particle on the 'quantum' line) can be obtained by the canonical quantization of classical Hamiltonian systems with commutative phase-space variables and a non-trivial symplectic structure. In the framework of this approach, classical dynamics of a particle on the q-line coincides with the one of a free particle with friction. It is argued that q-deformed systems can be treated as ordinary mechanical systems with the second-class constraints. In particular, second-class constrained systems corresponding to the q-oscillator and q-particle are given. A possibility of formulating q-deformed systems via gauge theories (first-class constrained systems) is briefly discussed. (orig.)

  4. Online constrained model-based reinforcement learning

    CSIR Research Space (South Africa)

    Van Niekerk, B

    2017-08-01

    Full Text Available Constrained Model-based Reinforcement Learning Benjamin van Niekerk School of Computer Science University of the Witwatersrand South Africa Andreas Damianou∗ Amazon.com Cambridge, UK Benjamin Rosman Council for Scientific and Industrial Research, and School... MULTIPLE SHOOTING Using direct multiple shooting (Bock and Plitt, 1984), problem (1) can be transformed into a structured non- linear program (NLP). First, the time horizon [t0, t0 + T ] is partitioned into N equal subintervals [tk, tk+1] for k = 0...

  5. Constraining supergravity models from gluino production

    International Nuclear Information System (INIS)

    Barbieri, R.; Gamberini, G.; Giudice, G.F.; Ridolfi, G.

    1988-01-01

    The branching ratios for gluino decays g tilde → qanti qΧ, g tilde → gΧ into a stable undetected neutralino are computed as functions of the relevant parameters of the underlying supergravity theory. A simple way of constraining supergravity models from gluino production emerges. The effectiveness of hadronic versus e + e - colliders in the search for supersymmetry can be directly compared. (orig.)

  6. Cosmicflows Constrained Local UniversE Simulations

    Science.gov (United States)

    Sorce, Jenny G.; Gottlöber, Stefan; Yepes, Gustavo; Hoffman, Yehuda; Courtois, Helene M.; Steinmetz, Matthias; Tully, R. Brent; Pomarède, Daniel; Carlesi, Edoardo

    2016-01-01

    This paper combines observational data sets and cosmological simulations to generate realistic numerical replicas of the nearby Universe. The latter are excellent laboratories for studies of the non-linear process of structure formation in our neighbourhood. With measurements of radial peculiar velocities in the local Universe (cosmicflows-2) and a newly developed technique, we produce Constrained Local UniversE Simulations (CLUES). To assess the quality of these constrained simulations, we compare them with random simulations as well as with local observations. The cosmic variance, defined as the mean one-sigma scatter of cell-to-cell comparison between two fields, is significantly smaller for the constrained simulations than for the random simulations. Within the inner part of the box where most of the constraints are, the scatter is smaller by a factor of 2 to 3 on a 5 h-1 Mpc scale with respect to that found for random simulations. This one-sigma scatter obtained when comparing the simulated and the observation-reconstructed velocity fields is only 104 ± 4 km s-1, I.e. the linear theory threshold. These two results demonstrate that these simulations are in agreement with each other and with the observations of our neighbourhood. For the first time, simulations constrained with observational radial peculiar velocities resemble the local Universe up to a distance of 150 h-1 Mpc on a scale of a few tens of megaparsecs. When focusing on the inner part of the box, the resemblance with our cosmic neighbourhood extends to a few megaparsecs (<5 h-1 Mpc). The simulations provide a proper large-scale environment for studies of the formation of nearby objects.

  7. Dynamic Convex Duality in Constrained Utility Maximization

    OpenAIRE

    Li, Yusong; Zheng, Harry

    2016-01-01

    In this paper, we study a constrained utility maximization problem following the convex duality approach. After formulating the primal and dual problems, we construct the necessary and sufficient conditions for both the primal and dual problems in terms of FBSDEs plus additional conditions. Such formulation then allows us to explicitly characterize the primal optimal control as a function of the adjoint process coming from the dual FBSDEs in a dynamic fashion and vice versa. Moreover, we also...

  8. Statistical mechanics of budget-constrained auctions

    OpenAIRE

    Altarelli, F.; Braunstein, A.; Realpe-Gomez, J.; Zecchina, R.

    2009-01-01

    Finding the optimal assignment in budget-constrained auctions is a combinatorial optimization problem with many important applications, a notable example being the sale of advertisement space by search engines (in this context the problem is often referred to as the off-line AdWords problem). Based on the cavity method of statistical mechanics, we introduce a message passing algorithm that is capable of solving efficiently random instances of the problem extracted from a natural distribution,...

  9. Constraining neutron star matter with Quantum Chromodynamics

    CERN Document Server

    Kurkela, Aleksi; Schaffner-Bielich, Jurgen; Vuorinen, Aleksi

    2014-01-01

    In recent years, there have been several successful attempts to constrain the equation of state of neutron star matter using input from low-energy nuclear physics and observational data. We demonstrate that significant further restrictions can be placed by additionally requiring the pressure to approach that of deconfined quark matter at high densities. Remarkably, the new constraints turn out to be highly insensitive to the amount --- or even presence --- of quark matter inside the stars.

  10. Cholesterol-lowering drugs: science and marketing.

    Science.gov (United States)

    Garattini, Livio; Padula, Anna

    2017-02-01

    Long-term use of statin therapy is essential to obtain clinical benefits, but adherence is often suboptimal and some patients are also reported to fail because of 'statin resistance'. The identification of PCSK9 as a key factor in the LDL clearance pathway has led to the development of new monoclonal antibodies. Here we critically review the economic evaluations published in Europe and focused on statins. We searched the PubMed database to select the studies published from July 2006 to June 2016 and finally selected 19 articles. Overall, the majority of studies were conducted from a third-party payer's viewpoint and recurred to modelling. Most studies were sponsored by industry and funding seemed to play a pivotal role in the study design. Patients resistant to LDL-C level reduction were considered only in a few studies. The place in therapy of the new class of biologic should be considered a kind of 'third line' for cholesterol-lowering, after patients have failed with restricted dietary regimens and then with current drug therapies. Otherwise they could result in hardly sustainable expenses even for developed countries.

  11. The effects of probiotics on total cholesterol

    Science.gov (United States)

    Wang, Lang; Guo, Mao-Juan; Gao, Qing; Yang, Jin-Feng; Yang, Lin; Pang, Xiao-Li; Jiang, Xi-Juan

    2018-01-01

    Abstract Background: Probiotics supplements provide a new nonpharmacological alternative to reduce cardiovascular risk factors. The impact of probiotics on the reduction of total cholesterol (TC) remains controversial. We conducted a meta-analysis to showcase the most updated and comprehensive evaluation of the studies. Methods: Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database dating from January 2007 to January 2017. The curative effects of probiotics on the reduction of TC were assessed using mean difference (MD), as well as their 95% confidence interval (CI). RevMan software (version 5.3) was used to carry out this meta-analysis. Results: Thirty-two RCTs including 1971 patients met the inclusion criteria. Results of this analysis showed that compared with the control group serum TC was significantly reduced in probiotics group [MD = −13.27, 95% CI (−16.74 to 9.80), P  6 weeks: [MD = −22.18, 95% CI (−28.73, −15.63), P probiotics forms and intervention duration might have a significant impact on the results. However, strains and doses of probiotics had no significant influence on curative effects. Conclusion: Available evidence indicates that probiotics supplements can significantly reduce serum TC. Furthermore, higher baseline TC, longer intervention time, and probiotics in capsules form might contribute to a better curative effect. PMID:29384846

  12. Introducing inducible fluorescent split cholesterol oxidase to mammalian cells.

    Science.gov (United States)

    Chernov, Konstantin G; Neuvonen, Maarit; Brock, Ivonne; Ikonen, Elina; Verkhusha, Vladislav V

    2017-05-26

    Cholesterol oxidase (COase) is a bacterial enzyme catalyzing the first step in the biodegradation of cholesterol. COase is an important biotechnological tool for clinical diagnostics and production of steroid drugs and insecticides. It is also used for tracking intracellular cholesterol; however, its utility is limited by the lack of an efficient temporal control of its activity. To overcome this we have developed a regulatable fragment complementation system for COase cloned from Chromobacterium sp. The enzyme was split into two moieties that were fused to FKBP (FK506-binding protein) and FRB (rapamycin-binding domain) pair and split GFP fragments. The addition of rapamycin reconstituted a fluorescent enzyme, termed split GFP-COase, the fluorescence level of which correlated with its oxidation activity. A rapid decrease of cellular cholesterol induced by intracellular expression of the split GFP-COase promoted the dissociation of a cholesterol biosensor D4H from the plasma membrane. The process was reversible as upon rapamycin removal, the split GFP-COase fluorescence was lost, and cellular cholesterol levels returned to normal. These data demonstrate that the split GFP-COase provides a novel tool to manipulate cholesterol in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Cholesterol-Lowering Effect of Allicin on Hypercholesterolemic ICR Mice

    Directory of Open Access Journals (Sweden)

    Yin Lu

    2012-01-01

    Full Text Available Allicin was discussed as an active compound with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the cholesterol-lowering properties of allicin. In order to examine its effects on hypercholesterolemia in male ICR mice, this compound with doses of 5, 10, or 20 mg/kg body weight was given orally daily for 12 weeks. Changes in body weight and daily food intake were measured regularly during the experimental period. Final contents of serum cholesterol, triglyceride, glucose, and hepatic cholesterol storage were determined. Following a 12-week experimental period, the body weights of allicin-fed mice were less than those of control mice on a high-cholesterol diet by 38.24±7.94% (P<0.0001 with 5 mg/kg allicin, 39.28±5.03% (P<0.0001 with 10 mg/kg allicin, and 41.18±5.00% (P<0.0001 with 20 mg/kg allicin, respectively. A decrease in daily food consumption was also noted in most of the treated animals. Meanwhile, allicin showed a favorable effect in reducing blood cholesterol, triglycerides, and glucose levels and caused a significant decrease in lowering the hepatic cholesterol storage. Accordingly, both in vivo and in vitro results demonstrated a potential value of allicin as a pronounced cholesterol-lowering candidate, providing protection against the onset of atherosclerosis.

  14. Break the fast? Update on patient preparation for cholesterol testing.

    Science.gov (United States)

    Naugler, Christopher; Sidhu, Davinder

    2014-10-01

    To provide an update on the clinical usefulness of nonfasting versus fasting lipid testing to improve patient compliance, patient safety, and clinical assessment in cholesterol testing. Recommendations are identified as supported by good, fair, and poor (conflicting or insufficient) evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care. Screening for dyslipidemia as a risk factor for coronary artery disease and management of lipid-lowering medications are key parts of primary care. Recent evidence has questioned the fasting requirement for lipid testing. In population-based studies, total cholesterol, high-density lipoprotein cholesterol, and non-low-density lipoprotein cholesterol all varied by an average of 2% with fasting status. For routine screening, nonfasting cholesterol measurement is now a reasonable alternative to a fasting cholesterol measurement. For patients with diabetes, the fasting requirement might be an important safety issue because of problems with hypoglycemia. For the monitoring of triglyceride and low-density lipoprotein cholesterol levels in patients taking lipid-lowering medications, fasting becomes more important. Fasting for routine lipid level determinations is largely unnecessary and unlikely to affect patient clinical risk stratification, while nonfasting measurement might improve patient compliance and safety. Copyright© the College of Family Physicians of Canada.

  15. Absorption and transport of cholesterol autoxidation derivatives in rabbits

    International Nuclear Information System (INIS)

    Peng, S.K.; Morin, R.J.; Phillips, G.A.; Xia, G.Z.

    1986-01-01

    Spontaneously autoxidized products of cholesterol have been demonstrated to be angiotoxic and possibly atherogenic. This study investigates the absorption and transport of these cholesterol oxidation derivatives (COD's) as compared to cholesterol. 14 C-labeled cholesterol autoxidized by incubation in a 60 0 C water bath for 5 weeks, then suspended in gelatin and given to New Zealand white rabbits by gastric gavage. Rabbits were sacrificed 24 hours after treatment. COD's were separated by thin layer chromatography (TLC) and radioactivities of each COD and cholesterol were measured. Percentages of each COD and cholesterol in the original mixture before administration and in the rabbits' serum after administration are almost identical, suggesting that the rates of absorption of COD's are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each COD separated by TLC in each lipoprotein fraction showed that cholestane-3β,5α,6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were predominantly present in VLDL (3 x serum concentration) and 25-hydroxycholesterol was predominantly in LDL (2.5 x serum concentration). HDL contained only minute amounts of COD's. The increased levels of COD's in VLDL and LDL may contribute to the atherogenicity of these lipoprotein

  16. Constraining the mass of the Local Group

    Science.gov (United States)

    Carlesi, Edoardo; Hoffman, Yehuda; Sorce, Jenny G.; Gottlöber, Stefan

    2017-03-01

    The mass of the Local Group (LG) is a crucial parameter for galaxy formation theories. However, its observational determination is challenging - its mass budget is dominated by dark matter that cannot be directly observed. To meet this end, the posterior distributions of the LG and its massive constituents have been constructed by means of constrained and random cosmological simulations. Two priors are assumed - the Λ cold dark matter model that is used to set up the simulations, and an LG model that encodes the observational knowledge of the LG and is used to select LG-like objects from the simulations. The constrained simulations are designed to reproduce the local cosmography as it is imprinted on to the Cosmicflows-2 data base of velocities. Several prescriptions are used to define the LG model, focusing in particular on different recent estimates of the tangential velocity of M31. It is found that (a) different vtan choices affect the peak mass values up to a factor of 2, and change mass ratios of MM31 to MMW by up to 20 per cent; (b) constrained simulations yield more sharply peaked posterior distributions compared with the random ones; (c) LG mass estimates are found to be smaller than those found using the timing argument; (d) preferred Milky Way masses lie in the range of (0.6-0.8) × 1012 M⊙; whereas (e) MM31 is found to vary between (1.0-2.0) × 1012 M⊙, with a strong dependence on the vtan values used.

  17. Does fat in milk, butter and and cholesterol differently?

    DEFF Research Database (Denmark)

    Tholstrup, T,; Høy, Carl-Erik; Andersen, L.N.

    2004-01-01

    and 8 hours following intake of the meals. Results: Fasting LDL cholesterol concentration was significantly higher after butter than cheese diet (p 0.037), with a borderline significant difference in total cholesterol (p = 0.054) after the experimental periods of three weeks. Postprandial glucose showed...... a higher response after cheese diet than after milk diet (p = 0.010, diet X time interaction). Conclusions: A different effect of fat in milk and butter could not be confirmed in this study. The moderately lower LDL cholesterol after cheese diet compared to butter diet should be investigated further....

  18. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

    Science.gov (United States)

    Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

    2013-02-15

    Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

  19. The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial.

    Science.gov (United States)

    Lin, X; Racette, S B; Lefevre, M; Spearie, C A; Most, M; Ma, L; Ostlund, R E

    2010-12-01

    Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism. In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers. The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), Pphytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 μg/mg (0.98, 1.53), Pphytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.

  20. Reverse Cholesterol Transport: Molecular Mechanisms and the Non-medical Approach to Enhance HDL Cholesterol

    Directory of Open Access Journals (Sweden)

    Leandro R. Marques

    2018-05-01

    Full Text Available Dyslipidemia (high concentrations of LDL-c and low concentrations of HDL-c is a major cause of cardiovascular events, which are the leading cause of death in the world. On the other hand, nutrition and regular exercise can be an interesting strategy to modulate lipid profile, acting as prevention or treatment, inhibiting the risk of diseases due to its anti-inflammatory and anti-atherogenic characteristics. Additionally, the possibility of controlling different training variables, such as type, intensity and recovery interval, can be used to maximize the benefits of exercise in promoting cardiovascular health. However, the mechanisms by which exercise and nutrients act in the regulation of cholesterol and its fractions, such as reverse cholesterol transport, receptors and transcription factors involved, such as PPARs and their role related to exercise, deserve further discussion. Therefore, the objective of this review is to debate about non-medical approaches to increase HDL-c, such as nutritional and training strategies, and to discuss the central mechanisms involved in the modulation of lipid profile during exercise, as well as that can be controlled by physical trainers or sports specialists in attempt to maximize the benefits promoted by exercise. The search for papers was performed in the databases: Medline (Pubmed, Science Direct, Scopus, Sport Discus, Web of Science, Scielo and Lilacs until February 2016.

  1. Induction of lipid peroxidation in erythrocytes during cholesterol oxidation catalyzed by cholesterol oxidase

    International Nuclear Information System (INIS)

    Kagan, V.E.; Monovich, O.; Ribarov, S.R.

    1986-01-01

    The authors study the ability of cholesterol oxidase (ChO), which catalyzes oxidation of cholesterol (Ch) to cholest-4-en-3-one and, at the same time, reduction of O 2 to H 2 O 2 , to induce the lipid peroxidation (LPO) in plasma membranes. Erythrocyte ghosts were obtained from guinea pig blood; the reaction of oxidation of Ch in the erythrocyte ghosts or in micelles with Triton X-100 was carried out in the following medium: Tris-HCl 0.2 M, pH 7.0 (at 37 C), Triton X-100 0.25%, and ChO 0.05 U/ml. At the present time ChO is often used to study the asymmetry of distribution of Ch in biomembranes and the velocity of its transbilayer migration. It is suggested that changes in membrane permeability do not take place during the reaction catalyzed by the enzyme, and no products capable of affecting flip-flop in biological are formed. Accumulation of LPO products in erythrocyte membranes discovered in this investigation under the influence of ChO compels critical re-examination of the resutls

  2. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian

    2016-08-01

    In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.

  3. Are You Taking the Right Treatment for Your High Cholesterol?

    Science.gov (United States)

    ... open('/content/cro/en/health/prescription-drugs/best-buy-drugs/evaluating-statin-drugs-to-treat--high-cholesterol-and- ... talking with your doctor How to share Best Buy Drug reports About us Less common issues: Diabetes, memory ...

  4. Cholesterol granuloma of the orbit: An atypical presentation

    Directory of Open Access Journals (Sweden)

    Syed A R Rizvi

    2014-01-01

    Full Text Available Cholesterol granuloma is a rare, well-defined lesion of the orbit. In the orbit, diploe of the frontal bone is involved almost exclusively. We report an atypical case of cholesterol granuloma involving superomedial quadrant of orbit. A 42-year-old male presented with progressive, painless, proptosis with infero-temporal displacement of left eye. A large mass was felt beneath the bony orbital margin in the superomedial quadrant of the left orbit. Computerized tomography (CT scan revealed an extraconal superomedial, heterogeneous enhancing mass which was isodense with brain and pushing the globe inferolaterally and anteriorly. Excision biopsy of the tumor revealed the typical features of a cholesterol granuloma without any epithelial elements. Cholesterol granuloma of the orbit is a rare entity, but it can be diagnosed and differentiated from other lesions of the superior orbit by its characteristic clinical, radiological and histopathological features. An appropriate intervention in time carries a good prognosis with almost no recurrence.

  5. Plasma Triglyceride and Cholesterol Levels in Normotensive and ...

    African Journals Online (AJOL)

    Plasma Triglyceride and Cholesterol Levels in Normotensive and Hypertensive Pregnant and Parturient Nigerian Women. Kashope D. Thomas, Oyebola G. Adeosun, Norah O. Akinola, Uche Onwudiegwu, Alexander T. Owolabi ...

  6. Atherosclerosis in familial lines of pigeons fed exogenous cholesterol.

    Science.gov (United States)

    Patton, N M; Brown, R V; Middleton, C C

    1975-01-01

    Exogenous cholesterol was fed to F1 pigeons of high and low serum cholesterol differentiated lines of White Carneau and Racing Homer pigeons that had previously been developed by selection and positive assortive mating. The serum cholesterol response of the various high and low lines was dependent upon the breed and the amount of cholesterol in the diet. Racing Homer pigeons were found to be more resistant to aortic atherosclerosis and more susceptible to coronary atherosclerosis than White Carneau pigeons. Data from necropsy examinations showed significant differences in both aortic and coronary atherosclerosis between lines within the White Carneau breed, but no differences between lines of the Racing Homer breed. Mean organ weights for the 4 lines of pigeons were reported.

  7. High Cholesterol and Complementary Health Practices: What the Science Says

    Science.gov (United States)

    ... professionals High Cholesterol and Complementary Health Practices: What the Science Says Share: February 2013 Dietary Supplements Red Yeast ... to exploring complementary health products and practices in the context of rigorous ... health researchers, and disseminating authoritative information ...

  8. Vertically aligned carbon nanotube probes for monitoring blood cholesterol

    Science.gov (United States)

    Roy, Somenath; Vedala, Harindra; Choi, Wonbong

    2006-02-01

    Detection of blood cholesterol is of great clinical significance. The amperometric detection technique was used for the enzymatic assay of total cholesterol. Multiwall carbon nanotubes (MWNTs), vertically aligned on a silicon platform, promote heterogeneous electron transfer between the enzyme and the working electrode. Surface modification of the MWNT with a biocompatible polymer, polyvinyl alcohol (PVA), converted the hydrophobic nanotube surface into a highly hydrophilic one, which facilitates efficient attachment of biomolecules. The fabricated working electrodes showed a linear relationship between cholesterol concentration and the output signal. The efficacy of the multiwall carbon nanotubes in promoting heterogeneous electron transfer was evident by distinct electrochemical peaks and higher signal-to-noise ratio as compared to the Au electrode with identical enzyme immobilization protocol. The selectivity of the cholesterol sensor in the presence of common interferents present in human blood, e.g. uric acid, ascorbic acid and glucose, is also reported.

  9. Cascading Constrained 2-D Arrays using Periodic Merging Arrays

    DEFF Research Database (Denmark)

    Forchhammer, Søren; Laursen, Torben Vaarby

    2003-01-01

    We consider a method for designing 2-D constrained codes by cascading finite width arrays using predefined finite width periodic merging arrays. This provides a constructive lower bound on the capacity of the 2-D constrained code. Examples include symmetric RLL and density constrained codes...

  10. Operator approach to solutions of the constrained BKP hierarchy

    International Nuclear Information System (INIS)

    Shen, Hsin-Fu; Lee, Niann-Chern; Tu, Ming-Hsien

    2011-01-01

    The operator formalism to the vector k-constrained BKP hierarchy is presented. We solve the Hirota bilinear equations of the vector k-constrained BKP hierarchy via the method of neutral free fermion. In particular, by choosing suitable group element of O(∞), we construct rational and soliton solutions of the vector k-constrained BKP hierarchy.

  11. Thermodynamic study on competitive solubilization of cholesterol and beta-sitosterol in bile salt micelles.

    Science.gov (United States)

    Matsuoka, Keisuke; Hirosawa, Takashi; Honda, Chikako; Endo, Kazutoyo; Moroi, Yoshikiyo; Shibata, Osamu

    2007-07-01

    Differences in the preferential solubilization of cholesterol and competitive solubilizates (beta-sitosterol and aromatic compounds) in bile salt micelles was systematically studied by changing the molar ratio of cholesterol to competitive solubilizates. The cholesterol solubility in a mixed binary system (cholesterol and beta-sitosterol) was almost half that of the cholesterol alone system, regardless of the excess beta-sitosterol quantity added. On the other hand, the mutual solubilities of cholesterol and pyrene were not inhibited by their presence in binary mixed crystals. Finally, the cholesterol solubility was measured by changing the alkyl chain length of n-alkylbenzenes. When tetradecylbenzene was added to the bile solution, the cholesterol solubility decreased slightly and was below the original cholesterol solubility. Based on Gibbs energy change (DeltaG degrees ) for solubilization, chemicals that inhibit cholesterol solubility in their combined crystal systems showed a larger negative DeltaG degrees value than cholesterol alone.

  12. Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2012-01-01

    Full Text Available Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface

  13. The origin of cholesterol in chyle demonstrated by nuclear indicator methods; Origines du cholesterol du chyle mises en evidence par la methode des indicateurs nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    Vyas, M

    1962-07-01

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-{sup 14}C- cholesterol subcutaneously or orally, or the 1-{sup 14}C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [French] Pour obtenir des renseignements concernant le mecanisme de l'absorption intestinale du cholesterol, on utilise des rats porteurs d'une fistule lymphatique abdominale. Les animaux recoivent soit du cholesterol 4-{sup 14}C par voie sous-cutanee ou par voie orale, soit de l'acetate 1-{sup 14}C. L'etude des radioactivites specifiques du cholesterol du chyle, du serum, de la paroi et du contenu intestinal permet de preciser les roles joues par le cholesterol de transfert d'origine serique, par le cholesterol de synthese intestinale et par le cholesterol d'absorption, dans la formation de la lymphe et des chylomicrons. Une theorie nouvelle concernant le mecanisme de l'absorption du cholesterol est proposee. (auteur)

  14. 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....

  15. Regulation of neuronal APL-1 expression by cholesterol starvation.

    Directory of Open Access Journals (Sweden)

    Mary Wiese

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP. While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD, sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1, and lrp-1 (lipoprotein receptor-related protein 1, suggesting a potential interaction between apl-1 and cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot. CONCLUSIONS: Our results show that cholesterol and lrp-1 are involved in the regulation of synaptic transmission, similar to apl-1. Both are able to modulate APL-1 protein levels in neurons, however cholesterol changes do not affect global apl-1 transcription or APL-1 protein indicating the changes are specific to neurons. Thus, regulation of synaptic transmission and molting by LRP-1 and cholesterol may be mediated by their ability to control APL-1 neuronal protein expression.

  16. Cholesterol, Triglycerides, and the Five-Factor Model of Personality

    OpenAIRE

    Sutin, Angelina R.; Terracciano, Antonio; Deiana, Barbara; Uda, Manuela; Schlessinger, David; Lakatta, Edward G.; Costa, Paul T.

    2010-01-01

    Unhealthy lipid levels are among the leading controllable risk factors for coronary heart disease. To identify the psychological factors associated with dyslipidemia, this study investigates the personality correlates of cholesterol (total, LDL, and HDL) and triglycerides. A community-based sample (N=5,532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses controlled for age, sex, BM...

  17. GUAVA JUICE REDUCES CHOLESTEROL LEVEL FOR ELDERLY WITH HYPERTENSION

    OpenAIRE

    Afitasari, Dian Rahma; Yusuf, Ah.; Effendi, Fery

    2017-01-01

    Introduction: Hypertensive disease is closely related to high cholesterol level, which may act as one of causes of death in elderly. The objective of this study was to analyze the effect of guava juice on the reduction of cholesterol level of hypertensive elderly at Community Health Center, Pacar Keling, Surabaya. Method: Quasy–experimental was used in this study. Sample comprised of 14 respondents who met the inclusion criteria. The independent variable was guava juice and the dependent vari...

  18. Guava Juice Reduces Cholesterol Level for Elderly with Hypertension

    OpenAIRE

    Afitasari, Dian Rahma; Yusuf, Ah; Effendi, Fery

    2010-01-01

    Introduction: Hypertensive disease is closely related to high cholesterol level, which may act as one of causes of death in elderly. The objective of this study was to analyze the effect of guava juice on the reduction of cholesterol level of hypertensive elderly at Community Health Center, Pacar Keling, Surabaya. Method: Quasy–experimental was used in this study. Sample comprised of 14 respondents who met the inclusion criteria. The independent variable was guava juice and the dependent vari...

  19. Cholesterol Check (A Minute of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-09-10

    Heart disease and stroke are among the leading causes of death in the U.S. One of the main risk factors is high blood cholesterol. In this podcast, Dr. Carla Mercado discusses the importance of a healthy diet and regular screening to prevent high blood cholesterol.  Created: 9/10/2015 by MMWR.   Date Released: 9/10/2015.

  20. Feature and Pose Constrained Visual Aided Inertial Navigation for Computationally Constrained Aerial Vehicles

    Science.gov (United States)

    Williams, Brian; Hudson, Nicolas; Tweddle, Brent; Brockers, Roland; Matthies, Larry

    2011-01-01

    A Feature and Pose Constrained Extended Kalman Filter (FPC-EKF) is developed for highly dynamic computationally constrained micro aerial vehicles. Vehicle localization is achieved using only a low performance inertial measurement unit and a single camera. The FPC-EKF framework augments the vehicle's state with both previous vehicle poses and critical environmental features, including vertical edges. This filter framework efficiently incorporates measurements from hundreds of opportunistic visual features to constrain the motion estimate, while allowing navigating and sustained tracking with respect to a few persistent features. In addition, vertical features in the environment are opportunistically used to provide global attitude references. Accurate pose estimation is demonstrated on a sequence including fast traversing, where visual features enter and exit the field-of-view quickly, as well as hover and ingress maneuvers where drift free navigation is achieved with respect to the environment.

  1. Investigating cholesterol metabolism and ageing using a systems biology approach.

    Science.gov (United States)

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2017-08-01

    CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-cholesterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the world's population will be over 60 years of age, in culmination with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholesterolaemia and CVD prevention is a growing necessity. However, it is also imperative to recognise this complex biological system cannot be studied using a reductionist approach; rather its biological uniqueness necessitates a more integrated methodology, such as that offered by systems biology. In this review, we firstly discuss cholesterol metabolism and how it is affected by diet and the ageing process. Next, we describe therapeutic strategies for hypercholesterolaemia, and finally how the systems biology paradigm can be utilised to investigate how ageing interacts with complex systems such as cholesterol metabolism. We conclude by emphasising the need for nutritionists to work in parallel with the systems biology community, to develop novel approaches to studying cholesterol metabolism and its interaction with ageing.

  2. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

    Directory of Open Access Journals (Sweden)

    Agostino Di Ciaula

    2013-01-01

    Full Text Available Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.

  3. Cholesterol Removal from Whole Egg by Crosslinked β-Cyclodextrin

    Directory of Open Access Journals (Sweden)

    H. J. Jeong

    2014-04-01

    Full Text Available This study was carried out to optimize cholesterol removal in whole egg using crosslinked β-cyclodextrin (β-CD and to recycle the β-CD. Various factors for optimizing conditions were concentration of the β-CD, mixing temperature, mixing time, mixing speed and centrifugal speed. In the result of this study, the optimum conditions of cholesterol removal were 25% crosslinked β-CD, 40°C mixing temperature, 30 min mixing time, 1,200 rpm mixing speed and 2,810×g centrifugal speed. The recycling was repeated five times. The cholesterol removal was 92.76% when treated with the optimum conditions. After determining the optimum conditions, the recyclable yields of the crosslinked β-CD ranged from 86.66% to 87.60% in the recycling and the percentage of cholesterol removal was over 80% until third recycling. However, the cholesterol removal efficiency was decreased when the number of repeated recycling was increased. Based on the result of this study, it was concluded that the crosslinked β-CD was efficient for cholesterol removal in whole egg, and recycling is possible for only limited repeating times due to the interaction of the β-CD and egg protein.

  4. Cholesterol in brain disease: sometimes determinant and frequently implicated

    Science.gov (United States)

    Martín, Mauricio G; Pfrieger, Frank; Dotti, Carlos G

    2014-01-01

    Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell–cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol-related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease-causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non-hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function. PMID:25223281

  5. Incomplete Dirac reduction of constrained Hamiltonian systems

    Energy Technology Data Exchange (ETDEWEB)

    Chandre, C., E-mail: chandre@cpt.univ-mrs.fr

    2015-10-15

    First-class constraints constitute a potential obstacle to the computation of a Poisson bracket in Dirac’s theory of constrained Hamiltonian systems. Using the pseudoinverse instead of the inverse of the matrix defined by the Poisson brackets between the constraints, we show that a Dirac–Poisson bracket can be constructed, even if it corresponds to an incomplete reduction of the original Hamiltonian system. The uniqueness of Dirac brackets is discussed. The relevance of this procedure for infinite dimensional Hamiltonian systems is exemplified.

  6. Capturing Hotspots For Constrained Indoor Movement

    DEFF Research Database (Denmark)

    Ahmed, Tanvir; Pedersen, Torben Bach; Lu, Hua

    2013-01-01

    Finding the hotspots in large indoor spaces is very important for getting overloaded locations, security, crowd management, indoor navigation and guidance. The tracking data coming from indoor tracking are huge in volume and not readily available for finding hotspots. This paper presents a graph......-based model for constrained indoor movement that can map the tracking records into mapping records which represent the entry and exit times of an object in a particular location. Then it discusses the hotspots extraction technique from the mapping records....

  7. Quantization of soluble classical constrained systems

    International Nuclear Information System (INIS)

    Belhadi, Z.; Menas, F.; Bérard, A.; Mohrbach, H.

    2014-01-01

    The derivation of the brackets among coordinates and momenta for classical constrained systems is a necessary step toward their quantization. Here we present a new approach for the determination of the classical brackets which does neither require Dirac’s formalism nor the symplectic method of Faddeev and Jackiw. This approach is based on the computation of the brackets between the constants of integration of the exact solutions of the equations of motion. From them all brackets of the dynamical variables of the system can be deduced in a straightforward way

  8. Quantization of soluble classical constrained systems

    Energy Technology Data Exchange (ETDEWEB)

    Belhadi, Z. [Laboratoire de physique et chimie quantique, Faculté des sciences, Université Mouloud Mammeri, BP 17, 15000 Tizi Ouzou (Algeria); Laboratoire de physique théorique, Faculté des sciences exactes, Université de Bejaia, 06000 Bejaia (Algeria); Menas, F. [Laboratoire de physique et chimie quantique, Faculté des sciences, Université Mouloud Mammeri, BP 17, 15000 Tizi Ouzou (Algeria); Ecole Nationale Préparatoire aux Etudes d’ingéniorat, Laboratoire de physique, RN 5 Rouiba, Alger (Algeria); Bérard, A. [Equipe BioPhysStat, Laboratoire LCP-A2MC, ICPMB, IF CNRS No 2843, Université de Lorraine, 1 Bd Arago, 57078 Metz Cedex (France); Mohrbach, H., E-mail: herve.mohrbach@univ-lorraine.fr [Equipe BioPhysStat, Laboratoire LCP-A2MC, ICPMB, IF CNRS No 2843, Université de Lorraine, 1 Bd Arago, 57078 Metz Cedex (France)

    2014-12-15

    The derivation of the brackets among coordinates and momenta for classical constrained systems is a necessary step toward their quantization. Here we present a new approach for the determination of the classical brackets which does neither require Dirac’s formalism nor the symplectic method of Faddeev and Jackiw. This approach is based on the computation of the brackets between the constants of integration of the exact solutions of the equations of motion. From them all brackets of the dynamical variables of the system can be deduced in a straightforward way.

  9. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey

    2015-01-01

    RATIONALE: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE: To test the hypothesis that the increased IHD risk because of obesity is mediated through...... variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood...... obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. CONCLUSIONS: The increased IHD risk because...

  10. Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

    Science.gov (United States)

    Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

    2017-06-02

    Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI -tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr 83 and Glu 73 , respectively. When Glu 73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr 62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu 73 residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice.

    Science.gov (United States)

    Zhu, Ru-Gang; Sun, Yan-Di; Hou, Yu-Ting; Fan, Jun-Gang; Chen, Gang; Li, Tuo-Ping

    2017-06-25

    Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Pole shifting with constrained output feedback

    International Nuclear Information System (INIS)

    Hamel, D.; Mensah, S.; Boisvert, J.

    1984-03-01

    The concept of pole placement plays an important role in linear, multi-variable, control theory. It has received much attention since its introduction, and several pole shifting algorithms are now available. This work presents a new method which allows practical and engineering constraints such as gain limitation and controller structure to be introduced right into the pole shifting design strategy. This is achieved by formulating the pole placement problem as a constrained optimization problem. Explicit constraints (controller structure and gain limits) are defined to identify an admissible region for the feedback gain matrix. The desired pole configuration is translated into an appropriate cost function which must be closed-loop minimized. The resulting constrained optimization problem can thus be solved with optimization algorithms. The method has been implemented as an algorithmic interactive module in a computer-aided control system design package, MVPACK. The application of the method is illustrated to design controllers for an aircraft and an evaporator. The results illustrate the importance of controller structure on overall performance of a control system

  13. Changes in epistemic frameworks: Random or constrained?

    Directory of Open Access Journals (Sweden)

    Ananka Loubser

    2012-11-01

    Full Text Available Since the emergence of a solid anti-positivist approach in the philosophy of science, an important question has been to understand how and why epistemic frameworks change in time, are modified or even substituted. In contemporary philosophy of science three main approaches to framework-change were detected in the humanist tradition:1. In both the pre-theoretical and theoretical domains changes occur according to a rather constrained, predictable or even pre-determined pattern (e.g. Holton.2. Changes occur in a way that is more random or unpredictable and free from constraints (e.g. Kuhn, Feyerabend, Rorty, Lyotard.3. Between these approaches, a middle position can be found, attempting some kind of synthesis (e.g. Popper, Lakatos.Because this situation calls for clarification and systematisation, this article in fact tried to achieve more clarity on how changes in pre-scientific frameworks occur, as well as provided transcendental criticism of the above positions. This article suggested that the above-mentioned positions are not fully satisfactory, as change and constancy are not sufficiently integrated. An alternative model was suggested in which changes in epistemic frameworks occur according to a pattern, neither completely random nor rigidly constrained, which results in change being dynamic but not arbitrary. This alternative model is integral, rather than dialectical and therefore does not correspond to position three. 

  14. Fringe instability in constrained soft elastic layers.

    Science.gov (United States)

    Lin, Shaoting; Cohen, Tal; Zhang, Teng; Yuk, Hyunwoo; Abeyaratne, Rohan; Zhao, Xuanhe

    2016-11-04

    Soft elastic layers with top and bottom surfaces adhered to rigid bodies are abundant in biological organisms and engineering applications. As the rigid bodies are pulled apart, the stressed layer can exhibit various modes of mechanical instabilities. In cases where the layer's thickness is much smaller than its length and width, the dominant modes that have been studied are the cavitation, interfacial and fingering instabilities. Here we report a new mode of instability which emerges if the thickness of the constrained elastic layer is comparable to or smaller than its width. In this case, the middle portion along the layer's thickness elongates nearly uniformly while the constrained fringe portions of the layer deform nonuniformly. When the applied stretch reaches a critical value, the exposed free surfaces of the fringe portions begin to undulate periodically without debonding from the rigid bodies, giving the fringe instability. We use experiments, theory and numerical simulations to quantitatively explain the fringe instability and derive scaling laws for its critical stress, critical strain and wavelength. We show that in a force controlled setting the elastic fingering instability is associated with a snap-through buckling that does not exist for the fringe instability. The discovery of the fringe instability will not only advance the understanding of mechanical instabilities in soft materials but also have implications for biological and engineered adhesives and joints.

  15. Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis.

    Science.gov (United States)

    Stoeck, Ina Karen; Lee, Ji-Young; Tabata, Keisuke; Romero-Brey, Inés; Paul, David; Schult, Philipp; Lohmann, Volker; Kaderali, Lars; Bartenschlager, Ralf

    2018-01-01

    Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double-membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER)-membrane contact sites. RNA interference (RNAi)-mediated knockdown identified several hitherto unknown HCV dependency factors, such as steroidogenic acute regulatory protein-related lipid transfer domain protein 3 (STARD3), oxysterol-binding protein-related protein 1A and -B (OSBPL1A and -B), and Niemann-Pick-type C1 (NPC1), all residing at late endosome and lysosome membranes and required for efficient HCV RNA replication but not for replication of the closely related dengue virus. Focusing on NPC1, we found that knockdown or pharmacological inhibition caused cholesterol entrapment in lysosomal vesicles concomitant with decreased cholesterol abundance at sites containing the viral replicase factor NS5A. In untreated HCV-infected cells, unesterified cholesterol accumulated at the perinuclear region, partially colocalizing with NS5A at DMVs, arguing for NPC1-mediated endosomal cholesterol transport to the viral replication organelle. Consistent with cholesterol being an important structural component of DMVs, reducing NPC1-dependent endosomal cholesterol transport impaired MW integrity. This suggests that HCV usurps lipid transfer proteins, such as NPC1, at ER-late endosome/lysosome membrane contact sites to recruit cholesterol to the viral replication organelle, where it contributes to MW functionality. IMPORTANCE A key feature of the replication of positive-strand RNA viruses is the rearrangement of the host cell

  16. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J. W. H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  17. DIETARY-CHOLESTEROL INDUCED DOWN-REGULATION OF INTESTINAL 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE-ACTIVITY IS DIMINISHED IN RABBITS WITH HYPERRESPONSE OF SERUM-CHOLESTEROL TO DIETARY-CHOLESTEROL

    NARCIS (Netherlands)

    MEIJER, GW; SMIT, MJ; VANDERPALEN, JGP; KUIPERS, F; VONK, RJ; VANZUTPHEN, BFM; BEYNEN, AC

    Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was

  18. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus : Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J.W.H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  19. Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Dávila-Román, Victor G; Ostlund, Richard E

    2017-12-01

    Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d 5 and the nonabsorbable stool marker sitostanol-d 4 . Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol ( r =-0.426; P cholesterol ( r =-0.472; P ≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool ( r =-0.343; P =0.0012) and was positively correlated with percent cholesterol absorption ( r =+0.279; P =0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant ( P =0.0008). Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of

  20. Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population.

    Science.gov (United States)

    Varbo, Anette; Freiberg, Jacob J; Nordestgaard, Børge G

    2015-03-01

    Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial infarction (MI), and all-cause mortality. We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died. Compared with participants with nonfasting remnant cholesterol cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2.4 (1.9-2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend LDL cholesterol LDL cholesterol of 3-3.99 mmol/L (115.8-154 mg/dL) to 2.3 (1.9-2.8) for LDL cholesterol of ≥5 mmol/L (193 mg/dL) (P cholesterol (P LDL cholesterol (P cholesterol concentrations were associated stepwise with all-cause mortality ranging from hazard ratio 1.0 (0.9-1.1) to 1.6 (1.4-1.9) (P LDL cholesterol concentrations were associated with decreased all-cause mortality risk in a U-shaped pattern, with hazard ratios from 0.8 (0.7-0.8) to 0.9 (0.8-1.0) (P = 0.002). After mutual adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best predicted all-cause mortality. Both lipoproteins were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk. © 2015 American Association for Clinical Chemistry.

  1. Measurement of Intestinal and Peripheral Cholesterol Fluxes by a Dual-Tracer Balance Method

    NARCIS (Netherlands)

    Ronda, Onne A. H. O.; van Dijk, Theo H.; Verkade, H. J.; Groen, Albert K.

    2016-01-01

    Long-term elevated plasma cholesterol levels put individuals at risk for developing atherosclerosis. Plasma cholesterol levels are determined by the balance between cholesterol input and output fluxes. Here we describe in detail the methodology to determine the different cholesterol fluxes in mice.

  2. Trans-intestinal cholesterol effl ux is not mediated through high density lipoprotein

    NARCIS (Netherlands)

    Vrins, C.L.; Ottenhoff, R.; Oever, K. van den; Waart, D.R. de; Kruyt, J.K.; Zhao, Y.; Berkel, T.J. van; Havekes, L.M.; Aerts, J.M.; Eck, M. van; Rensen, P.C.; Groen, A.K.

    2012-01-01

    Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding

  3. Trans-intestinal cholesterol efflux is not mediated through high density lipoprotein

    NARCIS (Netherlands)

    Vrins, Carlos L. J.; Ottenhoff, Roelof; van den Oever, Karin; de Waart, Dirk R.; Kruyt, J. Kar; Zhao, Ying; van Berkel, Theo J. C.; Havekes, Louis M.; Aerts, Johannes M.; van Eck, Miranda; Rensen, Patrick C. N.; Groen, Albert K.

    2012-01-01

    Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding

  4. Changes in the serum profiles of lipids and cholesterol in sheep ...

    African Journals Online (AJOL)

    The samples were used for haematological and parasitological analyses and determination of serum concentrations of total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol) and low density lipoproteincholesterol (LDL-cholesterol). All animals in the infected group showed parasitaemia by day ...

  5. Localization and movement of newly synthesized cholesterol in rat ovarian granulosa cells

    International Nuclear Information System (INIS)

    Lange, Y.; Schmit, V.M.; Schreiber, J.R.

    1988-01-01

    The distribution and movement of cholesterol were studied in granulosa cells from the ovaries of estrogen-stimulated hypophysectomized immature rats cultured in serum-free medium. Plasma membrane cholesterol was distinguished from intracellular cholesterol with cholesterol oxidase, an enzyme that converts cell surface cholesterol to cholestenone, leaving intracellular cholesterol untouched. Using this approach we showed that 82% of unesterified cholesterol was associated with the plasma membrane in granulosa cells cultured for 48 h in serum-free medium in both the presence and absence of added androstenedione and FSH. FSH and androstenedione stimulated a marked increase in steroid hormone (progestin) production. The movement of newly synthesized cholesterol to the plasma membrane also was followed using cholesterol oxidase. Newly synthesized cholesterol reached the plasma membrane too rapidly to be measured in unstimulated cells (t1/2 less than 20 min); however, in cells stimulated by FSH and androstenedione, this rate was considerably slower (t1/2 approximately 2h). Therefore, cholesterol movement to the plasma membrane appears to be regulated by gonadotropins in these cells. We tested whether steroid biosynthesis used all cell cholesterol pools equally. To this end we administered [3H]acetate and [14C]acetate at different times and determined their relative specific contents in various steroids after defined intervals. The relative ages of the steroids (youngest to oldest) were: lanosterol, progestins, intracellular cholesterol, and plasma membrane cholesterol. This finding suggests that progestins use newly synthesized intracellular cholesterol in preference to preexisting intracellular or cell surface cholesterol

  6. Cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Soneil Guptha

    2014-05-01

    Conclusions: Mean cholesterol and LDL cholesterol are low and triglycerides were high in urban Asian Indians. Most prevalent dyslipidemias are borderline high LDL, low HDL and high triglycerides. Subjects with high socioeconomic status, high fat intake and greater adiposity have higher total and LDL cholesterol and triglyceride and lower HDL cholesterol.

  7. Lack of Cholesterol Awareness among Physicians Who Smoke

    Directory of Open Access Journals (Sweden)

    Richard E. Scranton

    2009-02-01

    Full Text Available Cigarette use is a known risk factor for the development of coronary artery disease (CAD as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR and 95% confidence intervals (CI of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively, as did the diagnosis of diabetes (2.40 to 7.79%. Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively, however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol

  8. Influence of the membrane environment on cholesterol transfer.

    Science.gov (United States)

    Breidigan, Jeffrey Michael; Krzyzanowski, Natalie; Liu, Yangmingyue; Porcar, Lionel; Perez-Salas, Ursula

    2017-12-01

    Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ∼100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  9. Structural requirements of cholesterol for binding to Vibrio cholerae hemolysin.

    Science.gov (United States)

    Ikigai, Hajime; Otsuru, Hiroshi; Yamamoto, Koichiro; Shimamura, Tadakatsu

    2006-01-01

    Cholesterol is necessary for the conversion of Vibrio cholerae hemolysin (VCH) monomers into oligomers in liposome membranes. Using different sterols, we determined the stereochemical structures of the VCH-binding active groups present in cholesterol. The VCH monomers are bound to cholesterol, diosgenin, campesterol, and ergosterol, which have a hydroxyl group at position C-3 (3betaOH) in the A ring and a C-C double bond between positions C-5 and C-6 (C-C Delta(5)) in the B ring. They are not bound to epicholesterol and dihydrocholesterol, which form a covalent link with a 3alphaOH group and a C-C single bond between positions C-5 and C-6, respectively. This result suggests that the 3betaOH group and the C-CDelta(5) bond in cholesterol are required for VCH monomer binding. We further examined VCH oligomer binding to cholesterol. However, this oligomer did not bind to cholesterol, suggesting that the disappearance of the cholesterol-binding potential of the VCH oligomer might be a result of the conformational change caused by the conversion of the monomer into the oligomer. VCH oligomer formation was observed in liposomes containing sterols with the 3betaOH group and the C-C Delta(5) bond, and it correlated with the binding affinity of the monomer to each sterol. Therefore, it seems likely that monomer binding to membrane sterol leads to the assembly of the monomer. However, since oligomer formation was induced by liposomes containing either epicholesterol or dihydrocholesterol, the 3betaOH group and the C-C Delta(5) bond were not essential for conversion into the oligomer.

  10. Synthesis and characterization of a novel rhodamine labeled cholesterol reporter.

    Science.gov (United States)

    Maiwald, Alexander; Bauer, Olivia; Gimpl, Gerald

    2017-06-01

    We introduce the novel fluorescent cholesterol probe RChol in which a sulforhodamine group is linked to the sixth carbon atom of the steroid backbone of cholesterol. The same position has recently been selected to generate the fluorescent reporter 6-dansyl-cholestanol (DChol) and the photoreactive 6-azi-cholestanol. In comparison with DChol, RChol is brighter, much more photostable, and requires less energy for excitation, i.e. favorable conditions for microscopical imaging. RChol easily incorporates into methyl-β-cyclodextrin forming a water-soluble inclusion complex that acts as an efficient sterol donor for cells and membranes. Like cholesterol, RChol possesses a free 3'OH group, a prerequisite to undergo intracellular esterification. RChol was also able to support the growth of cholesterol auxotrophic cells and can therefore substitute for cholesterol as a major component of the plasma membrane. According to subcellular fractionation, slight amounts of RChol (~12%) were determined in low-density Triton-insoluble fractions whereas the majority of RChol was localized in non-rafts fractions. In phase-separated giant unilamellar vesicles, RChol preferentially partitions in liquid-disordered membrane domains. Intracellular RChol was transferred to extracellular sterol acceptors such as high density lipoproteins in a dose-dependent manner. Unlike DChol, RChol was not delivered to the cholesterol storage pathway. Instead, it translocated to endosomes/lysosomes with some transient contacts to peroxisomes. Thus, RChol is considered as a useful probe to study the endosomal/lysosomal pathway of cholesterol. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Measurement of rates of cholesterol synthesis using tritiated water

    International Nuclear Information System (INIS)

    Dietschy, J.M.; Spady, D.K.

    1984-01-01

    Rates of sterol synthesis in various tissues commonly are assessed by assaying levels of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase on isolated microsomes or by measuring the rates of incorporation of various 14 C-labeled substrates or [ 3 H]water into cholesterol by whole cell preparations in vitro or by the tissues of the whole animal in vivo. While measurement of activities of HMG-CoA reductase or rates of incorporation of 14 C-labeled substrates into cholesterol give useful relative rates of sterol production, neither method yields absolute rates of cholesterol synthesis. The use of [ 3 H]water circumvents the problem of variable and unknown dilution of the specific activity of the precursor pool encountered when 14 C-labeled substrates are used and does yield absolute rates of cholesterol synthesis provided that the 3 H/C incorporation ratio is known for a particular tissue. In 12 different experimental situations it has been found that from 21 to 27 micrograms atoms of 3 H are incorporated into cholesterol from [ 3 H]water in different tissues of several animal species, so that the 3 H/C incorporation ratio is similar under nearly all experimental conditions and varies from 0.78 to 1.00. When administered in vivo, [ 3 H]water rapidly equilibrates with intracellular water and is incorporated into sterols within the various organs at rates that are linear with respect to time. From such data it is possible to obtain absolute rates of cholesterol synthesis in the whole animal and in the various organs of the animal. Current data suggest, therefore, that use of [ 3 H]water yields the most accurate rates of cholesterol synthesis both in vitro and in vivo

  12. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Lei [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Xiao, Yongsheng [Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States); Wang, Yinsheng, E-mail: yinsheng.wang@ucr.edu [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States)

    2014-05-15

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

  13. The origin of cholesterol in chyle demonstrated by nuclear indicator methods

    International Nuclear Information System (INIS)

    Vyas, M.

    1962-01-01

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4- 14 C- cholesterol subcutaneously or orally, or the 1- 14 C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [fr

  14. Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.

    Science.gov (United States)

    Berryman, Claire E; Fleming, Jennifer A; Kris-Etherton, Penny M

    2017-08-01

    Background : Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function. Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes. Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants ( n = 48) and in normal-weight (body mass index: almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-β-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL ( P almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable circulating HDL subpopulation distribution and improve cholesterol efflux in normal-weight individuals with elevated LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01101230. © 2017

  15. Cholesterol-α-glucosyltransferase gene is present in most Helicobacter species including gastric non-Helicobacter pylori helicobacters obtained from Japanese patients.

    Science.gov (United States)

    Kawakubo, Masatomo; Horiuchi, Kazuki; Matsumoto, Takehisa; Nakayama, Jun; Akamatsu, Taiji; Katsuyama, Tsutomu; Ota, Hiroyoshi; Sagara, Junji

    2018-02-01

    Non-Helicobacter pylori helicobacters (NHPHs) besides H. pylori infect human stomachs and cause chronic gastritis and mucosa-associated lymphoid tissue lymphoma. Cholesteryl-α-glucosides have been identified as unique glycolipids present in H. pylori and some Helicobacter species. Cholesterol-α-glucosyltransferase (αCgT), a key enzyme for the biosynthesis of cholesteryl-α-glucosides, plays crucial roles in the pathogenicity of H. pylori. Therefore, it is important to examine αCgTs of NHPHs. Six gastric NHPHs were isolated from Japanese patients and maintained in mouse stomachs. The αCgT genes were amplified by PCR and inverse PCR. We retrieved the αCgT genes of other Helicobacter species by BLAST searches in GenBank. αCgT genes were present in most Helicobacter species and in all Japanese isolates examined. However, we could find no candidate gene for αCgT in the whole genome of Helicobacter cinaedi and several enterohepatic species. Phylogenic analysis demonstrated that the αCgT genes of all Japanese isolates show high similarities to that of a zoonotic group of gastric NHPHs including Helicobacter suis, Helicobacter heilmannii, and Helicobacter ailurogastricus. Of 6 Japanese isolates, the αCgT genes of 4 isolates were identical to that of H. suis, and that of another 2 isolates were similar to that of H. heilmannii and H. ailurogastricus. All gastric NHPHs examined showed presence of αCgT genes, indicating that αCgT may be beneficial for these helicobacters to infect human and possibly animal stomachs. Our study indicated that NHPHs could be classified into 2 groups, NHPHs with αCgT genes and NHPHs without αCgT genes. © 2017 John Wiley & Sons Ltd.

  16. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages.

    Directory of Open Access Journals (Sweden)

    Zahedi Mujawar

    2006-10-01

    Full Text Available Several steps of HIV-1 replication critically depend on cholesterol. HIV infection is associated with profound changes in lipid and lipoprotein metabolism and an increased risk of coronary artery disease. Whereas numerous studies have investigated the role of anti-HIV drugs in lipodystrophy and dyslipidemia, the effects of HIV infection on cellular cholesterol metabolism remain uncharacterized. Here, we demonstrate that HIV-1 impairs ATP-binding cassette transporter A1 (ABCA1-dependent cholesterol efflux from human macrophages, a condition previously shown to be highly atherogenic. In HIV-1-infected cells, this effect was mediated by Nef. Transfection of murine macrophages with Nef impaired cholesterol efflux from these cells. At least two mechanisms were found to be responsible for this phenomenon: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. HIV-infected and Nef-transfected macrophages accumulated substantial amounts of lipids, thus resembling foam cells. The contribution of HIV-infected macrophages to the pathogenesis of atherosclerosis was supported by the presence of HIV-positive foam cells in atherosclerotic plaques of HIV-infected patients. Stimulation of cholesterol efflux from macrophages significantly reduced infectivity of the virions produced by these cells, and this effect correlated with a decreased amount of virion-associated cholesterol, suggesting that impairment of cholesterol efflux is essential to ensure proper cholesterol content in nascent HIV particles. These results reveal a previously unrecognized dysregulation of intracellular lipid metabolism in HIV-infected macrophages and identify Nef and ABCA1 as the key players responsible for this effect. Our findings

  17. Scheduling of resource-constrained projects

    CERN Document Server

    Klein, Robert

    2000-01-01

    Project management has become a widespread instrument enabling organizations to efficiently master the challenges of steadily shortening product life cycles, global markets and decreasing profit margins. With projects increasing in size and complexity, their planning and control represents one of the most crucial management tasks. This is especially true for scheduling, which is concerned with establishing execution dates for the sub-activities to be performed in order to complete the project. The ability to manage projects where resources must be allocated between concurrent projects or even sub-activities of a single project requires the use of commercial project management software packages. However, the results yielded by the solution procedures included are often rather unsatisfactory. Scheduling of Resource-Constrained Projects develops more efficient procedures, which can easily be integrated into software packages by incorporated programming languages, and thus should be of great interest for practiti...

  18. Constrained mathematics evaluation in probabilistic logic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Arlin Cooper, J

    1998-06-01

    A challenging problem in mathematically processing uncertain operands is that constraints inherent in the problem definition can require computations that are difficult to implement. Examples of possible constraints are that the sum of the probabilities of partitioned possible outcomes must be one, and repeated appearances of the same variable must all have the identical value. The latter, called the 'repeated variable problem', will be addressed in this paper in order to show how interval-based probabilistic evaluation of Boolean logic expressions, such as those describing the outcomes of fault trees and event trees, can be facilitated in a way that can be readily implemented in software. We will illustrate techniques that can be used to transform complex constrained problems into trivial problems in most tree logic expressions, and into tractable problems in most other cases.

  19. Constraining dark sectors with monojets and dijets

    International Nuclear Information System (INIS)

    Chala, Mikael; Kahlhoefer, Felix; Nardini, Germano; Schmidt-Hoberg, Kai; McCullough, Matthew

    2015-03-01

    We consider dark sector particles (DSPs) that obtain sizeable interactions with Standard Model fermions from a new mediator. While these particles can avoid observation in direct detection experiments, they are strongly constrained by LHC measurements. We demonstrate that there is an important complementarity between searches for DSP production and searches for the mediator itself, in particular bounds on (broad) dijet resonances. This observation is crucial not only in the case where the DSP is all of the dark matter but whenever - precisely due to its sizeable interactions with the visible sector - the DSP annihilates away so efficiently that it only forms a dark matter subcomponent. To highlight the different roles of DSP direct detection and LHC monojet and dijet searches, as well as perturbativity constraints, we first analyse the exemplary case of an axial-vector mediator and then generalise our results. We find important implications for the interpretation of LHC dark matter searches in terms of simplified models.

  20. Constrained KP models as integrable matrix hierarchies

    International Nuclear Information System (INIS)

    Aratyn, H.; Ferreira, L.A.; Gomes, J.F.; Zimerman, A.H.

    1997-01-01

    We formulate the constrained KP hierarchy (denoted by cKP K+1,M ) as an affine [cflx sl](M+K+1) matrix integrable hierarchy generalizing the Drinfeld endash Sokolov hierarchy. Using an algebraic approach, including the graded structure of the generalized Drinfeld endash Sokolov hierarchy, we are able to find several new universal results valid for the cKP hierarchy. In particular, our method yields a closed expression for the second bracket obtained through Dirac reduction of any untwisted affine Kac endash Moody current algebra. An explicit example is given for the case [cflx sl](M+K+1), for which a closed expression for the general recursion operator is also obtained. We show how isospectral flows are characterized and grouped according to the semisimple non-regular element E of sl(M+K+1) and the content of the center of the kernel of E. copyright 1997 American Institute of Physics