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Sample records for duplicated fatty acid-binding

  1. Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio: evidence for subfunctionalization or neofunctionalization of duplicated genes

    Directory of Open Access Journals (Sweden)

    Denovan-Wright Eileen M

    2009-09-01

    Full Text Available Abstract Background In the Duplication-Degeneration-Complementation (DDC model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps genes by dietary fatty acids (FAs in zebrafish. We chose zebrafish for this study for two reasons: extensive bioinformatics resources are available for zebrafish at zfin.org and zebrafish contains many duplicated genes owing to a whole genome duplication event that occurred early in the ray-finned fish lineage approximately 230-400 million years ago. Adult zebrafish were fed diets containing either fish oil (12% lipid, rich in highly unsaturated fatty acid, sunflower oil (12% lipid, rich in linoleic acid, linseed oil (12% lipid, rich in linolenic acid, or low fat (4% lipid, low fat diet for 10 weeks. FA profiles and the steady-state levels of fabp mRNA and heterogeneous nuclear RNA in intestine, liver, muscle and brain of zebrafish were determined. Result FA profiles assayed by gas chromatography differed in the intestine, brain, muscle and liver depending on diet. The steady-state level of mRNA for three sets of duplicated genes, fabp1a/fabp1b.1/fabp1b.2, fabp7a/fabp7b, and fabp11a/fabp11b, was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR. In brain, the steady-state level of fabp7b mRNAs was induced in fish fed the linoleic acid-rich diet; in intestine, the transcript level of fabp1b.1 and fabp7b were elevated in fish fed the linolenic acid-rich diet; in liver, the level of fabp7a mRNAs was elevated in fish fed the low fat diet; and in muscle, the level of fabp7a and fabp11a mRNAs were elevated in fish fed the linolenic acid-rich or the low fat diets. In all cases

  2. Solution Structure and Backbone Dynamics of Human Liver Fatty Acid Binding Protein: Fatty Acid Binding Revisited

    OpenAIRE

    Cai, Jun; Lücke, Christian; Chen, Zhongjing; Qiao, Ye; Klimtchuk, Elena; Hamilton, James A.

    2012-01-01

    Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the p...

  3. Echinococcus granulosus fatty acid binding proteins subcellular localization.

    Science.gov (United States)

    Alvite, Gabriela; Esteves, Adriana

    2016-05-01

    Two fatty acid binding proteins, EgFABP1 and EgFABP2, were isolated from the parasitic platyhelminth Echinococcus granulosus. These proteins bind fatty acids and have particular relevance in flatworms since de novo fatty acids synthesis is absent. Therefore platyhelminthes depend on the capture and intracellular distribution of host's lipids and fatty acid binding proteins could participate in lipid distribution. To elucidate EgFABP's roles, we investigated their intracellular distribution in the larval stage by a proteomic approach. Our results demonstrated the presence of EgFABP1 isoforms in cytosolic, nuclear, mitochondrial and microsomal fractions, suggesting that these molecules could be involved in several cellular processes.

  4. The clinical significance of fatty acid binding proteins

    Directory of Open Access Journals (Sweden)

    Barbara Choromańska

    2011-11-01

    Full Text Available Excessive levels of free fatty acids are toxic to cells. The human body has evolved a defense mechanism in the form of small cytoplasmic proteins called fatty acid binding proteins (FABPs that bind long-chain fatty acids (LCFA, and then refer them to appropriate intracellular disposal sites (oxidation in mitochondria and peroxisomes or storage in the endoplasmic reticulum. So far, nine types of these proteins have been described, and their name refers to the place in which they were first identified or where they can be found in the greatest concentration. The most important FABPs were isolated from the liver (L-FABP, heart (H-FABP, intestine (I-FABP, brain (B-FABP, epidermis (E-FABP and adipocytes (A-FABP. Determination of H-FABP is used in the diagnosis of myocardial infarction, and L-FABP in kidney lesions of different etiologies. It is postulated that FABPs play an important role in the pathogenesis of metabolic diseases. Elevated levels of A-FABP have been found in the pericardial fat tissue and were associated with cardiac dysfunction in obese people. A rise in A-FABP has been observed in patients with type II diabetes. I-FABP is known as a marker of cell damage in the small intestine. Increased concentration of B-FABP has been associated with human brain tumors such as glioblastoma and astrocytoma, as well as with neurodegenerative diseases (Alzheimer’s, Parkinson’s and other disorders of cognitive function. The aim of this work was to present current data on the clinical significance of fatty acid binding proteins.

  5. Transcriptional regulation of muscle fatty acid-binding protein.

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    Carey, J O; Neufer, P D; Farrar, R P; Veerkamp, J H; Dohm, G L

    1994-03-15

    Heart fatty acid-binding protein (H-FABP) is present in a wide variety of tissues but is found in the highest concentration in cardiac and red skeletal muscle. It has been proposed that the expression of H-FABP correlates directly with the fatty acid-oxidative capacity of the tissue. In the present study, the expression of H-FABP was measured in red and white skeletal muscle under two conditions in which fatty acid utilization is known to be increased: streptozotocin-induced diabetes and fasting. Protein concentration, mRNA concentration and transcription rate were measured under both conditions. The level of both protein and mRNA increased approximately 2-fold under each condition. The transcription rate was higher in red skeletal muscle than in white muscle, was increased 2-fold during fasting, but was unchanged by streptozotocin-induced diabetes. In addition to supporting the hypothesis that H-FABP is induced during conditions of increased fatty acid utilization, these findings demonstrate that the regulation of H-FABP expression may or may not be at the level of transcription depending on the stimulus.

  6. Value of heart-type fatty acid-binding protein (H-FABP) for ...

    African Journals Online (AJOL)

    Key Words: heart-type fatty acid-binding protein, acute coronary syndrome, biomarker. ... facilitating the intracellular cytoplasmic transport of the fatty acids, and are highly expressed ..... nary syndrome: systematic review and critical appraisal.

  7. Dietary Fat Content Effects on Concentrations of Liver and Intestinal Fatty Acid Binding Proteins

    OpenAIRE

    Murakami, Hiroshi; Sakai, Yasuo; Ohta, Kazutoshi; Hatakeyama, Katsuyoshi

    1998-01-01

    Two fatty acid binding proteins, liver and intestinal, have been identified in the rat intestine. Both are thought to be closely related to the absorption and metabolism of fatty acids in the intestinal epithelium. However, the underlying mechanism is not clearly understood. The purpose of this study was therefore to investigate the roles of these two fatty acid binding proteins in the intestinal absorption of fatty acids. Rats were fed diets varying in fat content for two or four weeks. Live...

  8. Bile salt recognition by human liver fatty acid binding protein.

    Science.gov (United States)

    Favretto, Filippo; Santambrogio, Carlo; D'Onofrio, Mariapina; Molinari, Henriette; Grandori, Rita; Assfalg, Michael

    2015-04-01

    Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is prominent among FABPs for its wide ligand repertoire, which includes long-chain fatty acids as well as bile acids (BAs). In this work, we performed a detailed molecular- and atomic-level analysis of the interactions established by human L-FABP with nine BAs to understand the binding specificity for this important class of cholesterol-derived metabolites. Protein-ligand complex formation was monitored using heteronuclear NMR, steady-state fluorescence spectroscopy, and mass spectrometry. BAs were found to interact with L-FABP with dissociation constants in the narrow range of 0.6-7 μm; however, the diverse substitution patterns of the sterol nucleus and the presence of side-chain conjugation resulted in complexes endowed with various degrees of conformational heterogeneity. Trihydroxylated BAs formed monomeric complexes in which single ligand molecules occupied similar internal binding sites, based on chemical-shift perturbation data. Analysis of NMR line shapes upon progressive addition of taurocholate indicated that the binding mechanism departed from a simple binary association equilibrium, and instead involved intermediates along the binding path. The co-linear chemical shift behavior observed for L-FABP complexes with cholate derivatives added insight into conformational dynamics in the presence of ligands. The observed spectroscopic features of L-FABP/BA complexes, discussed in relation to ligand chemistry, suggest possible molecular determinants of recognition, with implications regarding intracellular BA transport. Our findings suggest that human L-FABP is a poorly selective, universal BA binder.

  9. Lack of upregulation of epidermal fatty acid binding protein in dithranol induced irritation.

    NARCIS (Netherlands)

    Kucharekova, M.; Vissers, W.H.P.M.; Schalkwijk, J.; Kerkhof, P.C.M. van de; Valk, P.G.M. van der

    2003-01-01

    The exact role of epidermal fatty acid binding protein (E-FABP) in skin is unknown. A restoration of the barrier function may be associated with an upregulation of E-FABP. Moreover, E-FABP is upregulated in a variety of cells in response to oxidative stress. A recent observation that dithranol induc

  10. Urinary excretion of fatty acid-binding proteins in idiopathic membranous nephropathy.

    NARCIS (Netherlands)

    Hofstra, J.M.; Deegens, J.K.J.; Steenbergen, E.J.; Wetzels, J.F.M.

    2008-01-01

    BACKGROUND: It is suggested that proteinuria contributes to progressive renal failure by inducing tubular cell injury. The site of injury is unknown. Most studies have used markers of proximal tubular cell damage. Fatty acid-binding proteins (FABPs) are intracellular carrier proteins with different

  11. Early Diagnosis of Intestinal Ischemia Using Urinary and Plasma Fatty Acid Binding Proteins

    NARCIS (Netherlands)

    Thuijls, Geertje; van Wijck, Kim; Grootjans, Joep; Derikx, Joep P. M.; van Bijnen, Annemarie A.; Heineman, Erik; Dejong, Cornelis H. C.; Buurman, Wim A.; Poeze, Martijn

    2011-01-01

    Objective: This study aims at improving diagnosis of intestinal ischemia, by measuring plasma and urinary fatty acid binding protein (FABP) levels. Methods: Fifty consecutive patients suspected of intestinal ischemia were included and blood and urine were sampled at time of suspicion. Plasma and uri

  12. Analysis of the ligand binding properties of recombinant bovine liver-type fatty acid binding protein

    DEFF Research Database (Denmark)

    Rolf, B; Oudenampsen-Krüger, E; Börchers, T

    1995-01-01

    The coding part of the cDNA for bovine liver-type fatty acid binding protein (L-FABP) has been amplified by RT-PCR, cloned and used for the construction of an Escherichia coli (E. coli) expression system. The recombinant protein made up to 25% of the soluble E. coli proteins and could be isolated...

  13. Kinetics of fatty acid binding ability of glycated human serum albumin

    Indian Academy of Sciences (India)

    Eiji Yamazaki; Minoru Inagaki; Osamu Kurita; Tetsuji Inoue

    2005-09-01

    Kinetics of fatty acid binding ability of glycated human serum albumin (HSA) were investigated by fluorescent displacement technique with 1-anilino-8-naphtharene sulphonic acid (ANS method), and photometric detection of nonesterified-fatty-acid (NEFA method). Changing of binding affinities of glycated HSA toward oleic acid, linoleic acid, lauric acid, and caproic acid, were not observed by the ANS method. However, decreases of binding capacities after 55 days glycation were confirmed by the NEFA method in comparison to control HSA. The decrease in binding affinities was: oleic acid (84%), linoleic acid (84%), lauric acid (87%), and caproic acid (90%), respectively. The decreases were consistent with decrease of the intact lysine residues in glycated HSA. The present observation indicates that HSA promptly loses its binding ability to fatty acid as soon as the lysine residues at fatty acid binding sites are glycated.

  14. Relationship between serum adiopocyte fatty acid binding protein and atherosclerosis in chronic kidney disease

    Institute of Scientific and Technical Information of China (English)

    吴晶

    2014-01-01

    Objective To investigate the expression of serum adiopocyte fatty acid binding protein(A-FABP)in chronic kidney disease(CKD)and the role that A-FABP plays in CKD with atherosclerosis.Methods A total of 138 patients with CKD and 20 health control volunteers(HC)were involved in this study.The levels of serum AFABP,free fatty acid(FFA),interleukin-6(IL-6),

  15. Hepatic phenotype of liver fatty acid binding protein gene-ablated mice

    OpenAIRE

    Martin, Gregory G.; Atshaves, Barbara P.; Huang, Huan; McIntosh, Avery L.; Williams, Brad J.; Pai, Pei-Jing; Russell, David H.; Kier, Ann B.; Schroeder, Friedhelm

    2009-01-01

    Although the function of liver fatty acid binding protein in hepatic fatty acid metabolism has been extensively studied, its potential role in hepatic cholesterol homeostasis is less clear. Although hepatic cholesterol accumulation was initially reported in L-FABP-null female mice, that study was performed with early N2 backcross generation mice. To resolve whether the hepatic cholesterol phenotype in these L-FABP−/− mice was attributable to genetic inhomogeneity, these L-FABP−/− mice were fu...

  16. Towards an understanding of Mesocestoides vogae fatty acid binding proteins' roles.

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    Gabriela Alvite

    Full Text Available Two fatty acid binding proteins, MvFABPa and MvFABPb were identified in the parasite Mesocestoides vogae (Platyhelmithes, Cestoda. Fatty acid binding proteins are small intracellular proteins whose members exhibit great diversity. Proteins of this family have been identified in many organisms, of which Platyhelminthes are among the most primitive. These proteins have particular relevance in flatworms since de novo synthesis of fatty acids is absent. Fatty acids should be captured from the media needing an efficient transport system to uptake and distribute these molecules. While HLBPs could be involved in the shuttle of fatty acids to the surrounding host tissues and convey them into the parasite, FABPs could be responsible for the intracellular trafficking. In an effort to understand the role of MvFABPs in fatty acid transport of M. vogae larvae, we analysed the intracellular localization of both MvFABPs and the co-localization with in vivo uptake of fatty acid analogue BODIPY FL C16. Immunohistochemical studies on larvae sections using specific antibodies, showed a diffuse cytoplasmic distribution of each protein with some expression in nuclei and mitochondria. MvFABPs distribution was confirmed by mass spectrometry identification from 2D-electrophoresis of larvae subcellular fractions. This work is the first report showing intracellular distribution of MvFABPs as well as the co-localization of these proteins with the BODIPY FL C16 incorporated from the media. Our results suggest that fatty acid binding proteins could target fatty acids to cellular compartments including nuclei. In this sense, M. vogae FABPs could participate in several cellular processes fulfilling most of the functions attributed to vertebrate's counterparts.

  17. Towards an Understanding of Mesocestoides vogae Fatty Acid Binding Proteins’ Roles

    Science.gov (United States)

    Alvite, Gabriela; Garrido, Natalia; Kun, Alejandra; Paulino, Margot; Esteves, Adriana

    2014-01-01

    Two fatty acid binding proteins, MvFABPa and MvFABPb were identified in the parasite Mesocestoides vogae (Platyhelmithes, Cestoda). Fatty acid binding proteins are small intracellular proteins whose members exhibit great diversity. Proteins of this family have been identified in many organisms, of which Platyhelminthes are among the most primitive. These proteins have particular relevance in flatworms since de novo synthesis of fatty acids is absent. Fatty acids should be captured from the media needing an efficient transport system to uptake and distribute these molecules. While HLBPs could be involved in the shuttle of fatty acids to the surrounding host tissues and convey them into the parasite, FABPs could be responsible for the intracellular trafficking. In an effort to understand the role of MvFABPs in fatty acid transport of M. vogae larvae, we analysed the intracellular localization of both MvFABPs and the co-localization with in vivo uptake of fatty acid analogue BODIPY FL C16. Immunohistochemical studies on larvae sections using specific antibodies, showed a diffuse cytoplasmic distribution of each protein with some expression in nuclei and mitochondria. MvFABPs distribution was confirmed by mass spectrometry identification from 2D-electrophoresis of larvae subcellular fractions. This work is the first report showing intracellular distribution of MvFABPs as well as the co-localization of these proteins with the BODIPY FL C16 incorporated from the media. Our results suggest that fatty acid binding proteins could target fatty acids to cellular compartments including nuclei. In this sense, M. vogae FABPs could participate in several cellular processes fulfilling most of the functions attributed to vertebrate’s counterparts. PMID:25347286

  18. Sex Steroid Modulation of Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

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    Ockner, Robert K.; Lysenko, Nina; Manning, Joan A.; Monroe, Scott E.; Burnett, David A.

    1980-01-01

    The mechanism by which sex steroids influence very low density hepatic lipoprotein triglyceride production has not been fully elucidated. In previous studies we showed that [14C]oleate utilization and incorporation into triglycerides were greater in hepatocyte suspensions from adult female rats than from males. The sex differences were not related to activities of the enzymes of triglyceride biosynthesis, whereas fatty acid binding protein (FABP) concentration in liver cytosol was greater in females. These findings suggested that sex differences in lipoprotein could reflect a sex steroid influence on the availability of fatty acids for hepatocellular triglyceride biosynthesis. In the present studies, sex steroid effects on hepatocyte [14C]oleate utilization and FABP concentration were investigated directly. Hepatocytes from immature (30-d-old) rats exhibited no sex differences in [14C]oleate utilization. With maturation, total [14C]oleate utilization and triglyceride biosynthesis increased moderately in female cells and decreased markedly in male cells; the profound sex differences in adults were maximal by age 60 d. Fatty acid oxidation was little affected. Rats were castrated at age 30 d, and received estradiol, testosterone, or no hormone until age 60 d, when hepatocyte [14C]oleate utilization was studied. Castration virtually eliminated maturational changes and blunted the sex differences in adults. Estradiol or testosterone largely reproduced the appropriate adult pattern of [14C]oleate utilization regardless of the genotypic sex of the treated animal. In immature females and males, total cytosolic FABP concentrations were similar. In 60-d-old animals, there was a striking correlation among all groups (females, males, castrates, and hormone-treated) between mean cytosolic FABP concentration on the one hand, and mean total [14C]oleate utilization (r = 0.91) and incorporation into triglycerides (r = 0.94) on the other. In 30-d-old animals rates of [14C

  19. Fatty Acid Binding Proteins—The Evolutionary Crossroads of Inflammatory and Metabolic Responses1

    OpenAIRE

    Makowski, Liza; Hotamisligil, Gökhan S.

    2004-01-01

    Fatty acid binding proteins (FABPs) are members of a highly conserved family of proteins with the task of protecting a cell’s delicate lipid balance. Yet they fail when faced with metabolic or inflammatory stress, turning the cytosol into an inhospitable environment with less than ideal outcomes. This review will focus on how FABPs direct lipid traffic and simultaneously control inflammatory and metabolic pathways under the pressures of the Metabolic Syndrome.

  20. Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

    OpenAIRE

    YAN, JING; Gong, Yuewen; She, Yi-Min; Wang, Guqi; Roberts, Michael S; Burczynski, Frank J.

    2009-01-01

    Hepatocytes expressing liver fatty acid binding protein (L-FABP) are known to be more resistant to oxidative stress than those devoid of this protein. The mechanism for the observed antioxidant activity is not known. We examined the antioxidant mechanism of a recombinant rat L-FABP in the presence of a hydrophilic (AAPH) or lipophilic (AMVN) free radical generator. Recombinant L-FABP amino acid sequence and its amino acid oxidative products following oxidation were identified by MALDI quadrup...

  1. Urinary liver-type fatty acid-binding protein change in gestational diabetes mellitus.

    Science.gov (United States)

    Fu, Wen-Jin; Wang, Du-Juan; Deng, Ren-Tang; Huang, Zhi-Hong; Chen, Mei-Lian; Jang, You-Ming; Wen, Shu; Yang, Hong-Ling; Huang, Xian-zhang

    2015-09-01

    We compared urinary liver-type fatty acid-binding protein (L-FABP) among non-pregnant and pregnant women with and without gestational diabetes mellitus (GDM). Higher urinary L-FABP was found in pregnant with and without GDM, and considerably higher urinary L-FABP was found in the GDM group compared with the non-GDM group. Hyperglycemia and anemia were related with high urinary L-FABP expression.

  2. Assessment of coronary reperfusion in patients with myocardial infarction using fatty acid binding protein concentrations in plasma

    NARCIS (Netherlands)

    M.J.M. de Groot; A.M.M. Muijtjens; M.L. Simoons (Maarten); W.T. Hermens (Wim); J.F.C. Glatz

    2001-01-01

    textabstractOBJECTIVE: To examine whether successful coronary reperfusion after thrombolytic treatment in patients with confirmed acute myocardial infarction can be diagnosed from the plasma marker fatty acid binding protein (FABP), for either acute clinical decision making or retrospective purposes

  3. Ligand specificity and conformational stability of human fatty acid-binding proteins.

    Science.gov (United States)

    Zimmerman, A W; van Moerkerk, H T; Veerkamp, J H

    2001-09-01

    Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually identical backbone structures that facilitate the solubility and intracellular transport of fatty acids. At least eight different types of FABP occur, each with a specific tissue distribution and possibly with a distinct function. To define the functional characteristics of all eight human FABPs, viz. heart (H), brain (B), myelin (M), adipocyte (A), epidermal (E), intestinal (I), liver (L) and ileal lipid-binding protein (I-LBP), we studied their ligand specificity, their conformational stability and their immunological crossreactivity. Additionally, binding of bile acids to I-LBP was studied. The FABP types showed differences in fatty acid binding affinity. Generally, the affinity for palmitic acid was lower than for oleic and arachidonic acid. All FABP types, except E-FABP, I-FABP and I-LBP interacted with 1-anilinonaphtalene-8-sulphonic acid (ANS). Only L-FABP, I-FABP and M-FABP showed binding of 11-((5-dimethylaminonaphtalene-1-sulfonyl)amino)undecanoic acid (DAUDA). I-LBP showed increasing binding of bile acids in the order taurine-conjugated>glycine-conjugated>unconjugated bile acids. A hydroxylgroup of bile acids at position 7 decreased and at position 12 increased the binding affinity to I-LBP. The fatty acid-binding affinity and the conformation of FABP types were differentially affected in the presence of urea. Our results demonstrate significant differences in ligand binding, conformational stability and surface properties between different FABP types which may point to a specific function in certain cells and tissues. The preference of I-LBP (but not L-FABP) for conjugated bile acids is in accordance with a specific role in bile acid reabsorption in the ileum.

  4. Liver-type fatty acid binding protein interacts with hepatocyte nuclear factor 4α

    OpenAIRE

    McIntosh, Avery L.; Petrescu, Anca D.; Hostetler, Heather A.; Kier, Ann B.; Schroeder, Friedhelm

    2013-01-01

    Hepatocyte nuclear factor 4α (HNF4α) regulates liver type fatty acid binding protein (L-FABP) gene expression. Conversely as shown herein, L-FABP structurally and functionally also interacts with HNF4α. Fluorescence resonance energy transfer (FRET) between Cy3-HNF4α (donor) and Cy5-L-FABP (acceptor) as well as FRET microscopy detected L-FABP in close proximity (~80 Å) to HNF4α, binding with high affinity Kd ~250–300 nM. Circular dichroism (CD) determined that the HNF4α/L-FABP interaction alte...

  5. Model of β-Sheet of Muscle Fatty Acid Binding Protein of Locusta migratoria Displays Characteristic Topology.

    Science.gov (United States)

    Kizilbash, Nadeem A; Hai, Abdul; Alruwaili, Jamal

    2013-01-01

    The β-sheet of muscle fatty acid binding protein of Locusta migratoria (Lm-FABP) was modeled by employing 2-D NMR data and the Rigid Body Assembly method. The model shows the β-sheet to comprise ten β-strands arranged anti-parallel to each other. There is a β-bulge between Ser 13 and Gln 14 which is a difference from the published structure of β-sheet of bovine heart Fatty Acid Binding Protein. Also, a hydrophobic patch consisting of Ile 45, Phe 51, Phe 64 and Phe 66 is present on the surface which is characteristic of most Fatty Acid Binding Proteins. A "gap" is present between βD and βE that provides evidence for the presence of a portal or opening between the polypeptide chains which allows ligand fatty acids to enter the protein cavity and bind to the protein.

  6. Biological characterization of liver fatty acid binding gene from miniature pig liver cDNA library.

    Science.gov (United States)

    Gao, Y H; Wang, K F; Zhang, S; Fan, Y N; Guan, W J; Ma, Y H

    2015-01-01

    Liver fatty acid binding proteins (L-FABP) are a family of small, highly conserved, cytoplasmic proteins that bind to long-chain fatty acids and other hydrophobic ligands. In this study, a full-length enriched cDNA library was successfully constructed from Wuzhishan miniature pig, and then the L-FABP gene was cloned from this cDNA library and an expression vector (pEGFP-N3-L-FABP) was constructed in vitro. This vector was transfected into hepatocytes to test its function. The results of western blotting analysis demonstrated that the L-FABP gene from our full-length enriched cDNA library regulated downstream genes, including the peroxisome proliferator-activated receptor family in hepatocytes. This study provides a theoretical basis and experimental evidence for the application of L-FABP for the treatment of liver injury.

  7. The human fatty acid-binding protein family: Evolutionary divergences and functions

    Directory of Open Access Journals (Sweden)

    Smathers Rebecca L

    2011-03-01

    Full Text Available Abstract Fatty acid-binding proteins (FABPs are members of the intracellular lipid-binding protein (iLBP family and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum and nucleus. FABPs are small, structurally conserved cytosolic proteins consisting of a water-filled, interior-binding pocket surrounded by ten anti-parallel beta sheets, forming a beta barrel. At the superior surface, two alpha-helices cap the pocket and are thought to regulate binding. FABPs have broad specificity, including the ability to bind long-chain (C16-C20 fatty acids, eicosanoids, bile salts and peroxisome proliferators. FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied.

  8. Effect of liver fatty acid binding protein on fatty acid movement between liposomes and rat liver microsomes.

    Science.gov (United States)

    McCormack, M; Brecher, P

    1987-01-01

    Although movement of fatty acids between bilayers can occur spontaneously, it has been postulated that intracellular movement is facilitated by a class of proteins named fatty acid binding proteins (FABP). In this study we have incorporated long chain fatty acids into multilamellar liposomes made of phosphatidylcholine, incubated them with rat liver microsomes containing an active acyl-CoA synthetase, and measured formation of acyl-CoA in the absence or presence of FABP purified from rat liver. FABP increased about 2-fold the accumulation of acyl-CoA when liposomes were the fatty acid donor. Using fatty acid incorporated into liposomes made either of egg yolk lecithin or of dipalmitoylphosphatidylcholine, it was found that the temperature dependence of acyl-CoA accumulation in the presence of FABP correlated with both the physical state of phospholipid molecules in the liposomes and the binding of fatty acid to FABP, suggesting that fatty acid must first desorb from the liposomes before FABP can have an effect. An FABP-fatty acid complex incubated with microsomes, in the absence of liposomes, resulted in greater acyl-CoA formation than when liposomes were present, suggesting that desorption of fatty acid from the membrane is rate-limiting in the accumulation of acyl-CoA by this system. Finally, an equilibrium dialysis cell separating liposomes from microsomes on opposite sides of a Nuclepore filter was used to show that liver FABP was required for the movement and activation of fatty acid between the compartments. These studies show that liver FABP interacts with fatty acid that desorbs from phospholipid bilayers, and promotes movement to a membrane-bound enzyme, suggesting that FABP may act intracellularly by increasing net desorption of fatty acid from cell membranes. PMID:3446187

  9. Fatty Acid-Binding Protein in Small Intestine IDENTIFICATION, ISOLATION, AND EVIDENCE FOR ITS ROLE IN CELLULAR FATTY ACID TRANSPORT

    Science.gov (United States)

    Ockner, Robert K.; Manning, Joan A.

    1974-01-01

    A soluble fatty acid-binding protein (FABP), mol wt ∼ 12,000 is present in intestinal mucosa and other tissues that utilize fatty acids, including liver, myocardium, adipose, and kidney. This protein binds long chain fatty acids both in vivo and in vitro. FABP was isolated from rat intestine by gel filtration and isoelectric focusing. It showed a reaction of complete immunochemical identity with proteins in the 12,000 mol wt fatty acid-binding fractions of liver, myocardium, and adipose tissue supernates. (The presence of immunochemically nonidentical 12,000 mol wt FABP in these tissues is not excluded.) By quantitative radial immunodiffusion, supernatant FABP concentration in mucosa from proximal and middle thirds of jejuno-ileum significantly exceeded that in distal third, duodenum, and liver, expressed as micrograms per milligram soluble protein, micrograms per gram DNA, and micrograms per gram tissue. FABP concentration in villi was approximately three times greater than in crypts. Small quantities of FABP were present in washed nuclei-cell membrane, mitochondrial and microsomal fractions. However, the amount of FABP solubilized per milligram membrane protein was similar for all particulate fractions, and total membrane-associated FABP was only about 16% of supernatant FABP. Intestinal FABP concentration was significantly greater in animals maintained on high fat diets than on low fat; saturated and unsaturated fat diets did not differ greatly in this regard. The preponderance of FABP in villi from proximal and middle intestine, its ability to bind fatty acids in vivo as well as in vitro, and its response to changes in dietary fat intake support the concept that this protein participates in cellular fatty acid transport during fat absorption. Identical or closely related 12,000 mol wt proteins may serve similar functions in other tissues. Images PMID:4211161

  10. Biochemical Roles for Conserved Residues in the Bacterial Fatty Acid-binding Protein Family.

    Science.gov (United States)

    Broussard, Tyler C; Miller, Darcie J; Jackson, Pamela; Nourse, Amanda; White, Stephen W; Rock, Charles O

    2016-03-18

    Fatty acid kinase (Fak) is a ubiquitous Gram-positive bacterial enzyme consisting of an ATP-binding protein (FakA) that phosphorylates the fatty acid bound to FakB. In Staphylococcus aureus, Fak is a global regulator of virulence factor transcription and is essential for the activation of exogenous fatty acids for incorporation into phospholipids. The 1.2-Å x-ray structure of S. aureus FakB2, activity assays, solution studies, site-directed mutagenesis, and in vivo complementation were used to define the functions of the five conserved residues that define the FakB protein family (Pfam02645). The fatty acid tail is buried within the protein, and the exposed carboxyl group is bound by a Ser-93-fatty acid carboxyl-Thr-61-His-266 hydrogen bond network. The guanidinium of the invariant Arg-170 is positioned to potentially interact with a bound acylphosphate. The reduced thermal denaturation temperatures of the T61A, S93A, and H266A FakB2 mutants illustrate the importance of the hydrogen bond network in protein stability. The FakB2 T61A, S93A, and H266A mutants are 1000-fold less active in the Fak assay, and the R170A mutant is completely inactive. All FakB2 mutants form FakA(FakB2)2 complexes except FakB2(R202A), which is deficient in FakA binding. Allelic replacement shows that strains expressing FakB2 mutants are defective in fatty acid incorporation into phospholipids and virulence gene transcription. These conserved residues are likely to perform the same critical functions in all bacterial fatty acid-binding proteins.

  11. Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken hepatocytes.

    Science.gov (United States)

    Gao, G L; Na, W; Wang, Y X; Zhang, H F; Li, H; Wang, Q G

    2015-01-01

    This study investigated the role of the chicken liver fatty acid-binding protein (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory relationships between L-FABP and genes related to lipid metabolism. The short hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after transfection with the interference or overexpression plasmids for L-FABP, PPARα and L-BABP expression levels, and the total amount of cholesterol, were significantly affected by L-FABP expression. L-FABP may affect lipid metabolism by regulating PPARα and L-BABP in chicken hepatocytes.

  12. Recent insights into the biological functions of liver fatty acid binding protein 1.

    Science.gov (United States)

    Wang, GuQi; Bonkovsky, Herbert L; de Lemos, Andrew; Burczynski, Frank J

    2015-12-01

    Over four decades have passed since liver fatty acid binding protein (FABP)1 was first isolated. There are few protein families for which most of the complete tertiary structures, binding properties, and tissue occurrences are described in such detail and yet new functions are being uncovered for this protein. FABP1 is known to be critical for fatty acid uptake and intracellular transport and also has an important role in regulating lipid metabolism and cellular signaling pathways. FABP1 is an important endogenous cytoprotectant, minimizing hepatocyte oxidative damage and interfering with ischemia-reperfusion and other hepatic injuries. The protein may be targeted for metabolic activation through the cross-talk among many transcriptional factors and their activating ligands. Deficiency or malfunction of FABP1 has been reported in several diseases. FABP1 also influences cell proliferation during liver regeneration and may be considered as a prognostic factor for hepatic surgery. FABP1 binds and modulates the action of many molecules such as fatty acids, heme, and other metalloporphyrins. The ability to bind heme is another cytoprotective property and one that deserves closer investigation. The role of FABP1 in substrate availability and in protection from oxidative stress suggests that FABP1 plays a pivotal role during intracellular bacterial/viral infections by reducing inflammation and the adverse effects of starvation (energy deficiency).

  13. Seasonal dynamics of flight muscle fatty acid binding protein and catabolic enzymes in a migratory shorebird.

    Science.gov (United States)

    Guglielmo, Christopher G; Haunerland, Norbert H; Hochachka, Peter W; Williams, Tony D

    2002-05-01

    We developed an ELISA to measure heart-type fatty acid binding protein (H-FABP) in muscles of the western sandpiper (Calidris mauri), a long-distance migrant shorebird. H-FABP accounted for almost 11% of cytosolic protein in the heart. Pectoralis H-FABP levels were highest during migration (10%) and declined to 6% in tropically wintering female sandpipers. Premigratory birds increased body fat, but not pectoralis H-FABP, indicating that endurance flight training may be required to stimulate H-FABP expression. Juveniles making their first migration had lower pectoralis H-FABP than adults, further supporting a role for flight training. Aerobic capacity, measured by citrate synthase activity, and fatty acid oxidation capacity, measured by 3-hydroxyacyl-CoA-dehydrogenase and carnitine palmitoyl transferase activities, did not change during premigration but increased during migration by 6, 12, and 13%, respectively. The greater relative induction of H-FABP (+70%) with migration than of catabolic enzymes suggests that elevated H-FABP is related to the enhancement of uptake of fatty acids from the circulation. Citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and carnitine palmitoyl transferase were positively correlated within individuals, suggesting coexpression, but enzyme activities were unrelated to H-FABP levels.

  14. Differential gene expression of fatty acid binding proteins during porcine adipogenesis.

    Science.gov (United States)

    Samulin, Johanna; Berget, Ingunn; Lien, Sigbjørn; Sundvold, Hilde

    2008-10-01

    Four different subtypes of fatty acid binding proteins i.e. liver-type FABP1, heart/muscle-type FABP3, adipocyte-type FABP4 and epithelial/epidermal-type FABP5 are expressed in adipose tissue. However, only the regulatory role of FABP4 in adipogenesis has been thoroughly investigated. To increase the knowledge on possible roles of these FABP subtypes in preadipocyte differentiation, gene expression patterns were examined during adipogenesis in pig (Sus scrofa). FABP1 expression was induced in proliferating cells, whereas FABP3, FABP4 and FABP5 expression increased throughout preadipocyte differentiation. Interestingly, the FABP4 and FABP5 expression increased early in the differentiation, followed by FABP3 later in the differentiation process. This indicates a role of FABP4 and FABP5 in intracellular fatty acid transport during initiation of differentiation, whereas, FABP3 likely is involved in the transport of fatty acids during intermediate stages of adipogenesis. In this study we demonstrate that FABP3, FABP4 and FABP5 expression is correlated with that of the peroxisome proliferator-activated receptors alpha and gamma (PPARA and PPARG). Altogether, this suggests a role of FABP1 during cell proliferation, whereas a coordinated expression of FABP3, FABP4 and FABP5 together with that of PPARA, PPARG1 and PPARG2 might be critical for the metabolic regulation during porcine adipogenesis.

  15. Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription.

    Science.gov (United States)

    Schroeder, Friedhelm; Petrescu, Anca D; Huang, Huan; Atshaves, Barbara P; McIntosh, Avery L; Martin, Gregory G; Hostetler, Heather A; Vespa, Aude; Landrock, Danilo; Landrock, Kerstin K; Payne, H Ross; Kier, Ann B

    2008-01-01

    Abnormal energy regulation may significantly contribute to the pathogenesis of obesity, diabetes mellitus, cardiovascular disease, and cancer. For rapid control of energy homeostasis, allosteric and posttranslational events activate or alter activity of key metabolic enzymes. For longer impact, transcriptional regulation is more effective, especially in response to nutrients such as long chain fatty acids (LCFA). Recent advances provide insights into how poorly water-soluble lipid nutrients [LCFA; retinoic acid (RA)] and their metabolites (long chain fatty acyl Coenzyme A, LCFA-CoA) reach nuclei, bind their cognate ligand-activated receptors, and regulate transcription for signaling lipid and glucose catabolism or storage: (i) while serum and cytoplasmic LCFA levels are in the 200 mircroM-mM range, real-time imaging recently revealed that LCFA and LCFA-CoA are also located within nuclei (nM range); (ii) sensitive fluorescence binding assays show that LCFA-activated nuclear receptors [peroxisome proliferator-activated receptor-alpha (PPARalpha) and hepatocyte nuclear factor 4alpha (HNF4alpha)] exhibit high affinity (low nM KdS) for LCFA (PPARalpha) and/or LCFA-CoA (PPARalpha, HNF4alpha)-in the same range as nuclear levels of these ligands; (iii) live and fixed cell immunolabeling and imaging revealed that some cytoplasmic lipid binding proteins [liver fatty acid binding protein (L-FABP), acyl CoA binding protein (ACBP), cellular retinoic acid binding protein-2 (CRABP-2)] enter nuclei, bind nuclear receptors (PPARalpha, HNF4alpha, CRABP-2), and activate transcription of genes in fatty acid and glucose metabolism; and (iv) studies with gene ablated mice provided physiological relevance of LCFA and LCFA-CoA binding proteins in nuclear signaling. This led to the hypothesis that cytoplasmic lipid binding proteins transfer and channel lipidic ligands into nuclei for initiating nuclear receptor transcriptional activity to provide new lipid nutrient signaling pathways that

  16. Intestinal fatty acid-binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study

    NARCIS (Netherlands)

    Schurink, M.; Kooi, E.M.; Hulzebos, C.V.; Kox, R.G.; Groen, H.; Heineman, E.; Bos, A.F; Hulscher, J.B.

    2015-01-01

    BACKGROUND: Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial w

  17. Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke

    DEFF Research Database (Denmark)

    Holm, Sverre; Ueland, Thor; Dahl, Tuva B

    2011-01-01

    Fatty acid binding protein 4 (FABP4) has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke....

  18. Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Sugaya, Takeshi; Hovind, Peter;

    2010-01-01

    Urinary liver-type fatty acid-binding protein (u-LFABP) is a marker of tubulointerstitial inflammation and has been shown to be increased in patients with type 1 diabetes and is further increased in patients who progress to micro- and macroalbuminuria. Our aim was to evaluate u-LFABP as a predict...

  19. The effects of methylene blue infusion on gastric tonometry and intestinal fatty acid binding protein levels in septic shock patients.

    NARCIS (Netherlands)

    Haren, F.M.P. van; Pickkers, P.; Foudraine, N.; Heemskerk, S.; Sleigh, J.; Hoeven, J.G. van der

    2010-01-01

    OBJECTIVE: We prospectively studied the effect of methylene blue (MB) infusion on gastric mucosal metabolism perfusion ratio, assessed by gastric tonometry, and on mucosal cell damage, assessed by urinary levels of intestinal fatty acid binding protein, in septic shock patients. METHODS: Methylene

  20. Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis.

    NARCIS (Netherlands)

    Reisinger, K.W.; Zee, D.C. van der; Brouwers, H.A.A.; Kramer, B.W.; Heurn, L.W.E. van; Buurman, W.A.; Derikx, J.P.

    2012-01-01

    BACKGROUND: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, s

  1. Noninvasive measurement of fecal calprotectin and serum amyloid A combined with intestinal fatty acid-binding protein in necrotizing enterocolitis

    NARCIS (Netherlands)

    Reisinger, Kostan W.; Van der Zee, David C.; Brouwers, Hens A. A.; Kramer, Boris W.; van Heurn, L. W. Ernest; Buurman, Wim A.; Derikx, Joep P. M.

    2012-01-01

    Background: Diagnosis of necrotizing enterocolitis (NEC), prevalent in premature infants, remains challenging. Enterocyte damage in NEC can be assessed by intestinal fatty acid-binding protein (I-FABP), with a sensitivity of 93% and a specificity of 90%. Numerous markers of inflammation are known, s

  2. Expression Pattern of Fatty Acid Binding Proteins in Celiac Disease Enteropathy

    Directory of Open Access Journals (Sweden)

    Natalia M. Bottasso Arias

    2015-01-01

    Full Text Available Celiac disease (CD is an immune-mediated enteropathy that develops in genetically susceptible individuals following exposure to dietary gluten. Severe changes at the intestinal mucosa observed in untreated CD patients are linked to changes in the level and in the pattern of expression of different genes. Fully differentiated epithelial cells express two isoforms of fatty acid binding proteins (FABPs: intestinal and liver, IFABP and LFABP, respectively. These proteins bind and transport long chain fatty acids and also have other important biological roles in signaling pathways, particularly those related to PPARγ and inflammatory processes. Herein, we analyze the serum levels of IFABP and characterize the expression of both FABPs at protein and mRNA level in small intestinal mucosa in severe enteropathy and normal tissue. As a result, we observed higher levels of circulating IFABP in untreated CD patients compared with controls and patients on gluten-free diet. In duodenal mucosa a differential FABPs expression pattern was observed with a reduction in mRNA levels compared to controls explained by the epithelium loss in severe enteropathy. In conclusion, we report changes in FABPs’ expression pattern in severe enteropathy. Consequently, there might be alterations in lipid metabolism and the inflammatory process in the small intestinal mucosa.

  3. Interactions between Human Liver Fatty Acid Binding Protein and Peroxisome Proliferator Activated Receptor Selective Drugs

    Directory of Open Access Journals (Sweden)

    Tony Velkov

    2013-01-01

    Full Text Available Fatty acid binding proteins (FABPs act as intracellular shuttles for fatty acids as well as lipophilic xenobiotics to the nucleus, where these ligands are released to a group of nuclear receptors called the peroxisome proliferator activated receptors (PPARs. PPAR mediated gene activation is ultimately involved in maintenance of cellular homeostasis through the transcriptional regulation of metabolic enzymes and transporters that target the activating ligand. Here we show that liver- (L- FABP displays a high binding affinity for PPAR subtype selective drugs. NMR chemical shift perturbation mapping and proteolytic protection experiments show that the binding of the PPAR subtype selective drugs produces conformational changes that stabilize the portal region of L-FABP. NMR chemical shift perturbation studies also revealed that L-FABP can form a complex with the PPAR ligand binding domain (LBD of PPARα. This protein-protein interaction may represent a mechanism for facilitating the activation of PPAR transcriptional activity via the direct channeling of ligands between the binding pocket of L-FABP and the PPARαLBD. The role of L-FABP in the delivery of ligands directly to PPARα via this channeling mechanism has important implications for regulatory pathways that mediate xenobiotic responses and host protection in tissues such as the small intestine and the liver where L-FABP is highly expressed.

  4. Inhibition of fatty acid binding proteins elevates brain anandamide levels and produces analgesia.

    Directory of Open Access Journals (Sweden)

    Martin Kaczocha

    Full Text Available The endocannabinoid anandamide (AEA is an antinociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by fatty acid amide hydrolase (FAAH. Fatty acid binding proteins (FABPs are intracellular carriers that deliver AEA and related N-acylethanolamines (NAEs to FAAH for hydrolysis. The mammalian brain expresses three FABP subtypes: FABP3, FABP5, and FABP7. Recent work from our group has revealed that pharmacological inhibition of FABPs reduces inflammatory pain in mice. The goal of the current work was to explore the effects of FABP inhibition upon nociception in diverse models of pain. We developed inhibitors with differential affinities for FABPs to elucidate the subtype(s that contributes to the antinociceptive effects of FABP inhibitors. Inhibition of FABPs reduced nociception associated with inflammatory, visceral, and neuropathic pain. The antinociceptive effects of FABP inhibitors mirrored their affinities for FABP5, while binding to FABP3 and FABP7 was not a predictor of in vivo efficacy. The antinociceptive effects of FABP inhibitors were mediated by cannabinoid receptor 1 (CB1 and peroxisome proliferator-activated receptor alpha (PPARα and FABP inhibition elevated brain levels of AEA, providing the first direct evidence that FABPs regulate brain endocannabinoid tone. These results highlight FABPs as novel targets for the development of analgesic and anti-inflammatory therapeutics.

  5. Heart-type Fatty Acid-binding Protein Is Essential for Efficient Brown Adipose Tissue Fatty Acid Oxidation and Cold Tolerance*

    OpenAIRE

    Vergnes, Laurent; Chin, Robert; Young, Stephen G.; Reue, Karen

    2010-01-01

    Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3−/− mice exhibit ...

  6. Fatty acids induce leukotriene C4 synthesis in macrophages in a fatty acid binding protein-dependent manner.

    Science.gov (United States)

    Long, Eric K a; Hellberg, Kristina; Foncea, Rocio; Hertzel, Ann V; Suttles, Jill; Bernlohr, David A

    2013-07-01

    Obesity results in increased macrophage recruitment to adipose tissue that promotes a chronic low-grade inflammatory state linked to increased fatty acid efflux from adipocytes. Activated macrophages produce a variety of pro-inflammatory lipids such as leukotriene C4 (LTC4) and 5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE) suggesting the hypothesis that fatty acids may stimulate eicosanoid synthesis. To assess if eicosanoid production increases with obesity, adipose tissue of leptin deficient ob/ob mice was analyzed. In ob/ob mice, LTC4 and 12-HETE levels increased in the visceral (but not subcutaneous) adipose depot while the 5-HETE levels decreased and 15-HETE abundance was unchanged. Since macrophages produce the majority of inflammatory molecules in adipose tissue, treatment of RAW264.7 or primary peritoneal macrophages with free fatty acids led to increased secretion of LTC4 and 5-HETE, but not 12- or 15-HETE. Fatty acid binding proteins (FABPs) facilitate the intracellular trafficking of fatty acids and other hydrophobic ligands and in vitro stabilize the LTC4 precursor leukotriene A4 (LTA4) from non-enzymatic hydrolysis. Consistent with a role for FABPs in LTC4 synthesis, treatment of macrophages with HTS01037, a specific FABP inhibitor, resulted in a marked decrease in both basal and fatty acid-stimulated LTC4 secretion but no change in 5-HETE production or 5-lipoxygenase expression. These results indicate that the products of adipocyte lipolysis may stimulate the 5-lipoxygenase pathway leading to FABP-dependent production of LTC4 and contribute to the insulin resistant state.

  7. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites.

    Science.gov (United States)

    Zahid, Henna; Miah, Layeque; Lau, Andy M; Brochard, Lea; Hati, Debolina; Bui, Tam T T; Drake, Alex F; Gor, Jayesh; Perkins, Stephen J; McDermott, Lindsay C

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigated. Analytical ultracentrifugation (AUC) and CD showed that zinc, but not other divalent metals, causes ZAG to oligomerize in solution. Thus ZAG dimers and trimers were observed in the presence of 1 and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting that the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG-zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-hexadecanoic acid). Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid-binding groove in ZAG contains at least two distinct fatty acid-binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally related immune protein CD1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid-binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homoeostasis occurs.

  8. Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4.

    Science.gov (United States)

    Gorbenko, O; Panayotou, G; Zhyvoloup, A; Volkova, D; Gout, I; Filonenko, V

    2010-04-01

    PTEN is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. Recent studies have also demonstrated that PTEN is a promising target in type II diabetes and obesity treatment. Using C-terminal PTEN sequence in pEG202-NLS as bait, yeast two-hybrid screening on Mouse Embryo, Colon Cancer, and HeLa cDNA libraries was carried out. Isolated positive clones were validated by mating assay and identified through automated DNA sequencing and BLAST database searches. Sequence analysis revealed a number of PTEN-binding proteins linking this phosphatase to a number of different signaling cascades, suggesting that PTEN may perform other functions besides tumor-suppressing activity in different cell types. In particular, the interplay between PTEN function and adipocyte-specific fatty-acid-binding protein FABP4 is of notable interest. The demonstrable tautology of PTEN to FABP4 suggested a role for this phosphatase in the regulation of lipid metabolism and adipocyte differentiation. This interaction was further studied using coimmunoprecipitation and gel-filtration assays. Finally, based on Biacore assay, we have calculated the K(D) of PTEN-FABP4 complex, which is around 2.8 microM.

  9. Fatty-acid binding proteins modulate sleep and enhance long-term memory consolidation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jason R Gerstner

    Full Text Available Sleep is thought to be important for memory consolidation, since sleep deprivation has been shown to interfere with memory processing. However, the effects of augmenting sleep on memory formation are not well known, and testing the role of sleep in memory enhancement has been limited to pharmacological and behavioral approaches. Here we test the effect of overexpressing the brain-type fatty acid binding protein (Fabp7 on sleep and long-term memory (LTM formation in Drosophila melanogaster. Transgenic flies carrying the murine Fabp7 or the Drosophila homologue dFabp had reduced baseline sleep but normal LTM, while Fabp induction produced increases in both net sleep and LTM. We also define a post-training consolidation "window" that is sufficient for the observed Fabp-mediated memory enhancement. Since Fabp overexpression increases consolidated daytime sleep bouts, these data support a role for longer naps in improving memory and provide a novel role for lipid-binding proteins in regulating memory consolidation concurrently with changes in behavioral state.

  10. [L-type fatty acid binding protein (L-FABP) and kidney disease].

    Science.gov (United States)

    Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Kimura, Kenjiro

    2014-02-01

    Liver-type fatty acid binding protein (L-FABP) is expressed in the cytoplasm of human renal proximal tubules. Renal L-FABP expression is up-regulated and urinary excretion of renal L-FABP is increased by various stressors, such as urinary protein, hyperglycemia, tubular ischemia, toxins, and salt-sensitive hypertension, which lead to the progression of kidney disease. Urinary L-FABP levels accurately reflect the degree of tubulointerstitial damage and are strongly correlated with the prognosis of chronic kidney disease (CKD) patients in clinical studies. In patients with type I or type II diabetes, urinary L-FABP levels were reported to be significantly higher in patients with normal levels of urinary albumin than in those with microalbuminuria. Urinary L-FABP may be useful for the early detection of diabetic nephropathy. Furthermore, in a longitudinal study, a higher level of urinary L-FABP was found to be a risk factor for the progression of diabetic nephropathy. With respect to acute kidney disease (AKI), urinary L-FABP facilitates the early detection of AKI before an increase in serum creatinine. Therefore, urinary L-FABP was approved as a new tubular biomarker by the Ministry of Health, Labour and Welfare of Japan.

  11. Identification of a fatty acid binding protein4-UCP2 axis regulating microglial mediated neuroinflammation.

    Science.gov (United States)

    Duffy, Cayla M; Xu, Hongliang; Nixon, Joshua P; Bernlohr, David A; Butterick, Tammy A

    2017-02-16

    Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism. Despite the widespread appreciation for the role of FABP4 in mediating peripheral inflammation, the expression of FABP4 and a potential FABP4-UCP2 axis regulating microglial inflammatory capacity is largely uncharacterized. To that end, we hypothesized that microglial cells express FABP4 and that inhibition would upregulate UCP2 and attenuate palmitic acid (PA)-induced pro-inflammatory response. Gene expression confirmed expression of FABP4 in brain tissue lysate from C57Bl/6J mice and BV2 microglia. Treatment of microglial cells with an FABP inhibitor (HTS01037) increased expression of Ucp2 and arginase in the presence or absence of PA. Moreover, cells exposed to HTS01037 exhibited attenuated expression of inducible nitric oxide synthase (iNOS) compared to PA alone indicating reduced NFκB signaling. Hypothalamic tissue from mice lacking FABP4 exhibit increased UCP2 expression and reduced iNOS, tumor necrosis factor-alpha (TNF-α), and ionized calcium-binding adapter molecule 1 (Iba1; microglial activation marker) expression compared to wild type mice. Further, this effect is negated in microglia lacking UCP2, indicating the FABP4-UCP2 axis is pivotal in obesity induced neuroinflammation. To our knowledge, this is the first report demonstrating a FABP4-UCP2 axis with the potential to modulate the microglial inflammatory response.

  12. Examination of the Addictive and Behavioral Properties of Fatty Acid Binding Protein Inhibitor SBFI26

    Directory of Open Access Journals (Sweden)

    Panayotis eThanos

    2016-04-01

    Full Text Available Abstract:The therapeutic properties of cannabinoids have been well demonstrated but are overshadowed by such adverse effects as cognitive and motor dysfunction, as well as their potential for addiction. Recent research on the natural lipid ligands of cannabinoid receptors, also known as endocannabinoids, have shed light on the mechanisms of intracellular transport of the endocannabinoid anandamide by fatty acid binding proteins (FABPs and subsequent catabolism by fatty acid amide hydrolase (FAAH. These findings facilitated the recent development of SBFI26, a pharmacological inhibitor of epidermal- and brain-specific FABP5 and FABP7, which effectively increases anandamide signaling. The goal of this study was to examine this compound for any possible rewarding and addictive properties as well as effects on locomotor activity, working / recognition memory, and propensity for sociability and preference for social novelty given its recently reported anti-inflammatory and analgesic properties. Male C57BL mice were split into four treatment groups and conditioned with 5.0 mg/kg, 20.0 mg/kg, 40.0 mg/kg SBFI26 or vehicle during a conditioned placed preference (CPP paradigm. Following CPP, mice underwent a battery of behavioral tests (open field, novel object recognition (NOR, and social interaction (SI and novelty (SN paired with acute SBFI26 administration. Results showed that SBFI26 did not produce conditioned placed preference or conditioned place aversion regardless of dose, and did not induce any differences in locomotor and exploratory activity during CPP or SBFI26-paired open field activity. We also observed no differences between treatment groups in NOR, SI, and SN. In conclusion, as SBFI26 was shown previously by our group to have significant analgesic and anti-inflammatory properties, here we show that it does not pose a risk of dependence or motor and cognitive impairment under the conditions tested.

  13. Heart-type fatty-acid-binding protein (FABP3 is a lysophosphatidic acid-binding protein in human coronary artery endothelial cells

    Directory of Open Access Journals (Sweden)

    Ryoko Tsukahara

    2014-01-01

    Full Text Available Fatty-acid-binding protein 3, muscle and heart (FABP3, also known as heart-type FABP, is a member of the family of intracellular lipid-binding proteins. It is a small cytoplasmic protein with a molecular mass of about 15 kDa. FABPs are known to be carrier proteins for transporting fatty acids and other lipophilic substances from the cytoplasm to the nucleus, where these lipids are released to a group of nuclear receptors such as peroxisome proliferator-activated receptors (PPARs. In this study, using lysophosphatidic acid (LPA-coated agarose beads, we have identified FABP3 as an LPA carrier protein in human coronary artery endothelial cells (HCAECs. Administration of LPA to HCAECs resulted in a dose-dependent increase in PPARγ activation. Furthermore, the LPA-induced PPARγ activation was abolished when the FABP3 expression was reduced using small interfering RNA (siRNA. We further show that the nuclear fraction of control HCAECs contained a significant amount of exogenously added LPA, whereas FABP3 siRNA-transfected HCAECs had a decreased level of LPA in the nucleus. Taken together, these results suggest that FABP3 governs the transcriptional activities of LPA by targeting them to cognate PPARγ in the nucleus.

  14. Single nucleotide polymorphism analysis on chicken extra-celluar fatty acid binding protein gene and its associations with fattiness trait

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Fattiness is an important parameter to estimate meat quality, which has high heritability. In this experiment, F2 chickens derived from Broilers crossing to Silky were used to study the effect of extracellular fatty acid binding protein (EX-FABP) gene on abdominal fat accumulation. 1.6 kb of the 5′ region of the gene was amplified by six pairs of primers, and then single nucleotide poly-morphisms (SNPs) were detected by the technique of single strand conformation polymorphism (SSCP) and then confirmed by sequencing. There were four nucleotides variations found, A-G at -1807, C-A at -1805, T-C at -1011 and a C insertion at -1000 respectively. The result of least square analysis suggests that the birds with BB genotype defined by the second pair of primer have a higher abdominal fat weight and abdominal fat percentage than the birds with the other genotypes (AA and AB). It implied that EX-FABP gene could be a candidate locus or linked to a major gene to significantly affect abdominal fat traits in chicken.

  15. Plasma Free Fatty Acids, Fatty Acid-binding Protein 4, and Mortality in Older Adults (From the Cardiovascular Health Study)

    Science.gov (United States)

    Miedema, Michael D.; Maziarz, Marlena; Biggs, Mary L.; Zieman, Susan J.; Kizer, Jorge R.; Ix, Joachim H.; Mozaffarian, Dariush; Tracy, Russell P.; Psaty, Bruce M.; Siscovick, David S.; Mukamal, Kenneth J.; Djousse, Luc

    2014-01-01

    Plasma free fatty acids (FFA) are largely derived from adipose tissue. Elevated levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic chaperone of fatty acids, have been associated with adverse cardiovascular outcomes but limited data are available on the relation of these biomarkers with cardiovascular and total mortality. We studied 4,707 participants with a mean age of 75 years who had plasma FFA and FABP4 measured in 1992–1993 as part of the Cardiovascular Health Study, an observational cohort of community dwelling older adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox proportional hazard regression was used to determine the association between FFA, FABP4, and mortality. In fully adjusted models, FFA were associated with dose-dependent significantly higher total mortality (hazard ratio (HR) per standard deviation (SD): 1.14, 95% confidence interval (CI) 1.09–1.18), but FABP4 levels were not (HR 1.04, 95% CI 0.98–1.09). In a cause-specific mortality analysis, higher concentrations of FFA were associated with significantly higher risk of death due to cardiovascular disease, dementia, infection, and respiratory causes, but not cancer or trauma. We did not find evidence of an interaction between FFA and FABP4 (p=0.45), but FABP4 appeared to be associated with total mortality differentially among men and women (HR 1.17 (1.08–1.26) for men, HR 1.02 (0.96–1.07) for women, interaction p-value <0.001). In conclusion, in a cohort of community-dwelling older individuals, elevated plasma concentrations of FFA, but not FABP4, were associated with cardiovascular and non-cardiovascular mortality. PMID:25073566

  16. Intestinal fatty acid-binding protein and gut permeability responses to exercise.

    Science.gov (United States)

    March, Daniel S; Marchbank, Tania; Playford, Raymond J; Jones, Arwel W; Thatcher, Rhys; Davison, Glen

    2017-05-01

    Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Two-way repeated measures ANOVA revealed an arm × time interaction for L/R and I-FABP (P exercise in Plac (273% of pre, P exercise values significantly lower with Col (P exercise in Plac (191% of pre-exercise, P = 0.002) but not in the Col arm (107%, P = 0.862) with post-exercise values significantly lower with Col (P = 0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P = 0.044) but not visit two (P = 0.200) although overall plots/patterns do appear similar for each. These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute.

  17. Heart fatty acid binding protein and myoglobin after reperfusion of acute myocardial infarction.

    Science.gov (United States)

    Ozdemir, Murat; Durakoğlugil, Emre; Gülbahar, Ozlem; Turkoglu, Sedat; Sancak, Banu; Paşaoğlu, Hatice; Cengel, Atiye

    2007-10-01

    The aim of this study was to disclose the release kinetics of heart fatty acid binding protein (HFABP) and myoglobin in acute myocardial infarction (AMI) reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influence of the quality of coronary flow post PPCI on the release properties of these markers. Twenty-four patients with AMI who underwent successful PPCI and had no evidence of reocclusion within the first 120 minutes were studied. Serum myoglobin and HFABP levels at baseline and at 15, 30, 45, 60, 90 and 120 minutes after reperfusion were measured. Corrected TIMI frame count (CTFC) in the relevant vessel post PPCI was used to categorize patients in group I (CTFC > 21) and group 2 (CTFC < or = 21). Biomarker ratios at each sampling point were calculated by dividing the serum level of the biomarker at the specific sampling time by its baseline level. Baseline myoglobin and HFABP levels rose significantly at 15 minutes (153 +/- 251.5 microg/L vs. 904.3 +/- 542.6 microg/L, 10.9 +/- 8 microg/L vs. 17.8 +/- 9.1 microg/L, both P < 0.0001) after successful PPCI. Group 2 patients tended to have higher biomarker ratios at each time point as compared to group I. Successful PPCI for AMI results in a significant increase of both HFABP and myoglobin levels within 15 minutes of vessel opening and the quality of flow in the infarction-related artery post PCI as evaluated by CTFC does not influence the release kinetics of these biomarkers.

  18. Serum Heart-Type Fatty Acid-Binding Protein Levels in Patients with Overt Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Esra Tutal

    2017-03-01

    Full Text Available Purpose: Overt hypothyroidism affects mostly women with an increasing prevalence with age. Hypothyroidism is associated with accelerated atherosclerotic cardiovascular diseases possibly caused by the higher incidence of hyperlipidemia, insulin resistance, and hypertension. Heart-type fatty acid-binding protein (H-FABP is specific for cardiomyocytes and a sensitive marker of myocardial injury. The purpose of this study was examining the effect of hypothyroidism on H-FABP levels and carotid artery intima-media thickness (CIMT. Material and Method: We measured serum H-FABP levels in 33 patients with overt hypothyroidism and age, gender, and body mass index-matched 39 control subjects. The patients were newly diagnosed with Hashimoto’s thyroiditis. All participants underwent high-resolution B-mode ultrasonography for the measurement of CIMT. Results: There was no significant difference in serum levels of H-FABP between the patient group and controls (1515.87±2143.0 pg/mL vs. 953.0±416.0 pg/mL, respectively; p=0.15. CIMT level was significantly higher in the patient group than in the control group (0.53±0.08 mm vs. 0.48±0.05 mm; p=0.02. However, the homeostasis model assessment of insulin resistance and fasting insulin levels did not differ between the two groups. Discussion: Based on the results of this study, we assume that H-FABP is not a useful marker in detecting preclinical atherosclerosis in patients with overt hypothyroidism associated with Hashimoto’s thyroiditis, however, CIMT might be a useful marker in detecting early atherosclerosis.

  19. Light microscopic immunocytochemical localization of hepatic and intestinal types of fatty acid-binding proteins in rat small intestine.

    Science.gov (United States)

    Shields, H M; Bates, M L; Bass, N M; Best, C J; Alpers, D H; Ockner, R K

    1986-05-01

    Monospecific antisera to purified hepatic fatty acid-binding protein (hFABP) and gut fatty acid-binding protein (gFABP) have been used to localize these two proteins in the small intestine of fed rats at the light microscopic level. Pieces of duodenum, jejunum, and ileum were removed from 4-, 10-, 20-, 22-, and 60-day-old Sprague-Dawley rats. Both cryostat and paraffin sections were studied for the presence of hFABP or gFABP by the avidin-biotin immunoperoxidase method. Slides were graded blind for the intensity of staining. Despite the structural and immunological differences between these two proteins, we showed no major differences between their staining patterns or their staining intensity throughout the intestine during postnatal development. The staining for both fatty acid-binding proteins was cytoplasmic. No brush border staining was found. Staining was more intense in the proximal rather than distal intestine, in the villus rather than crypt cells, and in the apex rather than the base of intestinal cells. Shifts in staining patterns, and staining intensity occurring during development may be related to variations in dietary fat intake, rates of cell proliferation, intestinal anatomy, and mechanisms for fat absorption.

  20. Sex Differences in Long Chain Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

    Science.gov (United States)

    Ockner, Robert K.; Burnett, David A.; Lysenko, Nina; Manning, Joan A.

    1979-01-01

    Female sex and estrogen administration are associated with increased hepatic production of triglyceride-rich lipoproteins; the basis for this has not been fully elucidated. Inasmuch as hepatic lipoprotein production is also influenced by FFA availability and triglyceride biosynthesis, we investigated sex differences in FFA utilization in rat hepatocyte suspensions and in the components of the triglyceride biosynthetic pathway. Isolated adult rat hepatocyte suspensions were incubated with albumin-bound [14C]oleate for up to 15 min. At physiological and low oleate concentrations, cells from females incorporated significantly more 14C into glycerolipids, especially triglycerides, and into oxidation products than did male cells, per milligram cell protein. At 0.44 mM oleate, incorporation into triglycerides in female cells was approximately twice that in male cells. Comparable sex differences were observed in cells from fasted animals and when [14C]-glycerol incorporation was measured. At higher oleate concentrations, i.e., fatty acid:albumin mole ratios in excess of 2:1, these sex differences were no longer demonstrable, suggesting that maximal rates of fatty acid esterification and oxidation were similar in female and male cells. In female and male hepatic microsomes, specific activities of long chain acyl coenzyme A synthetase, phosphatidate phosphohydrolase, and diglyceride acyltransferase were similar, but glycerol-3-phosphate acyltransferase activity was slightly greater in females at certain substrate concentrations. Microsomal incorporation of [14C]oleate into total glycerolipids was not significantly greater in females. In further contrast to intact cells, microsomal incorporation of [14C]oleate into triglycerides, although significantly greater in female microsomes, accounted for only a small fraction of the fatty acid esterified. The binding affinity and stoichiometry of partially purified female hepatic fatty acid binding protein (FABP) were similar to

  1. Liver fatty acid binding protein (L-Fabp) modifies intestinal fatty acid composition and adenoma formation in ApcMin/+ mice

    OpenAIRE

    Dharmarajan, Sekhar; Newberry, Elizabeth P.; Montenegro, Grace; Nalbantoglu, ILKe; Davis, Victoria R.; Clanahan, Michael J.; Blanc, Valerie; Xie, Yan; Luo, Jianyang; Fleshman, James W.; Kennedy, Susan; Davidson, Nicholas O.

    2013-01-01

    Evidence suggests a relationship between dietary fat intake, obesity and colorectal cancer, implying a role for fatty acid (FA) metabolism in intestinal tumorigenesis that is incompletely understood. Liver fatty acid binding protein (L-Fabp), a dominant intestinal FA binding protein, regulates intestinal FA trafficking and metabolism and L-Fabp deletion attenuates diet-induced obesity. Here we examined whether changes in intestinal FA metabolism following L-Fabp deletion modify adenoma develo...

  2. Fatty acid binding protein 7 and n-3 poly unsaturated fatty acid supply in early rat brain development.

    Science.gov (United States)

    Maximin, Elise; Langelier, Bénédicte; Aïoun, Josiane; Al-Gubory, Kaïs H; Bordat, Christian; Lavialle, Monique; Heberden, Christine

    2016-03-01

    Fatty acid binding protein 7 (FABP7), abundant in the embryonic brain, binds with the highest affinity to docosahexaenoic acid (DHA) and is expressed in the early stages of embryogenesis. Here, we have examined the consequences of the exposure to different DHA levels and of the in utero depletion of FABP7 on early rat brain development. Neurodevelopment was evaluated through the contents of two proteins, connexin 43 (Cx43) and cyclin-dependent kinase 5 (CDK5), both involved in neuroblast proliferation, differentiation, and migration. The dams were fed with diets presenting different DHA contents, from deficiency to supplementation. DHA brain embryos contents already differed at embryonic day 11.5 and the differences kept increasing with time. Cx43 and CDK5 contents were positively associated with the brain DHA levels. When FABP7 was depleted in vivo by injections of siRNA in the telencephalon, the enhancement of the contents of both proteins was lost in supplemented animals, but FABP7 depletion did not modify phospholipid compositions regardless of the diets. Thus, FABP7 is a necessary mediator of the effect of DHA on these proteins synthesis, but its role in DHA uptake is not critical, although FABP7 is localized in phospholipid-rich areas. Our study shows that high contents of DHA associated with FABP7 are necessary to promote early brain development, which prompted us to recommend DHA supplementation early in pregnancy.

  3. Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.

    Directory of Open Access Journals (Sweden)

    Yusuke Okazaki

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP, in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226 were enrolled. Urinary FABP4 (U-FABP4 and urinary albumin-to-creatinine ratio (UACR were measured. Change in estimated glomerular filtration rate (eGFR was followed up one year later.In 93 (23.7% of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4, triglycerides, hemoglobin A1c (HbA1c, urinary FABP1 (U-FABP1 and UACR (r = 0.360, p<0.001. Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

  4. Development of a radioiodinated triazolopyrimidine probe for nuclear medical imaging of fatty acid binding protein 4.

    Directory of Open Access Journals (Sweden)

    Kantaro Nishigori

    Full Text Available Fatty acid binding protein 4 (FABP4 is the most well-characterized FABP isoform. FABP4 regulates inflammatory pathways in adipocytes and macrophages and is involved in both inflammatory diseases and tumor formation. FABP4 expression was recently reported for glioblastoma, where it may participate in disease malignancy. While FABP4 is a potential molecular imaging target, with the exception of a tritium labeled probe there are no reports of other nuclear imaging probes that target this protein. Here we designed and synthesized a nuclear imaging probe, [123I]TAP1, and evaluated its potential as a FABP4 targeting probe in in vitro and in vivo assays. We focused on the unique structure of a triazolopyrimidine scaffold that lacks a carboxylic acid to design the TAP1 probe that can undergo facilitated delivery across cell membranes. The affinity of synthesized TAP1 was measured using FABP4 and 8-anilino-1-naphthalene sulfonic acid. [125I]TAP1 was synthesized by iododestannylation of a precursor, followed by affinity and selectivity measurements using immobilized FABPs. Biodistributions in normal and C6 glioblastoma-bearing mice were evaluated, and excised tumors were subjected to autoradiography and immunohistochemistry. TAP1 and [125I]TAP1 showed high affinity for FABP4 (Ki = 44.5±9.8 nM, Kd = 69.1±12.3 nM. The FABP4 binding affinity of [125I]TAP1 was 11.5- and 35.5-fold higher than for FABP3 and FABP5, respectively. In an in vivo study [125I]TAP1 displayed high stability against deiodination and degradation, and moderate radioactivity accumulation in C6 tumors (1.37±0.24% dose/g 3 hr after injection. The radioactivity distribution profile in tumors partially corresponded to the FABP4 positive area and was also affected by perfusion. The results indicate that [125I]TAP1 could detect FABP4 in vitro and partly in vivo. As such, [125I]TAP1 is a promising lead compound for further refinement for use in in vivo FABP4 imaging.

  5. Compartmentation of hepatic fatty-acid-binding protein in liver cells and its effect on microsomal phosphatidic acid biosynthesis.

    Science.gov (United States)

    Bordewick, U; Heese, M; Börchers, T; Robenek, H; Spener, F

    1989-03-01

    Fatty-acid-binding proteins are known to occur in the cytosol of mammalian cells and to bind fatty acids and their CoA-esters. Application of the postembedding protein A-gold labeling method with antibody against the hepatic type fatty-acid-binding protein (hFABP) to cross-sections of liver cells and a newly developed gel-chromatographic immunofluorescence assay established qualitatively (1) that hFABP in mitochondria was confined to outer mitochondrial membranes, (2) the presence of this protein in microsomes and (3) that nuclei were also filled with hFABP. Quantitative data elaborated with a non-competitive ELISA confirmed these results. A significant difference to the distribution of cardiac FABP in heart muscle cells, where this type of protein was found in cytosol, matrix and nuclei, was observed (Börchers et al. (1989) Biochim. Biophys. Acta, in the press). hFABP-containing rat liver microsomes were incubated with long-chain acyl-CoAs in the presence of hFABP (isolated from rat liver cytosol) in a study on the acylation of sn-glycerol-3-phosphate and lysophosphatidic acid. Both acyltransferases were stimulated by addition of hFABP to the incubation medium. The morphological, immunochemical as well as kinetic data infer a direct interaction of hFABP with microsomal membranes in liver cells.

  6. Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma

    OpenAIRE

    Ku, Chung-Yu; Liu, Yu-Huei; Lin, Hsuan-Yuan; Lu, Shao-Chun; Lin, Jung-Yaw

    2016-01-01

    Liver fatty acid-binding protein (L-FABP) is abundant in hepatocytes and known to be involved in lipid metabolism. Overexpression of L-FABP has been reported in various cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated L-FABP and its association with vascular endothelial growth factors (VEGFs) in 90 HCC patients. We found that L-FABP was highly expressed in their HCC tissues, and that this expression was positively correlated with tha...

  7. Molecular characterization, tissue expression, and polymorphism analysis of liver-type fatty acid binding protein in Landes geese.

    Science.gov (United States)

    Song, Z; Shao, D; Sun, X X; Niu, J W; Gong, D Q

    2015-01-01

    Liver weight is an important economic trait in the fatty goose liver industry. Liver-type fatty acid binding protein (L-FABP) is involved in the formation and metabolism of fatty acids. Thus, we hypothesized that sequence polymorphisms in L-FABP were associated with fatty liver weight in goose. We first isolated, sequenced, and characterized the goose L-FABP gene, which had not been previously reported. The goose L-FABP gene was 2490 bp and included 4 exons coding for a 126-amino acid protein. Analysis of expression levels of the goose L-FABP gene in different tissues showed that the expression level in the liver tissue was higher than in other tissues, and was significantly higher in the liver tissue of overfed geese than in control geese. Moreover, a single nucleotide polymorphism located at 774 bp in the gene was identified in a Landes goose population. To test whether this single nucleotide polymorphism was associated with fatty liver production, liver weight and the ratio of liver to carcass weights were determined for the 3 genotypes with this single nucleotide polymorphism (TT, TG, GG) in overfed Landes geese. Our data indicate that individuals with the GG genotype had higher values for the variables measured than those with the other 2 genotypes, suggesting that L-FABP can be a selection marker for the trait of fatty liver production in goose.

  8. Heart-type fatty acid-binding protein is essential for efficient brown adipose tissue fatty acid oxidation and cold tolerance.

    Science.gov (United States)

    Vergnes, Laurent; Chin, Robert; Young, Stephen G; Reue, Karen

    2011-01-07

    Brown adipose tissue has a central role in thermogenesis to maintain body temperature through energy dissipation in small mammals and has recently been verified to function in adult humans as well. Here, we demonstrate that the heart-type fatty acid-binding protein, FABP3, is essential for cold tolerance and efficient fatty acid oxidation in mouse brown adipose tissue, despite the abundant expression of adipose-type fatty acid-binding protein, FABP4 (also known as aP2). Fabp3(-/-) mice exhibit extreme cold sensitivity despite induction of uncoupling and oxidative genes and hydrolysis of brown adipose tissue lipid stores. However, using FABP3 gain- and loss-of-function approaches in brown adipocytes, we detected a correlation between FABP3 levels and the utilization of exogenous fatty acids. Thus, Fabp3(-/-) brown adipocytes fail to oxidize exogenously supplied fatty acids, whereas enhanced Fabp3 expression promotes more efficient oxidation. These results suggest that FABP3 levels are a determinant of fatty acid oxidation efficiency by brown adipose tissue and that FABP3 represents a potential target for modulation of energy dissipation.

  9. Liver fatty acid-binding protein (L-Fabp) modifies intestinal fatty acid composition and adenoma formation in ApcMin/+ mice.

    Science.gov (United States)

    Dharmarajan, Sekhar; Newberry, Elizabeth P; Montenegro, Grace; Nalbantoglu, Ilke; Davis, Victoria R; Clanahan, Michael J; Blanc, Valerie; Xie, Yan; Luo, Jianyang; Fleshman, James W; Kennedy, Susan; Davidson, Nicholas O

    2013-10-01

    Evidence suggests a relationship between dietary fat intake, obesity, and colorectal cancer, implying a role for fatty acid metabolism in intestinal tumorigenesis that is incompletely understood. Liver fatty acid-binding protein (L-Fabp), a dominant intestinal fatty acid-binding protein, regulates intestinal fatty acid trafficking and metabolism, and L-Fabp deletion attenuates diet-induced obesity. Here, we examined whether changes in intestinal fatty acid metabolism following L-Fabp deletion modify adenoma development in Apc(Min)(/+) mice. Compound L-Fabp(-/-)Apc(Min)(/+) mice were generated and fed a 10% fat diet balanced equally between saturated, monounsaturated, and polyunsaturated fat. L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in adenoma number and total polyp area compared with Apc(Min)(/+)controls, reflecting a significant shift in distribution toward smaller polyps. Adenomas from L-Fabp(-/-)Apc(Min)(/+) mice exhibited reductions in cellular proliferation, high-grade dysplasia, and nuclear β-catenin translocation. Intestinal fatty acid content was increased in L-Fabp(-/-)Apc(Min)(/+) mice, and lipidomic profiling of intestinal mucosa revealed significant shifts to polyunsaturated fatty acid species with reduced saturated fatty acid species. L-Fabp(-/-)Apc(Min)(/+) mice also showed corresponding changes in mRNA expression of enzymes involved in fatty acid elongation and desaturation. Furthermore, adenomas from L-Fabp(-/-)Apc(Min)(/+) mice displayed significant reductions in mRNA abundance of nuclear hormone receptors involved in cellular proliferation and in enzymes involved in lipogenesis. These findings collectively implicate L-Fabp as an important genetic modifier of intestinal tumorigenesis, and identify fatty acid trafficking and metabolic compartmentalization as an important pathway linking dietary fat intake, obesity, and intestinal tumor formation.

  10. Fatty Acid-binding Proteins Interact with Comparative Gene Identification-58 Linking Lipolysis with Lipid Ligand Shuttling.

    Science.gov (United States)

    Hofer, Peter; Boeszoermenyi, Andras; Jaeger, Doris; Feiler, Ursula; Arthanari, Haribabu; Mayer, Nicole; Zehender, Fabian; Rechberger, Gerald; Oberer, Monika; Zimmermann, Robert; Lass, Achim; Haemmerle, Guenter; Breinbauer, Rolf; Zechner, Rudolf; Preiss-Landl, Karina

    2015-07-24

    The coordinated breakdown of intracellular triglyceride (TG) stores requires the exquisitely regulated interaction of lipolytic enzymes with regulatory, accessory, and scaffolding proteins. Together they form a dynamic multiprotein network designated as the "lipolysome." Adipose triglyceride lipase (Atgl) catalyzes the initiating step of TG hydrolysis and requires comparative gene identification-58 (Cgi-58) as a potent activator of enzyme activity. Here, we identify adipocyte-type fatty acid-binding protein (A-Fabp) and other members of the fatty acid-binding protein (Fabp) family as interaction partners of Cgi-58. Co-immunoprecipitation, microscale thermophoresis, and solid phase assays proved direct protein/protein interaction between A-Fabp and Cgi-58. Using nuclear magnetic resonance titration experiments and site-directed mutagenesis, we located a potential contact region on A-Fabp. In functional terms, A-Fabp stimulates Atgl-catalyzed TG hydrolysis in a Cgi-58-dependent manner. Additionally, transcriptional transactivation assays with a luciferase reporter system revealed that Fabps enhance the ability of Atgl/Cgi-58-mediated lipolysis to induce the activity of peroxisome proliferator-activated receptors. Our studies identify Fabps as crucial structural and functional components of the lipolysome.

  11. Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine.

    Science.gov (United States)

    Gajda, Angela M; Storch, Judith

    2015-02-01

    Fatty acid-binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both liver- (LFABP; FABP1) and intestinal FABPs (IFABP; FABP2) are expressed. These proteins display high-affinity binding for long-chain fatty acids (FA) and other hydrophobic ligands; thus, they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand-binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have different functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte.

  12. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake.

    OpenAIRE

    1995-01-01

    To explore the relationship between mitochondrial aspartate aminotransferase (mAspAT; EC 2.6.1.1) and plasma membrane fatty acid-binding protein (FABPpm) and their role in cellular fatty acid uptake, 3T3 fibroblasts were cotransfected with plasmid pMAAT2, containing a full-length mAspAT cDNA downstream of a Zn(2+)-inducible metallothionein promoter, and pFR400, which conveys methotrexate resistance. Transfectants were selected in methotrexate, cloned, and exposed to increasing methotrexate co...

  13. Direct interaction between EgFABP1, a fatty acid binding protein from Echinococcus granulosus, and phospholipid membranes.

    Directory of Open Access Journals (Sweden)

    Jorge L Porfido

    Full Text Available BACKGROUND: Growth and maintenance of hydatid cysts produced by Echinococcus granulosus have a high requirement for host lipids for biosynthetic processes, membrane building and possibly cellular and developmental signalling. This requires a high degree of lipid trafficking facilitated by lipid transporter proteins. Members of the fatty acid binding protein (FABP family have been identified in Echinococcus granulosus, one of which, EgFABP1 is expressed at the tegumental level in the protoscoleces, but it has also been described in both hydatid cyst fluid and secretions of protoscoleces. In spite of a considerable amount of structural and biophysical information on the FABPs in general, their specific functions remain mysterious. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the way in which EgFABP1 may interact with membranes using a variety of fluorescence-based techniques and artificial small unilamellar vesicles. We first found that bacterial recombinant EgFABP1 is loaded with fatty acids from the synthesising bacteria, and that fatty acid binding increases its resistance to proteinases, possibly due to subtle conformational changes induced on EgFABP1. By manipulating the composition of lipid vesicles and the ionic environment, we found that EgFABP1 interacts with membranes in a direct contact, collisional, manner to exchange ligand, involving both ionic and hydrophobic interactions. Moreover, we observed that the protein can compete with cytochrome c for association with the surface of small unilamellar vesicles (SUVs. CONCLUSIONS/SIGNIFICANCE: This work constitutes a first approach to the understanding of protein-membrane interactions of EgFABP1. The results suggest that this protein may be actively involved in the exchange and transport of fatty acids between different membranes and cellular compartments within the parasite.

  14. Association of polymorphisms in adipocyte fatty acid binding protein gene with fat-related traits in chicken

    Institute of Scientific and Technical Information of China (English)

    Manhong YE; Jie WEN; Honghe CAO; Hongbin LI; Jilan CHEN; Guiping ZHAO; Maiqing ZHENG

    2008-01-01

    PCR-SSCP analysis was used to detect poly-morphic sites in chicken adipocyte fatty acid binding pro-tein (A-FABP) gene. Six Chinese local breeds, Beijing-You chicken, Dwarf chicken, Taihe silky chicken, Chong-renma chicken, Xiayan chicken, Luyuan chicken and an introduced foreign breed, Arbor Acre broiler, were used as test populations. Three PCR-SSCP loci were detected. Statistical results showed that frequencies of genotypes and alleles were significantly different in the test popula-tions. Sequence analysis revealed that C → T, G → A, and C → T transitions were responsible for the polymorph-isms. Some fat-related traits such as body weight, content of intramuscular fat (IMF) and percentage of abdominal fat (AFP) were measured in Dwarf chickens and male Beijing-You chickens. We found out that chicken quality was significantly related to different genotypes in these two populations.

  15. Structural and functional interaction of fatty acids with human liver fatty acid-binding protein (L-FABP) T94A variant.

    Science.gov (United States)

    Huang, Huan; McIntosh, Avery L; Martin, Gregory G; Landrock, Kerstin K; Landrock, Danilo; Gupta, Shipra; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2014-05-01

    The human liver fatty acid-binding protein (L-FABP) T94A variant, the most common in the FABP family, has been associated with elevated liver triglyceride levels. How this amino acid substitution elicits these effects is not known. This issue was addressed using human recombinant wild-type (WT) and T94A variant L-FABP proteins as well as cultured primary human hepatocytes expressing the respective proteins (genotyped as TT, TC and CC). The T94A substitution did not alter or only slightly altered L-FABP binding affinities for saturated, monounsaturated or polyunsaturated long chain fatty acids, nor did it change the affinity for intermediates of triglyceride synthesis. Nevertheless, the T94A substitution markedly altered the secondary structural response of L-FABP induced by binding long chain fatty acids or intermediates of triglyceride synthesis. Finally, the T94A substitution markedly decreased the levels of induction of peroxisome proliferator-activated receptor α-regulated proteins such as L-FABP, fatty acid transport protein 5 and peroxisome proliferator-activated receptor α itself meditated by the polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid in cultured primary human hepatocytes. Thus, although the T94A substitution did not alter the affinity of human L-FABP for long chain fatty acids, it significantly altered human L-FABP structure and stability, as well as the conformational and functional response to these ligands.

  16. Molecular characterization, functional expression, tissue localization and protective potential of a Taenia solium fatty acid-binding protein.

    Science.gov (United States)

    Illescas, Oscar; Carrero, Julio C; Bobes, Raúl J; Flisser, Ana; Rosas, Gabriela; Laclette, Juan P

    2012-12-01

    The fatty acid-binding proteins (FABPs) comprise a family of proteins that are widely expressed in animal cells and perform a variety of vital functions. Here, we report the identification, characterization, recombinant expression, tissue localization and protective potential of a Taenia solium FABP (TsFABP1). The TsFABP1 primary structure showed all the conserved residues characteristic of the subfamily iv of the intracellular Lipid-Binding Proteins (iLBPs), including those involved in the binding stabilization of the fatty acid molecule. Through a competitive binding assay we found that TsFABP1 is able to bind at least six different fatty acids with preference toward palmitic and stearic acid, suggesting that TsFABP1 is a member of the iLBP subfamily iv. Immunolocalization assays carried out on larval and adult tissues of four species of taeniids using anti-TsFABP1 hyperimmune sera produced in mice and rabbit, showed intense labeling in the tegument of the spiral canal and in subtegumental cytons of the larvae. These findings suggest that the spiral canal might be a major place for FA uptake in the developing scolex. In contrast, only subtegumental cytons in the adult worms stained positive. We propose that TsFABP1 is involved in the mechanism to mobilize fatty acids between compartments in the extensive syncytial tissue of taeniids. Protection assays carried out in a murine model of cysticercosis showed that subcutaneous immunization with TsFABP1 resulted in about 45% reduction of parasite load against an intraperitoneal challenge with Taenia crassiceps cysts. This reduction in parasite load correlated with the level of cellular and humoral immune responses against TsFABP1, as determined in spleen lymphocyte proliferation and ELISA testing.

  17. Low abdominal NIRS values and elevated plasma intestinal fatty acid-binding protein in a premature piglet model of necrotizing enterocolitis

    Science.gov (United States)

    To identify early markers of necrotizing enterocolitis (NEC), we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS) measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP) measured every 6 hours can detect NEC...

  18. Low heart-type fatty acid binding protein level during aging may protect down syndrome people against atherosclerosis

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    Vianello Elena

    2013-01-01

    Full Text Available Abstract Background Aging is considered an important independent risk factor for atherosclerosis. Down syndrome people (DS display an accelerated aging process compared to healthy subjects, anyway they are relatively resistant to developing atherosclerosis. The mechanisms involved in such protective effect are not well known. Since heart-type fatty acid binding protein (H-FABP is a protein involved in the transport of fatty acids and it has been recently correlated with the presence of atherosclerosis, we aimed to measure H-FABP level both in DS and in healthy subjects during aging to evaluate the association between this molecule, aging and atherosclerosis. Findings We quantified plasmatic H-FABP level in three groups of male DS and age-matched healthy subjects (children, age 2–14 years; adults, age 20–50 years; elderly, > 60 years using a biochip array analyzer. We observed that aging is associated with increased H-FABP level in healthy subjects but not in DS which display both the same protein level in the different ages of life and have also lower level compared to their age-matched healthy subjects. Conclusion Reduced H-FABP level during aging in DS may play a protective role against atherosclerosis. The potential involvement of H-FABP in the relationship between aging, atherosclerosis and development of coronary artery disease needs further investigations.

  19. High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells

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    Khanaki, Korosh; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Darabi, Masoud; Mehdizadeh, Amir; Shabani, Mahdi; Rahimipour, Ali; Nouri, Mohammad

    2014-01-01

    Background: Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases. Objective: Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells. Materials and Methods: Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique. Results: Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively). Conclusion: ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis. PMID:25709631

  20. Zinc-induced oligomerization of zinc α2 glycoprotein reveals multiple fatty acid-binding sites

    OpenAIRE

    Zahid, Henna; Miah, Layeque; Lau, Andy; Brochard, Lea; Hati, Debolina; Bui, T. T.; Drake, A. F.; Gor, Jayesh; Perkins, Stephen J.; McDermott, Lindsay C.

    2016-01-01

    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I MHC protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid 11-(dansylamino)undecanoic acid (DAUDA) in the groove between the α1 and α2 domains. The surface of ZAG has approximately 15 weak zinc-binding sites deemed responsible for precipitation from human plasma. In the present study the functional significance of these metal sites was investigate...

  1. Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events

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    Kamijo-Ikemori A

    2015-08-01

    Full Text Available Atsuko Kamijo-Ikemori,1,3 Nobuyuki Hashimoto,2 Takeshi Sugaya,1 Katsuomi Matsui,1 Mikako Hisamichi,1 Yugo Shibagaki,1 Fumihiko Miyake,2 Kenjiro Kimura1 1Department of Nephrology and Hypertension, 2Department of Cardiology, 3Department of Anatomy, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Contrast medium (CM induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP. Methods: Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29. Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. Results: Urinary L-FABP levels were significantly higher at 12 hours (P<0.05 and 24 hours (P<0.005 after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17, but not in those without cardiovascular events (n=12. The parameter with the largest area under the curve (0.816 for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 µg/g creatinine between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27–19.13; P=0.021. Conclusion: Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk

  2. Comparative study of the fatty acid binding process of a new FABP from Cherax quadricarinatus by fluorescence intensity, lifetime and anisotropy.

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    Jiayao Li

    Full Text Available Fatty acid-binding proteins (FABPs are small cytosolic proteins, largely distributed in invertebrates and vertebrates, which accomplish uptake and intracellular transport of hydrophobic ligands such as fatty acids. Although long chain fatty acids play multiple crucial roles in cellular functions (structural, energy metabolism, regulation of gene expression, the precise functions of FABPs, especially those of invertebrate species, remain elusive. Here, we have identified and characterized a novel FABP family member, Cq-FABP, from the hepatopancreas of red claw crayfish Cherax quadricarinatus. We report the characterization of fatty acid-binding affinity of Cq-FABP by four different competitive fluorescence-based assays. In the two first approaches, the fluorescent probe 8-Anilino-1-naphthalenesulfonate (ANS, a binder of internal cavities of protein, was used either by directly monitoring its fluorescence emission or by monitoring the fluorescence resonance energy transfer occurring between the single tryptophan residue of Cq-FABP and ANS. The third and the fourth approaches were based on the measurement of the fluorescence emission intensity of the naturally fluorescent cis-parinaric acid probe or the steady-state fluorescence anisotropy measurements of a fluorescently labeled fatty acid (BODIPY-C16, respectively. The four methodologies displayed consistent equilibrium constants for a given fatty acid but were not equivalent in terms of analysis. Indeed, the two first methods were complicated by the existence of non specific binding modes of ANS while BODIPY-C16 and cis-parinaric acid specifically targeted the fatty acid binding site. We found a relationship between the affinity and the length of the carbon chain, with the highest affinity obtained for the shortest fatty acid, suggesting that steric effects primarily influence the interaction of fatty acids in the binding cavity of Cq-FABP. Moreover, our results show that the binding affinities

  3. Lipid Transport through the Fetoplacental Barrier by the Fatty Acid-Binding Proteins in Pregnant Women with Herpes Virus Infection in the third Trimester

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    Michael T. Lucenko, PhD, ScD

    2012-12-01

    Full Text Available In this study, the transport of the long chain polyunsaturated fatty acids (LCPUFAs from the lacunar blood through the syncytiotrophoblast of the placental villi to the fetal cord blood via a saturable protein-mediated mechanism by the heart-type fatty acid-binding proteins (H-FABPs has been examined. Exacerbation of the herpes simplex viruses (HSV-1 in the third trimester of gestation reduces the delivery of the fatty acid-binding proteins to the syncytiotrophoblast. During exacerbation of the HSV-1 infection, the selective transfer of the LCPUFAs across the syncytiotrophoblast basal plasma membrane into the fetal cord blood was observed. The supply of anti-inflammatory ω-3 PUFAs was reduced; however, the inflow of inflammatory arachidonic acid and other ω-6 PUFAs into the fetal blood was increased.

  4. Structure of the human-heart fatty-acid-binding protein 3 in complex with the fluorescent probe 1-anilinonaphthalene-8-sulphonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Mika; Sugiyama, Shigeru, E-mail: sugiyama@chem.eng.osaka-u.ac.jp [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Ishida, Hanako; Niiyama, Mayumi [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Daisuke; Hara, Toshiaki [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Mizohata, Eiichi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Murakami, Satoshi [Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Kanagaw 226-8501 (Japan); Inoue, Tsuyoshi [Osaka University, 2-1 Yamadaoka, Suita 565-0871 (Japan); Matsuoka, Shigeru; Murata, Michio [Lipid Active Structure Project, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan); Osaka University, 1-1 Machikaneyama-cho, Toyonaka 560-0043 (Japan)

    2013-11-01

    The crystal structure of human-heart-type fatty-acid-binding protein in complex with anilinonaphthalene-8-sulfonate was solved at 2.15 Å resolution revealing the detailed binding mechanism of the fluorescent probe 1-anilinonaphthalene-8-sulfonate. Heart-type fatty-acid-binding protein (FABP3), which is a cytosolic protein abundantly found in cardiomyocytes, plays a role in trafficking fatty acids throughout cellular compartments by reversibly binding intracellular fatty acids with relatively high affinity. The fluorescent probe 1-anilinonaphthalene-8-sulfonate (ANS) is extensively utilized for examining the interaction of ligands with fatty-acid-binding proteins. The X-ray structure of FABP3 was determined in the presence of ANS and revealed the detailed ANS-binding mechanism. Furthermore, four water molecules were clearly identified in the binding cavity. Through these water molecules, the bound ANS molecule forms indirect hydrogen-bond interactions with FABP3. The adipocyte-type fatty-acid-binding protein (FABP4) exhibits 67% sequence identity with FABP3 and its crystal structure is almost the same as that of FABP3. However, FABP4 can bind with a higher affinity to ANS than FABP3. To understand the difference in their ligand specificities, a structural comparison was performed between FABP3–ANS and FABP4–ANS complexes. The result revealed that the orientation of ANS binding to FABP3 is completely opposite to that of ANS binding to FABP4, and the substitution of valine in FABP4 to leucine in FABP3 may result in greater steric hindrance between the side-chain of Leu115 and the aniline ring of ANS.

  5. Common FABP4 Genetic Variants and Plasma Levels of Fatty Acid Binding Protein 4 in Older Adults

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    Mukamal, Kenneth J.; Wilk, Jemma B.; Biggs, Mary L.; Jensen, Majken K.; Ix, Joachim H.; Kizer, Jorge R.; Tracy, Russell P.; Zieman, Susan J.; Mozaffarian, Dariush; Psaty, Bruce M.; Siscovick, David S.; Djoussé, Luc

    2013-01-01

    We examined common variants in the fatty acid binding protein 4 gene (FABP4) and plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409, rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190 European Americans and 660 African Americans. Among European Americans, the minor alleles of six single nucleotide polymorphisms (SNP) were associated with lower FABP4 levels (all p ≤ 0.01). Among African Americans, the SNP with the lowest minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C-A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in both European Americans (frequency = 16 %; p = 0.001) and African Americans (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron with one in the 3′untranslated region. However, the alleles associated with lower FABP4 levels were associated with higher fasting glucose in meta-analyses from the MAGIC consortium. These results demonstrate associations of common SNP and haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose levels. PMID:24043587

  6. Urinary l-type fatty acid-binding protein is a predictor of early renal function after partial nephrectomy.

    Science.gov (United States)

    Yanishi, Masaaki; Kinoshita, Hidefumi; Mishima, Takao; Taniguchi, Hisanori; Yoshida, Kenji; Komai, Yoshihiro; Yasuda, Kaneki; Watanabe, Masato; Sugi, Motohiko; Matsuda, Tadashi

    2017-11-01

    Urinary biomarkers of renal injury urinary may identify loss of renal function following nephron-sparing surgery (NSS). This study was designed to evaluate whether urinary l-type fatty acid-binding protein (l-FABP) is an early biomarker of loss of renal function after NSS. Specifically, the kinetics of urinary l-FABP level after NSS and its correlation with factors related to ischemic renal injury were analyzed. This study prospectively evaluated 18 patients who underwent NSS between July and December 2014, including 12 who underwent laparoscopic and six who underwent robot-assisted partial nephrectomy. Urinary l-FABP concentrations were measured preoperatively and 1, 2, 3, 6, 12, 24, 48, and 72 h after renal artery declamping. Loss of renal function loss was calculated by comparing the effective renal plasma flow, as determined by (99m)Tc-mercaptoacetyltriglycine (MAG3) clearance, on the operated and normal sides. The decrease in estimated glomerular filtration rate from before surgery to six months after surgery was also measured. Urinary l-FABP concentration peaked within 2 h of declamping, which may quantify nephron damage caused by ischemia. The decrease in MAG3 reduction ratio correlated with both the ischemia time and peak urinary l-FABP concentration. Peak urinary l-FABP concentration showed a significant correlation with MAG3 reduction ratio. l-FABP is a suitable urinary biomarker for predicting the extent of ischemic renal injury.

  7. Cloning and characterization of the fatty acid-binding protein gene from the protoscolex of Taenia multiceps.

    Science.gov (United States)

    Nie, Hua-Ming; Xie, Yue; Fu, Yan; Yang, Ying-Dong; Gu, Xiao-Bin; Wang, Shu-Xian; Peng, Xi; Lai, Wei-Ming; Peng, Xue-Rong; Yang, Guang-You

    2013-05-01

    Taenia multiceps (Cestoda: Taeniidae), a worldwide cestode parasite, is emerging as an important helminthic zoonosis due to serious or fatal central nervous system disease commonly known as coenurosis in domestic and wild ruminants including humans. Herein, a fatty acid-binding protein (FABP) gene was identified from transcriptomic data in T. multiceps. This gene, which contains a complete coding sequence, was amplified by reverse-transcriptase polymerase chain reaction. The corresponding protein, which was named TmFABP, had a molecular weight of 14 kDa, and subsequently was recombinantly expressed in Escherichia coli. The fusion protein was purified on Ni-NTA beads (Bio-Rad). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses showed that the purified recombinant protein caused immunogenicity. Immunohistochemical studies showed that TmFABP was expressed at the tegumental level in the protoscolices and in the cells between the body wall and parenchyma layer of the cestode. In sections from gravid proglottids, intense staining was detected in the uterus and eggs. Based on this, TmFABP could be switched on during differentiation of germinative layers to protoscoleces and from metacestodes to adult worms. Taken together, our results already reported for T. multiceps suggest the possibility of TmFABP developing a vaccine to control and prevent coenurosis.

  8. High Serum Adipocyte Fatty Acid Binding Protein Is Associated with Metabolic Syndrome in Patients with Type 2 Diabetes

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    Jer-Chuan Li

    2016-01-01

    Full Text Available Adipocyte fatty acid binding protein (A-FABP is a key mediator of obesity-related metabolic syndrome (MetS. The aim of this study was to evaluate the relationship between A-FABP concentration and MetS in type 2 diabetes mellitus (DM patients. Fasting blood samples were obtained from 165 type 2 DM volunteers. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Among 165 DM patients, 113 patients (68.5% had MetS. Diabetic persons who had MetS had significantly higher A-FABP levels (P<0.001 than those without MetS. Female DM persons had higher A-FABP level than man (P<0.001. No statistically significant differences in A-FABP levels were found in use of statin, fibrate, or antidiabetic drugs. Multivariate forward stepwise linear regression analysis revealed that body fat mass (P<0.001, logarithmically transformed creatinine (log-creatinine; P<0.001, female DM patients (P<0.001, and logarithmically transformed high sensitive C-reactive protein (log-hs-CRP; P=0.013 were positively correlated, while albumin (P=0.004 and glomerular filtration rate (GFR; P=0.043 were negatively correlated with serum A-FABP levels in type 2 DM patients. In this study, higher serum A-FABP level was positively associated with MetS in type 2 DM patients.

  9. Perbedaan Kadar Liver Fatty Acid Binding Protein (L-FABP Urine Penderita Diabetes Melitus Tipe 2 dengan Normoalbuminuria dan Mikroalbuminuria

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    Kristina Wiharjo

    2014-06-01

    Full Text Available Diabetes mellitus (DM is the leading cause of the end stage renal disease (ESRD. Around 20−40% patients with DM develop diabetic nephropathy and eventually progress into ESRD. Type 2 DM has a greater prevalence to develop diabetic nephropathy. Oxidative stress accumulation can increase permeability of the glomerulus which results in increased urine albumin excretion, which is divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Glomerulus dysfunction occurs after tubulointerstisial renal dysfunction which decreases peritubular capillary flow that leads to tubulointerstisial hypoxia. Liver fatty acid binding protein function is to reduce hypoxia by binding oxidative stress and excretes it into urine. The aim of this study was to analyze the differences in the urine L-FABP level between normoalbuminuria and microalbuminuria type 2 DM patients. The study design was observational analytic using cross-sectional method. Subjects were 70 DM type 2 patients with normoalbuminuria (38 patients and microalbuminuria (32 patients. Statistical analysis was performed using the Mann Whitney test The results found that there were significant differences in levels of urine L-FABP between normoalbuminuria and microalbuminuria type 2 DM patients (ZM-W=3.513, p<0.001 with medians of 5 and 7 in normoalbuminuria and microalbuminuria, respectively. The urine L-FABP level increased because of the oxidative stress and hypoxia that happened before the glomerulus dysfunction. In conclusion, urine L-FABP level in patients DM type 2 with microalbuminuria is higher than that of the normoalbuminuria.

  10. Liver fatty acid-binding protein (L-FABP) promotes cellular angiogenesis and migration in hepatocellular carcinoma.

    Science.gov (United States)

    Ku, Chung-Yu; Liu, Yu-Huei; Lin, Hsuan-Yuan; Lu, Shao-Chun; Lin, Jung-Yaw

    2016-04-01

    Liver fatty acid-binding protein (L-FABP) is abundant in hepatocytes and known to be involved in lipid metabolism. Overexpression of L-FABP has been reported in various cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated L-FABP and its association with vascular endothelial growth factors (VEGFs) in 90 HCC patients. We found that L-FABP was highly expressed in their HCC tissues, and that this expression was positively correlated with that of VEGF-A. Additionally, L-FABP significantly promoted tumor growth and metastasis in a xenograft mouse model. We also assessed the mechanisms of L-FABP activity in tumorigenesis; L-FABP was found to associate with VEGFR2 on membrane rafts and subsequently activate the Akt/mTOR/P70S6K/4EBP1 and Src/FAK/cdc42 pathways, which resulted in up-regulation of VEGF-A accompanied by an increase in both angiogenic potential and migration activity. Our results thus suggest that L-FABP could be a potential target for HCC chemotherapy.

  11. Circulating FABP4 (Fatty Acid-Binding Protein 4) Is a Novel Prognostic Biomarker in Patients With Acute Ischemic Stroke.

    Science.gov (United States)

    Tu, Wen-Jun; Zeng, Xian-Wei; Deng, Aijun; Zhao, Sheng-Jie; Luo, Ding-Zhen; Ma, Guo-Zhao; Wang, Hong; Liu, Qiang

    2017-06-01

    FABP4 (fatty acid-binding protein 4) is an intracellular lipid chaperone involved in coordination of lipid transportation and atherogenesis. This study aimed at observing the effect of FABP4 on the 3-month outcomes in Chinese patients with acute ischemic stroke. In a prospective multicenter observational study, serum concentrations of FABP4 were on admission measured in plasma of 737 consecutive patients with acute ischemic stroke. Serum concentrations of FABP4, National Institutes of Health Stroke Scale score, and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 3 months. During follow-up, an unfavorable functional outcome was found in 260 patients (35.3%), and 94 patients (12.8%) died. In multivariate models comparing the third and fourth quartiles to the first quartile of FABP4, the concentrations of FABP4 were associated with poor functional outcome and mortality. Compared with the reference category (Q1-Q3), the concentrations of FABP4 in Q4 had a relative risk of 4.77 (95% confidence interval [CI], 2.02-8.15; PStroke Scale score with combined areas under the curve of 0.83 (95% CI, 0.76-0.89; Pstroke patients. © 2017 American Heart Association, Inc.

  12. Heart-type fatty acid binding protein and vascular endothelial growth factor: cerebrospinal fluid biomarker candidates for Alzheimer's disease.

    Science.gov (United States)

    Guo, Liang-Hao; Alexopoulos, Panagiotis; Perneczky, Robert

    2013-10-01

    The main objective of the study was to validate the findings of previous cerebrospinal fluid (CSF) proteomic studies for the differentiation between Alzheimer's disease (AD) dementia and physiological ageing. The most consistently significant proteins in the separation between AD dementia versus normal controls using CSF proteomics were identified in the literature. The classification performance of the four pre-selected proteins was explored in 92 controls, 149 patients with mild cognitive impairment (MCI), and 69 patients with AD dementia. Heart-type fatty acid binding protein (hFABP) and vascular endothelial growth factor (VEGF) CSF concentrations distinguished between healthy controls and patients with AD dementia with a sensitivity and specificity of 57 and 35%, and 76 and 84%, respectively. The optimal classification was achieved by a combination of the two additional CSF biomarker candidates in conjunction with the three established markers Amyloid-β (Aβ)1-42, total-Tau (tTau), and phosphorylated-Tau (pTau)181, which resulted in a sensitivity of 83% and a specificity of 86%. hFABP also predicted the progression from MCI to AD dementia. The present study provides evidence in support of hFABP and VEGF in CSF as AD biomarker candidates to be used in combination with the established markers Aβ1-42, tTau, and pTau181.

  13. [Selective regulation of peroxisome proliferator-activated receptors on fatty acid binding protein-4 in human syncytiotrophoblast cells].

    Science.gov (United States)

    Li, Yuan; Gu, Hang

    2012-10-01

    To observe the selective regulation of peroxisome proliferator-activated receptors (PPAR) on fatty acid binding protein-4 (FABP4) in human syncytiotrophoblasts. Cultivate normal human syncytiotrophoblast cells, and put in the specific antagonists and agonists of PPAR each subtypes receptors, then observe the different expression of FABP4 mRNA and protein. Pretreated the human syncytiotrophoblast cells with the agonists (GW7647, GW0742) and antagonists (GW6471, GSK0660) of PPARα and PPARβ receptors, the expression of the FABP4 was not significantly change (P > 0.05). However pretreated with PPAR γ agonists (rosiglitazone, 1×10(-9), 1×10(-8), 1×10(-7) and 1×10(-6) mol/L), the expression of FABP4 mRNA and protein could be dose dependent-promoted significantly (mRNA: 1.27 ± 0.12, 1.45 ± 0.14, 1.57 ± 0.14, 1.72 ± 0.12, protein:1.10 ± 0.08, 1.37 ± 0.09, 1.60 ± 0.13, 1.79 ± 0.14; P PPARγ regulated the expression of FABP4 mRNA and protein selectively. And the regulation will not be influenced by the other two PPAR subtypes.

  14. CD36 binds oxidized low density lipoprotein (LDL) in a mechanism dependent upon fatty acid binding.

    Science.gov (United States)

    Jay, Anthony G; Chen, Alexander N; Paz, Miguel A; Hung, Justin P; Hamilton, James A

    2015-02-20

    The association of unesterified fatty acid (FA) with the scavenger receptor CD36 has been actively researched, with focuses on FA and oxidized low density lipoprotein (oxLDL) uptake. CD36 has been shown to bind FA, but this interaction has been poorly characterized to date. To gain new insights into the physiological relevance of binding of FA to CD36, we characterized FA binding to the ectodomain of CD36 by the biophysical method surface plasmon resonance. Five structurally distinct FAs (saturated, monounsaturated (cis and trans), polyunsaturated, and oxidized) were pulsed across surface plasmon resonance channels, generating association and dissociation binding curves. Except for the oxidized FA HODE, all FAs bound to CD36, with rapid association and dissociation kinetics similar to HSA. Next, to elucidate the role that each FA might play in CD36-mediated oxLDL uptake, we used a fluorescent oxLDL (Dii-oxLDL) live cell assay with confocal microscopy imaging. CD36-mediated uptake in serum-free medium was very low but greatly increased when serum was present. The addition of exogenous FA in serum-free medium increased oxLDL binding and uptake to levels found with serum and affected CD36 plasma membrane distribution. Binding/uptake of oxLDL was dependent upon the FA dose, except for docosahexaenoic acid, which exhibited binding to CD36 but did not activate the uptake of oxLDL. HODE also did not affect oxLDL uptake. High affinity FA binding to CD36 and the effects of each FA on oxLDL uptake have important implications for protein conformation, binding of other ligands, functional properties of CD36, and high plasma FA levels in obesity and type 2 diabetes.

  15. Characterization and functional analysis of fatty acid binding protein from the carcinogenic liver fluke, Opisthorchis viverrini.

    Science.gov (United States)

    Sripa, Jittiyawadee; Laha, Thewarach; Sripa, Banchob

    2017-08-01

    In the present study, the cDNA encoding FABP (Ov-FABP) was isolated from the adult stage of Opisthorchis viverrini and characterized. The Ov-FABP protein sequence (107 amino acids) was predicted to have a molecular mass of 12.26kDa and an isoelectric point (PI) of 6.82. This sequence had a high identity and similarity to Cs-FABP of the related opisthorchid Clonorchis sinensis. Multiple sequence alignment with FABPs from other parasitic flatworms and mammals showed a number of conserved amino acids including Phe(34), Gly(37), Glu(38), Glu(39),Val(50), Iso(62), Gly(81), Ile(84), Ser(87) and Arg(101). In addition, the structure of Ov-FABP was predicted to have eleven β-sheets and one α-helix based on the known structures for FABPs from human (hL-FABP), rat and a schistosome. Phylogenetic analysis of amino acid sequence data revealed a close relationship of Ov-FABP with Cs-FABP and hL-FABP. Reverse transcription-PCR revealed that Ov-FABP was transcribed in the egg, metacercaria, juvenile and adult stages. The soluble form of recombinant Ov-FABP (rOv-FABP) was shown to specifically bind fatty acids, including oleic acid, palmitic acid and linoleic acid, as shown for other animals. Anti-serum against rOv-FABP (produced in mice) located the protein to parenchyma, egg, sucker musculature, testes and tegument of adult O. viverrini. Taken together, the findings suggest key functional roles for Ov-FABP in development, reproduction and/or host-parasite interactions. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder.

    Science.gov (United States)

    Iwayama, Yoshimi; Hattori, Eiji; Maekawa, Motoko; Yamada, Kazuo; Toyota, Tomoko; Ohnishi, Tetsuo; Iwata, Yasuhide; Tsuchiya, Kenji J; Sugihara, Genichi; Kikuchi, Mitsuru; Hashimoto, Kenji; Iyo, Masaomi; Inada, Toshiya; Kunugi, Hiroshi; Ozaki, Norio; Iwata, Nakao; Nanko, Shinichiro; Iwamoto, Kazuya; Okazaki, Yuji; Kato, Tadafumi; Yoshikawa, Takeo

    2010-03-05

    Deficits in prepulse inhibition (PPI) are a biological marker for psychiatric illnesses such as schizophrenia and bipolar disorder. To unravel PPI-controlling mechanisms, we previously performed quantitative trait loci (QTL) analysis in mice, and identified Fabp7, that encodes a brain-type fatty acid binding protein (Fabp), as a causative gene. In that study, human FABP7 showed genetic association with schizophrenia. FABPs constitute a gene family, of which members FABP5 and FABP3 are also expressed in the brain. These FABP proteins are molecular chaperons for polyunsaturated fatty acids (PUFAs) such as arachidonic and docosahexaenoic acids. Additionally, the involvement of PUFAs has been documented in the pathophysiology of schizophrenia and mood disorders. Therefore in this study, we examined the genetic roles of FABP5 and 3 in schizophrenia (N = 1,900 in combination with controls) and FABP7, 5, and 3 in bipolar disorder (N = 1,762 in the case-control set). Three single nucleotide polymorphisms (SNPs) from FABP7 showed nominal association with bipolar disorder, and haplotypes of the same gene showed empirical associations with bipolar disorder even after correction of multiple testing. We could not perform association studies on FABP5, due to the lack of informative SNPs. FABP3 displayed no association with either disease. Each FABP is relatively small and it is assumed that there are multiple regulatory elements that control gene expression. Therefore, future identification of unknown regulatory elements will be necessary to make a more detailed analysis of their genetic contribution to mental illnesses.

  17. Serum liver fatty acid binding protein levels correlate positively with obesity and insulin resistance in Chinese young adults.

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    Juan Shi

    Full Text Available BACKGROUND: Liver fatty acid-binding protein (FABP1 plays an inconclusive role in adiposity. We investigated the association of serum FABP1 levels with obesity and insulin resistance in Chinese young people under 30 years old. METHODOLOGY AND PRINCIPAL FINDINGS: Cross-sectional analysis including 200 obese and 172 normal-weight subjects matched for age and sex, anthropometric measurements were performed and serum FABP1 and biochemical characteristics were measured. Insulin resistance was determined by homeostasis model assessment of insulin resistance (HOMA-IR and by the insulin sensitivity index (S(i derived from Bergman's minimal model. FABP1 levels in obese subjects were significantly higher than those in normal-weight subjects (p<0.001 and the significance remained after adjustment for age, gender, alanine and aspartate aminotransferases (p<0.001. Serum FABP1 levels were significantly correlated with many metabolic-related parameters, with BMI and triglycerides as the independent determinants. FABP1 levels remained an independent risk factor of insulin resistance assessed by binary S(i (OR = 1.868 per SD unit, 95% CI [1.035-3.373], p = 0.038 after adjustment for age, sex, BMI, waist circumference, systolic blood pressure, serum triacylglycerol, total cholesterol, HDL- and LDL-cholesterol,. FABP1 levels were also elevated with an increasing number of components of the metabolic syndrome (p for trend <0.001. Multiple regression modeling for the MetS and its components demonstrated that hypertriglyceridemia and low HDL-cholesterol were significantly correlated to serum FABP1 levels. CONCLUSIONS AND SIGNIFICANCE: Serum FABP1 correlates positively with obesity and insulin resistance in Chinese young adults. Our data supports the fact that FABP1 might be an important mediator participating in fatty acid metabolism and energy balance.

  18. Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus.

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    Khattab, Salma A; Abo-Elmatty, Dina M; Ghattas, Maivel H; Mesbah, Noha M; Mehanna, Eman T

    2017-09-01

    Intestinal fatty acid-binding protein 2 (FABP2) is expressed in enterocytes and binds saturated and unsaturated long-chain fatty acids. The FABP2 Ala54Thr polymorphism has been reported to effect lipid metabolism. The aim of the present study was to assess the relationship between this polymorphism and peripheral atherosclerosis combined with type 2 diabetes mellitus (T2DM) in an Egyptian population. The study was performed on 100 T2DM patients with peripheral atherosclerosis and 100 control subjects. The Ala54Thr polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism, whereas serum FABP2 levels were determined using ELISA. Fasting blood glucose, fasting serum insulin concentrations, HbA1c, lipid profile, body mass index (BMI) and systolic and diastolic blood pressure (SBP and DBP, respectively) were determined. There was a higher frequency of the Thr54 allele among the patient group (P = 0.002). In Ala54/Thr54 heterozygotes and carriers of the rare Thr54/Thr54 genotype, there were significant increases in BMI and FABP2. Those with the Thr54/Thr54 genotype had significantly decreased high-density lipoprotein cholesterol (HDL-C) concentrations; in addition, those with the Thr54/Thr54 genotype had significantly higher SBP and DBP than subjects with the Ala54/Ala54 and Ala54/Thr54 genotypes. There was a positive correlation between FABP2 levels and BMI, SBP and DBP, and a negative correlation with HDL-C. The Thr54 allele of the FABP2 Ala54Thr polymorphism was associated with an increased incidence of peripheral atherosclerosis combined with T2DM in the population studied. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  19. Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

    Science.gov (United States)

    Elmes, Matthew W; Kaczocha, Martin; Berger, William T; Leung, KwanNok; Ralph, Brian P; Wang, Liqun; Sweeney, Joseph M; Miyauchi, Jeremy T; Tsirka, Stella E; Ojima, Iwao; Deutsch, Dale G

    2015-04-03

    Δ(9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified. Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid-binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs. Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption. Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders.

  20. Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)*

    Science.gov (United States)

    Elmes, Matthew W.; Kaczocha, Martin; Berger, William T.; Leung, KwanNok; Ralph, Brian P.; Wang, Liqun; Sweeney, Joseph M.; Miyauchi, Jeremy T.; Tsirka, Stella E.; Ojima, Iwao; Deutsch, Dale G.

    2015-01-01

    Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified. Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid-binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs. Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption. Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders. PMID:25666611

  1. Structural and binding properties of two paralogous fatty acid binding proteins of Taenia solium metacestode.

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    Seon-Hee Kim

    Full Text Available BACKGROUND: Fatty acid (FA binding proteins (FABPs of helminths are implicated in acquisition and utilization of host-derived hydrophobic substances, as well as in signaling and cellular interactions. We previously demonstrated that secretory hydrophobic ligand binding proteins (HLBPs of Taenia solium metacestode (TsM, a causative agent of neurocysticercosis (NC, shuttle FAs in the surrounding host tissues and inwardly transport the FAs across the parasite syncytial membrane. However, the protein molecules responsible for the intracellular trafficking and assimilation of FAs have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: We isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2, which encoded 133- and 136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa, respectively. They shared 45% sequence identity with each other and 15-95% with other related-members. Homology modeling demonstrated a characteristic β-barrel composed of 10 anti-parallel β-strands and two α-helices. TsMFABP2 harbored two additional loops between β-strands two and three, and β-strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and surrounding environments, whereas TsMFABP2 was intracellularly confined. Partially purified native proteins migrated to 15 kDa with different isoelectric points of 9.2 (TsMFABP1 and 8.4 (TsMFABP2. Both native and recombinant proteins bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]aminoundecannoic acid, dansyl-DL-α-amino-caprylic acid, cis-parinaric acid and retinol, which were competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed relatively high affinity. Isolation of two distinct genes from an individual genome strongly suggested their paralogous nature. Abundant expression of TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the histological distributions

  2. Structural and Binding Properties of Two Paralogous Fatty Acid Binding Proteins of Taenia solium Metacestode

    Science.gov (United States)

    Yang, Hyun-Jong; Shin, Joo-Ho; Diaz-Camacho, Sylvia Paz; Nawa, Yukifumi; Kang, Insug; Kong, Yoon

    2012-01-01

    Background Fatty acid (FA) binding proteins (FABPs) of helminths are implicated in acquisition and utilization of host-derived hydrophobic substances, as well as in signaling and cellular interactions. We previously demonstrated that secretory hydrophobic ligand binding proteins (HLBPs) of Taenia solium metacestode (TsM), a causative agent of neurocysticercosis (NC), shuttle FAs in the surrounding host tissues and inwardly transport the FAs across the parasite syncytial membrane. However, the protein molecules responsible for the intracellular trafficking and assimilation of FAs have remained elusive. Methodology/Principal Findings We isolated two novel TsMFABP genes (TsMFABP1 and TsMFABP2), which encoded 133- and 136-amino acid polypeptides with predicted molecular masses of 14.3 and 14.8 kDa, respectively. They shared 45% sequence identity with each other and 15–95% with other related-members. Homology modeling demonstrated a characteristic β-barrel composed of 10 anti-parallel β-strands and two α-helices. TsMFABP2 harbored two additional loops between β-strands two and three, and β-strands six and seven, respectively. TsMFABP1 was secreted into cyst fluid and surrounding environments, whereas TsMFABP2 was intracellularly confined. Partially purified native proteins migrated to 15 kDa with different isoelectric points of 9.2 (TsMFABP1) and 8.4 (TsMFABP2). Both native and recombinant proteins bound to 11-([5-dimethylaminonaphthalene-1-sulfonyl]amino)undecannoic acid, dansyl-DL-α-amino-caprylic acid, cis-parinaric acid and retinol, which were competitively inhibited by oleic acid. TsMFABP1 exhibited high affinity toward FA analogs. TsMFABPs showed weak binding activity to retinol, but TsMFABP2 showed relatively high affinity. Isolation of two distinct genes from an individual genome strongly suggested their paralogous nature. Abundant expression of TsMFABP1 and TsMFABP2 in the canal region of worm matched well with the histological distributions of lipids

  3. The pathogen-related yeast protein Pry1, a member of the CAP protein superfamily, is a fatty acid-binding protein.

    Science.gov (United States)

    Darwiche, Rabih; Mène-Saffrané, Laurent; Gfeller, David; Asojo, Oluwatoyin A; Schneiter, Roger

    2017-05-19

    Members of the CAP superfamily (cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins), also known as SCP superfamily (sperm-coating proteins), have been implicated in many physiological processes, including immune defenses, venom toxicity, and sperm maturation. Their mode of action, however, remains poorly understood. Three proteins of the CAP superfamily, Pry1, -2, and -3 (pathogen related in yeast), are encoded in the Saccharomyces cerevisiae genome. We have shown previously that Pry1 binds cholesterol in vitro and that Pry function is required for sterol secretion in yeast cells, indicating that members of this superfamily may generally bind sterols or related small hydrophobic compounds. On the other hand, tablysin-15, a CAP protein from the horsefly Tabanus yao, has been shown to bind leukotrienes and free fatty acids in vitro Therefore, here we assessed whether the yeast Pry1 protein binds fatty acids. Computational modeling and site-directed mutagenesis indicated that the mode of fatty acid binding is conserved between tablysin-15 and Pry1. Pry1 bound fatty acids with micromolar affinity in vitro, and its function was essential for fatty acid export in cells lacking the acyl-CoA synthetases Faa1 and Faa4. Fatty acid binding of Pry1 is independent of its capacity to bind sterols, and the two sterol- and fatty acid-binding sites are nonoverlapping. These results indicate that some CAP family members, such as Pry1, can bind different lipids, particularly sterols and fatty acids, at distinct binding sites, suggesting that the CAP domain may serve as a stable, secreted protein domain that can accommodate multiple ligand-binding sites. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

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    Moch Holger

    2009-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP are involved in the intracellular transport of fatty acids (FA. We examined the level of brain-type (B and liver-type (L FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test, correlations and survival analyses. Results B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4 showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2. Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. Conclusion While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients

  5. Serum high-sensitivity C-reaction protein and heart fatty acid binding protein level and cardiac accidents in patients with unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    朱红秋

    2006-01-01

    Objective To investigate the relationship between serum high-sensitivity C-reaction protein (hs-CRP) and heart fatty acid binding protein (h-FABP) on cardiac accidents in patients with unstable angina pectoris (UAP). Methods Serum levels of hs-CRP, h-FABP, cardiac troponin-Ⅰ(cTn-Ⅰ) and creatine kinase MB isoenzyme (CK-MB) were measured and cardiac accidents within 2 weeks after the test were observed in 74 patients (male

  6. Serum fatty acid-binding protein 4 is a predictor of cardiovascular events in end-stage renal disease.

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    Masato Furuhashi

    Full Text Available BACKGROUND: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2, a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown that FABP4 is secreted from adipocytes and that FABP4 level is associated with obesity, insulin resistance, and atherosclerosis. However, little is known about the impact of FABP4 concentrations on prognosis. We tested the hypothesis that FABP4 level predicts prognosis of patients with end-stage renal disease (ESRD, a group at high risk for atherosclerosis-associated morbidity and mortality. METHODS AND RESULTS: Biochemical markers including FABP4 were determined in 61 ESRD patients on chronic hemodialysis (HD. Serum FABP4 level in females (404.2±30.5 ng/ml was significantly higher than that in males (315.8±30.0 ng/ml, and the levels in ESRD patients were about 20-times higher than those in age-, gender- and body mass index (BMI-matched control subjects with normal renal function. FABP4 level was decreased by 57.2% after HD and was positively correlated with blood pressure, BMI, and levels of lipids and insulin. Multiple regression analysis indicated that HD duration, BMI, and triglycerides level were independent determinants for FABP4 level. ESRD patients with high FABP4 levels had higher cardiovascular mortality during the 7-year follow-up period. Cox proportional hazard regression analysis showed that logarithmically transformed FABP4 level was an independent predictor of cardiovascular death adjusted for age, gender, HD duration, BMI, and triglycerides level (hazard ratio, 7.75; 95% CI, 1.05-25.31. CONCLUSION: These findings suggest that FABP4 level, being related to adiposity and metabolic disorders, is a novel predictor of cardiovascular mortality in ESRD.

  7. Metformin reduces lipid accumulation in macrophages by inhibiting FOXO1-mediated transcription of fatty acid-binding protein 4

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    Song, Jun [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Ren, Pingping; Zhang, Lin [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Wang, Xing Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States); Chen, Li [Qilu Hospital, Shandong University, Jinan, Shandong (China); Shen, Ying H., E-mail: hyshen@bcm.edu [Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX (United States); Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, TX (United States)

    2010-02-26

    Objective: The accumulation of lipids in macrophages contributes to the development of atherosclerosis. Strategies to reduce lipid accumulation in macrophages may have therapeutic potential for preventing and treating atherosclerosis and cardiovascular complications. The antidiabetic drug metformin has been reported to reduce lipid accumulation in adipocytes. In this study, we examined the effects of metformin on lipid accumulation in macrophages and investigated the mechanisms involved. Methods and results: We observed that metformin significantly reduced palmitic acid (PA)-induced intracellular lipid accumulation in macrophages. Metformin promoted the expression of carnitine palmitoyltransferase I (CPT-1), while reduced the expression of fatty acid-binding protein 4 (FABP4) which was involved in PA-induced lipid accumulation. Quantitative real-time PCR showed that metformin regulates FABP4 expression at the transcriptional level. We identified forkhead transcription factor FOXO1 as a positive regulator of FABP4 expression. Inhibiting FOXO1 expression with FOXO1 siRNA significantly reduced basal and PA-induced FABP4 expression. Overexpression of wild-type FOXO1 and constitutively active FOXO1 significantly increased FABP4 expression, whereas dominant negative FOXO1 dramatically decreased FABP4 expression. Metformin reduced FABP4 expression by promoting FOXO1 nuclear exclusion and subsequently inhibiting its activity. Conclusions: Taken together, these results suggest that metformin reduces lipid accumulation in macrophages by repressing FOXO1-mediated FABP4 transcription. Thus, metformin may have a protective effect against lipid accumulation in macrophages and may serve as a therapeutic agent for preventing and treating atherosclerosis in metabolic syndrome.

  8. Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture

    Science.gov (United States)

    Lee, K.; Santibanez-Koref, M.; Polvikoski, T.; Birchall, D.; Mendelow, A.D.; Keavney, B.

    2013-01-01

    Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences (p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques (p = 5.4 × 10−7). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold (p = 0.0086) and five-fold (p = 0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential. PMID:23122912

  9. Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity.

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    Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

    2011-03-01

    Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of N(ε)-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of N(ε)-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID.

  10. Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury.

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    Negishi, Kousuke; Noiri, Eisei; Doi, Kent; Maeda-Mamiya, Rui; Sugaya, Takeshi; Portilla, Didier; Fujita, Toshiro

    2009-04-01

    The present study aimed to evaluate whether levels of urinary L-type fatty acid-binding protein (L-FABP) could be used to monitor histological injury in acute kidney injury (AKI) induced by cis-platinum (CP) injection and ischemia reperfusion (IR). Different degrees of AKI severity were induced by several renal insults (CP dose and ischemia time) in human L-FABP transgenic mice. Renal histological injury scores increased with both CP dose and ischemic time. In CP-induced AKI, urinary L-FABP levels increased exponentially even in the lowest dose group as early as 2 hours, whereas blood urea nitrogen (BUN) levels increased at 48 hours. In IR-induced AKI, BUN levels increased only in the 30-minute ischemia group 24 hours after reperfusion; however, urinary L-FABP levels increased more than 100-fold, even in the 5-minute ischemia group after 1 hour. In both AKI models, urinary L-FABP levels showed a better correlation with final histological injury scores and glomerular filtration rates measured by fluorescein isothiocyanate-labeled inulin injection than with levels of BUN and urinary N-acetyl-D-glucosaminidase, especially at earlier time points. Receiver operating characteristic curve analysis demonstrated that urinary L-FABP was superior to other biomarkers for the detection of significant histological injuries and functional declines. In conclusion, urinary L-FABP levels are better suited to allow the accurate and earlier detection of both histological and functional insults in ischemic and nephrotoxin-induced AKI compared with conventional renal markers.

  11. Fatty Acid binding protein 4 is associated with carotid atherosclerosis and outcome in patients with acute ischemic stroke.

    Science.gov (United States)

    Holm, Sverre; Ueland, Thor; Dahl, Tuva B; Michelsen, Annika E; Skjelland, Mona; Russell, David; Nymo, Ståle H; Krohg-Sørensen, Kirsten; Clausen, Ole Petter; Atar, Dan; Januzzi, James L; Aukrust, Pål; Jensen, Jesper K; Halvorsen, Bente

    2011-01-01

    Fatty acid binding protein 4 (FABP4) has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke. We examined plasma FABP4 levels in asymptomatic (n = 28) and symptomatic (n = 31) patients with carotid atherosclerosis, as well as in 202 subjects with acute ischemic stroke. In a subgroup of patients we also analysed the expression of FABP4 within the atherosclerotic lesion. In addition, we investigated the ability of different stimuli with relevance to atherosclerosis to regulate FABP4 expression in monocytes/macrophages. FABP4 levels were higher in patients with carotid atherosclerosis, both systemically and within the atherosclerotic lesion, with particular high mRNA levels in carotid plaques from patients with the most recent symptoms. Immunostaining of carotid plaques localized FABP4 to macrophages, while activated platelets and oxidized LDL were potent stimuli for FABP4 expression in monocytes/macrophages in vitro. When measured at the time of acute ischemic stroke, high plasma levels of FABP4 were significantly associated with total and cardiovascular mortality during follow-up, although we did not find that addition of FABP4 to the fully adjusted multivariate model had an effect on the prognostic discrimination for all-cause mortality as assessed by c-statistics. FABP4 is linked to atherogenesis, plaque instability and adverse outcome in patients with carotid atherosclerosis and acute ischemic stroke.

  12. Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

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    Ashraf H. ElGhandour

    2009-04-01

    Full Text Available Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin’s lymphoma (NHL may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP, not exceeding the total allowed dose of doxorubicin (500 mg/m2. Ten healthy controls were included in our study. Human heart-type fatty acid binding protein (H-FABP was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

  13. Fatty acid binding protein 4 expression marks a population of adipocyte progenitors in white and brown adipose tissues.

    Science.gov (United States)

    Shan, Tizhong; Liu, Weiyi; Kuang, Shihuan

    2013-01-01

    Adipose tissues regulate metabolism, reproduction, and life span. The development and growth of adipose tissue are due to increases of both adipocyte cell size and cell number; the latter is mediated by adipocyte progenitors. Various markers have been used to identify either adipocyte progenitors or mature adipocytes. The fatty acid binding protein 4 (FABP4), commonly known as adipocyte protein 2 (aP2), has been extensively used as a marker for differentiated adipocytes. However, whether aP2 is expressed in adipogenic progenitors is controversial. Using Cre/LoxP-based cell lineage tracing in mice, we have identified a population of aP2-expressing progenitors in the stromal vascular fraction (SVF) of both white and brown adipose tissues. The aP2-lineage progenitors reside in the adipose stem cell niche and express adipocyte progenitor markers, including CD34, Sca1, Dlk1, and PDGFRα. When isolated and grown in culture, the aP2-expressing SVF cells proliferate and differentiate into adipocytes upon induction. Conversely, ablation of the aP2 lineage greatly reduces the adipogenic potential of SVF cells. When grafted into wild-type mice, the aP2-lineage progenitors give rise to adipose depots in recipient mice. Therefore, the expression of aP2 is not limited to mature adipocytes, but also marks a pool of undifferentiated progenitors associated with the vasculature of adipose tissues. Our finding adds to the repertoire of adipose progenitor markers and points to a new regulator of adipose plasticity.

  14. Activity-based targeting of secretory phospholipase A2 enzymes: A fatty-acid-binding-protein assisted approach.

    Science.gov (United States)

    Keshavarz, Amir; Zelaya, Ligia; Singh, Jasmeet; Ranganathan, Radha; Hajdu, Joseph

    2017-01-01

    Syntheses and enzymological characterization of fluorogenic substrate probes targeting secretory phospholipase A2 (sPLA2) for detection and quantitative assays are presented. Three fluorogenic phosphatidylcholine analogs PC-1, PC-2, and PC-3 each containing the duo of 7-mercapto-4-methyl-coumarin fluorophore and 2,4-dinitroanaline quencher on either tail were synthesized from (R)-3-amino-1,2-propanediol and R-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol. These small reporter groups are advantageous in preserving natural membrane integrity. Phosphocholine was incorporated into the sn-3 position of the glycerol backbone. Acyl amino group at the sn-1 position in PC-1 and PC-2 is meant to block sPLA1. The sn-1 and sn-2 positions of the glycerol backbone in PC-1 have a quencher terminated 12-carbon chain and fluorophore terminated 11-carbon chain respectively. PC-2 has a quencher terminated 3-carbon chain at the sn-2 and chain terminating fluorescent reporter at the sn-1 positions. PC-3 resembles PC-1 except for an ester instead of amide at the sn-1 position, because of which it is more similar to natural phospholipids than PC-1. It was designed to elucidate the effect of replacing the ester group with amide by comparing its hydrolysis rate with that of PC-1. Design principles apply to synthesis of other labeled phospholipids. Enzymological characterization using bee-venom sPLA2 was performed by a fatty-acid-binding-protein fluorescence assay and by pH-Stat method in which the amount of fatty acid released by hydrolysis is given by the amount of base required to maintain a constant pH of 8.0. Hydrolytic activity toward PC-1 and PC-3 were each about 238±25μmol/mg/min and 537μmol/mg/min on unmodified phospholipid. Ester to amide change did not affect hydrolysis rates. Activity toward PC-2 was about 45-μmol/mg/min. PC-1 and PC-3 show potential for targeted real-time spectrophotometric assay of sPLA2. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5.

    Science.gov (United States)

    Levi, Liraz; Wang, Zeneng; Doud, Mary Kathryn; Hazen, Stanley L; Noy, Noa

    2015-11-23

    Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes and precursors for signalling molecules. Here we show that these biological compounds also regulate gene expression and that they do so by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARβ/δ. The data indicate that these activities of LCFA are mediated by FABP5, which delivers ligands from the cytosol to nuclear PPARβ/δ. Both saturated and unsaturated LCFA (SLCFA, ULCFA) bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARβ/δ pathway. We show further that, by concomitantly promoting the activation of RAR and inhibiting the activation of PPARβ/δ, SLCFA suppress the oncogenic properties of FABP5-expressing carcinoma cells in cultured cells and in vivo. The observations suggest that compounds that inhibit FABP5 may constitute a new class of drugs for therapy of certain types of cancer.

  16. Plasma-free fatty acids, fatty acid-binding protein 4, and mortality in older adults (from the Cardiovascular Health Study).

    Science.gov (United States)

    Miedema, Michael D; Maziarz, Marlena; Biggs, Mary L; Zieman, Susan J; Kizer, Jorge R; Ix, Joachim H; Mozaffarian, Dariush; Tracy, Russell P; Psaty, Bruce M; Siscovick, David S; Mukamal, Kenneth J; Djousse, Luc

    2014-09-15

    Plasma-free fatty acids (FFAs) are largely derived from adipose tissue. Elevated levels of FFA and fatty acid-binding protein 4 (FABP4), a key cytoplasmic chaperone of fatty acids, have been associated with adverse cardiovascular outcomes, but limited data are available on the relation of these biomarkers with cardiovascular and total mortality. We studied 4,707 participants with a mean age of 75 years who had plasma FFA and FABP4 measured in 1992 to 1993 as part of the Cardiovascular Health Study, an observational cohort of community-dwelling older adults. Over a median follow-up of 11.8 years, 3,555 participants died. Cox proportional hazard regression was used to determine the association between FFA, FABP4, and mortality. In fully adjusted models, FFA were associated with dose-dependent significantly higher total mortality (hazard ratio [HR] per SD: 1.14, 95% confidence interval [CI] 1.09 to 1.18), but FABP4 levels were not (HR 1.04, 95% CI 0.98 to 1.09). In a cause-specific mortality analysis, higher concentrations of FFA were associated with significantly higher risk of death because of cardiovascular disease, dementia, infection, and respiratory causes but not cancer or trauma. We did not find evidence of an interaction between FFA and FABP4 (p = 0.45), but FABP4 appeared to be associated with total mortality differentially in men and women (HR 1.17, 95% CI 1.08 to 1.26 for men; HR 1.02, 95% CI 0.96 to 1.07 for women, interaction p value <0.001). In conclusion, in a cohort of community-dwelling older subjects, elevated plasma concentrations of FFA, but not FABP4, were associated with cardiovascular and noncardiovascular mortality.

  17. Analysis of the regulation of fatty acid binding protein 7 expression in human renal carcinoma cell lines

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    Sugiyama Takayuki

    2011-07-01

    Full Text Available Abstract Background Improving the treatment of renal cell carcinoma (RCC will depend on the development of better biomarkers for predicting disease progression and aiding the design of appropriate therapies. One such marker may be fatty acid binding protein 7 (FABP7, also known as B-FABP and BLBP, which is expressed normally in radial glial cells of the developing central nervous system and cells of the mammary gland. Melanomas, glioblastomas, and several types of carcinomas, including RCC, overexpress FABP7. The abundant expression of FABP7 in primary RCCs compared to certain RCC-derived cell lines may allow the definition of the molecular components of FABP7's regulatory system. Results We determined FABP7 mRNA levels in six RCC cell lines. Two were highly expressed, whereas the other and the embryonic kidney cell line (HEK293 were weakly expressed FABP7 transcripts. Western blot analysis of the cell lines detected strong FABP7 expression only in one RCC cell line. Promoter activity in the RCC cell lines was 3- to 21-fold higher than that of HEK293. Deletion analysis demonstrated that three FABP7 promoter regions contributed to upregulated expression in RCC cell lines, but not in the HEK293 cell. Competition analysis of gel shifts indicated that OCT1, OCT6, and nuclear factor I (NFI bound to the FABP7 promoter region. Supershift experiments indicated that BRN2 (POU3F2 and NFI bound to the FABP7 promoter region as well. There was an inverse correlation between FABP7 promoter activity and BRN2 mRNA expression. The FABP7-positive cell line's NFI-DNA complex migrated faster than in other cell lines. Levels of NFIA mRNA were higher in the HEK293 cell line than in any of the six RCC cell lines. In contrast, NFIC mRNA expression was lower in the HEK293 cell line than in the six RCC cell lines. Conclusions Three putative FABP7 promoter regions drive reporter gene expression in RCC cell lines, but not in the HEK293 cell line. BRN2 and NFI may be key

  18. Protection against Schistosoma mansoni infection using a Fasciola hepatica-derived fatty acid binding protein from different delivery systems.

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    Vicente, Belén; López-Abán, Julio; Rojas-Caraballo, Jose; del Olmo, Esther; Fernández-Soto, Pedro; Muro, Antonio

    2016-04-18

    Schistosomiasis is a water-borne disease afflicting over 261 million people in many areas of the developing countries with high morbidity and mortality. The control relies mainly on treatment with praziquantel. Fatty acid binding proteins (FABP) have demonstrated high levels of immune-protection against trematode infections. This study reports the immunoprotection induced by cross-reacting Fasciola hepatica FABP, native (nFh12) and recombinantly expressed using two different expression systems Escherichia coli (rFh15) and baculovirus (rFh15b) against Schistosoma mansoni infection. BALB/c mice were vaccinated with native nFh12 or recombinant rFh15 and rFh15 FABP from F. hepatica formulated in adjuvant adaptation (ADAD) system with natural or chemical synthesised immunomodulators (PAL and AA0029) and then challenged with 150 cercariae of S. mansoni. Parasite burden, hepatic lesions and antibody response were studied in vaccination trials. Furthermore differences between rFh15 and rFh15b immunological responses (cytokine production, splenocyte population and antibody levels) were studied. Vaccination with nFh12 induced significant reductions in worm burden (83%), eggs in tissues (82-92%) and hepatic lesions (85%) compared to infected controls using PAL. Vaccination with rFh15 showed lower total worm burden (56-64%), eggs in the liver (21-61%), eggs in the gut (30-77%) and hepatic damage (67-69%) using PAL and AA0029 as immunomodulators. In contrast, mice vaccinated with rFh15b showed only reductions in eggs trapped in the liver and intestine (53 and 60%, respectively), and hepatic lesions (45%). We observed a significant rise in TNFα, IL-6, IL-2, IL-4 and high antibody response (IgG, IgG1, IgG2a, IgM and IgE) in mice immunised with either rFh15 or rFh15b. Moreover, mice immunised with rFh15b showed an increase in IFNγ and a decrease in B220 cells compared to untreated mice, and less production of IgG1 and IgM than in mice immunised by rFh15. Higher level of

  19. Influence of Ala54Thr polymorphism of fatty acid-binding protein 2 on histological alterations and insulin resistance of non alcoholic fatty liver disease.

    Science.gov (United States)

    Aller, R; De Luis, D A; Fernandez, L; Calle, F; Velayos, B; Izaola, O; Gonzalez Sagrado, M; Conde, R; Gonzalez, J M

    2009-01-01

    A transition G to A at codon 54 of fatty acid binding protein type 2 (FABP2) produces an amino acid substitution (Ala 54 to Thr 54). This amino acid substitution was associated with modifications of insulin resistance, adipokines and insulin concentrations. The aim of this study was to evaluate the influence of Ala54Thr polymorphism in the FABP2 gene on the histological alterations of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Thirty subjects with the presence of biopsy-proven NAFLD were enrolled for this study. Glucose, Insulin, Insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, resistin, leptin, adiponectin, interleukin-6 and TNF-alfa serum levels were measured at basal time. A tetrapolar bioimpedance, BMI, waist circumference, waist to hip ratio, blood pressure and a prospective serial assessment of nutritional intake with 3 days written food records were examined. Genotype of Ala54Thr FABP2 gene polymorphism was studied. The mean age was 41.6 +/- 11 years and the mean BMI 29.2 +/- 6.6 with 24 males (80%) and 6 females (20%). Fifteen patients (50%) had the genotype Ala54/Ala54 (wild type group) and 15 (50%) patients Ala54/Thr54 (13 patients) or Thr54/Thr54 (2 patients) (mutant type group). Both genotype groups have the similar anthropometric parameters. Serum aspartate aminotransferase and alcaline phosfatase were higher in wild type group than mutant type group, with an unclear explanation. Dietary intake was similar in both groups. A non-statistical significant low levels of adiponectin in mutant group was observed. No differences were detected among other adipokines. There were no differences between genotypes in histological results of inflammation (portal or lobular inflammation) or grade of steatosis or fibrosis. In conclusion, the present study demonstrates that the polymorphism Ala54Thr of FABP in patients with NAFLD doesn't predict liver histological changes, nor both insulin resistance

  20. Ala54Thr fatty acid-binding protein 2 (FABP2 polymorphism in recurrent depression: associations with fatty acid concentrations and waist circumference.

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    Roel J T Mocking

    Full Text Available BACKGROUND: Fatty acid (FA-alterations may mediate the mutual association between Major Depressive Disorder (MDD and cardiovascular disease (CVD. However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid-binding protein 2 (FABP2-gene, because it regulates dietary FA-uptake. Therefore, we aimed to test the hypotheses that in MDD-patients the FABP2 Ala54Thr-polymorphism would be (I more prevalent than in sex- and age-matched controls, (II associated with observed alterations in FA-metabolism, and (III associated with CVD-risk factor waist circumference. METHODS: We measured concentrations of 29 different erythrocyte FAs, FABP2-genotype, and waist circumference in recurrent MDD-patients and matched never-depressed controls. RESULTS: FABP2-genotype distribution did not significantly differ between the 137 MDD-patients and 73 matched controls. However, patients with the Ala54Thr-polymorphism had (I higher concentrations of especially eicosadienoic acid (C20:2ω6; P=.009 and other 20-carbon FAs, and associated (II lower waist circumference (P=.019. In addition, FABP2-genotype effects on waist circumference in patients seemed (I mediated by its effect on C20:2ω6, and (II different from controls. CONCLUSIONS: Although Ala54Thr-polymorphism distribution was not associated with recurrent MDD, our results indicate that FABP2 may play a role in the explanation of observed FA-alterations in MDD. For Ala54Thr-polymorphism patients, potentially adaptive conversion of increased bioavailable dietary precursors into eicosadienoic acid instead of arachidonic acid might be related to a low waist circumference. Because this is the first investigation of these associations, replication is warranted, preferably by nutrigenetic studies applying lipidomics and detailed dietary assessment.

  1. Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in aP2, the Adipocyte Fatty Acid Binding Protein

    Science.gov (United States)

    Hotamisligil, Gokhan S.; Johnson, Randall S.; Distel, Robert J.; Ellis, Ramsey; Papaioannou, Virginia E.; Spiegelman, Bruce M.

    1996-11-01

    Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2-/- animals failed to express in adipose tissue tumor necrosis factor-α (TNF-α), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-α.

  2. Fatty acid-binding proteins and its biological characteristics%脂肪酸结合蛋白及其生物学功能

    Institute of Scientific and Technical Information of China (English)

    陈轶霞; 骆学农; 王红宁

    2012-01-01

    脂肪酸结合蛋白(fatty acid-binding protein,FABP)是胞内脂质结合蛋白超家族成员,存在于脊椎动物和无脊椎动物的细胞内,在长链脂肪酸的摄取、转运及代谢调节中发挥重要作用,并涉及生物体的其他生命过程.本文从FABP的分布、类型、结构、结合及表达特征、生物学功能,特别是近来发现的免疫调节功能等方面阐述了FABP的研究进展,为深入研究该基因家族提供参考.%Fatty acid-binding proteins (FABPs) are members of intracellular lipid binding protein superfamily. These proteins are extensively expressed in animals including invertebrates and vertebrates, and responsible for long chain fatty acid uptake, transport and metabolic regulation and also be involved in many other biological processes. This article reviews research advances in the distribution, type, structure, binding and expression features, immune regulation and the other important biological roles of FABPs. This information presented here will put insights into further studies on FABPs.

  3. 肝型脂肪酸结合蛋白研究进展%Progress in liver type fatty acid binding protein

    Institute of Scientific and Technical Information of China (English)

    王南南; 徐力致; 王亚平

    2012-01-01

    Liver fatty acid binding protein (L-FABP) which mainly expresses in liver, intestine and kidney, is an important member of FABP family. It is found that L-FABP is related to the translocation of saturated fatty acid, unsaturated fatty acid, cholesterol, bile acid and so on. Many studies have indicated that L-FABP was involved in fatty liver, cirrhosis and hepatocarcinoma. Moreover, L-FABP can be an appropriate biomarker in predicting the progression of liver injury. Recent researches have demonstrated that u-LFABP might be a new tool in the prediction of diabetic nephropathy in type 1 diabetic patients. Besides, L-FABP levels reflect the severity of diabetic nephropathy accurately in type 2 diabetes. This article aims to review the characteristics, conformation of L-FABP, and its relationship with some diseases.%肝型脂肪酸结合蛋白(liver fatty acid binding protein,L-FABP)是脂肪酸结合蛋白(fatty acid binding proteins,FABPs)家族重要的成员,在肝脏、小肠、肾脏等组织中均有表达.L-FABP在不饱和脂肪酸、饱和脂肪酸、胆固醇、胆汁酸等转运过程中扮演重要角色.目前研究显示L-FABP在脂肪肝、肝硬化以及肝癌发生发展中起到重要作用,并有望作为肝损伤的早期检测指标.此外,新近研究发现尿中L-FABP水平还可以用于预测1型糖尿病患者的临床结局.在2型糖尿病中,尿中L-FABP与糖尿病性肾病的病程有密切关系.主要就L-FABP的特性、结构及其与疾病的关系做一综述.

  4. Rapid Diagnosis of acute kidney injury (AKI associated with cardiac surgery, using the liver type fatty acid binding protein (L-FABP biomarker

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    Mirbagheri L

    2012-01-01

    Full Text Available Background and objectives: cardiac surgery is often associated with acutekidney injury (AKI. Nowadays, AKI is typically diagnosed by an increase inserum creatinine, which is a delayed and unreliable biomarker. Recent studiesrecommended using the liver type fatty acid binding protein (L-FABP as anearly biomarker.Material and Methods: The urine samples of 18 adult patients undergoingcardiac surgery were collected in different times before (2, 4,8,24 hour andafter cardiac surgery for detection of L-FABP by Elisa.Results: The results from ELISA test show that the increasing amount of LFABPin urine samples of 4 patients is a diagnostic indicator for AKI. Themean concentration of L-FABP has increased up to 17 times at 8 hours aftercardiac surgery compared to before surgery.Conclusion: according to our findings, we speculated that the urinary L-FABPcan be a reliable and rapid biomarker for diagnosis of acute kidney injury.Key words: Acute Kidney Injury, Liver type Fatty Acid Binding Protein,Cardiac surgery

  5. 心肌型脂肪酸结合蛋白的临床应用进展%Clinical Application of Heart Fatty Acid-binding Protein

    Institute of Scientific and Technical Information of China (English)

    范树虹

    2011-01-01

    Heart fatty-acid-binding protein (H-FABP) is a low molecular weight cytostolic protein. It is abundant in the myocardium and has high tissue specificity. Concentration of H-FABP changes regularly in serum after myocardial injury, and is positively correlated with the degree of myocardial injury. H-FABP has been used as an early diagnostic biochemical marker of acute myocardial ischemia. The physio-chemical nature, detection of H-FABP, and its application in the diagnosis of myocardial injury are reviewed in this article.%心肌型脂肪酸结合蛋白(heart fatty acid-binding protein,H-FABP)是一种低分子量可溶性蛋白,在心肌细胞胞浆中含量丰富.具有组织特异性,心肌损伤后血浆中H-FABP水平变化有时间规律性,且血浆H-FABP水平与心肌损伤程度成正相关,故H-FABP可作为诊断早期心肌缺血的生化标志物.现就H-FABP的生理化学特性、检测方法及其在心肌损伤诊断中的应用做一综述.

  6. Comparison of purified 12 kDa and recombinant 15 kDa Fasciola hepatica antigens related to a Schistosoma mansoni fatty acid binding protein

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    George V. Hillyer

    1995-04-01

    Full Text Available Vaccines in schistosomiasis using homologous antigens have been studied extensively in experimentally infected mammalian hosts. Vaccines using heterologous antigens have received comparatively less attention. This review summarizes recent work on a heterologous 12 kDa Fasciola hepatica antigenic polypeptide which cross reacts with Schistosoma mansoni. A cDNA has been cloned and sequenced, and the predicted amino acid sequence of the recombinant protein has been shown to have significant (44 identity with a 14 kDa S. mansoni fatty acid binding protein. Thus in the parasitic trematodes fatty acid binding proteins may be potential vaccine candidates. The F. hepatica recombinant protein has been overexpressed and purified and denoted rFh15. Preliminary rFh15 migrates more slowly (i.e. may be slightly larger than nFh12 on SDS-PAGE and has a predicted pI of 6.01 vs. observed pI of 5.45. Mice infected with F. hepatica develop antibodies to nFh12 by 2 weeks of infection vs. 6 weeks of infection to rFh15; on the other hand, mice with schistosomiasis mansoni develop antibodies to both nFh12 and rFh15 by 6 weeks of infection. Both the F. hepatica and S. mansoni cross-reactive antigens may be cross-protective antigens with the protection inducing capability against both species.

  7. Effects of linoleic and gamma-linolenic acids (efamol evening primrose oil) on fatty acid-binding proteins of rat liver.

    Science.gov (United States)

    Dutta-Roy, A K; Demarco, A C; Raha, S K; Shay, J; Garvey, M; Horrobin, D F

    We have studied the effects of Efamol evening primrose oil (EPO) on fatty acid-binding proteins (L-FABP) of rat liver. EPO contains 72% cis-linoleic acid and 9% cis-gamma linolenic acid. EPO has been clinically used for treatment of a number of diseases in humans and animals. EPO is also known to lower cholesterol level in humans and animals. Feeding of an EPO supplemented diet to rats (n = 9) for 2 months decreases the oleate binding capacity of purified L-FABP of rat liver whereas the palmitate binding activity was increased by 38%. However, EPO feeding did not alter the L-FABP concentrations significantly as measured by using the fluorescence fatty acid probe, dansylamino undecanoic acid. Endogenous fatty acid analysis of L-FABPs revealed significant qualitative and quantitative changes in fatty acid pattern after EPO feeding. EPO feeding decreased the endogenous palmitate level by 53% and oleate level by 64% in L-FABPs and also EPO feeding decreased the total endogenous fatty acid content from 62 nanomole per mg of protein to 42 nanomole per mg of L-FABP (n = 3).

  8. Fatty Acids Bind Tightly to the N-terminal Domain of Angiopoietin-like Protein 4 and Modulate Its Interaction with Lipoprotein Lipase*

    Science.gov (United States)

    Robal, Terje; Larsson, Mikael; Martin, Miina; Olivecrona, Gunilla; Lookene, Aivar

    2012-01-01

    Angiopoietin-like protein 4 (Angptl4), a potent regulator of plasma triglyceride metabolism, binds to lipoprotein lipase (LPL) through its N-terminal coiled-coil domain (ccd-Angptl4) inducing dissociation of the dimeric enzyme to inactive monomers. In this study, we demonstrate that fatty acids reduce the inactivation of LPL by Angptl4. This was the case both with ccd-Angptl4 and full-length Angptl4, and the effect was seen in human plasma or in the presence of albumin. The effect decreased in the sequence oleic acid > palmitic acid > myristic acid > linoleic acid > linolenic acid. Surface plasmon resonance, isothermal titration calorimetry, fluorescence, and chromatography measurements revealed that fatty acids bind with high affinity to ccd-Angptl4. The interactions were characterized by fast association and slow dissociation rates, indicating formation of stable complexes. The highest affinity for ccd-Angptl4 was detected for oleic acid with a subnanomolar equilibrium dissociation constant (Kd). The Kd values for palmitic and myristic acid were in the nanomolar range. Linoleic and linolenic acid bound with much lower affinity. On binding of fatty acids, ccd-Angptl4 underwent conformational changes resulting in a decreased helical content, weakened structural stability, dissociation of oligomers, and altered fluorescence properties of the Trp-38 residue that is located close to the putative LPL-binding region. Based on these results, we propose that fatty acids play an important role in modulating the effects of Angptl4. PMID:22773878

  9. Ischemia-modified albumin and heart fatty acid-binding protein: could early ischemic cardiac biomarkers be used in acute stroke management?

    Science.gov (United States)

    Herisson, Fanny; Delaroche, Odile; Auffray-Calvier, Elisabeth; Duport, Benjamin Daumas; Guillon, Benoit

    2010-01-01

    The detection of biomarkers such as ischemia-modified albumin (IMA) and heart fatty acid-binding protein (HFABP) is used in the early diagnosis of acute myocardial infarction. As these biomarkers are not organ specific, we tested them in the neurovascular field. A total of 41 patients with acute stroke were enrolled (31 ischemic strokes and 10 intracerebral hemorrhages). IMA and HFABP levels were measured in serum samples collected within 4.5 hours of stroke onset. Clinical, imaging, and outcome data were recorded. No difference in baseline IMA or HFABP was found between patients with ischemic and hemorrhagic stroke. There was no correlation among biomarker levels at admission, National Institutes of Health Stroke Scale score, or stroke volume. Neither of the biomarkers could predict short-term prognosis. IMA and HFABP do not appear to be relevant in acute stroke management. Copyright (c) 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. Time course characterization of serum cardiac troponins, heart fatty acid-binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat.

    Science.gov (United States)

    Clements, Peter; Brady, Sally; York, Malcolm; Berridge, Brian; Mikaelian, Igor; Nicklaus, Rosemary; Gandhi, Mitul; Roman, Ian; Stamp, Clare; Davies, Dai; McGill, Paul; Williams, Thomas; Pettit, Syril; Walker, Dana; Turton, John

    2010-08-01

    We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 microg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.

  11. Upregulation of peroxisome proliferator-activated receptors and liver fatty acid binding protein in hepatic cells of broiler chicken supplemented with conjugated linoleic acids

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    Suriya Kumari Ramiah

    2015-09-01

    Full Text Available Since conjugated linoleic acid (CLA has structural and physiological characteristics similar to peroxisome proliferators, it is hypothesized that CLA would upregulate peroxisome proliferator-activated receptor (PPAR and liver fatty acid binding protein (LFABP in the liver of broiler chicken. The aim of the present study was to determine fatty acid composition of liver in CLA-fed broiler chickens and the genes associated with hepatic lipid metabolism. A total of 180-day-old broiler chicks were randomly assigned to two diets containing 0 and 2.5% CLA and fed for 6 weeks. Fatty acid (FA composition of liver and PPAR α and γ and L-FABP were analyzed. It has been demonstrated that CLA was found in the liver of CLA-feed chicken compared to control group. Hepatic PPAR α and γ mRNA levels were upregulated 1.2 and 3-fold in CLA-fed chickens compared to chickens fed diet without CLA respectively. A similar response of upregulation was observed for L-FABP mRNA expression. Our data highlights the role of PPARs as a core regulator in the regulation of lipid metabolism in chicken liver.

  12. Induction of fatty acid-binding protein 3 in brown adipose tissue correlates with increased demand for adaptive thermogenesis in rodents.

    Science.gov (United States)

    Yamashita, Hitoshi; Wang, Zuocheng; Wang, Youxue; Segawa, Masahiko; Kusudo, Tatsuya; Kontani, Yasuhide

    2008-12-12

    We investigated the contribution of fatty acid-binding protein 3 (FABP3) to adaptive thermogenesis in brown adipose tissue (BAT) in rodents. The expression of FABP3 mRNA in BAT was regulated discriminatively in response to alteration of the ambient temperature, which regulation was similar and reciprocal to the regulation of uncoupling protein 1 (UCP1) and leptin, respectively. FABP3 expression in the BAT was significantly higher in the UCP1-knockout (KO) mice than in the wild-type ones, and these KO mice showed a higher clearance rate of free fatty acid from the plasma. In addition, FABP3 expression in the BAT was increased greatly with the development of diet-induced obesity in mice. These results indicate that the induction of FABP3 in BAT correlates with an increased demand for adaptive thermogenesis in rodents. FABP3 appears to be essential for accelerating fatty acid flux and its oxidation through UCP1 activity for non-shivering thermogenesis in BAT.

  13. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats.

    Science.gov (United States)

    Elsherbiny, Marwa E; Goruk, Susan; Monckton, Elizabeth A; Richard, Caroline; Brun, Miranda; Emara, Marwan; Field, Catherine J; Godbout, Roseline

    2015-10-22

    Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7), a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains.

  14. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

    Directory of Open Access Journals (Sweden)

    Marwa E. Elsherbiny

    2015-10-01

    Full Text Available Arachidonic (AA and docosahexaenoic acid (DHA brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7, a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains.

  15. [Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan].

    Science.gov (United States)

    Kamijo-Ikemori, Atsuko; Ichikawa, Daisuke; Matsui, Katsuomi; Yokoyama, Takeshi; Sugaya, Takeshi; Kimura, Kenjiro

    2013-07-01

    Liver-type fatty acid binding protein (L-FABP) is a 14kDa protein found in the cytoplasm of human renal proximal tubules. Fatty acids are bound with L-FABP and transported to the mitochondria or peroxisomes, where fatty acids are beta-oxidized, and this may play a role in fatty acid homeostasis. Moreover, L-FABP has high affinity and capacity to bind long-chain fatty acid oxidation products, and may be an effective endogenous antioxidant. Renal L-FABP is rarely expressed in the kidneys of rodents. In order to evaluate the pathological dynamics of renal L-FABP in kidney disease, human L-FABP chromosomal transgenic mice were generated. Various stress, such as massive proteinuria, hyperglycemia, hypertension, and toxins overloaded in the proximal tubules were revealed to up-regulate the gene expression of renal L-FABP and increase the excretion of L-FABP derived from the proximal tubules into urine. In clinical studies of chronic kidney disease (CKD), urinary L-FABP accurately reflected the degree of tubulointerstitial damage and correlated with the rate of CKD progression. Furthermore, a multicenter trial has shown that urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. With respect to diabetic nephropathy and acute kidney disease (AKI), urinary L-FABP is an early diagnostic of kidney disease or a predictive marker for renal prognosis. After many clinical studies, urinary L-FABP was approved as a new tubular biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan.

  16. 肝型脂肪酸结合蛋白研究进展%Advance in Liver-type Fatty Acid Binding Protein

    Institute of Scientific and Technical Information of China (English)

    蔡璨

    2011-01-01

    Liver-type fatty acid binding protein ( L-FABP) is a key member of FABP superfamily, mainly functioning to regulate the absorption and transportation of fatty acid, intracellular transportation of long-chained fatty acid,and redistribution and use of fatty acids in organelles.L-FABP also regulates the target gene transcription mediated by peroxisome proliferator-activated receptor α and impacts on the lipid metabolism and energy balance,as a signalling transduction molecule.L-FABP is closely associated with metabolic diseases and isrhemic injuries of tissues and organs,as a potential sensitive marker of liver,intestinal and renal injuries and target of drug treatment for some metabolic diseases.%肝型脂肪酸结合蛋白(L-FABP)是脂肪酸结合蛋白超家族中的重要成员,主要功能是机体对脂肪酸的吸收、转运及细胞内长链脂肪酸的转运,以及脂肪酸在细胞器内的再分布利用.L-FABP调节过氧化物酶体增殖子激动受体α介导的靶基因转录,影响机体的脂质代谢和能量平衡,起到信号转导分子的作用.L-FABP与代谢性疾病及组织器官缺血损伤等密切相关,有望成为肝、肠、肾等组织损伤的敏感标志物,并可能成为某些代谢性疾病的药物治疗靶点.

  17. Statin induction of liver fatty acid-binding protein (L-FABP) gene expression is peroxisome proliferator-activated receptor-alpha-dependent.

    Science.gov (United States)

    Landrier, Jean-François; Thomas, Charles; Grober, Jacques; Duez, Hélène; Percevault, Frédéric; Souidi, Maâmar; Linard, Christine; Staels, Bart; Besnard, Philippe

    2004-10-29

    Statins are drugs widely used in humans to treat hypercholesterolemia. Statins act by inhibiting cholesterol synthesis resulting in the activation of the transcription factor sterol-responsive element-binding protein-2 that controls the expression of genes involved in cholesterol homeostasis. Statin therapy also decreases plasma triglyceride and non-esterified fatty acid levels, but the mechanism behind this effect remains more elusive. Liver fatty acid-binding protein (L-FABP) plays a role in the influx of long-chain fatty acids into hepatocytes. Here we show that L-FABP is a target for statins. In rat hepatocytes, simvastatin treatment induced L-FABP mRNA levels in a dose-dependent manner. Moreover, L-FABP promoter activity was induced by statin treatment. Progressive 5'-deletion analysis revealed that the peroxisome proliferator-activated receptor (PPAR)-responsive element located at position -67/-55 was responsible for the statin-mediated transactivation of the rat L-FABP promoter. Moreover, treatment with simvastatin and the PPARalpha agonist Wy14,649 resulted in a synergistic induction of L-FABP expression (mRNA and protein) in rat Fao hepatoma cells. This effect was also observed in vivo in wild-type mice but not in PPARalpha-null animals demonstrating the direct implication of PPARalpha in L-FABP regulation by statin treatment. Statin treatment resulted in a rise in PPARalpha mRNA levels both in vitro and in vivo and activated the mouse PPARalpha promoter in a reporter assay. Altogether, these data demonstrate that L-FABP expression is up-regulated by statins through a mechanism involving PPARalpha. Moreover, PPARalpha might be a statin target gene. These effects might contribute to the triglyceride/non-esterified fatty acid-lowering properties of statins.

  18. Fatty Acid-Binding Protein 5 at the Blood-Brain Barrier Regulates Endogenous Brain Docosahexaenoic Acid Levels and Cognitive Function.

    Science.gov (United States)

    Pan, Yijun; Short, Jennifer L; Choy, Kwok H C; Zeng, Annie X; Marriott, Philip J; Owada, Yuji; Scanlon, Martin J; Porter, Christopher J H; Nicolazzo, Joseph A

    2016-11-16

    Fatty acid-binding protein 5 (FABP5) at the blood-brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA), a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition, the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5(+/+) and FABP5(-/-) mice using a battery of memory paradigms. FABP5(-/-) mice exhibited impaired working memory and short-term memory, and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood-brain barrier transport of DHA was assessed by measuring (14)C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5(+/+) and FABP5(-/-) mice. In line with a crucial role of FABP5 in the brain uptake of DHA, (14)C-DHA uptake into brain endothelial cells and brain capillaries of FABP5(-/-) mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%, respectively, relative to those of FABP5(+/+) mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA, and that cognitive deficits observed in FABP5(-/-) mice are associated with reduced CNS access of DHA. Genetic deletion of fatty acid-binding protein 5 (FABP5) in mice reduces uptake of exogenous docosahexaenoic acid (DHA) into brain endothelial cells and brain capillaries and reduces brain parenchymal levels of endogenous DHA. Therefore, FABP5 in the brain endothelial cell is a crucial contributor to the brain levels of DHA. Critically, lowered brain DHA levels in FABP5(-/-) mice occurred in tandem with cognitive deficits in a battery of memory paradigms. This study provides evidence of a critical role

  19. Molecular cloning and tissue expression of the fatty acid-binding protein (Es-FABP gene in female Chinese mitten crab (Eriocheir sinensis

    Directory of Open Access Journals (Sweden)

    He Lin

    2010-09-01

    Full Text Available Abstract Background Fatty acid-binding proteins (FABPs, small cytosolic proteins that function in the uptake and utilization of fatty acids, have been extensively studied in higher vertebrates while invertebrates have received little attention despite similar nutritional requirements during periods of reproductive activity. Results Therefore, a cDNA encoding Eriocheir sinensis FABP (Es-FABP was cloned based upon EST analysis of a hepatopancreas cDNA library. The full length cDNA was 750 bp and encoded a 131 aa polypeptide that was highly homologous to related genes reported in shrimp. The 9108 bp Es-FABP gene contained four exons that were interrupted by three introns, a genomic organization common among FABP multigene family members in vertebrates. Gene expression analysis, as determined by RT-PCR, revealed the presence of Es-FABP transcripts in hepatopancreas, hemocytes, ovary, gills, muscle, thoracic ganglia, heart, and intestine, but not stomach or eyestalk. Real-time quantitative RT-PCR analysis revealed that Es-FABP expression in ovary, hemocytes, and hepatopancreas was dependent on the status of ovarian development, with peak expression observed in January. Conclusions Evidence provided in the present report supports a role of Es-FABP in lipid transport during the period of rapid ovarian growth in E. sinensis, and indirectly confirms the participation of the hepatopancreas, ovary, and hemocytes in lipid nutrient absorption and utilization processes.

  20. Research Progress in Intestinal-type Fatty Acid Binding Protein%肠型脂肪酸结合蛋白研究进展

    Institute of Scientific and Technical Information of China (English)

    王家胜; 杨强

    2012-01-01

    肠型脂肪酸结合蛋白( Ⅰ-FABP,FABP2)是脂肪酸结合蛋白超家族中的重要成员,主要参与机体对脂肪酸的吸收、转运、以及在细胞器内的再分布及利用.近年研究表明,FABP2与代谢性疾病、炎症性疾病、肠组织缺血损伤等密切相关,不但是肠组织损伤的敏感性标志,而且可以作为炎症严重程度的评价指标,并可能成为某些代谢性疾病的药物治疗靶点.%Intestinal-type fatty acid binding protein (I-FABP, FABP2 ) is a key member of the FABP super family, participating in the organism's absorption,transferring,intracellular redistribution and use of fatty acids. Recent research has demonstrated that FABP2 is closely related with metabolic diseases,inflammatory diseases and ischemic injuries of intestinal tissue. It is not only a sensitive sign of intestinal injuries but also a severity evaluation indicator of inflammation. What's more,it can probably be a pharmacotherapy target of some metabolic diseases.

  1. Fatty Acid Binding Protein-1 (FABP1) and the Human FABP1 T94A Variant: Roles in the Endocannabinoid System and Dyslipidemias.

    Science.gov (United States)

    Schroeder, Friedhelm; McIntosh, Avery L; Martin, Gregory G; Huang, Huan; Landrock, Danilo; Chung, Sarah; Landrock, Kerstin K; Dangott, Lawrence J; Li, Shengrong; Kaczocha, Martin; Murphy, Eric J; Atshaves, Barbara P; Kier, Ann B

    2016-06-01

    The first discovered member of the mammalian FABP family, liver fatty acid binding protein (FABP1, L-FABP), occurs at high cytosolic concentration in liver, intestine, and in the case of humans also in kidney. While the rat FABP1 is well studied, the extent these findings translate to human FABP1 is not clear-especially in view of recent studies showing that endocannabinoids and cannabinoids represent novel rat FABP1 ligands and FABP1 gene ablation impacts the hepatic endocannabinoid system, known to be involved in non-alcoholic fatty liver (NAFLD) development. Although not detectable in brain, FABP1 ablation nevertheless also impacts brain endocannabinoids. Despite overall tertiary structure similarity, human FABP1 differs significantly from rat FABP1 in secondary structure, much larger ligand binding cavity, and affinities/specificities for some ligands. Moreover, while both mouse and human FABP1 mediate ligand induction of peroxisome proliferator activated receptor-α (PPARα), they differ markedly in pattern of genes induced. This is critically important because a highly prevalent human single nucleotide polymorphism (SNP) (26-38 % minor allele frequency and 8.3 ± 1.9 % homozygous) results in a FABP1 T94A substitution that further accentuates these species differences. The human FABP1 T94A variant is associated with altered body mass index (BMI), clinical dyslipidemias (elevated plasma triglycerides and LDL cholesterol), atherothrombotic cerebral infarction, and non-alcoholic fatty liver disease (NAFLD). Resolving human FABP1 and the T94A variant's impact on the endocannabinoid and cannabinoid system is an exciting challenge due to the importance of this system in hepatic lipid accumulation as well as behavior, pain, inflammation, and satiety.

  2. Structural basis for the ligand-binding specificity of fatty acid-binding proteins (pFABP4 and pFABP5) in gentoo penguin.

    Science.gov (United States)

    Lee, Chang Woo; Kim, Jung Eun; Do, Hackwon; Kim, Ryeo-Ok; Lee, Sung Gu; Park, Hyun Ho; Chang, Jeong Ho; Yim, Joung Han; Park, Hyun; Kim, Il-Chan; Lee, Jun Hyuck

    2015-09-11

    Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic fatty acids between various aqueous compartments of the cell by directly binding ligands inside their β-barrel cavities. Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5, obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 Å, 2.2 Å, and 2.3 Å, respectively. The pFABP4 and pFABP5 proteins have a canonical β-barrel structure with two short α-helices that form a cap region and fatty acid ligand binding sites in the hydrophobic cavity within the β-barrel structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different ligand-binding modes and a unique ligand-binding pocket due to several sequence dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between the two proteins. Structural comparison revealed significantly different conformational changes in the β3-β4 loop region (residues 57-62) as well as the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding residue is Phe58). A ligand-binding study using fluorophore displacement assays shows that pFABP4 has a relatively strong affinity for linoleate as compared to pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for pFABP4. In conclusion, our high-resolution structures and ligand-binding studies provide useful insights into the ligand-binding preferences of pFABPs based on key protein-ligand interactions.

  3. Ala54Thr fatty acid-binding protein 2 (FABP2) polymorphism in recurrent depression : associations with fatty acid concentrations and waist circumference

    NARCIS (Netherlands)

    Mocking, Roel J T; Lok, Anja; Assies, Johanna; Koeter, Maarten W J; Visser, Ieke; Ruhe, Eric; Bockting, Claudi L H; Schene, Aart H

    2013-01-01

    BACKGROUND: Fatty acid (FA)-alterations may mediate the mutual association between Major Depressive Disorder (MDD) and cardiovascular disease (CVD). However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid-bindi

  4. Lack of association between the fatty acid binding protein 2 (FABP2) polymorphism with obesity and insulin resistance in two aboriginal populations from Chile.

    Science.gov (United States)

    Pérez-Bravo, F; Fuentes, M; Angel, B; Sanchez, H; Carrasco, E; Santos, J L; Lera, L; Albala, C

    2006-12-01

    The aim of this study was to assess the frequency of fatty acid binding protein 2 (FABP2) Ala54Thr genetic polymorphism and to evaluate its association with obesity and insulin resistance in Chilean aboriginal populations. A sample of 96 urban Aymara and 111 urban Mapuche subjects aged 20-80 years were recruited for this cross-sectional study. Glucose, insulin and lipid profile were measured in fasting plasma samples. Insulin resistance was estimated through the HOMA-IR model. FABP2 Ala54Thr genotypes were determined by PCR followed by RFLP analysis. The allele frequency of Thr54 variant was estimated as 18.2% in Aymara subjects, which is one of the lowest reported to date. The corresponding frequency in Mapuche subjects was 31.9% (pMapuche group: OR=2.37, 95% CI 1.319-4.277, p=0.004) It is unlikely that Ala54Thr polymorphism of the FABP2 gene plays a relevant role in obesity and insulin resistance in Chilean ethnic groups.

  5. Identification of polymorphism in fatty acid binding protein 3 (FABP3) gene and its association with milk fat traits in riverine buffalo (Bubalus bubalis).

    Science.gov (United States)

    Dubey, Praveen Kumar; Goyal, Shubham; Mishra, Shailendra Kumar; Arora, Reena; Mukesh, Manishi; Niranjan, Saket Kumar; Kathiravan, Periasamy; Kataria, Ranjit Singh

    2016-04-01

    The fatty acid binding protein 3 (FABP3) gene, known to be associated with fat percentage of milk and meat in bovines, was screened among swamp and riverine buffaloes for polymorphism detection and further association with milk fat contents. An SNP g.307C > T was identified in the intron 2 (+53 exon 2) region of FABP3 gene of Indian buffaloes. The SNP identified was genotyped in 692 animals belonging to 15 riverine, swamp and hybrid (riverine × swamp) buffalo populations of diverse phenotypes and utilities, by PCR-RFLP. A marked contrast was observed between the C and T allele frequencies in three types of buffaloes. The frequency of C allele ranged from 0.67 to 0.96 in pure swamp buffalo populations, with the highest in Mizoram (0.96). Whereas the frequency of T allele was high across all the Indian riverine buffalo breeds, ranging from 0.57 to 0.96. None of the genotypes at FABP3 g.307C > T locus was found to have significant association with milk fat and other production traits in Mehsana dairy buffalo breed. Our study revealed marked differences in the allele frequencies between riverine and swamp buffaloes at FABP3 g.307C > T locus, without any significant association with different milk traits in riverine buffaloes.

  6. High sensitive troponin T and heart fatty acid binding protein: Novel biomarker in heart failure with normal ejection fraction?: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Barroso Michael

    2011-07-01

    Full Text Available Abstract Background High sensitive troponin T (hsTnT and heart fatty acid binding protein (hFABP are both markers of myocardial injury and predict adverse outcome in patients with systolic heart failure (SHF. We tested whether hsTnT and hFABP plasma levels are elevated in patients with heart failure with normal ejection fraction (HFnEF. Methods We analyzed hsTnT, hFABP and N-terminal brain natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients with asymptomatic left ventricular diastolic dysfunction (LVDD, and 30 controls with normal diastolic function. Patients were classified to have HFnEF when the diagnostic criteria as recommended by the European Society of Cardiology were met. Results Levels of hs TnT and hFABP were significantly higher in patients with asymptomatic LVDD and HFnEF (both p Conclusion In HFnEF patients, hsTnT and hFABP are elevated independent of coronary artery disease, suggesting that ongoing myocardial damage plays a critical role in the pathophysiology. A combination of biomarkers and echocardiographic parameters might improve diagnostic accuracy and risk stratification of patients with HFnEF.

  7. NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5

    Energy Technology Data Exchange (ETDEWEB)

    Volakakis, Nikolaos; Joodmardi, Eliza [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); Perlmann, Thomas, E-mail: thomas.perlmann@licr.ki.se [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); The Department of Cell and Molecular Biology, Karolinska Institute, S-17177 Stockholm (Sweden)

    2009-12-25

    The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPAR{beta}/{delta} signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPAR{beta}/{delta} and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels.

  8. Changes in serum adipocyte fatty acid-binding protein in women with gestational diabetes mellitus and normal pregnant women during mid- and late pregnancy.

    Science.gov (United States)

    Zhang, Ying; Zhang, Hao-Hang; Lu, Jia-Hui; Zheng, Si-Yuan; Long, Tao; Li, Ying-Tao; Wu, Wei-Zhen; Wang, Fang

    2016-09-01

    To observe the longitudinal changes in serum adipocyte fatty acid-binding protein (AFABP), carbohydrate, and lipid metabolism parameters in women with and without gestational diabetes mellitus (GDM) during mid- and late pregnancy periods, as well as to identify whether there is any association between AFABP and development of GDM. A total of 40 GDM and 240 normal glucose tolerance participants were enrolled at 24-28 weeks and completed the study. The clinical features, serum AFABP, other adipocytokines (leptin, adiponectin, retinol-binding protein 4), homeostasis model assessment of insulin resistance, and lipid profiles were measured in the second and third trimesters of pregnancy. Compared with the normal glucose tolerance group, the GDM group showed greater levels of AFABP, leptin and retinol-binding protein 4; and a decreased level of adiponectin (P body mass index was the independent factor impacting serum AFABP levels in the second (β = 0.567, P = 0.004) and third trimesters (β = 0.619, P = 0.001). Furthermore, GDM was independently associated with AFABP concentrations in multiple regression analysis in the second and third trimester (all P body mass index and GDM were the independent factors with respect to serum AFABP. AFABP might be closely related to obesity, insulin resistance and leptin resistance in pregnancy, and is a major risk factor for GDM. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  9. Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein.

    Science.gov (United States)

    Asada, Toshifumi; Isshiki, Rei; Hayase, Naoki; Sumida, Maki; Inokuchi, Ryota; Noiri, Eisei; Nangaku, Masaomi; Yahagi, Naoki; Doi, Kent

    2016-01-01

    Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793-0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741-0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697-0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers.

  10. Adipocyte Fatty Acid Binding Protein Potentiates Toxic Lipids-Induced Endoplasmic Reticulum Stress in Macrophages via Inhibition of Janus Kinase 2-dependent Autophagy

    Science.gov (United States)

    Hoo, Ruby L. C.; Shu, Lingling; Cheng, Kenneth K. Y.; Wu, Xiaoping; Liao, Boya; Wu, Donghai; Zhou, Zhiguang; Xu, Aimin

    2017-01-01

    Lipotoxicity is implicated in the pathogenesis of obesity-related inflammatory complications by promoting macrophage infiltration and activation. Endoplasmic reticulum (ER) stress and adipocyte fatty acid binding protein (A-FABP) play key roles in obesity and mediate inflammatory activity through similar signaling pathways. However, little is known about their interplay in lipid-induced inflammatory responses. Here, we showed that prolonged treatment of palmitic acid (PA) increased ER stress and expression of A-FABP, which was accompanied by reduced autophagic flux in macrophages. Over-expression of A-FABP impaired PA-induced autophagy associating with enhanced ER stress and pro-inflammatory cytokine production, while genetic ablation or pharmacological inhibition of A-FABP reversed the conditions. PA-induced expression of autophagy-related protein (Atg)7 was attenuated in A-FABP over-expressed macrophages, but was elevated in A-FABP-deficient macrophages. Mechanistically, A-FABP potentiated the effects of PA by inhibition of Janus Kinase (JAK)2 activity, thus diminished PA-induced Atg7 expression contributing to impaired autophagy and further augmentation of ER stress. These findings suggest that A-FABP acts as autophagy inhibitor to instigate toxic lipids-induced ER stress through inhibition of JAK2-dependent autophagy, which in turn triggers inflammatory responses in macrophages. A-FABP-JAK2 axis may represent an important pathological pathway contributing to obesity-related inflammatory diseases. PMID:28094778

  11. Conserved charged amino acids are key determinants for fatty acid binding proteins (FABPs)-membrane interactions. A multi-methodological computational approach.

    Science.gov (United States)

    Zamarreño, Fernando; Giorgetti, Alejandro; Amundarain, María Julia; Viso, Juan Francisco; Córsico, Betina; Costabel, Marcelo D

    2017-03-16

    Based on the analysis of the mechanism of ligand transfer to membranes employing in vitro methods, Fatty Acid Binding Protein (FABP) family has been divided in two subgroups: collisional and diffusional FABPs. Although the collisional mechanism has been well characterized employing in vitro methods, the structural features responsible for the difference between collisional and diffusional mechanisms remain uncertain. In this work, we have identified the amino acids putatively responsible for the interaction with membranes of both, collisional and diffusional, subgroups of FABPs. Moreover, we show how specific changes in FABPs' structure could change the mechanism of interaction with membranes. We have computed protein-membrane interaction energies for members of each subgroup of the family, and performed Molecular Dynamics simulations that have shown different configurations for the initial interaction between FABPs and membranes. In order to generalize our hypothesis, we extended the electrostatic and bioinformatics analysis over FABPs of different mammalian genus. Also, our methodological approach could be used for other systems involving protein-membrane interactions.

  12. Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study.

    Science.gov (United States)

    Liu, Gang; Ding, Ming; Chiuve, Stephanie E; Rimm, Eric B; Franks, Paul W; Meigs, James B; Hu, Frank B; Sun, Qi

    2016-11-01

    To examine select adipokines, including fatty acid-binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus. Plasma levels of fatty acid-binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993-2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid-binding protein 4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22-2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the hazard ratio (95% confidence interval) was 2.07 (1.42-3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50-1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance. These data suggest that higher levels of fatty acid-binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus. © 2016 American Heart Association, Inc.

  13. Adipocyte fatty acid-binding protein and metabolic syndrome%脂肪细胞型脂肪酸结合蛋白与代谢综合征

    Institute of Scientific and Technical Information of China (English)

    李秋桂; 肖永康; 蒋建华

    2009-01-01

    脂肪细胞型脂肪酸结合蛋白(A-FABP)是近年来新发现的脂肪因子.动物实验表明其可以促进代谢综合征各组分如胰岛素抵抗、血脂紊乱、2型糖尿病和动脉粥样硬化的发生、发展.人群研究也发现,其过度表达而导致血浆中含量增加是反映代谢综合征的一个可靠生物标志物.随着研究的深入,A-FABP对于治疗代谢综合征的作用也日益受到人们的关注.以下主要就近年来有关A-FABP的分布、结构、特性及其与代谢综合征组分的关系作一综述.%Adipocyte fatty acid-binding protein(A-FABP) is a new-found adipocytokine which secreted from adipocyte. Animal experiment indicated that A-FABP can promote the development of insulin resistance, dyslipidemia, type 2 diabetes mellitns and artheroaclerosis in metabolic syndrome. Population studies found that serum A-FABP level might be an independent biomarker of metabolic syndrome. The effect of A-FABP in treating metabolic syndrome is concerned by people gradually. This article introduces the distribution, structure, property of A-FABP, and the relationship between A-FABP and the components of metabolic syndrome.

  14. Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME: Background and design of a diagnostic study in primary care

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    Doevendans Pieter A

    2008-04-01

    Full Text Available Abstract Background Currently used biomarkers for cardiac ischemia are elevated in blood plasma after a delay of several hours and therefore unable to detect acute coronary syndrome (ACS in a very early stage. General practitioners (GPs, however, are often confronted with patients suspected of ACS within hours after onset of complaints. This ongoing study aims to evaluate the added diagnostic value beyond clinical assessment for a rapid bedside test for heart-type fatty-acid binding protein (H-FABP, a biomarker that is detectable as soon as one hour after onset of ischemia. Methods Participating GPs perform a blinded H-FABP rapid bedside test (Cardiodetect® in patients with symptoms suggestive of ACS such as chest pain or discomfort at rest. All patients, whether referred to hospital or not, undergo electrocardiography (ECG and venapunction for a plasma troponin test within 12–36 hours after onset of complaints. A final diagnosis will be established by an expert panel consisting of two cardiologists and one general practitioner (blinded to the H-FABP test result, using all available patient information, also including signs and symptoms. The added diagnostic value of the H-FABP test beyond history taking and physical examination will be determined with receiver operating characteristic curves derived from multivariate regression analysis. Conclusion Reasons for presenting the design of our study include the prevention of publication bias and unacknowledged alterations in the study aim, design or data-analysis. To our knowledge this study is the first to assess the diagnostic value of H-FABP outside a hospital-setting. Several previous hospital-based studies showed the potential value of H-FABP in diagnosing ACS. Up to now however it is unclear whether these results are equally promising when the test is used in primary care. The first results are expected in the end of 2008.

  15. Elevation of fatty acid-binding protein 4 is predisposed by family history of hypertension and contributes to blood pressure elevation.

    Science.gov (United States)

    Ota, Hideki; Furuhashi, Masato; Ishimura, Shutaro; Koyama, Masayuki; Okazaki, Yusuke; Mita, Tomohiro; Fuseya, Takahiro; Yamashita, Tomohisa; Tanaka, Marenao; Yoshida, Hideaki; Shimamoto, Kazuaki; Miura, Tetsuji

    2012-10-01

    Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, and atherosclerosis. However, little is known about the role of FABP4 in essential hypertension. We first examined serum FABP4 concentrations in 18 normotensives (NT) and 30 nontreated essential hypertensives (EHT). The EHT were divided into 18 insulin-sensitive EHT (EHT-S) and 12 insulin-resistant EHT (EHT-R) based on their insulin-sensitivity index, the M value, determined by the hyperinsulinemic-euglycemic clamp technique. In the second study, we determined FABP4 levels in 30 young NT men with or without a family history of hypertension (FH(+) and FH(-), respectively; n = 15 each). Serum FABP4 level was significantly higher in the EHT-R than in the NT, whereas elevation of FABP4 level in the EHT-S was not statistically significant. FABP4 level was positively correlated with age, body mass index (BMI), blood pressure, and triglycerides and negatively correlated with the M value. FABP4 level was an independent predictor of mean arterial pressure after adjustment of age, gender, and adiposity. The FH(+) group had a significantly lower level of M value and higher level of FABP4 than did the FH(-) group, and FABP4 concentration was an independent determinant of the M value. FABP4 contributes to blood pressure elevation and atherogenic metabolic phenotype in hypertensives, and the elevation of FABP4 is predisposed by a family history of hypertension.

  16. [Relation of heart-type fatty acid-binding protein with the degree and extent of atherosclerosis in patients with non-ST elevation acute coronary syndrome].

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    Zeren, Gönül; Erer, Hatice Betül; Kırış, Tuncay; Sahin, Osman; Aksu, Hüseyin; Köprülü, Diyar; Güvenç, Tolga Sinan; Erdoğan, Güney; Sayar, Nurten; Günaydın, Zeki Yüksel; Eren, Mehmet

    2013-10-01

    The relationship between markers of myocardial ischemia and severity of coronary artery disease (CAD) has been investigated in several studies. In this study, we examined the relationship between severity of CAD and heart-type fatty acid-binding protein (H-FABP), a new marker of ischemia in patients with non-ST-segment elevation acute coronary syndrome (ACS). This prospective study comprised 49 patients who were referred to the emergency room with a diagnosis of non-ST elevation myocardial infarction. Troponins, creatine kinase-MB, lactate dehydrogenase, and aspartate aminotransferase levels were measured quantitatively, while blood H-FABP levels were measured qualitatively in the 4th-8th hour from the onset of symptoms. All patients underwent coronary angiography within 72 hours after admission. Clinical and coronary angiographic characteristics of patients with positive and negative values of H-FABP were compared. Gensini and SYNTAX scores were used to determine the severity of CAD. There were no statistically significant differences in mean age, gender distribution, risk factors for CAD, ischemic changes on ECG, or Gensini and SYNTAX scores between the H-FABP-negative and -positive groups (p>0.05). The duration of chest pain in the H-FABP-positive group was significantly longer than in the negative group (p<0.001). Troponin, CK-MB, and AST levels as well as thrombolysis in myocardial infarction (TIMI) risk scores were found to be significantly higher in the H-FABP-positive group (p<0.05). H-FABP is a useful marker for the diagnosis and risk evaluation of patients with non-ST elevation ACS. However, it is insufficient in evaluating the severity of CAD.

  17. Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo.

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    Martin, Ivelisse; Cabán-Hernández, Kimberly; Figueroa-Santiago, Olgary; Espino, Ana M

    2015-04-15

    TLR4, the innate immunity receptor for bacterial endotoxins, plays a pivotal role in the induction of inflammatory responses. There is a need to develop molecules that block either activation through TLR4 or the downstream signaling pathways to inhibit the storm of inflammation typically elicited by bacterial LPS, which is a major cause of the high mortality associated with bacterial sepsis. We report in this article that a single i.p. injection of 15 μg fatty acid binding protein from Fasciola hepatica (Fh12) 1 h before exposure to LPS suppressed significantly the expression of serum inflammatory cytokines in a model of septic shock using C57BL/6 mice. Because macrophages are a good source of IL-12p70 and TNF-α, and are critical in driving adaptive immunity, we investigated the effect of Fh12 on the function of mouse bone marrow-derived macrophages (bmMΦs). Although Fh12 alone did not induce cytokine expression, it significantly suppressed the expression of IL-12, TNF-α, IL-6, and IL-1β cytokines, as well as inducible NO synthase-2 in bmMΦs, and also impaired the phagocytic capacity of bmMΦs. Fh12 had a limited effect on the expression of inflammatory cytokines induced in response to other TLR ligands. One mechanism used by Fh12 to exert its anti-inflammatory effect is binding to the CD14 coreceptor. Moreover, it suppresses phosphorylation of ERK, p38, and JNK. The potent anti-inflammatory properties of Fh12 demonstrated in this study open doors to further studies directed at exploring the potential of this molecule as a new class of drug against septic shock or other inflammatory diseases.

  18. Sequencing of Intron 3 of Porcine Heart Fatty Acid-Binding Protein Gene%猪H-FABP基因intron3全序列测定

    Institute of Scientific and Technical Information of China (English)

    杨文平; 张家琦; 李彩桃; 王明艳; 张红梅; 李超; 曹果清; 周忠孝

    2012-01-01

    [目的]为将H-FABP基因应用于猪育种过程中的标记辅助选择提供基础资料.[方法]根据GenBank数据库上公开发表的相关的猪H-FABP基因序列设计特异性扩增引物,对H-FABP基因内含子3的PCR产物纯化后直接进行测序.[结果]成功扩增出猪H-FABP基因intron 3的全序列,全长为1 350 bp,已向GenBank数据库提交,检索号为DQ 002993.[结论]该研究为确定影响肌内脂肪沉积的主效基因奠定了理论基础.%[ Objective ]The aim of this paper is to provide the basic data for marker-assisted selection of pig breeding using porcine heart fatty acid-binding protein (H-FABP) gene. [Method]According to the related sequences of porcine H-FABP gene released in GenBank,specific primers were designed to amplify the intron 3 of porcine H-FABP gene. [ Result] The intron 3 of porcine H-FABP gene was amplified successfully. Its whole sequence was 1 350 bp in length and had been submitted to GenBank (Accesion no. :DQ 002993). [Conclusion] The study lays a theoretical foundation for deter ruination of the major genes affecting intramuscular fat deposition.

  19. A radial glia gene marker, fatty acid binding protein 7 (FABP7, is involved in proliferation and invasion of glioblastoma cells.

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    Antonella De Rosa

    Full Text Available Glioblastoma multiforme (GBM is among the most deadly cancers. A number of studies suggest that a fraction of tumor cells with stem cell features (Glioma Stem-like Cells, GSC might be responsible for GBM recurrence and aggressiveness. GSC similarly to normal neural stem cells, can form neurospheres (NS in vitro, and seem to mirror the genetic features of the original tumor better than glioma cells growing adherently in the presence of serum. Using cDNA microarray analysis we identified a number of relevant genes for glioma biology that are differentially expressed in adherent cells and neurospheres derived from the same tumor. Fatty acid-binding protein 7 (FABP7 was identified as one of the most highly expressed genes in NS compared to their adherent counterpart. We found that down-regulation of FABP7 expression in NS by small interfering RNAs significantly reduced cell proliferation and migration. We also evaluated the potential involvement of FABP7 in response to radiotherapy, as this treatment may cause increased tumor infiltration. Migration of irradiated NS was associated to increased expression of FABP7. In agreement with this, in vivo reduced tumorigenicity of GBM cells with down-regulated expression of FABP7 was associated to decreased expression of the migration marker doublecortin. Notably, we observed that PPAR antagonists affect FABP7 expression and decrease the migration capability of NS after irradiation. As a whole, the data emphasize the role of FABP7 expression in GBM migration and provide translational hints on the timing of treatment with anti-FABP7 agents like PPAR antagonists during GBM evolution.

  20. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery.

    Science.gov (United States)

    Parikh, Chirag R; Thiessen-Philbrook, Heather; Garg, Amit X; Kadiyala, Deepak; Shlipak, Michael G; Koyner, Jay L; Edelstein, Charles L; Devarajan, Prasad; Patel, Uptal D; Zappitelli, Michael; Krawczeski, Catherine D; Passik, Cary S; Coca, Steven G

    2013-07-01

    AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period. This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis. KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2. Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.

  1. Serum fatty acid-binding protein 4 (FABP4) concentration is associated with insulin resistance in peripheral tissues, A clinical study.

    Science.gov (United States)

    Nakamura, Risa; Okura, Tsuyoshi; Fujioka, Yohei; Sumi, Keisuke; Matsuzawa, Kazuhiko; Izawa, Shoichiro; Ueta, Etsuko; Kato, Masahiko; Taniguchi, Shin-Ichi; Yamamoto, Kazuhiro

    2017-01-01

    Type 2 diabetes mellitus (T2DM) is caused by insulin resistance and β cell dysfunction. In recent studies reported that several markers associated with insulin sensitivity in skeletal muscle, Adiponectin and other parameters, such as fatty acid-binding protein (FABP4), have been reported to regulate insulin resistance, but it remains unclear which factor mostly affects insulin resistance in T2DM. In this cross-sectional study, we evaluated the relationships between several kinds of biomarkers and insulin resistance, and insulin secretion in T2DM and healthy controls. We recruited 30 participants (12 T2DM and 18 non-diabetic healthy controls). Participants underwent a meal tolerance test during which plasma glucose, insulin and serum C-peptide immunoreactivity were measured. We performed a hyperinsulinemic-euglycemic clamp and measured the glucose-disposal rate (GDR). The fasting serum levels of adiponectin, insulin-like growth factor-1, irisin, autotaxin, FABP4 and interleukin-6 were measured by ELISA. We found a strong negative correlation between FABP4 concentration and GDR in T2DM (r = -0.657, p = 0.020). FABP4 also was positively correlated with insulin secretion during the meal tolerance test in T2DM (IRI (120): r = 0.604, p = 0.038) and was positively related to the insulinogenic index in non-DM subjects (r = 0.536, p = 0.022). Autotaxin was also related to GDR. However, there was no relationship with insulin secretion. We found that serum FABP4 concentration were associated with insulin resistance and secretion in T2DM. This suggests that FABP4 may play an important role in glucose homeostasis.

  2. Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

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    Janyaporn Phuchareon

    2014-12-01

    Full Text Available Adenoid cystic carcinoma (ACC is an aggressive malignant neoplasm of the salivary glands. Its diagnosis is difficult due to overlapping features with other salivary tumors. Gene expression analysis may complement traditional diagnostic methods. We searched gene expression patterns in the Gene Expression Omnibus (GEO database and in our tumor and normal samples. The biologic and prognostic potential of the identified genes was analyzed. The GEO data set of primary xenografted ACCs revealed that expression of five genes, engrailed homeobox 1 (EN1, fatty acid binding protein 7 (FABP7, hemoglobin epsilon 1, MYB, and versican (VCAN, was dramatically increased. mRNA expression of EN1, FABP7, MYB, and VCAN distinguished our sporadic ACCs from normal tissues and benign tumors. FABP7 expression appeared to be regulated differently from EN1 and MYB and was crossly correlated with poor prognosis in our ACC cohort. Immunohistochemistry showed that FABP7 protein was predominantly expressed in the nucleus of myoepithelial cells of both tubular and cribriform subtypes. In contrast, in the solid subtype, which is often associated with a lower survival rate, FABP7 protein was uniformly expressed in cancerous cells. One case with cribriform architecture and the highest level of FABP7 mRNA showed strong FABP7 staining in both duct-type epithelial and myoepithelial cells, suggesting that diffuse expression of FABP7 protein might be related to aggressive tumor behavior and poor prognosis. We propose FABP7 as a novel biomarker in ACC. The molecule may be useful in diagnosis and for identifying more effective therapies targeting this protein or upstream molecules that regulate it.

  3. Role of Heart-Type Fatty Acid Binding Protein in Early Detection of Acute Myocardial Infarction in Comparison with cTnI, CK-MB and Myoglobin

    Institute of Scientific and Technical Information of China (English)

    陈莉莉; 郭小梅; 杨霏

    2004-01-01

    Heart fatty acid-binding protein (H-FABP) is supposed to be the most sensitive biomarker of early acute myocardial infarction (AMI). To evaluate the diagnostic value of H-FABP for AMI in the early stage, the plasma levels of H-FABP were measured by sandwich ELISA in 93 patients with suspected AMI at admission within 6 h after onset of chest pain and 69 normal healthy subjects. The plasma concentrations of cardiac troponin-I (cTnI), creatine kinase-MB (CK-MB)and myoglobin (Mb) were assayed at the same time by using corpuscle chemiluminescence for those patients. The patients were classified as AMI group (n= 32) and non-AMI group (n= 61) retrospectively. The diagnostic validity was evaluated in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve analysis. The results showed the cutoff value of H-FABP for AMI was 16.8 ng/ml, and its diagnostic sensitivity for AMI was 64.29 % within 3 h and 84.38 %within 6 h after onset of chest pain, and the diagnostic specificity for non-AMI was 100 % within 3h and 91.8 % within 6 h. H-FABP had higher sensitivity than that of cTnI and CK-MB at all time points (P<0.05), whereas there was no significant difference in specificity among the four markers. But the area under the ROC curve of H-FABP was significantly greater than that of cTnI, CKMB and Mb within 3 h. These results revealed that H-FABP possessed high diagnostic sensitivity and specificity for AMI in early stage, especially within 3 h after onset of persistent angina pectoris.In conclusion, H-FABP can be used as a sensitive marker for AMI in the early stage.

  4. Influence of berberine combining with atorvastatin on serum high-sensitivity C-reactive protein and adipocyte fatty acid-binding protein in patients with acute ischemic stroke

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    Fei-qi ZHU

    2015-01-01

    Full Text Available Objective To observe the influence of berberine combining with atorvastatin on serum high-sensitivity C-reactive protein (hs-CRP and adipocyte fatty acid-binding protein (A-FABP in patients with acute ischemic stroke.  Methods Ischemic stroke patients (N = 55 were randomized into 3 groups: atorvastatin 20 mg/d (N = 28, atorvastatin 40 mg/d (N = 11 and berberine 0.40 g three times a day + atorvastatin 20 mg/d (combined treatment, N = 16. They were treated for 3 months. The expression changes of serum hs-CRP and A-FABP before and after treatment were compared among 3 groups.  Results There were significant decreases between before and 3 months after treatment on the expression of hs-CRP and A-FABP in 3 groups (P = 0.023, 0.000. After treatment, both the expression of hs-CRP and A-FABP significantly decreased, and the decreases were (1.69 ± 2.29 and (281.43 ± 311.05 mg/L in atorvastatin 20 mg/d group, (7.81 ± 12.48 and (321.59 ± 289.35 mg/L in atorvastatin 40 mg/d group, and (2.16 ± 3.34 and (376.55 ± 249.72 mg/L in combined treatment group. However, there was no significant difference among 3 groups (P > 0.05, for all, and there was no correlation between drugs and observation time points (P > 0.05, for all.  Conclusions The effect of berberine combined with atorvastatin on hs-CRP and A-FABP is similar to atorvastation (40 mg/d therapy. DOI: 10.3969/j.issn.1672-6731.2015.01.010

  5. Correlation between Heart-type Fatty Acid-binding Protein Gene Polymorphism and mRNA Expression with Intramuscular Fat in Baicheng-oil Chicken.

    Science.gov (United States)

    Wang, Yong; He, Jianzhong; Yang, Wenxuan; Muhantay, Gemenggul; Chen, Ying; Xing, Jinming; Liu, Jianzhu

    2015-10-01

    This study aims to determine the polymorphism and mRNA expression pattern of the heart-type fatty acid-binding protein (H-FABP) gene and their association with intramuscular fat (IMF) content in the breast and leg muscles of Baicheng oil chicken (BOC). A total of 720 chickens, including 240 black Baicheng oil chicken (BBOC), 240 silky Baicheng oil chicken (SBOC), and 240 white Baicheng oil chicken (WBOC) were raised. Three genotypes of H-FABP gene second extron following AA, AB, and BB were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) strategy. The G939A site created AA genotype and G956A site created BB genotype. The content of IMF in AA genotype in breast muscle of BBOC was significantly higher than that of AB (p = 0.0176) and the genotype in leg muscle of WBOC was significantly higher than that of AB (p = 0.0145). The G939A site could be taken as genetic marker for higher IMF content selecting for breast muscle of BBOC and leg muscle of WBOC. The relative mRNA expression of H-FABP was measured by real-time PCR at 30, 60, 90, and 120 d. The IMF content significantly increased with age in both muscles. The mRNA expression level of H-FABP significantly decreased with age in both muscles of the three types of chickens. Moreover, a significant negative correlation between H-FABP abundance and IMF content in the leg muscles of WBOC (p = 0.035) was observed. The mRNA expression of H-FABP negatively correlated with the IMF content in both breast and leg muscles of BOC sat slaughter time.

  6. Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats

    Institute of Scientific and Technical Information of China (English)

    Yoon Shin Park; Yoosik Yoon; Hong Seok Ahn

    2007-01-01

    AIM: To investigate the effect of Platycodon grandiflorum extract (PGE) on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats.METHODS: PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03 ± 7.61 g were divided into four groups: the control groups that fed an experimental diet alone (C and H group) and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight (C + PGE and H + PGE group, respectively) for 7 wk. Plasma total cholesterol (TC) and triglycerol (TG) concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein (FABP) mRNA expression was analyzed by northern blot analysis.RESULTS: PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE significantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue.CONCLUSION: PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat diet.From these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.

  7. Low Abdominal NIRS Values and Elevated Plasma Intestinal Fatty Acid-Binding Protein in a Premature Piglet Model of Necrotizing Enterocolitis.

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    Irving J Zamora

    Full Text Available To identify early markers of necrotizing enterocolitis (NEC, we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP measured every 6 hours can detect NEC prior to onset of clinical symptoms. Premature piglets received parenteral nutrition for 48-hours after delivery, followed by enteral feeds every three hours until death or euthanasia at 96-hours. Continuous A-NIRS, systemic oxygen saturation (SpO2, and heart rate were measured while monitoring for clinical signs of NEC. Blood samples obtained at 6-hour intervals were used to determine pI-FABP levels by ELISA. Piglets were classified as fulminant-NEC (f-NEC, non-fulminant-NEC (nf-NEC and No-NEC according to severity of clinical and histologic features. Of 38 piglets, 37% (n=14 developed nf-NEC, 18% (n=7 developed f-NEC and 45% (n=17 had No-NEC. There were significant differences in baseline heart rate (p=0.008, SpO2 (p0.25ng/mL identified animals with NEC (68% sensitivity and 90% specificity. NIRS is a real-time, non-invasive tool that can serve as a diagnostic modality for NEC. In premature piglets, low A-NIRS in the early neonatal period and increased variability during initial feeds are highly predictive of NEC, which is then confirmed by rising plasma I-FABP levels. These modalities may help identify neonates with NEC prior to clinical manifestations of disease.

  8. Increase in skin autofluorescence and release of heart-type fatty acid binding protein in plasma predicts mortality of hemodialysis patients.

    Science.gov (United States)

    Arsov, Stefan; Trajceska, Lada; van Oeveren, Wim; Smit, Andries J; Dzekova, Pavlina; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Graaff, Reindert

    2013-07-01

    Advanced glycation end-products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1-year increase in skin autofluorescence (ΔAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients. One hundred sixty-nine HD patients were enrolled in this study. Skin autofluorescence was measured twice, 1 year apart using an AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). Besides routine blood chemistry, additional plasma markers including superoxide dismutase, myeloperoxydase, intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (hs-CRP), heart-type fatty acid binding protein (H-FABP), and von Willebrand factor were measured at baseline. The mortality of HD patients was followed for 36 months. Skin autofluorescence values of the HD patients at the two time points were significantly higher (P < 0.001) than those of healthy subjects of the same age. Mean 1-year ΔAF of HD patients was 0.16 ± 0.06, which was around seven- to ninefold higher than 1-year ΔAF in healthy subjects. Multivariate Cox regression showed that age, hypertension, 1-year ΔAF, hs-CRP, ICAM-1, and H-FABP were independent predictors of overall mortality. Hypertension, 1-year ΔAF, hs-CRP, and H-FABP were also independent predictors of cardiovascular mortality. One-year ΔAF and plasma H-FABP, used separately and in combination, are strong predictors of overall and cardiovascular mortality in HD patients.

  9. Conjugated linoleic acid and fatty acid binding protein as antioxidants Ácido linoleico conjugado y proteína transportadora de ácidos grasos como antioxidantes

    Directory of Open Access Journals (Sweden)

    V.A. Piergiacomi

    2006-12-01

    Full Text Available Studies were carried out to determine the effect of conjugated linoleic acid (CLA and rat liver cytosolic protein enriched in fatty acid binding protein (FABP on the non-enzymatic lipid peroxidation of rat liver microsomes. The inhibition of lipid peroxidation was more evident when the FABP containing fraction obtained from CLA-group was used with either kind of microsomes (CLA and control. The chemiluminescence and polyunsaturated fatty acid composition of rat liver microsomes changed after CLA treatment. When native and peroxidized microsomes obtained from control group were compared, the most affected polyunsaturated fatty acids were: C18:2, C18:3 and C20:4, while in CLA-group C20:4 was mainly peroxidized The simultaneous analysis of chemiluminescence and fatty acid composition demonstrated that CLA and FABP play a role protecting rat liver microsomes against the harmful effect of lipid peroxidation.El objetivo del trabajo fue determinar el efecto del ácido linoleico conjugado (ALC y de la proteína citosólica de hígado de rata enriquecida en Proteína Transportadora de Ácidos Grasos (PTAG, sobre la peroxidación no enzimática de lípidos de microsomas hepáticos de rata. Luego de la incubación de éstos en un sistema ascorbato-Fe++ se observó que el total de cpm/mg de proteina originada por quimioluminiscencia fue menor en los microsomas obtenidos de las ratas del grupo ALC respecto a los del grupo control. Cuando la fracción PTAG obtenida del grupo ALC fue agregada a la peroxidación de microsomas de ambos grupos de animales ALC y control, la inhibición de la lipoperoxidación fue más evidente. Además se encontró que ambas fracciones PTAG, tanto la obtenida de animales del grupo ALC como la obtenida del grupo control, tuvieron mayor efecto como antioxidantes cuando se usaron microsomas ALC respecto a microsomas control. La composición de ácidos grasos de los microsomas cambió luego del tratamiento con ALC. Comparando

  10. Clinical Usefulness of Urinary Fatty Acid Binding Proteins in Assessing the Severity and Predicting Treatment Response of Pneumonia in Critically Ill Patients: A Cross-Sectional Study.

    Science.gov (United States)

    Tsao, Tsung-Cheng; Tsai, Han-Chen; Chang, Shi-Chuan

    2016-05-01

    To investigate the clinical relevance of urinary fatty acid binding proteins (FABPs), including intestinal-FABP, adipocyte-FABP, liver-FABP, and heart-FABP in pneumonia patients required admission to respiratory intensive care unit (RICU).Consecutive pneumonia patients who admitted to RICU from September 2013 to October 2014 were enrolled except for those with pneumonia for more than 24 h before admission to RICU. Pneumonia patients were further divided into with and without septic shock subgroups. Twelve patients without infection were enrolled to serve as control group. Urine samples were collected on days 1 and 7 after admission to RICU for measuring FABPs and inflammatory cytokines. Clinical and laboratory data were collected and compared between pneumonia and control groups, and between the pneumonia patients with and without septic shock.There were no significant differences in urinary levels of various FABPs and inflammatory cytokines measured on day 1 between control and pneumonia groups. Urinary values of intestine-FABP (P = 0.020), adipocyte-FABP (P = 0.005), heart-FABP (P = 0.025), and interleukin-6 (P = 0.019) were significantly higher and arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2, P/F) ratio (P = 0.024) was significantly lower in pneumonia patients with septic shock on day 1 than in those without septic shock. After multivariate analysis, adipocyte-FABP was the independent factor (P = 0.026). Urinary levels of FABPs measured on day 7 of pneumonia patients were significantly lower in the improved than in nonimproved groups (P = 0.030 for intestine-FABP, P = 0.003 for adipocyte-FABP, P = 0.010 for heart-FABP, and P = 0.008 for liver-FABP, respectively). After multivariate analysis, adipocyte-FABP was the independent factor (P = 0.023).For pneumonia patients required admission to RICU, urinary levels of adipocyte-FABP on days 1 and 7 after admission to RICU may be valuable in assessing the

  11. Common genetic variants in fatty acid-binding protein-4 (FABP4) and clinical diabetes risk in the Women's Health Initiative Observational Study.

    Science.gov (United States)

    Chan, Kei-Hang K; Song, Yiqing; Hsu, Yi-Hsiang; You, Nai-Chieh Y; F Tinker, Lesley; Liu, Simin

    2010-09-01

    Adipocypte fatty acid-binding protein-4 (FABP4/adipocyte P2) may play a central role in energy metabolism and inflammation. In animal models, defects of the aP2 gene (aP2(-/-)) partially protected against the development of obesity-related insulin resistance, dyslipidemia, and atherosclerosis. However, it is unclear whether common genetic variation in FABP4 gene contributes to risk of type 2 diabetes (T2D) or diabetes-related metabolic traits in humans. We comprehensively assess the genetic associations of variants in the FABP4 gene with T2D risk and diabetes-associated biomarkers in a prospective study of 1,529 cases and 2,147 controls among postmenopausal women aged 50-79 years who enrolled in the Women's Health Initiative Observational Study (WHI-OS). We selected and genotyped a total of 11 haplotype-tagging single-nucleotide polymorphisms (tSNPs) spanning 41.3 kb across FABP4 in all samples. None of the SNPs and their derived haplotypes showed significant association with T2D risk. There were no significant associations between SNPs and plasma levels of inflammatory and endothelial biomarkers, including C-reactive protein, tumor necrosis factor (TNF), interleukin-6 (IL-6), E-selectin, and intercellular adhesion molecule (ICAM-1). Among African-American women, several SNPs were significantly associated with lower levels of vascular cell adhesion molecule-1 (VCAM-1), especially among those with incident T2D. On average, plasma levels of VCAM-1 were significantly lower among carriers of each minor allele at rs1486004(C/T; -1.08 ng/ml, P = 0.01), rs7017115(A/G; -1.07 ng/ml, P = 0.02), and rs2290201(C/T; -1.12 ng/ml, P = 0.002) as compared with the homozygotes of the common allele, respectively. After adjusting for multiple testing, carriers of the rs2290201 minor allele remained significantly associated with decreasing levels of plasma VCAM-1 in these women (P = 0.02). In conclusion, our finding from a multiethnic cohort of postmenopausal women did not support the

  12. Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation.

    Science.gov (United States)

    Ichikawa, Daisuke; Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Shibagaki, Yugo; Yasuda, Takashi; Katayama, Kimie; Hoshino, Seiko; Igarashi-Migitaka, Junko; Hirata, Kazuaki; Kimura, Kenjiro

    2014-03-15

    The aim of this study was to assess the renoprotective effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained. To activate the renal RAS, wild-type mice (L-FABP(-/-)AT1a(+/+)), L-FABP(+/-)AT1a(+/+), L-FABP(-/-)AT1a(+/-), L-FABP(+/-)AT1a(+/-), L-FABP(-/-)AT1a(-/-), and L-FABP(+/-)AT1a(-/-) were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP(-/-)AT1a(+/+), RAS activation (L-FABP(-/-)AT1a(+/+)RAS) caused hypertension and tubulointerstitial damage. In the L-FABP(+/-)AT1a(+/+)RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP(-/-)AT1a(+/+)RAS. In the AT1a partial knockout (AT1a(+/-)) or complete knockout (AT1a(-/-)) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP(-/-)AT1a(+/+)RAS or L-FABP(+/-)AT1a(+/+)RAS mice. Renal injury in L-FABP(+/-)AT1a(+/-)RAS mice was significantly attenuated compared with L-FABP(-/-)AT1a(+/-)RAS mice. In both L-FABP(-/-)AT1a(-/-)RAS and L-FABP(+/-)AT1a(-/-)RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.

  13. Point-of-care heart-type fatty acid binding protein versus high-sensitivity troponin T testing in emergency patients at high risk for acute coronary syndrome.

    Science.gov (United States)

    Kellens, Sebastiaan; Verbrugge, Frederik H; Vanmechelen, Maxime; Grieten, Lars; Van Lierde, Johan; Dens, Joseph; Vrolix, Mathias; Vandervoort, Pieter

    2016-04-01

    High-sensitivity cardiac troponin testing is used to detect myocardial damage in patients with acute chest pain. Heart-type fatty acid binding protein (H-FABP) may be an alternative, available as point-of-care test. Patients (n=203) referred by general practitioners for suspected acute coronary syndrome or presenting with typical chest pain and one major cardiovascular risk factor at the emergency department were prospectively included in a single-centre cohort study. High-sensitivity cardiac troponin T (hs-TnT) and point-of-care H-FABP testing were concomitantly performed at admission and after 6h. Maximal hs-TnT levels above the 99th percentile were observed in 152 patients (75%) with 127 (63%) fulfilling criteria for myocardial infarction. Upon admission, hs-TnT and H-FABP were associated with an area under the curve (95% CI) of 0.83 (0.77-0.89) and 0.79 (0.73-0.85), respectively, to predict myocardial infarction, which increased to 0.93 (0.90-0.97) and 0.88 (0.84-0.93), respectively, after 6h. The diagnostic accuracy for non-ST-segment elevation myocardial infarction was somewhat lower with an area under the curve (95% CI) of 0.80 (0.72-0.87), 0.90 (0.84-0.96), 0.73 (0.64-0.81) and 0.77 (0.67-0.86), respectively. When assessment was performed within 3h of chest pain onset, diagnostic accuracy of H-FABP versus hs-TnT was similar. Each standard deviation increase in admission H-FABP was associated with a 68% relative risk increase of all-cause mortality (p-value=0.027) during 666 ± 155 days of follow-up. Point-of-care H-FABP testing has lower diagnostic accuracy compared with hs-TnT assessment in patients with high pre-test acute coronary syndrome probability, but might be of interest when assessment is possible early after chest pain onset. © The European Society of Cardiology 2015.

  14. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

    Directory of Open Access Journals (Sweden)

    Zulezwan A. Malik

    2013-12-01

    Full Text Available Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC coupled to mass spectrometry (MS affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group bred as either high- or low-capacity runners (HCR and LCR, respectively that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p < 0.0001 in running capacity during a standardized treadmill test. Soluble muscle proteins were extracted, digested with trypsin and individual biological replicates (50 ng of tryptic peptides subjected to LC-MS profiling. Proteins were identified by triplicate LC-MS/MS analysis of a pooled sample of each biological replicate. Differential expression profiling was performed on relative abundances (RA of parent ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897 and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5. Sixteen proteins were significantly (p < 0.05 more abundant in HCR muscle and hierarchal clustering of the profiling data highlighted two protein subgroups, which encompassed proteins associated with either the respiratory chain or fatty acid oxidation. Heart-type fatty acid binding protein (FABPH was 1

  15. An acyl-CoA-binding protein (FcACBP) and a fatty acid binding protein (FcFABP) respond to microbial infection in Chinese white shrimp, Fenneropenaeus chinensis.

    Science.gov (United States)

    Ren, Qian; Du, Zhi-Qiang; Zhao, Xiao-Fan; Wang, Jin-Xing

    2009-12-01

    Acyl-CoA-binding protein (ACBP) and fatty acid-binding protein (FABP) are involved in lipid metabolism. ACBP plays a key role in multiple cellular tasks including modulation of fatty acid biosynthesis, enzyme regulation, vesicular trafficking, and gene regulation. In our study, a 536 bp cDNA of ACBP (FcACBP) was cloned and identified as a widely distributed gene in the Chinese white shrimp, Fenneropenaeus chinensis. Its expression in intestine was upregulated in response to white spot syndrome virus (WSSV) or Vibrio anguillarum infection. The expression patterns were confirmed by Western blot analysis. FABPs, members of the lipid-binding protein superfamily, play an important role in lipid metabolism and also participate in vertebrate innate immunity. A cDNA of FABP (FcFABP) cloned from the hepatopancreas of the shrimp was 715 bp in size and encoded a 14 kDa protein. FcFABP appeared to be a basic fatty acid binding protein with a predicted isoelectric point of 9.16. It showed sequence similarity to both vertebrate and invertebrate FABPs. Phylogenetic analysis showed that FcFABP, together with LvFABP, were clustered into one group. FcFABP was detected mainly in the hepatopancreas and expression level increased after a challenge with WSSV. FcFABP was down-regulated by V. anguillarum challenge. The protein also had bacterial binding activity. These two lipid metabolism related proteins may play important roles in shrimp innate immunity.

  16. 脂肪细胞型脂肪酸结合蛋白与肥胖及代谢综合征%Association of adipocyte fatty acid-binding protein with obesity and metabolism syndrome

    Institute of Scientific and Technical Information of China (English)

    黄岚; 邹大进

    2009-01-01

    脂肪细胞型脂肪酸结合蛋白(A-FABP)主要在脂肪组织中大量表达,其主要生理作用为参与细胞内部的脂肪酸转运和靶向定位.近期的研究发现,A-FABP是全身胰岛素敏感性以及糖脂代谢的重要调节冈素,与肥胖及代谢综合征的发生发展有紧密联系.%Adipocyte fatty acid-binding protein(A-FABP)belongs to the fatty acid-binding protein super-family, and it is highly expressed in adipose tissue.The physiologic function of A-FABP is involved in the intracellular trafficking and targeting of fatty acids inside cells.Recent research indicated that this protein may be all important regulator of systemic insulin sensitivity as well as lipid and glucose metabolism,indicating that A-FABP participates in the pathogenesis of obesity and metabolic syndrome.

  17. Diagnosis of Non-ST-Elevation Acute Coronary Syndrome by the Measurement of Heart-Type Fatty Acid Binding Protein in Serum: A Prospective Case Control Study

    Directory of Open Access Journals (Sweden)

    Priscilla Abraham Chandran

    2014-01-01

    Full Text Available A prospective case control study was undertaken to evaluate the diagnostic performance of serum heart-type fatty acid binding protein (HFABP in comparison to cardiac TnT and TnI in 33 patients admitted with chest pain, diagnosed as NSTE-ACS (non ST elevation acute coronary syndrome and 22 healthy controls. Area under the receiver operating curve (AUC was highest for H-FABP (AUC 0.79; 95% CI 0.66–0.89 versus cTnI (AUC 0.73; 95% CI 0.59–0.84 and cTnT (AUC 0.71; 95% CI 0.57–0.83. The H-FABP level above 6.5 ng/mL showed 56.7% (CI 37.4–74.5 sensitivity, 0.5 (95% CI 0.3–0.7 negative likelihood ratio (−LR, 100% (CI 84.6–100.0 specificity, and 100% (CI 79.4–100.0 positive predictive value (PPV, 62.9% (CI 44.9–78.5 negative predictive value (NPV. cTnI level above 0.009 μg/L had 40% (CI 22.7–59.4 sensitivity, 0.6 (95% CI 0.4–0.8 −LR, 100% (CI 84.6–100.0 specificity, 100% (CI 73.5–100.0 PPV, and 55% (CI 38.5–70.7 NPV. cTnT showed 46.7% (CI 28.3–65.7 sensitivity, 0.5 (95% CI 0.4–0.7 −LR, 100% (CI 84.6–100.0 specificity, 100% (CI 76.8–100.0 PPV, and 57.9% (CI 40.8–73.7 NPV at level above 9 μg/L. +LR were 12.5 (95% CI 1.8–86.8, 1.7 (95% CI 1.0–3.0, and 1.2 (95% CI 0.8–1.9 for H-FABP, cTnI, and cTnT respectively. In conclusion measurement of H-FABP is a valuable tool in the early diagnosis of patients with chest pain (6–8 hrs and seems to be a preferred biomarker in the differential diagnosis of NSTE-ACS. More studies are needed to determine whether serum H-FABP further improves diagnostic performance.

  18. [Expression of peroxisome proliferator-activated receptors, fatty acid binding protein-4 in placenta and their correlations with the prognosis of pre-eclampsia].

    Science.gov (United States)

    Li, Y; Chen, W L; Liu, L; Gu, H

    2017-07-25

    Objective: To examine the mRNA and protein expression of peroxisome proliferator-activated receptors (PPAR) and fatty acid binding protein-4 (FABP-4) in placenta, and to investigate their correlation with the prognosis of pre-eclampsia. Methods: The data of 177 women who delivered from January 2013 to December 2015 in Chinese People's Liberation Army No.94 Hospital were collected. Among them, 60 cases were term pregnancy and not in labor (TN); 46 cases were term pregnancy with preeclampsia and not in labor (TPE); 42 cases were preterm pregnancy and not in labor (PN); 29 cases were preterm pregnancy with pre-eclampsia and not in labor (PPE). Real-time PCR and western blot were used to examine the PPAR and FABP-4 mRNA expression and protein expression in placentas. And linear correlation was used to analyze the relationship between PPAR and FABP-4 protein expression and the prognosis of pre-eclampsia. Results: (1) Real-time PCR showed that: ① PPAR-α, PPAR-β mRNA expression were not statistically different between placentas from TN and TPE (P>0.05), but PPAR-γ mRNA level in TPE (0.59±0.17) was significantly lower than that in TN (0.81±0.19, P0.05) . However, PPAR-γ mRNA in the PPE group (0.33±0.14) was significantly lower than that in PN (0.52±0.16, P<0.01), and FABP-4 mRNA level in the PPE group (0.80±0.29) was significantly higher than in the PN group (0.63±0.22, P<0.01). (2) Western-blot showed the same tendency as the mRNA results. ①There were no statistical differences in the protein expression of PPAR-α, PPAR-β, not in term groups (TN and TPE) , nor in premature groups (PN and PPE) . PPAR-γ protein level in the TPE group (0.46±0.17) was significantly lower than that in TN (0.65±0.20, P<0.01) and FABP-4 protein level in the TPE group (0.60±0.19) was significantly higher than that in the TN group (0.50±0.21, P<0.05). ②The PPAR-γ protein level in the PPE group (0.30±0.16) was significantly lower than that in the PN group (0.61±0.16, P<0

  19. 大鼠非酒精性脂肪肝中L-FABP的动态表达%Expression of liver fatty acid binding protein in rat nonalcoholic fatty liver

    Institute of Scientific and Technical Information of China (English)

    冯爱娟; 陈东风

    2004-01-01

    目的:研究L-FABP(liver fatty acid binding protein)在大鼠非酒精性脂肪肝形成中的作用.方法:建立高脂饮食脂肪肝模型,用半定量逆转录聚合酶链反应(RT-PCR)与聚丙烯凝胶蛋白电泳(Western Blot)方法测定脂肪肝肝组织中L-FABP表达变化.结果:高脂饮食脂肪肝大鼠肝脏中L-FABP于2 wk时其mRNA及蛋白表达增强,于12 wk时表达最为明显,与正常组比较相差显著(1.42±0.034vs0.90±0.04;13 372.00±23.86vs6857.33±32.9 6637;P<0.05).结论:高脂饮食引起L-FABP表达增强,最初是一种适应性反应,随着L-FABP表达进一步增强,导致脂肪酸代谢失衡,引起脂肪肝的发生.

  20. Suspected acute coronary syndrome in the emergency room: Limited added value of heart type fatty acid binding protein point of care or ELISA tests: The FAME-ER (Fatty Acid binding protein in Myocardial infarction Evaluation in the Emergency Room) study.

    Science.gov (United States)

    Bank, Ingrid Em; Dekker, Marieke S; Hoes, Arno W; Zuithoff, Nicolaas Pa; Verheggen, Peter Whm; de Vrey, Evelyn A; Wildbergh, Thierry X; Timmers, Leo; de Kleijn, Dominique Pv; Glatz, Jan Fc; Mosterd, Arend

    2016-08-01

    Timely recognition of acute coronary syndrome remains a challenge as many biomarkers, including troponin, remain negative in the first hours following the onset of chest pain. We assessed the diagnostic accuracy of heart-type fatty acid binding protein (H-FABP), a cardiac biomarker with potential value immediately post symptom onset. Prospective monocentre diagnostic accuracy study of H-FABP bedside point of care (CardioDetect®) and ELISA tests in acute coronary syndrome suspected patients presenting within 24 hours of symptom onset to the emergency department, in addition to clinical findings, electrocardiography and the currently recommended biomarker high sensitivity troponin-T (hs-cTnT). The final diagnosis of acute coronary syndrome was adjudicated by two independent cardiologists, blinded to H-FABP results. Acute coronary syndrome was diagnosed in 149 (32.9%) of 453 unselected patients with suspected acute coronary syndrome (56% men, mean age 62.6 years). Negative predictive values were similar for H-FABP point of care and ELISA tests (79% vs. 78% respectively), but inferior to initial hs-cTnT (negative predictive value 86%). The addition of H-FABP point of care results to hs-cTnT increased the negative predictive value to 89%. In a multivariable logistic regression model, H-FABP point of care and ELISA tests yielded relevant diagnostic information in addition to clinical findings and ECG (likelihood ratio test pcoronary syndrome presenting to the emergency department, H-FABP testing improves diagnostic accuracy in addition to clinical findings and electrocardiography. H-FABP, however, has no additional diagnostic value when hs-cTnT measurements are also available. © The European Society of Cardiology 2015.

  1. Sequence-specific {sup 1}H, {sup 13}C, and {sup 15}N resonance assignments for intestinal fatty-acid-binding protein complexed with palmitate (15.4 kDA)

    Energy Technology Data Exchange (ETDEWEB)

    Hodsdon, M.E.; Toner, J.J.; Cistola, D.P. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-12-01

    Intestinal fatty-acid-binding protein (I-FABP) belongs to a family of soluble, cytoplasmic proteins that are thought to function in the intracellular transport and trafficking of polar lipids. Individual members of this protein family have distinct specificities and affinities for fatty acids, cholesterol, bile salts, and retinoids. We are comparing several retinol- and fatty-acid-binding proteins from intestine in order to define the factors that control molecular recognition in this family of proteins. We have established sequential resonance assignments for uniformly {sup 13}C/{sup 15}N-enriched I-FABP complexed with perdeuterated palmitate at pH7.2 and 37{degrees}C. The assignment strategy was similar to that introduced for calmodulin. We employed seven three-dimensional NMR experiments to establish scalar couplings between backbone and sidechain atoms. Backbone atoms were correlated using triple-resonance HNCO, HNCA, TOCSY-HMQC, HCACO, and HCA(CO)N experiments. Sidechain atoms were correlated using CC-TOCSY, HCCH-TOCSY, and TOCSY-HMQC. The correlations of peaks between three-dimensional spectra were established in a computer-assisted manner using NMR COMPASS (Molecular Simulations, Inc.) Using this approach, {sup 1}H, {sup 13}C, and {sup 15}N resonance assignments have been established for 120 of the 131 residues of I-FABP. For 18 residues, amide {sup 1}H and {sup 15}N resonances were unobservable, apparently because of the rapid exchange of amide protons with bulk water at pH 7.2. The missing amide protons correspond to distinct amino acid patterns in the protein sequence, which will be discussed. During the assignment process, several sources of ambiguity in spin correlations were observed. To overcome this ambiguity, the additional inter-residue correlations often observed in the HNCA experiment were used as cross-checks for the sequential backbone assignments.

  2. Cytochrome P450, peroxisome proliferation, and cytoplasmic fatty acid-binding protein content in liver, heart and kidney of the diabetic rat

    NARCIS (Netherlands)

    Engels, W; van Bilsen, M; Wolffenbuttel, B H; van der Vusse, G J; Glatz, J F

    1999-01-01

    Diabetes mellitus generally results in an increased systemic fatty acid mobilization which can be associated with an increase in mitochondrial and peroxisomal beta-oxidation of fatty acids in selected tissues. The latter is usually accompanied by a concomitant increase in the tissue content of cytop

  3. Cytochrome P450, peroxisome proliferation, and cytoplasmic fatty acid-binding protein content in liver, heart and kidney of the diabetic rat

    NARCIS (Netherlands)

    Engels, W; van Bilsen, M; Wolffenbuttel, B H; van der Vusse, G J; Glatz, J F

    1999-01-01

    Diabetes mellitus generally results in an increased systemic fatty acid mobilization which can be associated with an increase in mitochondrial and peroxisomal beta-oxidation of fatty acids in selected tissues. The latter is usually accompanied by a concomitant increase in the tissue content of cytop

  4. Backbone and sidechain 1H, 13C and 15N resonance assignments of the human brain-type fatty acid binding protein (FABP7) in its apo form and the holo forms binding to DHA, oleic acid, linoleic acid and elaidic acid

    DEFF Research Database (Denmark)

    Oeemig, Jesper S; Jørgensen, Mathilde L; Hansen, Mikka S

    2009-01-01

    In this manuscript, we present the backbone and side chain assignments of human brain-type fatty acid binding protein, also known as FABP7, in its apo form and in four different holo forms, bound to DHA, oleic acid, linoleic acid and elaidic acid.......In this manuscript, we present the backbone and side chain assignments of human brain-type fatty acid binding protein, also known as FABP7, in its apo form and in four different holo forms, bound to DHA, oleic acid, linoleic acid and elaidic acid....

  5. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

    OpenAIRE

    2015-01-01

    Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DH...

  6. 脂肪酸结合蛋白与心脑血管病的早期诊断%Fatty acid-binding proteins and the early diagnosis of cardio-cerebrovascular diseases

    Institute of Scientific and Technical Information of China (English)

    张黎军; 赵中

    2010-01-01

    Currently, the commonly used diagnostic markers have the shortcomings of lower sensitivity or specificity in the early diagnosis of cardio-cerebrovascular diseases. Therefore, it needs to use the novel specific biochemical markers for the early diagnosis arid treatment, so as to decrease the high mortality and disability caused by cardio-cerebrovascular events. Fatty acid-binding proteins (FABPs) are a family of low-molecular-weight intracellular lipid-binding proteins. They are divided into 9 different subtypes, including the liver-, intestinal-, heart-, brain-, adipocyte-, skin-, ileal-, myelin-, and testis-subtype. Their primary function is to transport long-chain fatty acids into the cells, and thus regulate intracellular lipid metabolism. The structures of all FABP subtypes are similar, inclusive of two α2 helices arid one β2 fold structure. Among them, the sensitivities and specificities of the heart- and brain-subtype FABPs are higher in the early diagnosis of cardio-cerebrovascular diseases. It is promising to become the novel markers in the early diagnosis of cardio-cerebrovascular diseases.%在心脑血管病的早期诊断方面,目前常用的诊断标志物存在敏感性或特异性较低的缺点,因此需要利用新的生化特异标志物来进行早期诊断和早期治疗,以降低心脑血管事件导致的高病死率和高致残率.脂肪酸结合蛋白(fatty acid-binding protein,FABP)是一种低分子胞内脂质结合蛋白,分为肝脏型、肠型、心型、脑型、脂肪细胞型、表皮型、回肠型、髓磷脂型和睾丸型等9种亚型,其主要功能是转运长链脂肪酸至细胞内,从而调节细胞内脂质代谢.各种FABP亚型的结构相似,均含有2个α2螺旋和1个β2折叠结构.其中,心型和脑型FABP早期诊断心脑血管病的敏感性和特异性较高,有望成为心脑血管病早期诊断的新型标志物.

  7. Purification and initial characterization of the 71-kilodalton rat heat-shock protein and its cognate as fatty acid binding proteins.

    Science.gov (United States)

    Guidon, P T; Hightower, L E

    1986-06-03

    The major rat heat-shock (stress) protein and its cognate were purified to electrophoretic homogeneity from livers of heat-shocked rats. Both proteins exhibited similar behavior on a variety of column chromatography matrices but were separable by preparative isoelectric focusing under nondenaturing conditions by virtue of a 0.2 pH unit difference in isoelectric point. Both purified proteins had similar physical properties, suggesting the possibility that they may have similar biological functions as well. Both proteins were homodimers under nondissociative conditions (Mr 150 000) with isoelectric points of 5.0 (cognate) and 5.2 (major stress protein). After denaturation, both proteins had an increase in isoelectric point of 0.6 pH unit, and the resulting polypeptide chains had apparent molecular weights of 73 000 (cognate) and 71 000 (major stress protein). Similarities in the electrophoretic properties of these two proteins and serum albumin, which also undergoes a large basic shift in isoelectric point due to loss of fatty acids and conformational changes accompanying denaturation, prompted us to search for lipids associated with the purified 71-kilodalton stress protein and its cognate. Thin-layer chromatography of chloroform/methanol extracts of these two proteins revealed nonesterified fatty acids bound to both proteins. Palmitic acid, stearic acid, and a small amount of myristic acid were identified by gas chromatography/mass spectroscopy. Both proteins contained approximately four molecules of fatty acid per dimer with palmitate and stearate present in a one to one molar ratio. Possible roles of the major stress protein and its cognate as fatty acid associated proteins in cellular responses to stress are discussed.

  8. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

    OpenAIRE

    2015-01-01

    however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lact...

  9. Fatty acid binding protein in children with obesity%脂肪酸结合蛋白与肥胖的关系

    Institute of Scientific and Technical Information of China (English)

    武明雷

    2013-01-01

    随着人们生活水平的提高、饮食结构的改变,肥胖问题凸显,已成为严重威胁人类健康的重要隐患.在这个庞大的群体中,儿童所占比例越来越高.在肥胖的相关研究领域中,许多因子扮演着重要角色,其中脂肪酸结合蛋白在肥胖发生发展中的作用近年来成为研究热点.该文就脂肪酸结合蛋白与儿童肥胖之间的联系作一综述.%With the improvement of living standards and dietary changes,obesity has become a serious threat to human health.In this huge group,the proportion of children is increasing.Many factors play significant roles in obesity-related research areas.Fatty acid blinding protein has become a hot topic in recent years.

  10. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein.

    Science.gov (United States)

    Alqahtani, Mashael F; Smith, Craig M; Weiss, Scott L; Dawson, Susan; Ralay Ranaivo, Hantamalala; Wainwright, Mark S

    2016-01-01

    Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), mid-regional pro-atrial natriuretic peptide (mrProANP), and adipocyte fatty-acid-binding proteins (A-FaBPs) have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n) were reduced on day 1 (0.024, 0.004-0.174, 13), day 2 (0.020, 0.002-0.109, 10), and day 3 (0.018, 0.003-0.058, 23) compared with febrile (0.705, 0.187-1.778, 22) and healthy (0.7, 0.4-1.2, 29) (psepsis.

  11. Role of Fatty Acid-Binding Protein 2 Ala54Thr Genotype on Weight Loss and Cardiovascular Risk Factors after a High-Protein/Low-Carbohydrate versus a Standard Hypocaloric Diet during 9 Months.

    Science.gov (United States)

    de Luis, Daniel Antonio; Izaola, Olatz; de la Fuente, Beatriz; Primo, David; Romero, Enrique

    2015-01-01

    It has been found that the expression of fatty acid-binding protein 2 gene mRNA is under dietary control. The polymorphism Ala54Thr of this protein was associated with high insulin resistance. The aim of our study was to investigate the influence of Thr54 polymorphism on metabolic response, weight loss and serum adipokine levels secondary to high-protein/low-carbohydrate vs. standard hypocaloric diets during 9 months. A population of 193 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high-protein/low-carbohydrate vs. diet S: standard diet). With both diets and in both genotype groups, body mass index, weight, fat mass, waist circumference, systolic blood pressure and leptin levels decreased. With both diets and only in wild genotype (diet HP vs. diet S), glucose (-6.2 ± 2.1 vs. -4.9 ± 2.0 mg/dl; p metabolic response after weight loss than wild type non-A carriers obese, with a lack of decrease of LDL-cholesterol, glucose, insulin levels and HOMA-R. © 2015 S. Karger AG, Basel.

  12. 心型脂肪酸结合蛋白在急性冠状动脉综合征中的研究进展%Research of Heart-type Fatty Acid-Binding Protein in Acute Coronary Syndrome

    Institute of Scientific and Technical Information of China (English)

    黄艳

    2011-01-01

    Acute coronary syndrome ( ACS) is a major cause of death. In order to reduce the chances of cardiac deformity and death, it is important to diagnose ACS early and monitor its progression. Heart-type fatty acid-binding protein is a marker that has a high degree of specificity for the myocardium and may be viable as a diagnostic tool for early stage ACS. This article reviews the potential for ACS to serve as a biochemical cardiac marker for the early diagnosis of ACS.%急性冠状动脉综合征已成为严重危害人类健康的重要致死病因,它的早期预测及预防其进展,对它的发生率、致残率、病死率的降低具有重要意义.心型脂肪酸结合蛋白作为心肌损伤标志物,具有较高的心肌特异性,对于诊断早期急性冠状动脉综合征具有较高的敏感性和良好的特异性,更适合于临床急性冠状动脉综合征的早期诊断,对于心肌损伤诊断的准确性和及时性都会有极大的提高.

  13. A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting

    Science.gov (United States)

    Syamsunarno, Mas Rizky A. A.; Iso, Tatsuya; Hanaoka, Hirofumi; Yamaguchi, Aiko; Obokata, Masaru; Koitabashi, Norimichi; Goto, Kosaku; Hishiki, Takako; Nagahata, Yoshiko; Matsui, Hiroki; Sano, Motoaki; Kobayashi, Masaki; Kikuchi, Osamu; Sasaki, Tsutomu; Maeda, Kazuhisa; Murakami, Masami; Kitamura, Tadahiro; Suematsu, Makoto; YoshitoTsushima; Endo, Keigo; Hotamisligil, Gökhan S.; Kurabayashi, Masahiko

    2013-01-01

    During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the 125I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the

  14. Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.

    Directory of Open Access Journals (Sweden)

    Mas Rizky A A Syamsunarno

    Full Text Available Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA utilization, are disturbed. FA binding protein 4 (FABP4 and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice, as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT and glycogen in skeletal muscle (SkM was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation.

  15. Polymorphism of Adipocyte Fatty Acid-binding Protein Gene(A-FABP) in Yak (Bos grunniens)%牦牛脂肪型脂肪酸结合蛋白基因(A-FABP)多态性分析

    Institute of Scientific and Technical Information of China (English)

    曹健; 罗玉柱; 胡江; 成述儒; 杨果; 刘秀

    2012-01-01

    脂肪型脂肪酸结合蛋白(A-FABP)属脂肪酸结合蛋白家族(FABPs)成员,参与调节哺乳动物细胞内脂肪浓度,进而影响肌肉内脂肪含量(IMF),因此A-FABP可作为影响IMF的候选基因.本研究采用PCR-SSCP技术检测甘南牦牛、青海牦牛、天祝白牦牛(Bos grunniens)A-FABP基因部分第3内含子、第4外显子及部分3'-UTR区单核苷酸多态性( SNPs),分析检测区域分子遗传特征.结果表明,3类群牦牛引物扩增区域发现5种等位基因A-E;同普通牛A-FABP基因序列比对发现6处SNPs,其中第4外显子区存在c.4222A>G的同义突变;3'-UTR区c.* 94T>A只存在于牦牛群体,是其区别于普通牛的遗传特征之一.各等位基因在群体间分布差异较大,其中天祝白牦牛只发现3种等位基因,而青海牦牛发现4种等位基因,这可能与牦牛类群的地域分布及选育程度有关.3类群牦牛A-FABP基因检测位点表现为中度多态(PIC为0.29 ~0.36),有效等位基因数较高,可作为潜在的牦牛肉质性状分子标记位点.%Adipocyte fatty acid-binding protein( A-FABP) ,as a member of the fatty acid binding protein(FAB-Ps) family,play a pivotal role in regulating intracellular fat concentration and then affect intramuscular fat(IMF) in mammalian. So A-FABP was suggested as a candidate gene of IMF in some species of livestock and poultry. In this study, single nucleotide polymorphisms (SNPs) was investigated at A-FABP intron 3,exon4 and 3'-UTR in Gannan yak,Qinghai yak and Tianzhu white yak (Bos grunniens) by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) so as to analyse their molecular genetic characteristics. Five novel SSCP patterns,representing five different alleles A-E were identified in three yak populations. With alignment of the bovine (Bos tauras) and yak A-FABP allelic sequences, six SNPs including a synonymous mutation ( c. 4222A > G) at exon 4 were checked in yak. SNP c. * 94T > A in 3'-UTR of A

  16. Relationship of Urinary Liver-Type Fatty Acid-Binding Protein to Kidney Damage in Diabetic Patients%尿肝型脂肪酸结合蛋白与糖尿病肾损伤的相关性

    Institute of Scientific and Technical Information of China (English)

    曾宪飞; 李军民; 谈昀; 王小刚

    2013-01-01

    目的 探讨在1型和2型糖尿病患者中尿肝型脂肪酸结合蛋白(liver-type fatty-acid binding protein,L-FABP)与糖尿病肾损伤程度的关系.方法 选择2011年8月~10月门诊确诊1型糖尿病患者119例,2型糖尿病患者128例,以及103例体检确认的健康者,依据尿蛋白/血肌酐比(albumin-to-creatinine rate,ACR)和血清肌酐水平将糖尿病确诊患者分为无蛋白尿组(ACR176.8 mmol/L).酶联免疫吸附法(ELISA)测定受试者尿L-FABP浓度,同时检测全血糖化血红蛋白(HbA1c)、血清肌酐(Scr)、尿肌酐、尿清蛋白和尿胱抑素C等指标,MDRD校正方程估算肾小球滤过率(eGFR).结果 健康人群尿L-FABP水平为13.0(10.8~14.8)μg/g·cr,95%参考值范围为9.0~17.5 μg/g·cr;随着糖尿病肾损伤程度的加重,尿L-FABP水平增高(各组间比较H=282.5,P0.05).结论 尿L-FABP水平能准确反映糖尿病肾损伤程度,可作为诊断糖尿病肾损伤的标志物.%Objective To study the relationship of urinary liver type fatty acid binding protein (L FABP) and kidney damage in type 1 and 2 diabetic patients. Methods 103 healthy subjects from physical examination people and 247 diabetic patients (119 type 1 and 128 type 2) from outpatients were recruited in this study. Patients were divided into four diabetic nephropa thy groups based on the degree of albumin to creatinine rate or renal function,as follows:normoalbuminuria (ACR176. 8 mmol/L). Urinary L FABP was measured by ELISA and whole blood HbAlc,serum creati nine,urinary creatiine,urinary albumin,and urinary cstatin C were measured by respective biochemical or immunological methods. MDRD equation was used to evaluate the glomemlar filtration rate. Results The level of urinary L FABP was 13. 0 (10. 8~14. 8)μg/g · cr in 103 healthy subjects. The high urinary L FABP levels were associated with the progression of dia betic nephropathy. There was a significant difference of urinary L FABP among groups ( H= 282. 5, P<0. 005

  17. Selective staining of CdS on ZnO biolabel for ultrasensitive sandwich-type amperometric immunoassay of human heart-type fatty-acid-binding protein and immunoglobulin G.

    Science.gov (United States)

    Qin, Xiaoli; Xu, Aigui; Liu, Ling; Sui, Yuyun; Li, Yunlong; Tan, Yueming; Chen, Chao; Xie, Qingji

    2017-05-15

    We report on an ultrasensitive metal-labeled amperometric immunoassay of proteins, which is based on the selective staining of nanocrystalline cadmium sulfide (CdS) on ZnO nanocrystals and in-situ microliter-droplet anodic stripping voltammetry (ASV) detection on the immunoelectrode. Briefly, antibody 1 (Ab1), bovine serum albumin (BSA), antigen and ZnO-multiwalled carbon nanotubes (MWCNTs) labeled antibody 2 (Ab2-ZnO-MWCNTs) were successively anchored on a β-cyclodextrin-graphene sheets (CD-GS) nanocomposite modified glassy carbon electrode (GCE), forming a sandwich-type immunoelectrode (Ab2-ZnO-MWCNTs/antigen/BSA/Ab1/CD-GS/GCE). CdS was selectively grown on the catalytic ZnO surfaces through chemical reaction of Cd(NO3)2 and thioacetamide (ZnO-label/CdS-staining), due to the presence of an activated cadmium hydroxide complex on ZnO surfaces that can decompose thioacetamide. A beforehand cathodic "potential control" in air and then injection of 7μL of 0.1M aqueous HNO3 on the immunoelectrode allow dissolution of the stained CdS and simultaneous cathodic preconcentration of atomic Cd onto the electrode surface, thus the following in-situ ASV detection can be used for immunoassay with enhanced sensitivity. Under optimized conditions, human immunoglobulin G (IgG) and human heart-type fatty-acid-binding protein (FABP) are analyzed by this method with ultrahigh sensitivity, excellent selectivity and small reagent-consumption, and the limits of detection (LODs, S/N=3) are 0.4fgmL(-1) for IgG and 0.3fgmL(-1) for FABP (equivalent to 73 FABP molecules in the 6μL sample employed).

  18. A single-nucleotide polymorphism in the 3'-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple-negative breast cancer.

    Science.gov (United States)

    Wang, Wenmiao; Yuan, Peng; Yu, Dianke; Du, Feng; Zhu, Anjie; Li, Qing; Zhang, Pin; Lin, Dongxin; Xu, Binghe

    2016-04-05

    Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and high heterogeneity. The aim of this study was to screen patients for single-nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC. Database-derived SNPs (NextBio, Ensembl, NCBI and MirSNP) located in the 3'-untranslated regions (3'-UTRs) of genes that are differentially expressed in breast cancer were selected. The possible associations between 111 SNPs and progression risk among 323 TNBC patients were investigated using a two-step case-control study with a discovery cohort (n=162) and a validation cohort (n=161). We identified the rs1054135 SNP in the adipocyte fatty acid binding protein 4 (FABP4) gene as a predictor of TNBC recurrence. The G allele of rs1054135 was associated with a reduced risk of disease progression as well as a prolonged disease-free survival time (DFS), with a hazard ratio (HR) for recurrence in the combined sample of 0.269 [95%CI: 0.098-0.735;P=0.001]. Notably, for individuals having the rs1054135 SNP with the AA/AG genotype, the magnitude of increased tumour recurrence risk for overweight patients (BMI≥25kg/m2) was significantly elevated (HR2.53; 95%CI: 1.06-6.03). Immunohistochemical staining of adipocytes adjacent to TNBC tissues showed that the expression level of FABP4 was statistically significantly lower in patients with the rs1054135-GG genotype and those in the disease-free group (P=0.0004 and P=0.0091, respectively). These results suggested that the expression of a lipid metabolism-related gene and an important SNP in the 3'-UTR of FABP4 are associated with TNBC prognosis, which may aid in the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents.

  19. A newly developed kit for the measurement of urinary liver-type fatty acid-binding protein as a biomarker for acute kidney injury in patients with critical care.

    Science.gov (United States)

    Sato, Ryo; Suzuki, Yasushi; Takahashi, Gaku; Kojika, Masahiro; Inoue, Yoshihiro; Endo, Shigeatsu

    2015-03-01

    In recent years, it has been reported that the urinary level of Liver-type fatty acid-binding protein (L-FABP) serves as a useful biomarker for diagnosing acute kidney injury (AKI) or sepsis complicated by AKI. However, because the urinary level of L-FABP is currently measured by enzyme-linked immunosorbent assay (ELISA), several days may elapse before the results of the measurement become available. We have newly developed a simplified kit, the Dip-test, for measuring the urinary level of L-FABP. The Dip-test was measured at 80 measurement points (22 points in noninfectious disease, 13 points in SIRS, 20 points in infectious disease, and 25 points in sepsis) in 20 patients. The urinary L-FABP levels as determined by ELISA in relation to the results of the Dip-test were as follows: 10.10 ± 12.85 ng/ml in patients with a negative Dip-test ([-] group), 41.93 ± 50.51 ng/ml in patients with a ± test ([±] group), 70.36 ± 73.70 ng/ml in patients with a positive test ([+] group), 1048.96 ± 2117.68 ng/ml in patients with a 2 + test ([2+] group), and 23,571.55 ± 21,737.45 ng/ml in patients with a 3 + test ([3+] group). The following tendency was noted: the stronger the positive Dip-test reaction, the higher the urinary L-FABP level. Multigroup comparison revealed a significant differences in the urinary L-FABP levels between the Dip-test (-) group and each of the other groups. In this study, the usefulness of the Dip-test, our newly developed simplified kit for measuring the urinary L-FABP level, is suggested.

  20. Level of urinary liver-type fatty acid-binding protein is associated with cardiac markers and electrocardiographic abnormalities in type-2 diabetes with chronic kidney disease stage G1 and G2.

    Science.gov (United States)

    Maeda, Yoshiteru; Suzuki, Atsushi; Ishii, Junnichi; Sekiguchi-Ueda, Sahoko; Shibata, Megumi; Yoshino, Yasumasa; Asano, Shogo; Hayakawa, Nobuki; Nakamura, Kazuhiro; Akiyama, Yasukazu; Kitagawa, Fumihiko; Sakuishi, Toshiaki; Fujita, Takashi; Hashimoto, Shuji; Ozaki, Yukio; Itoh, Mitsuyasu

    2015-05-01

    Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

  1. Recent Studies in Clinical Application of Heart Fatty Acid Binding Protein in Pediatric Diseases%心型脂肪酸结合蛋白在儿科疾病的临床应用新进展

    Institute of Scientific and Technical Information of China (English)

    李婷(综述); 徐家丽(审校)

    2015-01-01

    Heart-type fatty acid binding protein ( H-FABP) is one of the promising biological markers for the evaluation of myocardial injury.H-FABP is known to be rapid released from injured myocardium into the blood.With the progress of the study, it is discovered that H-FABP is also expressed in brain, skeletal muscle,lung,kidney,adrenal,mammary gland and so on.Because it is an effective marker for early diagno-sis,risk stratification,and assessing prognosis,it′s more and more widely applied in clinical.At present,the study of H-FABP is focused on adult disease,but rarely reported in pediatric disease.%心型脂肪酸结合蛋白( H-FABP)是评价心肌组织损伤的一种更为敏感的新型生物标志物,其能从损伤的心肌组织中快速释放到血液中。随着对H-FABP越来越深入的研究,研究者发现其也在脑、骨骼肌、肺、肾、肾上腺和乳腺等组织中表达,故其在临床中的应用(如早期诊断、危险分层、预后评估等)越来越广泛。目前的研究主要集中在成人疾病中,在儿科疾病中报道不多。

  2. Sex-specific association of fatty acid binding protein 2 and microsomal triacylglycerol transfer protein variants with response to dietary lipid changes in the 3-mo Medi-RIVAGE primary intervention study.

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    Gastaldi, Marguerite; Dizière, Sophie; Defoort, Catherine; Portugal, Henri; Lairon, Denis; Darmon, Michel; Planells, Richard

    2007-12-01

    The dietary guidelines targeted at reducing cardiovascular risk lead to largely heterogeneous responses in which genetic determinants are largely involved. We evaluated the effect of fatty acid binding protein 2 (FABP2) Ala54Thr and microsomal triacylglycerol transfer protein (MTTP) -493G/T allelic variations on plasma lipid markers, at baseline and on the response to the 3-mo Medi-RIVAGE primary prevention study. Subjects with moderate cardiovascular disease risk (n = 169) were advised to reduce total and saturated dietary fats and to increase intake of monounsaturated and polyunsaturated fats. They were genotyped for FABP2 Ala54Thr and MTTP -493G/T allelic variations, and plasma was processed for cardiovascular risk marker analyses. At baseline, men and women homozygous for Thr54 presented a significant opposite profile for plasma oleic acid (18:1), triacylglycerol-rich lipoprotein (TRL) cholesterol, and TRL phospholipids. In addition, all Thr/Thr men presented higher 18:1 values than did women. For the MTTP -493G/T polymorphism, although all TT subjects presented high apolipoprotein B-48, a genotype x sex interaction was present for palmitic acid, linolenic acid, eicosatrienoic acid, and insulin. The prudent diet clearly improved plasma lipid markers. FABP2 genotype did not interact much with the amplitude of the response. However, for MTTP polymorphism, men homozygous for the T allele displayed a significantly more pronounced response than did men carrying the G allele, which is particularly evident by their larger decrease in the Framingham score. These 2 polymorphic loci are thus differently associated with the baseline lipid markers as well as with the response to nutritional recommendations, but both presented a marked sex-specific profile, with the response to diet being particularly efficient in men homozygous for the MTTP -493T allele.

  3. Critical review and meta-analysis on the combination of heart-type fatty acid binding protein (H-FABP) and troponin for early diagnosis of acute myocardial infarction.

    Science.gov (United States)

    Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco

    2013-01-01

    An early diagnosis is crucial for effective triage and management of patients with suspected acute myocardial infarction (AMI). Although troponin testing is the cornerstone of diagnosis, the sensitivity of this biomarker is still suboptimal at patient admission. The heart-type fatty acid binding protein (H-FABP) is an early and sensitive biomarker of myocardial ischemia, whose appropriate setting is in combination with troponin testing. We performed a systematic review and meta-analysis of articles that have assessed the combination of troponin and H-FABP in the early diagnosis of AMI. Eight studies, totaling 2735 patients, met the inclusion criteria but none of them used a high-sensitivity troponin immunoassay. The between-study variation was high (98.5%), and attributable to heterogeneity. When considered alone, troponin exhibited a significantly greater pooled area under the curve (AUC) than H-FABP alone (0.820 versus 0.784; ptroponin alone than for H-FABP alone (0.94 versus 0.83; ptroponin than for H-FABP (0.73 versus 0.80; p=0.02). The combination of both biomarkers exhibited a greater AUC than troponin alone (0.881; ptroponin immunoassay seems advantageous for increasing the sensitivity of the former biomarker, at the expense of a lower specificity. The introduction of H-FABP testing would hence require careful assessment of laboratory data or clinical signs and symptoms for excluding sources of elevation different from AMI. Further studies are needed to assess the diagnostic effectiveness of combining H-FABP with a high-sensitivity troponin immunoassay.

  4. Diagnostic accuracy of heart fatty acid binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) in diagnosis of acute myocardial infarction in patients with acute coronary syndrome.

    Science.gov (United States)

    Cubranic, Zlatko; Madzar, Zeljko; Matijevic, Sanja; Dvornik, Stefica; Fisic, Elizabeta; Tomulic, Vjekoslav; Kunisek, Juraj; Laskarin, Gordana; Kardum, Igor; Zaputovic, Luka

    2012-01-01

    This study aimed to assess whether heart fatty acid-binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) could be used for the accurate diagnosis of acute myocardial infarction (AMI) in acute coronary syndrome (ACS) patients. The study included 108 ACS patients admitted to a coronary unit within 3 h after chest pain onset. AMI was distinguished from unstable angina (UA) using a classical cardiac troponin I (cTnI) assay. H-FABP and GPBB were measured by ELISA on admission (0 h) and at 3, 6, 12, and 24 h after admission; their accuracy to diagnose AMI was assessed using statistical methods. From 92 patients with ACS; 71 had AMI. H-FABP and GPBB had higher peak value after 3 h from admission than cTnI (P = 0.001). Both markers normalized at 24 h. The area under the receiver operating characteristic curves was significantly greater for both markers in AMI patients than in UA patients at all time points tested, including admission (P < 0.001). At admission, the H-FABP (37%) and GPBB (40%) sensitivities were relatively low. They increased at 3 and 6 h after admission for both markers and decreased again after 24 h. It was 40% for H-FABP and approximately 2-times lower for GPBB (P < 0.01). In AMI patients, both biomarkers had similar specificities, positive- and negative-predictive values, positive and negative likelihood ratios, and risk ratios for AIM. H-FABP and GPBB can contribute to early AMI diagnosis and can distinguish AMI from UA.

  5. Heart-type fatty acid binding protein (H-FABP) in patients in an emergency department setting, suspected of acute coronary syndrome: optimal cut-off point, diagnostic value and future opportunities in primary care.

    Science.gov (United States)

    Willemsen, Robert T A; van Severen, Evie; Vandervoort, Pieter M; Grieten, Lars; Buntinx, Frank; Glatz, Jan F C; Dinant, Geert Jan

    2015-01-01

    Most patients presenting chest complaints in primary care are referred to secondary care facilities, whereas only a few are diagnosed with acute coronary syndrome (ACS). The aim is to determine the optimal cut-off value for a point-of-care heart-type fatty acid binding protein (H-FABP) test in patients presenting to the emergency department and to evaluate a possible future role of H-FABP in safely ruling out ACS in primary care. Serial plasma H-FABP (index test) and high sensitivity troponin T (hs-cTnT) (reference test) were determined in patients with any new-onset chest complaint. In a receiver operating characteristic (ROC) curve, the optimal cut-off value of H-FABP for ACS was determined. Predictive values of H-FABP for ACS were calculated. For 202 consecutive patients (prevalence ACS 59%), the ROC curve based on the results of the first H-FABP was equal to the ROC curve of hs-cTnT (AUC 0.79 versus 0.80). Using a cut-off value of 4.0 ng/ml for H-FABP, sensitivity for ACS of the H-FABP (hs-cTnT) tests was 73.9% (70.6%). Negative predictive value (NPV) of H-FABP for ACS in a population representative for primary care (incidence of ACS 22%) thus could reach 90.8%. In patients presenting chest pain, plasma H-FABP reaches the highest diagnostic value when a cut-off value of 4 ng/ml is used. Diagnostic values of an algorithm combining point-of-care H-FABP measurement and a score of signs and symptoms should be studied in primary care, to learn if such an algorithm could safely reduce referral rate by GPs.

  6. A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects.

    Science.gov (United States)

    Weickert, Martin O; Loeffelholz, Christian V; Roden, Michael; Chandramouli, Visvanathan; Brehm, Attila; Nowotny, Peter; Osterhoff, Martin A; Isken, Frank; Spranger, Jochen; Landau, Bernard R; Pfeiffer, Andreas F H; Möhlig, Matthias

    2007-10-01

    Liver fatty acid-binding protein (L-FABP) is a highly conserved key factor in lipid metabolism. Amino acid replacements in L-FABP might alter its function and thereby affect glucose metabolism in lipid-exposed subjects, as indicated by studies in L-FABP knockout mice. Amino acid replacements in L-FABP were investigated in a cohort of 1,453 Caucasian subjects. Endogenous glucose production (EGP), gluconeogenesis, and glycogenolysis were measured in healthy carriers of the only common Thr(94)-to-Ala amino acid replacement (Ala/Ala(94)) vs. age-, sex-, and BMI-matched wild-type (Thr/Thr(94)) controls at baseline and after 320-min lipid/heparin-somatostatin-insulin-glucagon clamps (n = 18). Whole body glucose disposal was further investigated (subset; n = 13) using euglycemic-hyperinsulinemic clamps without and with lipid/heparin infusion. In the entire cohort, the only common Ala/Ala(94) mutation was significantly associated with reduced body weight, which is in agreement with a previous report. In lipid-exposed, individually matched subjects there was a genotype vs. lipid-treatment interaction for EGP (P = 0.009) driven mainly by reduced glycogenolysis in Ala/Ala(94) carriers (0.46 +/- 0.05 vs. 0.59 +/- 0.05 mgxkg(-1)xmin(-1), P = 0.013). The lipid-induced elevation of plasma glucose levels was smaller in Ala/Ala(94) carriers compared with wild types (P glycogenolysis and less severe hyperglycemia in lipid-exposed humans and was further associated with reduced body weight in a large cohort. Data clearly show that investigation of L-FABP phenotypes in the basal overnight-fasted state yielded incomplete information, and a challenge test was essential to detect phenotypical differences in glucose metabolism between L-FABP genotypes.

  7. Evolution of the duplicated intracellular lipid-binding protein genes of teleost fishes.

    Science.gov (United States)

    Venkatachalam, Ananda B; Parmar, Manoj B; Wright, Jonathan M

    2017-08-01

    Increasing organismal complexity during the evolution of life has been attributed to the duplication of genes and entire genomes. More recently, theoretical models have been proposed that postulate the fate of duplicated genes, among them the duplication-degeneration-complementation (DDC) model. In the DDC model, the common fate of a duplicated gene is lost from the genome owing to nonfunctionalization. Duplicated genes are retained in the genome either by subfunctionalization, where the functions of the ancestral gene are sub-divided between the sister duplicate genes, or by neofunctionalization, where one of the duplicate genes acquires a new function. Both processes occur either by loss or gain of regulatory elements in the promoters of duplicated genes. Here, we review the genomic organization, evolution, and transcriptional regulation of the multigene family of intracellular lipid-binding protein (iLBP) genes from teleost fishes. Teleost fishes possess many copies of iLBP genes owing to a whole genome duplication (WGD) early in the teleost fish radiation. Moreover, the retention of duplicated iLBP genes is substantially higher than the retention of all other genes duplicated in the teleost genome. The fatty acid-binding protein genes, a subfamily of the iLBP multigene family in zebrafish, are differentially regulated by peroxisome proliferator-activated receptor (PPAR) isoforms, which may account for the retention of iLBP genes in the zebrafish genome by the process of subfunctionalization of cis-acting regulatory elements in iLBP gene promoters.

  8. Fatty acid binding proteins (FABPs in prostate, bladder and kidney cancer cell lines and the use of IL-FABP as survival predictor in patients with renal cell carcinoma

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    Jung Klaus

    2011-07-01

    Full Text Available Abstract Background Fatty acid binding proteins (FABP play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. Methods Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. Results General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. Conclusions Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the

  9. Clinical Value of Heart Type Fatty Acid-binding Protein in Pulmonary Disease%心型脂肪酸结合蛋白在肺疾病中的临床应用进展

    Institute of Scientific and Technical Information of China (English)

    王宇宏; 李敏

    2015-01-01

    The heart type fatty acid-binding protein (H-FABP) as a new biological marker receives closely attention in recent years. It characteristics of high specificity and strong sensitivity and has a value to screen early myocardial damage. When pulmonary parenchyma and pulmonary vascular disease involved right heart function, the prognosis is poor. Always, the majority of patients died from right heart failure. If we can early detect myocardial injury, we would take measures as soon as possible. H-FABP can be used as a marker of early myocardial damage caused by pulmonary disease. The detection of H-FABP can be help for assessment risk stratification and prognosis. In this paper, we reviewed the clinical value of H-FABP in acute pulmonary embolism (APE), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), obstructive sleep apnea hypopnea syndrome (OSAHS) in recent years.%心型脂肪酸结合蛋白(H-FABP)作为一种新生的生物学标志物近些年来获得研究者们的青睐,它是心肌损伤早期检测的标志物,具有高度特异性及敏感性。肺组织和肺血管疾病因并发右心功能不全而预后差,大部分患者死于右心衰竭。若临床早期发现肺疾病所致心肌受损,则有利于及早采取治疗措施,延缓病情进展。H-FABP可以作为所致肺疾病早期心肌损伤检测的标志物,用于评估病情危险程度及预后。本文就近年来H-FABP在急性肺栓塞(APE),慢性阻塞性肺疾病(COPD)、肺动脉高压(PH)、呼吸睡眠暂停(OSAHS)等疾病的临床应用进行综述。

  10. СHARACTERISTICS OF THE HEART FATTY ACID-BINDING PROTEIN, INTERLEUKIN-6 AND INTERLEUKIN-8 AS ALTERNATIVE MARKERS OF DIABETIC NEPHROPATHY PROGRESSION IN PATIENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Yu. A. Ryzhikova

    2015-01-01

    Full Text Available The aim of this work was to study the levels of the heart fatty acid-binding protein (h-FABP, interleukin6 (IL-6 and interleukin-8 (IL-8, in diabetic nephropathy (DN in patients with type 1 diabetes mellitus (T1DM. Material and methods. We examined 87 patients aged 18 to 54 with T1DM within the study group. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients – with proteinuria. The control group consisted of 24 healthy donor aged 22 to 29. The comparison group included 22 patients aged 20 to 42 with verified diagnosis of essential arterial hypertension (AH without carbohydrate metabolism disorders. The daily urinary albumin excretion was determined by immunoturbidimetric technique. 30 patients with type 1 diabetes were diagnosed with normoalbuminuria, 29 patients – with microalbuminuria and 28 patients with proteinuria.Calculation of glomerular filtration rate was performed according to the Hoek formula with the use of cystatinС serum concentrations. Contents of h-FABP, IL-6 and cystatin C in serum and h-FABP, IL-8 inurine were determined by enzyme-linked immunosorbent assay. Results. Analysis of the h-FABP content in serum showed that the concentration of this marker in individuals with T1DM was higher than in patients of the control group and the comparison group. Analysis of the h-FABP content in the urine revealed that individuals with essential hypertension showed an increased level of h-FABP while patients with T1DM demonstrated the highest concentration of h-FABP. The concentration of IL-6 inindividuals with T1DM and in individuals with AH significantly exceeded the control values. The contents of h-FABP and IL-6 inserum and h-FABP and IL-8 inurine increased with the progression of DN and reached maximum in individuals of the proteinuria subgroup. At the same time, the levels of h-FABP and IL-8 inthe urine of patients in the microalbuminuria (MAU subgroup were

  11. Evaluation of New Diagnostic Biomarkers in Pediatric Sepsis: Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, Mid-Regional Pro-Atrial Natriuretic Peptide, and Adipocyte Fatty-Acid Binding Protein.

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    Mashael F Alqahtani

    Full Text Available Elevated plasma concentrations of matrix metalloproteinase-9 (MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1, mid-regional pro-atrial natriuretic peptide (mrProANP, and adipocyte fatty-acid-binding proteins (A-FaBPs have been investigated as biomarkers for sepsis or detection of acute neurological injuries in adults, but not children. We carried out a single-center, prospective observational study to determine if these measures could serve as biomarkers to identify children with sepsis. A secondary aim was to determine if these biomarkers could identify children with neurologic complications of sepsis. A total of 90 patients ≤ 18 years-old were included in this study. 30 with severe sepsis or septic shock were compared to 30 age-matched febrile and 30 age-matched healthy controls. Serial measurements of each biomarker were obtained, beginning on day 1 of ICU admission. In septic patients, MMP9-/TIMP-1 ratios (Median, IQR, n were reduced on day 1 (0.024, 0.004-0.174, 13, day 2 (0.020, 0.002-0.109, 10, and day 3 (0.018, 0.003-0.058, 23 compared with febrile (0.705, 0.187-1.778, 22 and healthy (0.7, 0.4-1.2, 29 (p< 0.05 controls. A-FaBP and mrProANP (Median, IQR ng/mL, n were elevated in septic patients compared to control groups on first 2 days after admission to the PICU (p <0.05. The area under the curve (AUC for MMP-9/TIMP-1 ratio, mrProANP, and A-FaBP to distinguish septic patients from healthy controls were 0.96, 0.99, and 0.76, respectively. MMP-9/TIMP-1 ratio was inversely and mrProANP was directly related to PIM-2, PELOD, and ICU and hospital LOS (p<0.05. A-FaBP level was associated with PELOD, hospital and ICU length of stay (p<0.05. MMP-9/TIMP-1 ratio associated with poor Glasgow Outcome Score (p<0.05. A-FaBP levels in septic patients with neurological dysfunction (29.3, 17.2-54.6, 7 were significantly increased compared to septic patients without neurological dysfunction (14.6, 13.3-20.6, 11. MMP-9/TIMP-1 ratios were

  12. Relationship between serum adipocyte fatty acid-binding protein and coronary heart disease%脂肪细胞型脂肪酸结合蛋白与冠心病临床相关性的研究

    Institute of Scientific and Technical Information of China (English)

    牛海军; 张宁汝; 张恒; 刘进军; 李妙男; 王本芳; 耿家峰

    2012-01-01

    目的:比较不同类型、不同病变支数冠心病患者的血清脂肪细胞型脂肪酸结合蛋白(A-FABP)的血清水平,分析其与冠心病的关系.方法:选择冠心病患者64例,同期造影阴性对照组24例.采用固相夹心酶偶联免疫吸附法(ELISA)检测A-FABP、白细胞介素6(IL-6)含量,免疫散射比浊法测定血清高敏C反应蛋白(hs-CRP).结果:A-FABP水平在对照组[5.96(4.87~7.99)ng/ml]较冠心病组[7.76(6.28~9.12)ng/ml]明显降低(P<0.05).A-FABP水平在多支病变组[9.33(8.04~11.09)ng/ml]较单支病变组[6.61(5.62~7.59)ng/ml](P<0.01)高.A-FABP与IL-6呈正相关(r=0.592,P<0.01),与hs-CRP呈正相关(r=0.604,P<0.01).Logistic回归分析示血清A-FABP水平与冠心病危险度呈正相关(x2=21.734,P<0.01).结论:血清A-FABP水平与冠心病的病变程度、IL-6、hs-CRP及冠心病危险度呈正相关.%Objective:To detect the serum adipocyte fatty acid-binding protein (A-FABP) in patients with coronary heart disease (CHD). Methods: 64 patients with CHD and 24 controls with normal coronary arteris were enrolled. Serum A-FABP and interleukin-6 (IL-6) were detected by ELISA, while serum hs-CRP was detected by immunoturbidimetry. Results:Serum A-FABP was significantly higher in patients with CHD [7. 76(6. 28 —9. 12) ng/ml] than that in control group [5. 96(4. 87 — 7. 99)ng/ml] (P<0. 05). Serum A-FABP in multi-vessel lesions group [9. 33(8. 04—11. 09)ng/ml] was significantly higher than that in single-vessel lesion group [6. 61(5. 62—7. 59)ng/ml] (P<0. 01). Serum A-FABP positively correlated with serum IL-6 (r=0. 592, P<0. 01) and hs-CRP (r=0. 604, P<0. 01). Logistic regression analysis showed that serum A-FABP level and CHD were closely related (x2 =21. 734, P<0. 01). Conclusion:Serum levels of A-FABP is positively correlated with the coronary lesions, IL-6, hs-CRP, which may be a risk factor of CHD.

  13. The change and significance of heart fatty acid-binding protein and cardiac troponin Ⅰ in valve replacement patients%心脏瓣膜置换围手术期H-FABP和cTnI的变化及意义

    Institute of Scientific and Technical Information of China (English)

    陈志军; 王永连; 王忠民

    2011-01-01

    目的 探讨心脏瓣膜置换术后心肌肌钙蛋白I(cTnI)和心型脂肪酸结合蛋白(H-FABP)的变化规律.方法 选本院风湿性心脏病手术患者40例,随机分为晶体停搏液灌注组和冷血停搏液灌注组,选取8个时间点,分析和比较各时点血清cTnI和H-FABP浓度变化规律.结果 晶体停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=2744.397,P<0.01; F交互=125.345,P<0.01),冷血停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=1056.357,P<0.01; F交互 =64.242,P<0.01);晶体停搏液灌注组H- FABP组间及交互效应差异均有统计学意义(F组间=1775.022,P<0.01;F交互=34.297,P<0.01),冷血停搏液灌注组H -FABP组间及交互效应差异均有统计学意义(F组间=3064.451,P<0.01;F交互=60.472,P<0.01).结论 H-FABP心肌的特异性强,有效诊断窗口期短,较符合心肌损伤的理想判定标志物.%Objective To explore change trend of Cardiac Troponin Ⅰ (cTnI) and Heart Fatty Acid-binding Protein(H-FABP) in serum during the perioperation of valve replacement.Methods Forty patients with heumatoid valvular heart disease were selected for this study,and the patients were randomly divided into two groups.Blood samples were taken from center vein,and the serum levels of cTnI and H-FABP were determined.The change of the serum levels of these two markers at different time points was recorded and compared between two groups.Results There were significant differences in the concentration of cTnl in the cold crystalloid cardioplegia group ( F between group =2744.397,P <0.01 ; F interaction =125.345,P <0.01 ).There were significant differences in the concentration of cTnI in the cold blood cardioplegia group ( F between group =1056.357,P < 0.01 ; Finteraction =64.242,P < 0.01 ).There were significant differences in the concentration of H - FABP in the cold crystalloid cardioplegia group ( F between group =1775.022,P <0.01; F

  14. 川崎病患儿心型脂肪酸结合蛋白和脑利钠肽的变化及与心功能的关系%Changes of serum heart type fatty acid binding protein and brain natriuretic peptide and their clinical significance in children with Kawasaki disease

    Institute of Scientific and Technical Information of China (English)

    王金菊; 陈宗波; 王文棣

    2015-01-01

    Objective To explore the serum levels changes of heart-type fatty acid-binding protein and brain natriuretic peptide in children with Kawasaki disease,as well as their links with the heart function. Methods A total of 53 children with Kawasaki disease admitted to our hospital from February 2008 to March 2012 were selected and at the same time 50 healthy controls were randomly selected. The serum levels for the children in acute phase,recovery period of Kawasaki disease and control group children were determined by en-zyme-linked immnoabsorbent assay. The internal diameter of coronary artery,LVEF,LVSF,CI and E/A of chil-dren were measured by two-dimensional echocardiography. Results The heart-type fatty acid-binding protein and brain natriuretic peptide concentrations of children with Kawasaki disease in acute stage[(18. 23 ± 13. 81) ng/ml,(517. 2 ±213. 2) pg/ml] were higher than those in recovery stage[(6. 29 ± 1. 26) ng/ml,(92. 1 ± 46. 0) pg/ml](P<0. 05). They were also higher for children in acute stage than those of control group[(6. 26 ± 1. 60) ng/ml,(37. 6 ± 7. 6) pg/ml]. The LVEF,LVSF,CI of Kawasaki disease for children in acute stage were lower than those in recovery phase[(60. 3 ± 3. 6)% vs. (64. 8 ± 4. 3)%,(30. 6 ± 2. 5)% vs. (34. 9 ± 1. 9)%,(3. 1 ± 0. 3)% vs. (3. 5 ± 0. 3)%]. Linear correlation analysis showed the heart-type fatty acid-binding protein and brain natriuretic peptide′concentrations in Kawasaki disease were negatively correlated with LVEF (P<0. 05). The heart-type fatty acid-binding protein′positive rates were also higher than brain natriuretic peptide for the children in acute and recovery phase. Conclusion The heart-type fatty acid-binding protein and brain na-triuretic peptide could be used as the biochemical markers for myocardial damage of children with Kawasaki dis-ease. The heart-type fatty acid-binding protein was more significant than brain natriuretic peptide. The heart-type fatty acid-binding protein and brain

  15. 缺血修饰清蛋白和心型脂肪酸结合蛋白检测在不稳定性心绞痛诊断及危险分层中的应用%Application of ischemia modified albumin and heart-type fatty acid-binding protein for the diagnosis and risk stratification of unstable angina

    Institute of Scientific and Technical Information of China (English)

    辛增莲; 杨丽; 郭宇璇; 彭辉; 徐菲莉

    2015-01-01

    Objective To determine the value of ischemia modified albumin,heart-type fatty acid-binding protein,B-type natri-uretic peptide and homocysteine in the risk stratification of patients with unstable angina pectoris;thus to provide an assessment for the condition of patients in clinic.Methods 135 patients with unstable angina were included in the disease group and subjected to risk stratification according to GRACE risk score software,70 cases of low-risk group,60 cases in the middle-risk group and 5 cases in the high-risk group.Another 145 healthy people were in the control group.The levels of ischemia modified albumin,heart-type fatty acid-binding protein,B-type natriuretic peptide and homocysteine were detected and compared.Results Between the control group and the disease group,significant difference of heart-type fatty acid-binding protein,B-type natriuretic peptide and homocys-teine was found (P 0.05).In the dis-ease group,the levels of ischemia modified albumin,heart-type fatty acid-binding protein and homocysteine in each risk stratification showed no significant difference(P >0.05).The level of B-type natriuretic peptide in high-risk group was higher than that in the low-risk group and in the middle-risk group and the difference was statistically significant (P 0.05 ).Conclusion The detection of heart-type fatty acid-binding protein,B-type natriuretic peptide and homocysteine possesses certain meaning in diagnosing unstable angi-na,and the level of B-type natriuretic peptide indicates the risk degree of the disease.%目的:探讨血清缺血修饰清蛋白(IMA)、心型脂肪酸结合蛋白(H-FABP)、B 型利钠肽(BNP)、同型半胱氨酸(Hcy)与不稳定性心绞痛(UA)危险分层的关联性,为临床提供评估患者病情的依据。方法选取135例不稳定性心绞痛(UA)患者作为病例组,根据全球急性冠状动脉事件注册(GRACE)危险评分软件,将病例组分为低危组70例、中危组60例及高危组5

  16. Significance of heart-type fatty acid binding protein in patients with acute coronary syndrome%心脏型脂肪酸结合蛋白在急性冠脉综合征中检测的意义

    Institute of Scientific and Technical Information of China (English)

    王斌

    2014-01-01

    目的:探讨心脏型脂肪酸结合蛋白(H-FABP)在急性冠脉综合征中检测的意义。方法将102例急性冠脉综合征分为不稳定型心绞痛(UA)35例,非 ST 段抬高急性心肌梗死(NSTEMI)49例和 ST 段抬高急性心肌梗死(STEMI)18例。另外选择40例健康人为正常组。测定血清肌钙蛋白(cTnI)和 H-FABP。结果 UA、NSTEMI、STEMI 组血清 cTnI 和 H-FABP 均高于正常组(P ﹤0.01),NSTEMI 组血清 cTnI 和 H-FABP 均高于 UA 组( P ﹤0.01),STEMI 组血清 cTnI 和 H-FABP 均高于 NSTEMI 组(P ﹤0.01)。在胸痛发作后2、4、6 h 血清中 H-FABP 阳性率明显高于 cTnI 阳性率,两者比较差异有统计学意义(P ﹤0.05),胸痛发作后12 h,血清中 H-FABP 阳性率明显低于 cTnI 阳性率,两者比较差异有统计学意义(P ﹤0.05)。血清 cTnI 和 H-FABP 在高危组均高于中危组、低危组(P 均﹤0.05),在中危组高于低危组(P 均﹤0.05)。血清 cTnI 和 GRACE 评分呈正相关(r =0.27,P ﹤0.05),血清H-FABP 和 GRACE 评分呈正相关(r =0.58,P ﹤0.05)。血清 H-FABP 和 GRACE 评分的相关系数大于血清 cTnI 和GRACE 评分的相关系数。结论 H-FABP 对急性冠脉综合征的诊断和危险分层更敏感。%Objective To study the significance of heart-type fatty acid binding protein( H-FABP)in patients with acute coronary syndrome. Methods One hundred and two cases of acute coro-nary syndrome were divided into unstable angina(UA)(35 cases),non-ST segment elevation acute my-ocardial infarction(NSTEMI)(49 cases)and ST segment elevation acute myocardial infarction(STE-MI)(18 cases). Forty cases of normal healthy people were enrolled into the normal group. Serum cTnI and H-FABP levels were detected. Results Serum cTnI and H-FABP levels in UA,NSTEMI,STEMI were higher than those in the normal group(P ﹤ 0. 01). Serum cTnI and H-FABP levels in NSTEMI were higher than those in the UP

  17. Correlation of intestinal fatty acid binding protein and intestinal injury in severe sepsis%肠脂肪酸结合蛋白与严重脓毒症患者肠道损伤的相关性研究

    Institute of Scientific and Technical Information of China (English)

    朱承睿; 丁仁彧; 孙旖旎; 马晓春

    2014-01-01

    Objective To investigate the content of intestinal fatty acid binding protein (IFABP) and its clinical significance in patients with severe sepsis.Methods A prospective observational study was conducted.Fifty patients with severe sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from July to December 2012 were enrolled,and 20 healthy patients served as control group.The concentrations of serum IFABP,interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α) were determined with enzyme-linked immunosorbent assay (ELISA) on days 0,1 and 3 after ICU admission.Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score,28-day prognosis,acute gastrointestinal injury (AGI) grade were recorded at the same time.Furthermore,the contents of IFABP were compared between control group and the severe sepsis group,abdominal infection group and non-abdominal infection group,the survival group and the death group,as well as among different AGI-grade groups.Correlation analysis of IFABP and inflammatory factors,IFABP and two scores,and IFABP and time of stay in ICU and mechanical ventilation were studied.Multivariate logistic regression and analysis of 28-day outcome of the patients were also studied.Results IFABP levels were increased in severe sepsis patients on days 0,1 and 3 compared with those of healthy control group (mg/L:731.90 ±53.91,592.07 ±41.94,511.85 ±47.97 vs.439.88 ±23.68,all P =0.000).There was no statistical significance of IFABP levels between abdominal infection group and non-abdominal infection group,the survival group and the death group,or among different AGI-grade groups.The correlation analysis showed that IFABP was statistically related with IL-6 (r=0.794,P=0.000),TNF-α (r=0.878,P=0.010),APACHE Ⅱ score (r=0.428,P=0.000) in patients with severe sepsis.Significant correlations were also found between IFABP and IL-6 (r=0.812,P=0.000),TNF-α (r

  18. 急性心肌梗死疾病实施心型脂肪酸结合蛋白浓度水平检测意义的探讨%To explore the clinical significance of the early Acute myocardial infarction diagnosis by the Heart-type Fatty Acid-Binding Protein testing

    Institute of Scientific and Technical Information of China (English)

    陈明; 韩帅

    2014-01-01

    Objective To explore the clinical significance of the early Acute myocardial infarction diagnosis by the Heart-type Fatty Acid-Binding Protein testing.Methods Choosing 86 cases of patients with Acute myocardial infarc-tion disease for the experimental group,according to the time we can be divided for the (0-3 h)group of 30 cases,the (3-6 h)group of 28 cases and(≥6 h)group of 28 cases,and 30 cases of healthy check-up for the control group,testing the Heart-type Fatty Acid-Binding Protein and Ischemia Modified Albumin,analyze the results comprehensively.Results Compared with the control group,there were significantly higher of the experimental group of the Heart-type Fatty Acid-Binding Protein and Ischemia Modified Albumin results(P0.05).Clinical specimens correlation analysis results show that the Heart-type Fatty Acid-Binding Protein and the correlation of clinical diagnosis result is good(Kappa=0.81).Conclusion There is a good indicators for the early Acute myocardial infarction diagnosis which as same as to the Ischemia Modified Albumin,and worthy to clin-ical promotion.%目的:探讨检测心型脂肪酸结合蛋白浓度水平对于早期诊断急性心肌梗死疾病的应用价值。方法选择86例确诊为急性心肌梗死的患者设为试验组,根据疾病发作时间可分为(0-3 h)组30例、(3-6 h)组28例和(≥6 h)组28例,并选择同期进行健康体检且结果为健康的人30例设为参照组,所以纳入对象均进行心型脂肪酸结合蛋白浓度水平的检测,同时进行缺血修饰白蛋白浓度水平检测,对结果进行综合分析。结果与参照组比较,(0-3 h)组、(3-6 h)组和(≥6 h)组的患者检测心型脂肪酸结合蛋白浓度水平和缺血修饰白蛋白浓度水平均有显著性升高,差异有统计学意义(P<0.05);阳性检出率分析可见,试验各组的心型脂肪酸结合蛋白和缺血修饰白蛋白的阳性检出率均在80.00%以上且两

  19. The Correlation Between Serum Liver-type Fatty Acid Binding Protein and non-Alcoholic Fatty Liver Extent and its Clinical Indexes%血清肝型脂肪酸结合蛋白与非酒精性脂肪肝病程度及相关临床指标的关联及其意义

    Institute of Scientific and Technical Information of China (English)

    刘晓军; 杜亚奇; 刘东屏

    2012-01-01

    Objective To investigate the correlation of serum liver-type fatty acid binding protein( L-FABP) and degree of fatty liver and its clinical parameters in nonalcoholic fatty liver (NAFLD) patients. Methods 60 cases of NAFLD and 60 cases of healthy controls were selected. The levels of serum L- FABP( g/L) and blood biochemical indexes were measured by ELJSA. In addition,we calculated body mass index(BMI) ,waist to hip ratio(WHR)and homeostasis model assessment insulin resistance index( HOMA-IR). Results In the NAFLD group serum L-FABP was obviously higher( 19.35 ±6.55 vs 15.31 ± 2.49) ,and ALT,TG,FBC,BMI,WHR were also markedly higher compared with the control group,while the difference was statistically significant( P 0.05). Correlation test results suggested L-FABP level was positively related with ALT (r =0. 624,p0. 05,moderate vs severe( 18. 37 ±3. 80 vs 25.03 ±5.26) (g/L) P< 0.05, compared with the healthy control group(15.31 ±2.49) (g/L) , only severe fatty liver group, but not other groups, had significant difference. Conclusion Serum L-FABP level of severe NAFLD patients was significantly increased,and L-FABP level was related with biochemical parameters of liver function.%目的 探讨非酒精性脂肪肝(non- alcoholic- fatty liver disease,NAFLD)患者血清肝型脂肪酸结合蛋白(liver-type fatty acid binding protein,L-FABP)与脂肪肝程度及相关临床指标的关系及其意义.方法 入选NAFLD 60例,健康对照60例.ELISA法测定血清L-FABP(g/L)及血生化指标,同时计算体重指数(BMl),腰臀比(WHR)及稳态模型评估胰岛素抵抗指数(HOMA-IR),B超判定脂肪肝程度.结果 NAFLD组与对照组相比,血清L-FABP明显增高,( 19.35 ±6.55 vs 15.31±2.49).NAFLD组ALT、TG、FBG,BMI、WHR水平明显高于对照组,差异显著(P<0.05),TC、AST、GGT两组间差异无统计学意义(P>0.05).相关性检测结果L-FABP水平与ALT(r=0.624,P<0.05)、TG(r=0.617,P<0.05)、FBG(r =0.579,P<0.05)、WHR(r =0.692,P <0

  20. 心脏型脂肪酸结合蛋白对急性肺栓塞早期预后评估的价值%Prognostic Value of Heart Type Fatty Acid Binding Protein in Acute Pulmonary Embolism

    Institute of Scientific and Technical Information of China (English)

    黄奕奕; 沈翔; 张淑云

    2015-01-01

    Objective To assess the value of heart type fat y acid binding protein (H-FABP)for prognosis of patients with acute pulmonary embolism(APE).Methods There were 51 patients with APE, divided into two groups:H-FABP≥10μg/l group (n=21)and H-FABP<10μg/l group (n=30),The relations between H-FABP and risk stratification and prognosis evaluating were evaluated in the two groups.Results In the positive group,there were 9 high-risk PE,10 middle-risk PE,2 low-risk PE,6 died within 1 months.In the negative group,there were 4 high-risk PE,14 middle-risk PE,12 low-risk PE,2 died within 1 months. There was statistical significance in the occur ence of hypotension,right heart dysfunction and myocardial damage between the two groups ( <0.05).Also there was statistical significance in the cases with high-risk,low-risk and death( <0.05).Conclusion H-FABP is a reliable predictor of short-term of patient with APE.%目的:探讨心脏型脂肪酸结合蛋白(heart type fat y acid binding protein,H-FABP)水平对急性肺栓塞(acute pulmonary embolism,APE)早期预后的评估价值。方法51例急性肺栓塞患者根据H-FABP测定值分为阳性组21例(H-FABP≥10μg/l)及阴性组30例(H-FABP<10μg/l),分析H-FABP升高对APE患者危险分层与临床预后的关系。结果阳性组中高危9例,中危10例,低危2例,死亡6例。阴性组中高危4例,中危14例,低危12例,死亡2例。两组比较低血压、右心室功能不全以及心肌损伤的发生率之间差异有统计学意义(<0.05);在高危、低危及1月内死亡人数方面相比差异亦具有统计学意义(<0.05)。结论 H-FABP对急性肺栓塞患者的早期预后判定有着很好的相关性。

  1. 阿司匹林及其衍生物与脂肪酸结合蛋白4复合物的晶体学研究%Crystallography study of the complexes of human fatty acid binding protein 4 with aspirin and its derivative

    Institute of Scientific and Technical Information of China (English)

    黄佩; 李敏军; 左刚; 郭豪杰; 周欢; 谢牧云; 郁峰; 徐春艳; 何建华

    2016-01-01

    脂肪酸结合蛋白4(Fatty Acid Binding Protein 4, FABP4)作为脂肪酸伴侣,参与调节脂肪酸代谢、运输、脂介导的信号转导以及巨噬细胞的炎症反应。该蛋白的抑制经常作为治疗脂肪代谢疾病的有效方案。本文报道了经典非甾体抗炎药阿司匹林及其水解物水杨酸与FABP4蛋白复合物的晶体结构,从而推测阿司匹林可能通过FABP4蛋白途径抑制动脉粥样硬化的分子机制。结构分析进一步阐明了FABP4蛋白疏水残基Phe16苯环侧链与水杨酸之间的 C-H-π相互作用比亲水位点静电相互作用提供更稳定的结合。该发现为设计更高选择性FABP4抑制剂提供了新的途径。%Background:Fatty acid binding protein 4 (FABP4), as fatty acid chaperone, plays center roles in lipid transport, lipolysis and liposynthesis, and it has been proved to be involved in the lipid signaling and inflammatory responses. Inhibitors of FABP4 are promising treatments for the diabetes and atherosclerosis. Purpose:The aim is to reveal the structural conformation of aspirin and salicylic acid binding to the FABP4, and to explore the novel structural features for the design of high-selective FABP4 inhibitors. Methods: Single crystal X-ray diffraction is applied to solve the structure of the ligand-protein complexes. Results:We have determined the crystal structures of FABP4 in complex with aspirin and its derivative, and from which a special C-H-πinteraction between the residues Phe16, Arg126 and the benzyl ring of aspirin has been defined. Conclusion:The complex structures of FABP4 bound with aspirin and its derivative show that the edge-to-face C-H-πinteraction between the residues Phe16, Arg126 and the benzyl ring of aspirin is a critical intermolecular force between the ligand-FABP4 interactions, which enables us to consciously apply these interactions in hit and lead optimization in rational structure based drug design.

  2. Association of the heart fatty acid-binding protein gene with quality of carcass and meat traits in pigs Associação entre o gene da proteína de ligação de ácidos graxos - coração com características de carcaça e qualidade da carne em suínos

    OpenAIRE

    Figueiredo, F C; P.S. Lopes; A.P.G. Pinto; Paiva,D.A.F.; Mendonça,P.T.; GUIMARÃES, S. E. F.

    2008-01-01

    The heart fatty acid-binding protein (HFABP) gene was sequenced in parental animals of a F2 crossing of boars of the Brazilian native Piau breed with commercial sows (Landrace x Large White Pietrain). Primers used for PCR were designed to amplify four exons of the gene. The PCR products were sequenced and compared with the GenBank sequences. Differences between the generated sequences and the GenBank sequences were observed for both genetic groups. A total of 246 F2 animals were genotyped usi...

  3. 肝型脂肪酸结合蛋白与非酒精性脂肪性肝病严重程度及其他指标关系探讨%Correlation between liver-type fatty acid binding protein and nonalcoholic fatty liver disease extent and other clinical parameters

    Institute of Scientific and Technical Information of China (English)

    李冰; 沈芊; 黄辉红; 郭娟荪; 汪道伟

    2013-01-01

    目的 探讨血清肝型脂肪酸结合蛋白(L-FABP)与非酒精性脂肪性肝病(NAFLD)患者疾病严重程度及脂代谢相关临床生化指标的相互关系.方法 选择96例NAFLD患者(观察组)及100例健康体检者(对照组),用酶联免疫吸附法测定血清L-FABP及血生化指标,超声判定病变程度,同时计算体质指数(BMI)、腰臀比(WHR)及稳态模型评估法胰岛素抵抗指数(HOMA-IR).结果 观察组WHR、BMI、空腹血糖(FBG)、三酰甘油(TG)、丙氨酸氨基转移酶(ALT)、HOMA-IR及L-FABP水平明显高于对照组,差异均有统计学意义(P<0.05).相关性分析结果表明,L-FABP水平与ALT(r=0.735)、TG(r=0.728)、FBG(r=0.681)、WHR(r=0.713)、BMI(r=0.699)、HOMA-IR(r=0.673)均呈正相关(P<0.05),与HDL-C呈负相关(r=-0.607,P< 0.05).对照组L-FABP水平为(15.42±2.51) g/L,轻度NAFLD为(15.96±2.92) g/L,中度NAFLD为(17.48±3.91) g/L,重度NAFLD为(25.14±5.37) g/L.重度NAFLD患者L-FABP水平与对照组及轻、中度NAFLD患者比较差异均有统计学意义(P<0.05).结论 重度NAFLD患者血清L-FABP水平明显增高,L-FABP水平与一些肝功能生化指标有关.%Objective To investigate the correlation between liver-type fatty acid binding protein (L-FABP) and nonalcoholic fatty liver disease (NAFLD) extent and other clinical parameters.Methods Ninety-six patients of NAFLD (NAFLD group) and 100 cases of healthy controls (control group) were selected.The levels of serum L-FABP and blood biochemical parameters were measured by enzyme-linked immunosorbent assay.The lesion degree was assessed by ultrasound.The body mass index (BMI),waist to hip ratio (WHR) and homeostasis model assessment insulin resistance index (HOMA-IR) were calculated.Results The WHR,BMI,fasting plasma glucose (FBG),triglycerides (TG),alanine aminotransferase (ALT),HOMA-IR and L-FABP in NAFLD group were higher than those in control group,there were statistical differences (P < 0.05).The result of correlation

  4. Value of heart-type fatty acid-binding protein to the early diagnosis of acute myocardial infarction%心型脂肪酸结合蛋白在急性心肌梗死早期诊断中价值

    Institute of Scientific and Technical Information of China (English)

    马春华; 王文红; 曲淑杰; 张彦宗; 秦笛

    2012-01-01

    Objective To investigate the value of heart-type fatty acid-binding protein (H-FABP) to the early diagnosis of acute myocardial infarction. Methods A total of 83 patients were suspected acute myocardial infarction at admission in 6 hours after onset of acute chest pain. They were randomly divided into AMI group (n = 32) and non-AMI group (n = 51) including 33 patients with unstable angina pectoris (UAP group) and 18 patients with non-cardiogenic chest pain (NCCP group). Another 40 healthy volunteers were as controls (control group). The plasma level of H-FABP was measured with ELISA, and compared with the traditional cardiac markers. Results The H-FABP level was significantly higher in AMI group than that in the other three groups (P<0. 01). ROC curve showed AUC of H-FABP was 0. 954 (95%CI: 0. 912 to 0. 997). The optimum cut-off point of H-FABP for diagnosing AMI was 6. 65 ng/mL. The sensitivity, specificity, negative prediction value and accuracy of H-FABP for diagnosing AMI in 6 hours were 90. 26%, 80.39%, 93.18% and 84. 34% respectively. The sensitivity, negative prediction value and accuracy of H-FABP were significantly higher than those of the traditional cardiac markers as myoglobin, creatine kinase-myocardial band and cardiac troponin I (P<0. 05). Conclusion H-FABP has better value to diagnosing AMI in the early stage.%目的 探讨血浆心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)对早期诊断急性心肌梗死(acute myocardial infarction,AMI)的意义.方法 发病6h内以急性胸痛就诊的疑似AMI患者83例,根据出院诊断分为AMI组32例与非AMI组51例,非AMI组又分为不稳定型心绞痛33例(UAP组)与非心源性胸痛18例(NCCP组),选择体检健康者40名为对照组,采用ELISA法检测各组血清H-FABP水平,并与传统心肌标志物的诊断效能进行比较.结果 AMI组血清H-FABP水平明显高于非AMI组和对照组(P均<0.01);ROC曲线显示,H-FABP的AUC为0.954(95%CI:0.912~0

  5. Predictive value of heart fatty acid-binding protein to major adverse cardiovascular events in patients with acute myocardial infarction%心型脂肪酸结合蛋白对急性心肌梗死患者主要不良心脏事件的预测价值

    Institute of Scientific and Technical Information of China (English)

    魏庆民; 周彬; 史永堂; 张友良

    2012-01-01

    Objective To observe the predictive value of peak concentration of plasma heart fatty acid-binding protein (H-FABP) to major adverse cardiovascular events ( MACE ) in patients with acute myocardial infarction ( AMI) . Methods The AMI patients ( n=60) were selected within two hours from admission to disease attack from Jan. 2010 to Jim. 2011. The concentration of plasma H-FABP was detected every two hours in the patients from admission to disease attack for 10 hours. According to the average value of H-FABP peak value, all the patients were divided into group A ( with higher H-FABP than average ) and group B ( with lower H-FABP than average ) . The occurrence status of MACE [severe heart failure, malignant arrhythmia, recurrent myocardial infarction, cardiac death and target lesion revascularization ( TLR ) ] was compared between two groups after disease attack for one month and one year. Results After disease attack for one month and one year, the incidence of severe heart failure was higher in group A than that in group B (P<0.05 ) , and the incidence of other events had no statistical difference between two groups. Conclusion The increase of H-FABP peak value has some predictive value to severe heart failure of MACE in AMI patients.%目的 观察血浆心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)的峰值浓度对急性心肌梗死(AMI)患者主要不良心脏事件(MACE)的预测价值.方法 入选2010年1月至2011年6月入院距发病时间2h以内的AMI患者60例,于入院即刻至发病10h期间,每2h测定1次血浆H-FABP的浓度.根据H-FABP峰值水平的平均值将患者划分为H-FABP高值组和低值组,比较两组患者发病后1个月、1年的主要不良心脏事件(严重心力衰竭、恶性心律失常、再发心肌梗死、心源性死亡、靶病变血管重建)的发生率.结果 与H-FABP低值组相比,H-FABP高值组发病后1个月、1年,MACE及严重心力衰竭的发生率更

  6. 心型脂肪酸结合蛋白在心梗患者行介入治疗中的意义%Significance of Heart-type Fatty Acid Binding Protein in Interventional Therapy for Patients With Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    刘伟忠

    2015-01-01

    Objective To study the applications of heart-type fatty acid binding protein in interventional treatment for patients with myocardial infarction, to explore the change of heart-type fatty acid binding protein(H-FABP)in patients with percutaneous coronary intervention(PCI). Methods 178 cases of ST-segment elevation myocardial infarction patients were selected for research and analysis. After coronary intervention in patients with ST fall down as the ST group,the other for non-ST group. For patients with H-FABP and troponin(cTnI)were measured, observed ST decline rate after two hours. Results There was no statistical difference between two groups,H-FABP after six hours was better than before surgery. H-FABP within 24 hours of ST group patients to return to a normal state,non-ST group did not fall back to normal state. Conclusion H-FABP of ST elevation myocardial infarction is directly linked to the severity of coronary artery disease. Surgery will affect the H-FABP levels in patients. The patients of ST fal by more than 50%and H-FABP decreased to normal status,clinical myocardial injury lighter, reperfusion effect was better.%目的:研究分析心型脂肪酸结合蛋白对心梗患者介入治疗的应用情况,探讨患者使用经皮冠脉介入治疗对患者心型脂肪酸结合蛋白变化的影响。方法选取我院178例ST段抬高型心肌梗死患者来进行研究分析,将冠脉介入治疗后ST回落患者作为ST回落组,其余为ST无回落组。对患者的心型脂肪酸结合蛋白以及心肌肌钙蛋白进行测定,观察术后2小时ST回落幅度。结果两组患者术前无统计学差异性,术后6 h的心型脂肪酸结合蛋白均要优于术前。ST回落组患者的心型脂肪酸结合蛋白在24 h内恢复到正常状态,ST无回落组没有恢复正常状态。结论 ST抬高型心肌梗死患者的心型脂肪酸结合蛋白和冠脉病变程度有直接联系,手术会影响患者的心型脂肪酸结合蛋

  7. 心型脂肪酸结合蛋白在急性心肌梗死早期诊断中的临床应用%The clinical application of heart-fatty acid binding protein in AMI early diagnosis

    Institute of Scientific and Technical Information of China (English)

    罗俭权; 李竞春; 龙振洪; 徐超成; 江金萍

    2016-01-01

    目的探讨心型脂肪酸结合蛋白(heart-fatty acid binding protein, H-FABP)对早期诊断急性心肌梗死(acute myocardial infarction, AMI)的临床应用价值。方法选取2013年1月至2015年6月我院诊断为AMI的患者151例为AMI组,同期选择有胸痛指征但最终排除AMI诊断的其他疾病患者68例为对照组,检测两组患者发病后0-3 h、3-6 h、6-12 h血清H-FABP、心肌肌钙蛋白I(cardiac tro-ponin I, cTnI)、肌酸激酶(creatine kinase, CK)及肌酸激酶同工酶(MB isoenzyme of creatine kinase, CK-MB)水平,对检测结果进行统计学分析。结果 AMI组0-3 h、3-6 h、6-12 h的H-FABP、cTnI、CK、CK-MB检测水平均显著高于对照组,且差异均具有统计学意义(P均<0.05)。血清H-FABP诊断AMI的灵敏度、特异性及受试者工作特征曲线下面积分别为78.8%、89.7%及0.919,均高于其他三项指标。所有AMI患者中,H-FABP与cTnI、CK及CK-MB在不同时间段的检测结果均有较好的相关性,且相关系数r均>0.8。结论 H-FABP对早期诊断AMI有较好的临床应用价值,优于cTnI、CK及CK-MB。%Objective To investigate the clinical application value of heart-fatty acid binding protein (H-FABP) in acute myocardial infarction(AMI) diagnosis. Methods 151 cases AMI patients in our hospital from January 2013 to June 2015 were collected as the AMI group. 68 cases patients with chest pain indications but obviated AMI during the same period were selected as the control group. The levels of H-FABP , cardiac troponin I(cTnI), creatine kinase(CK) and MB isoenzyme of creatine kinase(CK-MB) at 0-3 h, 3-6 h, 6-12 h of all the patients to fall in disease were detected. The results were analyzed statistically. Results The levels of H-FABP, cTnI, CK and CK-MB at 0-3 h, 3-6 h, 6-12 h in AMI group were all higher than that of control group, and the differences all had statistical significance

  8. Value of heart-type fatty acid binding protein to predicting senile unstable angina pectoris%心脏型脂肪酸结合蛋白预测老年不稳定型心绞痛患者预后的价值

    Institute of Scientific and Technical Information of China (English)

    钱海燕; 黄觊; 杨跃进; 杨艳敏; 张朝阳

    2013-01-01

    Objective To explore the value of heart fatty acid binding protein (H-FABP) to predicting the prognosis of senile unstable angina pectoris (UAP).Methods A total of 175 UAP patients aged 60 years or older were divided into positive H-FABP group and negative H-FABP group,and were recorded and analyzed the clinical data and 12-month follow-up survey results.Results The age was older,body mass index was larger,and the proportions of smoking history,family history of coronary heart disease,previous myocardial infarction and coronary artery bypass history,and diabetes mellitus were higher in positive group than those in negative group (P<0.05).The left ventricular ejection fraction was lower in positive group than that in negative group (P<0.05).Coronary angiography results showed that the rates of multi-vessel lesions,diffusive and occlusive lesions,and left main and left anterior descending lesions were higher in positive group than those in negative group (P<0.05).After the follow-up survey for 12 months,the incidence of major adverse cardiovascular events was significantly higher in positive group than that in negative group (P<0.01).Conclusion H FABP is valuable to identify the high risk population and to predict the prognosis of UAP patients aged 60 years or older.%目的 探讨心脏型脂肪酸结合蛋白(heart type fatty acid binding protein,H-FABP)预测老年不稳定型心绞痛患者预后的价值.方法 年龄≥60岁不稳定型心绞痛患者175例,分为H-FABP阳性组48例和阴性组127例,记录并分析2组资料及12个月随访结果.结果 阳性组年龄、体质量指数大于阴性组(P<0.05),吸烟、冠心病家族史、既往心肌梗死病史、冠状动脉介入和旁路移植手术史及合并糖尿病比例明显高于阴性组(P<0.05),左室射血分数低于阴性组(P<0.05);冠状动脉造影显示,阳性组多支、弥漫甚至闭塞病变、累及左主干和前降支比例高于阴性组(P<0.05);随访12个

  9. Effect of silent adipocyte fatty acid-binding protein gene on secretion of adipocyte-synthesized triglyceride and adiponectin%沉默脂肪细胞型脂肪酸结合蛋白基因对脂肪细胞合成甘油三酯及脂联素分泌的影响

    Institute of Scientific and Technical Information of China (English)

    吴洁; 钟敏; 邹瑾

    2012-01-01

    Objective To study the effect of 3T3-L1 adipocyte fatty acid-binding protein(A-FABP) gene on secretion of adipocyte-synthesized triglyceride and adiponectin by constructing its micro RNA expression vector using RNAi technology. Methods A microRMA expression vector for A-FABP gene was constructed and transfected into 3T3-L1 adipocytes. Expression of A-FABP mRNA and protein was detected by RT-PCR and Western blot, respectively. A model of silent A-FABP gene was established. Free fatty acid(FFA) cells(0. 5 mmol/L) and mature adpocytes were incubated for 24 h and divided into control group,FFA group,RNAi group,and RNAi + FFA group. Triglyceride and adiponectin levels were measured by ELISA. Expression of A-FABP and adiponectin mRNA was detected by RT-PCR. Results The microRNA expression vector after transfected into 3T3-L1 adipocytes could significantly inhibit the expression of A-FABP mRNA and protein. The synthesis of triglyceride increased significantly while the secretion of adiponectin decreased significantly with the increasing fatty acid concentration in adipocytes(P<0. 05). The triglyceride level was significantly lower while the adiponectin secretion level and the adiponectin mRNA expression level were significantly higher in RNAi and RNAi+ groups than in control and fatty acid groups(P<0. 05). Conclusion Silent A-FABP gene may become a new target for preventing and treating atherosclerosis and diabetes mellitus.%目的 应用RNA干扰(RNAi)技术,构建针对3T3-L1脂肪细胞型脂肪酸结合蛋白(A-FABP)的microRNA表达载体,研究沉默A-FABP基因的表达对脂肪细胞合成甘油三酯及脂联素分泌的影响.方法 构建靶向A-FABP基因的microRNA表达载体转染3T3-L1脂肪细胞后,RT PCR及Western blot法检测A-FABP mRNA 及蛋白表达.建立A-FABP基因沉默细胞模型,0.5 mmol/L游离脂肪酸和成熟脂肪细胞共孵育24 h,分为对照组、脂肪酸组、RNAi组、RNAi+脂肪酸组.ELISA法分别检测甘油三酯及脂联

  10. Role of heart-type fatty acid-binding protein in assessing the prognosis of acute pulmonary embolism%心肌型脂肪酸结合蛋白在急性肺栓塞预后中的作用

    Institute of Scientific and Technical Information of China (English)

    李宾公; 郑泽琪; 王梦洪; 彭景添; 颜琼; 肖坚

    2011-01-01

    Objective To study the role of heart - type fatty acid - binding protein ( H - FABP) in assessing the prognosis of acute pulmonary embolism (APE).Methods The levels of plasma H - FABP, cTnI and D - dimer were determined in 72 patients with APE and 30 healthy controls.The associations between the biomarkers and severe complications were determined by Logistic regression model.Results The levels of D - dimer in the patients with APE were significantly higher than that in healthy controls (P < 0.01).The incidence of severe complications was higher in the H FABP positive group of APE than in the H - FABP negative group (66.7% vs 3.5%, P < 0.05).By Logistic regression analysis, elevated H -FABP was associated with a 50.44 -fold increase in the death or complication risk (95% CI 7.40 ~ 342.38, P < 0.001).Conclusion The H - FABP might be a useful biomarker for prediction prognosis of patients with APE.%目的 探讨心肌型脂肪酸结合蛋白(H-FABP)在急性肺栓塞(APE)预后中的作用.方法 检测72例确诊为急性肺栓塞(APE)患者及对照组30例健康受试者血浆H-FABP、心肌肌钙蛋白I(cTnI)、D-二聚体水平.应用Logistic回归模型分析各生化标志物与APE预后的关系.结果 APE组血浆D-二聚体水平较对照组明显增高(P<0.01).APE组中H-FABP阳性组30 d内不良事件发生率高于H-FABP阴性组(66.7% vs 3.5%,P<0.05).Logistic回归分析显示,H-FABP为APE预后的独立危险因素,H-FABP阳性者发生不良事件的危险性是H-FABP阴性者的50.44倍(95%CI 7.40~342.38,P<0.001).结论 H-FABP阳性APE者预后较差,H-FABP可用于APE的危险分层.

  11. 急性ST段抬高型心肌梗死患者心型脂肪酸结合蛋白水平与GRACE危险评分的相关性研究%Relationship between Heart-type Fatty Acid-binding Protein and GRACE Risk Score in Patients with Acute ST-elevation Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    魏庆民; 周彬; 王晓纲; 樊延明; 王爱平; 刘翠华

    2013-01-01

    Objective To study the relationship between heart - type fatty acid - binding protein ( H - FABP ) level and Global Registry of Acute Coronary Events ( GRACE ) risk score in patients with acute ST - elevation myocardial infarction ( STEMI ). Methods From April 2010 to December 2011 , 60 STEM patients admitted to our hospital within 2 hours of symptom onset were enrolled in this study. Twelve hours after admission, blood samples were obtained for H - FABP measurement every two hours. Then, H - FABP peak values were found. The baseline data were recorded and the GRACE risk score were calculated. The Pearson's correlation analysis were used to analyze the relationship between the H - FABP peak value and GRACE risk score. Results The peak value of H - FABP was ( 59. 4 ± 23. 1 ) μg/L, which occmed 4~8 hours after admission. It was positively correlated with GRACE risk score in these patients ( r = 0.701 , P<0. 05 ). Conclusion H -FABP peak value is directly relevant with GRACE risk score in STEMI patients. Measurement of H - FABP level can provide additional risk stratification information in these patients.%目的 探讨急性ST段抬高型心肌梗死(STEMI)患者血浆心型脂肪酸结合蛋白(H-FABP)的峰值水平与全球急性冠状动脉事件注册(GRACE)风险评分的相关性.方法 选择2010年4月-2011年12月我科收治的发病2 h内的STEMI患者60例,于患者发病后2、4、6、8、10、12 h采血,检测H-FABP水平,找出其峰值.记录患者的基线资料,计算GRACE风险评分,对GRACE评分和H-FABP的峰值水平进行Pearson直线相关分析.结果 H-FABP的达峰时间为4~8 h,平均峰值为(59.4±23.1)μg/L;STEMI患者H-FABP峰值水平与GRACE危险评分呈正相关(r=0.701,P<0.05).结论 STEMI的H-FABP峰值水平与GRACE评分相关,检测H-FABP峰值水平可以为STEMI患者的危险分层提供参考.

  12. Difference of heart fatty acid binding protein in acute ischemic stroke and heamorrhage stroke and its significance%急性脑梗死和脑出血患者心型脂肪酸结合蛋白表达差异及临床意义

    Institute of Scientific and Technical Information of China (English)

    贺桂女; 韩雄; 马勇

    2016-01-01

    目的 探讨血清心型脂肪酸结合蛋白(heart fatty acid binding protein,H-FABP)在急性脑梗死(acute ischemic stroke,AIS)和脑出血(intraeerebral hemorrhage,ICH)患者中的表达差异,分析其与病理特征间的关系.方法 发病12h内AIS患者89例(AIS组)和ICH患者66例(ICH组),采用双抗体夹心ELISA法检测2组血清H-FABP水平,分析血清H-FABP水平与梗死部位、梗死灶大小和梗死病因分型间的关系.结果 AIS组血清H-FABP水平[132.14(81.63,324.26)ng/L]与ICH组[171.35(102.86,382.65)ng/L]比较差异无统计学意义(P>0.05);AIS组和ICH组血清H-FABP水平与初始NIHSS评分均无明显相关性(r=-0.110,P=0.307;r=0.094,P=0.451);AIS组血清H-FABP水平在梗死灶大小和梗死部位上差异无统计学意义(P>0.05);心源性脑梗死患者血清H-FABP水平[263.65(126.32,627.17)ng/L]高于动脉硬化性脑梗死[115.36(82.14,232.48) ng/L]、小血管性梗死[123.06(74.95,288.82)ng/L]和其他病因梗死患者[130.43(59.88,268.10)ng/L](P<0.05).结论 血清H-FABP水平不能鉴别AIS和ICH,可能是预测心源性脑梗死的潜在分子标志物.

  13. The changes and clinical significance of heart fatty acid-binding protein concentrations in children patients after open heart surgery%儿童心脏直视术后心肌脂肪酸结合蛋白水平的变化及意义

    Institute of Scientific and Technical Information of China (English)

    王永连; 王忠民; 陈志军; 姚文健; 卢建国; 李汉臣

    2009-01-01

    Objective To observe the changes and clinical significance of plasma heart fatty acid-binding protein(H-FABP)in children after open heart surgery. Methods Forty patients with congenital heart disease(CHD) who had undergone cardiac operation with cardiopulmonary bypass(CPB) were selected in this study,and were randomly divided into two groups (each 20 cases): cold crystalloid cardioplegia perfusion group (Ⅰ group) and cold blood cardioplegia perfusion group(Ⅱ group). Blood samples were taken to check the plasma H-FABP concentration before CPB and different time after CPB. Plasma H-FABP concentration was estimated by enzyme-linked immunosorbent assay (ELISA). Results The difference of plasma concentration of H-FABP before operation was not obvious between Ⅰ group and Ⅱ group. The plas-ma concentration of H-FABP intraoperation and different time after operation was higher than that before anesthesia induction obviously in two groups, and Ⅰ group rose more significantly [(50.13±3.98) μg/L vs (39.27±4.22) μg/L, P0.05),体外循环结束即刻,1、4、12、24 hH-FABP水平较麻醉诱导前均有不同程度的升高(P<0.01),于体外循环结束后1 h达峰值(P<0.01),Ⅰ组升高比Ⅱ组更明显[(50.13±3.98)μg/L比(39.27±4.22)μg/L,P<0.01].结论 体外循环心脏术后H-FABP显著升高,峰值浓度出现早,可作为一项早期判断心肌损伤的敏感指标.与灌注晶体停搏液相比,含血停搏液有良好的心肌保护作用.

  14. 心肌脂肪酸结合蛋白对急性冠脉综合征患者病情转归的预测价值%The value of heart-type fatty acid-binding protein in predicting disease outcome of patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    谢明水; 刘杨; 蒋守涛; 李玲; 晏文强; 张振建

    2013-01-01

    OBJECTIVE To investigate the value of heart-type fatty acid-binding protein in predicting disease outcome of patients with acute coronary syndrome (ACS). METHODS The H-FABP levels of 81 patients with acute coronary syndrome were detected. In 30 cases of acute myocardial infarction (AMI), there were 26 cases of unstable angina pectoris (UAP), 25 cases of stable angina pectoris (SAP). At the same period, 27 healthy volunteers were selected as the control group. The disease outcome of various types of ACS were analyzed and compared. RESULTS The H-FABP level (73.35 ± 56.73ngml) in AMI group was highest, and the H-FABP level (13.50 ± 5.64ng/ml) in UAP group was higher (P 0.05). Compared with all groups, the H-FABP level of AMI group was highest, but the disease outcome and prognosis were the worst (P < 0.05). CONCLUSION The H-FABP level could be used as an effective predictive indicator in disease outcome of patients with acute coronary syndrome.%目的 探讨心肌脂肪酸结合蛋白对急性冠脉综合征患者病情转归的预测价值.方法 81例急性冠脉综合征患者检测血浆心肌脂肪酸结合蛋白表达水平,其中急性心肌梗死(AMI) 30例,不稳定型心绞痛(UAP) 26例,稳定型心绞痛(SAP) 25例,同期选择27例健康体检者为对照组.对各组疾病患者病情转归进行分析比较.结果 AMI组的H-FABP水平(73.35±56.73 ng/ml)最高,UAP组(13.50±5.64 ng/ml)次之(P< 0.01); SAP组(4.65±3.38 ng/ml)与对照组(3.42±1.53 ng/ml)比较差异无统计学意义(P>0.05);各组观察对比,H-FABP水平最高的AMI组病情转归及预后最差(P<0.05).结论 H-FABP可作为一种预测急性冠脉综合征患者病情转归情况的有效指标.

  15. The research progress on the diagnosis of myocardial injury of heart-type fatty acid-binding protein%心型脂肪酸结合蛋白在心肌损伤诊断中的研究进展

    Institute of Scientific and Technical Information of China (English)

    李继元; 李洪; 杨天德

    2011-01-01

    背景 心肌标志物的正确应用为临床准确诊断、鉴别心血管疾病和判断治疗效果起到了革命性的作用,目前已经有越来越多的心肌损伤标志物在临床中得到应用,现对心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)的研究相关进展作一综述.目的 了解H-FABP的理化性质和临床检测方法,认识H-FABP在早期心肌梗塞诊断中的独特优势.内容 结合国内外文献对H-FABP的基础和临床研究现状进行了阐述,对目前临床检测的方法进行了介绍,并对发展的趋势做了进一步展望.趋向 随着H-FABP测定方法的不断改进及临床研究的不断深入,H-FABP正逐渐成为诊断心肌损伤的重要生化标志物.%Background The correct application of cardiac markers have played a revolutionary role for clinical accurate diagnosis,identification and treatment of cardiovascular disease. Now more and more cardiac biochemical markers have been applied in clinic researches,and the latest research progress in the field of H-FABP is reviewed in this paper.Objective To understand the physical and chemical properties and clinical detection methods of H-FABP,to recognize the unique advantages in diagnosis of the early AMI.Content To survey the basic and clinical research of H-FABP by reviewing domestic and international literatures, and to introduce the current clinical detection methods.Trend With the development of H-FABP determination methods and clinical research,H-FABP is becoming an important biochemical marker of myocardial injury.

  16. Study on the relationship of urinary liver-type fatty-acid binding protein and progression of nephropathy in diabetic patients%尿肝型脂肪酸结合蛋白与糖尿病肾病进展的关系研究

    Institute of Scientific and Technical Information of China (English)

    曾学辉; 李忠新; 张春雷; 宋林立

    2014-01-01

    Objective To investigate the relationship of urinary liver-type fatty-acid binding protein and progression of ne-phropathy in diabetic patients .Methods A total of 132 cases of type 1 and type 2 diabetic patients were recruited in this study , and were divided into four groups based on the urine albumin /creatinine and serum creatinine levels , including normal albuminuria group ( n =45), microalbuminuria group ( n =36), clinical albuminuria group ( n =30), and renal failure group ( n =21), Additional 65 healthy subjects were recruited as control group .The levels of urinary liver-type fatty-acid binding protein ( L-FABP) were measured with enzyme-linked immunosorbent assay (ELISA), and serum creatinine, urine creatinine, Liver function, hemoglobin, glycated he-moglobin (HbA1c), albumin (Alb), and 24h urinary protein were measured by respective biochemical or immunological methods . Results With the progression of diabetic nephropathy , the level of urinary L-FABP was gradually increased ( P 0.05).Conclusions The uri-nary L-FABP level can predict the occurrence of early diabetic nephropathy , and also monitor the progression of diabetic nephropathy .%目的:探讨尿肝型脂肪酸结合蛋白( L-FABP)与糖尿病肾病进展的关系。方法选择1型和2型糖尿病患者132例,依据尿蛋白/肌酐比(ACR)和血清肌酐水平分为正常蛋白尿组(45例),微量蛋白尿组(36例),临床白蛋白尿组(30例),肾功能衰竭组(21例),以65例健康体检者为对照组,酶联免疫吸附法( ELISA )测定尿L-FABP含量,同时检测血肌酐(Scr)、尿肌酐、肝功能、血红蛋白、糖化血红蛋白(HbA1c)、白蛋白(Alb)、24 h尿蛋白量、尿白蛋白等指标。结果随着糖尿病肾病的进展,尿L-FABP水平逐渐增高(各组间比较P <0.01),亚组分析显示正常白蛋白组尿L-FABP水平高于健康组( P<0.05),微量白蛋白组尿L-FABP水

  17. 心脏脂肪酸结合蛋白对冠状动脉搭桥术后心肌损伤的诊断价值%The diagnosis value of heart fatty acid binding protein for myocardial injury in patients after coronary artery bypass graft

    Institute of Scientific and Technical Information of China (English)

    张兰; 宋丹; 苏晞; 陈国洪; 王琳; 陈运清

    2011-01-01

    目的:探讨心脏脂肪酸结合蛋白(H-FABP)对冠状动脉(冠脉)搭桥术(CABG)患者术后心肌损伤的诊断价值.方法:分别在术前、术中解除主动脉十字夹钳即再灌注即刻、30 min、60 min、90 min、2 h、3 h、4 h、5 h、6 h、12 h、24 h采取动脉血检测H-FABP、肌酸激酶同工酶(CK-MB)、肌钙蛋蛋白I(cTnI).共连续检测了50例.按临床表现分为心肌损伤组和对照组.结果:①对照组(40例)的H-FABP、CK-MB、cTnI在手术前后均没有明显变化.②在心肌损伤组中(10例),在手术前血清H-FABP值为(3.56±1.2)μg/L,在术后(0.85±0.2)h血清H-FABP开始升高并达到峰值(72.4±18.1)μg/L,比CK-MB和cTnI均明显提前(P<0.0001);血清CK-MB值于(4.9±0.6)h开始升高,于(5.9±0.2)h到达峰值(64.4±17.6)IU/L;cTnI值于6 h开始升高,于(13.8±5.7)h达峰值(11.6±4.6)μg/L;再灌注即刻的H-FABP值和H-FABP的峰值呈显著正相关(r=0.88,P<0.0001);H-FABP的峰值分别与CK-MB峰值、cTnI亦呈显著正相关(r=0.91,P<0.0001和r=0.87,P<0.0001).结论:CABG术后监测H-FABP能早期发现心肌损害,并能预示心肌损害的程度,H-FABP是极具前途的血清心脏标记物之一.%Objective:To investigate the diagnosis value of heart fatty acid binding protein for myocardial injury in patients after coronary artery bypass graft (CABG).Method:Serum level of creatine kinase-MB (CK-MB), troponin-Ⅰ (cTnI), and human heart fatty acid binding protein (H-FABP) were detected in continued patients being undergone CABG at before operation,and the time interval reperfusion at 0 min, 30 min, 60 min, 90 min, 2 hr, 3 hr, 4 hr, 5 hr, 6 hr, 12 hr, 24 hr, respectively.Patients were divided into two groups (myocardial injury group and control group) according to the clinic characteristic information.Result:In the control group, the serum levels of H-FABP, CK-MB and cTnI did not change before and after CABG.In the myocardial injury group, the serum levels of H-FABP, CK-MB and c

  18. Relationship between serum concentration of heart-type fatty acid binding protein and severity of coronary artery lesion in patients with acute coronary syndrome%心型脂肪酸结合蛋白与急性冠脉综合征患者冠状动脉病变程度的关系

    Institute of Scientific and Technical Information of China (English)

    王亚蓉; 郭壮波; 黄丽萍; 徐元杰

    2013-01-01

    目的 探讨心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)与近期发作急性冠脉综合征患者的冠状动脉病变严重程度的相关性及原因分析.方法 入选暨南大学医学院附属第四医院急性冠脉综合征(发作12h内)患者168例,其中急性心肌梗死86例、不稳定型心绞痛82例.采用双抗体夹心酶联免疫吸附试验(ELISA)法检测血清H-FABP、肌钙蛋白(cardiac troponin T,CTnT)及肌酸磷酸激酶同工酶(creatine phosphokinase isoenzyme,CK-MB)浓度.采用Gensini积分系统对冠状动脉血管病变狭窄程度、病变部位及范围进行定量评定.比较急性心肌梗死组与不稳定型心绞痛组血清H-FABP浓度及冠状动脉病变Gensini积分;比较Gensini积分、冠状动脉狭窄程度、病变支数亚组之间H-FABP浓度;采用直线回归分析方法分析血清H-FABP浓度与冠状动脉病变严重程度、血清cTnT浓度、血清CK-MB浓度的相关性.结果 急性心肌梗死组血清H-FABP浓度显著高于不稳定型心绞痛组,差异有统计学意义[(88.5±32.9)pg/mL vs.(14.3±5.4)pg/mL,P<0.01].随着冠状动脉狭窄程度加重、累及支数增加及Gensini积分增加,血清H-FABP浓度显著升高,差异有统计学意义(P<0.05).血清H-FABP浓度与cTnT (r=0.627,P<0.05)及CK-MB (r=0.530,P<0.05)具有相关性;与患者冠状动脉病变严重程度呈正相关(r=0.538,P<0.01),其相关系数高于cTnT与冠状动脉病变严重程度的相关性(r=0.385,P<0.05).结论 血清H-FABP浓度升高反映了冠状动脉病变严重程度,临床可根据血清H-FABP浓度升高推断冠状动脉病变的严重程度,并采取积极的治疗措施.%Objectives To study the correlation between serum concentration of heart-type fatty acid binding protein (HFABP) and severity of coronary artery lesion in patients with acute coronary syndrome.Methods Serum concentrations of H-FABP,cardiac troponin T (cTnT) and creatine phosphokinase

  19. Cloning, Expression and Structure Modeling Analysis of Adipocyte Fatty Acid Binding Protein Gene (FA BP4) of Sheep%绵羊脂肪细胞型脂肪酸结合蛋白基因(FABP4)cDNA的克隆、表达及其结构模拟分析

    Institute of Scientific and Technical Information of China (English)

    徐秋良; 张庆莉; 陈玉林

    2011-01-01

    For investigated the expression level of adipocyte fatty acid binding protein gene (FABP4) at different stages of sheep longissimus muscle, in this paper, the eDNA of sheep (Ovis aries) adipocyte fatty acid binding protein gene (FA BP4 ) was cloned by the method of RT-PCR using designed primer pairs of Ff and Fr according to the FA BP4 gene eDNA conservative region.The putative protein spatial structure of FABP4 was analyzed by biology software.Additionally, the expression of FABP4 in sheep longissimus muscle and the correlation between FABP4 expressions of longissimus muscle and intramuscular fat contents at different days were tested by real time RT-PCR.The results showed that the sequence of eDNA of sheep FABP4 was 464 bp containing a 399 bp of open reading frame which encoded 132 amino acids and the amino acid of FABP4 was conserved in evolution, and the FABP4 protein was assembled as a barrel conformation by two a helixes and ten 3 folds.The real time RT-PCR revealed that expressions of FABP4 in longissimus muscle from 160 and 200-day's sheep were higher than those from 90-day's (P<0.O5), respectively.The expression of FABP4 longissmus muscle at different days was positive correlated with longissimus muscle intramuscular fat contents (R2=0.1796, P<0.01).The result indicated that regulated the expression of FABP4 in sheep longissimus muscle is a potential approach for improving sheep meat quality traits.%为探讨绵羊脂肪细胞型脂肪酸结合蛋白(FABP4)在不同生长阶段背最长肌中的表达特性,本实验以成年小尾寒羊(Ovis aries)皮下脂肪组织总RNA为实验材料,在脂肪细胞型脂肪酸结合蛋白基因(FABP4)cDNA保守区域设计1对引物Ff和Fr,采用RT-PCR方法克隆了绵羊FABP4全编码序列,并运用生物软件对FABP4蛋白空间结构进行分析.同时运用实时荧光定量PCR法,对FABP4在皮下脂肪和背最长肌中的表达以及不同日龄在背最长肌中的表达量与背最长肌肌内脂肪

  20. Gallbladder duplication

    Directory of Open Access Journals (Sweden)

    Yagan Pillay

    2015-01-01

    Conclusion: Duplication of the gallbladder is a rare congenital abnormality, which requires special attention to the biliary ductal and arterial anatomy. Laparoscopic cholecystectomy with intraoperative cholangiography is the appropriate treatment in a symptomatic gallbladder. The removal of an asymptomatic double gallbladder remains controversial.

  1. 心型脂肪酸结合蛋白在心梗患者行介入治疗中的意义%The study of heart-type fatty acid binding protein in the PCI therapy for patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    张健; 李春盛

    2013-01-01

    目的 观察ST段拾高型心肌梗死患者行经皮冠脉介入治疗(PCI)前后心型脂肪酸结合蛋白(H-FABP)变化及意义.方法 选择北京朝阳医院急诊科确诊ST段抬高型心肌梗死患者178例,根据PCI术后ST段回落程度分为两组,即ST段回落组及ST段无回落组,分别为137人及41人.所有病例均于入院即刻测定H-FABP及心肌肌钙蛋白(cTnI),并在PCI术后1h,6h,12 h和24 h再分别测定H-FABP质量浓度,PCI术后12h及24 h测定cTnI.测定PCI术后2 hST段回落幅度(ΣSTR).结果 ST段回落组及ST段无回落组PCI术前人口统计学资料差异无统计学意义.两组患者术后6 h H-FABP明显高于术前(P<0.05),ST段回落组患者于24 h H-FABP恢复至正常水平,而ST段无回落组患者H-FABP未降至正常水平.结论 ST段抬高型心肌梗死患者血清H-FABP升高与冠脉病变程度有关,PCI术可影响H-FABP变化,ΣSTR≥50%与H-FABP降至正常水平以下有利于判断患者的心肌损伤程度和心肌再灌注.%Objective To observe the change and clinical significance of the heart type fatty acid binding protein (H-FABP) in ST Segment Elevation Myocardial Infarction (STEMI) after percutaneous coronary intervention (PCI).Methods Of 178 STEMI patients were recruited and were separated as ST segment drop group (137) and ST segment non-drop group (41).All the patients received H-FABP and cTnI tests,and re-tested H-FABP on 1 h,6 h,12 h and 24 h after the PCI,and re-tested cTnI on 12 h and 24 h after the PCI.Also,the ST segment drop amplitude (ΣSTR) was measured 2 h after the PCI.Results The demographics of both groups were similar.In both groups,the H-FABP on 6 h after PCI was significantly higher than the value measured prior to PCI.In the ST segment drop group,the H-FABP was reduced to normal value on 24 h after PCI,while it was not in the ST segment non-drop group.Conclusions The H-FABP elevation is associated with the severity of coronary lesions in ST segment elevation

  2. Diagnostic Value of Heart Fatty Acid-Binding Protein among Early Acute Coronary Syndrome Patients%心肌脂肪酸结合蛋白对急性冠脉综合征患者的早期诊断价值

    Institute of Scientific and Technical Information of China (English)

    陈可; 王春明; 刘海波; 刘艳红; 鲍迎春; 方裕; 张丽梅; 赵乾磊

    2011-01-01

    Objective To determine the value of heart fatty acid - binding protein ( H - FABP ) in early diagnosis of acute coronary syndrome ( ACS ). Methods Serum concentrations of H - FABP were measured in 172 consecutive patients hospitalized for ACS within 6 h of the onset of chest pain. Of these patients, 96 were with established AMI and 76 were with unstable angina pectoris. Still, 74 normal healthy subjects matched for age and sex were enrolled as controls. Results Levels of HFABP in the AMI group and the UA group were ( 82.2±96.6 ) μg/L and ( 7.9±5.1 ) μg/L, significantly higher than those in controls [ ( 4.2 ± 1.8 ) μg/L ] ( P < 0.01 ). Area under the curve for receiver operating characteristic curve ( ROC ) of HFABP - diagnosed AMI was 0.952 [ 95% CI ( 0.919, 0.984 ) ], and the correspondence value for UA was 0.787 [ 95% CI ( 0.714,0.859 ) ]. Diagnostic sensitivity and specificity of H - FABP were 81.5% and 97.3% for AMI when cut - off value was defined as 7.47μg/L; diagnostic sensitivity and specificity for UA were 71.1% and 71.6% when cut - off value was defined as 5.20 μg/L. Conclusion Serum levels of H - FABP can serve as an early diagnostic index for myocardial necrosis or damage ,and could be applied to the early diagnosis of acute coronary syndrome.%目的 探讨血浆心肌脂肪酸结合蛋白(H-FABP)对急性冠脉综合征(ACS)的诊断价值.方法 对172例连续入选的ACS住院患者出现胸痛6 h内测定血浆H-FABP水平,其中急性心肌梗死(AMI)组96 例,不稳定性心绞痛(UA)组76例;并选择74例健康体检正常者为对照组.结果 AMI组、UA组的H-FABP水平分别为(82.2±96.6)μg/L、(7.9±5.1)μg/L,与对照组(4.2±1.8)μg/L比较,差异均有统计学意义(P<0.01).H-FABP诊断AMI的受试者工作特征(ROC)曲线下面积为0.952[95%CI(0.919,0.984)];而诊断UA的ROC曲线下面积为0.787[95%CI(0.714,0.859)];以7.47 μg/L作为H-FABP早期诊断AMI的最佳临界值,其敏感性为81.5%,

  3. 肠脂肪酸结合蛋白在急腹症患者中鉴别急性肠缺血的价值%The value of serum intestinal fatty acid binding protein measurement in discriminating intestinal ischemia in patients with acute abdomen

    Institute of Scientific and Technical Information of China (English)

    石卉; 吴本俨; 刘文徽; 苏斌斌; 李婷婷

    2012-01-01

    目的 评估肠脂肪酸结合蛋白( I-FABP)在急腹症患者中鉴别急性肠缺血的价值.方法 2009年11月至2011年8月解放军总医院151例住院急腹症患者及17例健康对照者纳入本研究,测定其血清I-FABP水平,根据ROC曲线计算I-FABP诊断急性肠缺血的临界值、敏感性、特异性、阳性似然比、阴性似然比、阳性预测值、阴性预测值,评估其诊断及鉴别诊断价值.结果 151例急腹症患者中急性肠缺血24例,非肠缺血127例.肠缺血组的I-FABP水平[(109.67 ±48.82)μg/L]明显高于非肠缺血组[(36.78±11.25) μg/L]和健康对照组[(8.33±6.25) μg/L],P值均<0.01.I-FABP的诊断临界值为87.52 μg/L,I-FABP诊断急性肠缺血的敏感度为0.762,阴性预测值为0.963,阳性似然比3.05,阴性似然比0.24.结论 血清I-FABP用于鉴别急腹症中急性肠缺血患者具有临床诊断价值.%Objective To assess the differential diagnostic value of serum intestinal fatty acid binding protein (I-FABP) in distinguishing intestinal ischemia patients from acute abdomen patients.Methods A total of 151 patients with acute abdomen and 17 healthy controls from the PLA General Hospital were enrolled from November,2009 to August,2011. Serum I-FABP levels were measured by ELISA.According to the ROC curve,the cut-off value,sensitivity,specificity,positive likelihood ratio (PLR),negative likelihood ratio ( NLR),positive predietive value (PPV) and negative predictive value (NPV) were calculated. Results Of the 151 acute abdomen patients,there were 24 intestinal ischemia patients and 127 without intestinal ischemia.Serum I-FABP level in intestinal ischemia group [( 109.67 ±48.82) μg/L]was significantly higher than those in patients without intestinal ischemia [(36.78 ± 11.25) μg/L]and healthy controls[(8.33 ±6.25) μg/L]( all P values <0.01 ).The serum I-FABP cut-off value for the diagnosis of intestinal ischemia was 87.52 μg/L.Serum I-FABP was efficient in terms of

  4. Heart-type fatty acid-binding protein in plasma and urine for the early diagnosis of acute myocardial infarction%血浆和尿液心型脂肪酸结合蛋白与急性心肌梗死的早期诊断

    Institute of Scientific and Technical Information of China (English)

    王宏运; 何海超; 王绍欣; 李转珍; 姚慧霞; 张东江

    2012-01-01

    目的 通过心型脂肪酸结合蛋白(H-FABP)与其他生化标记物的比较,探讨心型脂肪酸结合蛋白(H-FABP)对急性心肌梗死(AMI)患者的早期诊断价值.方法 本研究采用固相夹心酶联免疫法(ELISA)测定64例AMI患者血浆心肌肌钙蛋白(cTnI)、肌酸激酶同工酶(CK-MB)、肌红蛋白(MYO)、H-FABP浓度;同时选取非急性心肌梗死患者53例作为对照组.H-FABP采用两种检测方法:固相夹心酶联免疫法和胶乳比浊法免疫测定(LTIA).结果 cTnT,CK-MB,MYO,H-FABP( by ELISA),H-FABP (by LTIA),心电图(ECG)诊断AMI敏感性分别为39.1%,59.4%,64.1%,68.7%,70.3%和54.7%;特异性为:98.1%,71.7%,81.1%,77.4%,90.6%和92.5%.结论 对AMI患者的诊断,H-FABP(by LTIA)优于cTnT,CK-MB,MYO,H-FABP( by ELISA),ECG.%Objective To investigate the early diagnostic value of heart-type fatty acid-binding protein ( H-FABP) for acute myocardial infarction( AMI),by comparing with other biochemical markers.Methods The concentrations of serum H-FABP,cTnI.CK-MB,MYO of 64 patients with AMI were detected by ELISA.Meanwhile 53 patients without acuter myocardial infarction were also selected as the control group.H-FABP was measured by two immunoassays,the H-FABP enzyme-linked immunosorbent assay( ELISA) and the H-FABP latex turbidimetric immunoassay ( LTIA).Results Sensitivities of cTnI,CK-MB,MYO,H-FABP ( by ELISA).H-FABP ( by LTIA),and electrocardiogram ( ECC) for the diagnosis of AMI were 39.1%,59.4%,64.1%,68.7%,70.3% and 54.7%,respectively.Specificities of cTnT,CK-MB,myoglobin,H-FABP ( by ELISA),H-FABP ( by LTIA),and ECG were 98.1%,71.7%,81.l%,77.4%,90.6% and 92.5%,respectively.Conelusions H-FABP ( by LTIA) is superior to cTnT,CK-MB,MYO,and H-FABP ( by ELISA) tests for the diagnosis of AMI in patients.

  5. Heart-type fatty acid binding protein in the early diagnosis of myocardial infarction after off-pump coronary artery bypass%心肌型脂肪酸结合蛋白早期快速诊断OPCAB术后心肌梗死

    Institute of Scientific and Technical Information of China (English)

    孟冬梅; 李培军; 刘子后; 李杰; 孙静; 郭志刚; 刘建实

    2012-01-01

    目的 探讨心肌型脂肪酸结合蛋白(H-FABP)对非体外循环不停跳冠状动脉旁路移植术(OPCAB)术后心肌梗死的早期快速诊断价值.方法 2009年3月至7月,59例患者行首次单纯OPCAB.根据围手术期肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白Ⅰ(cTnI)值及心电图、超声心动图的变化将患者分为正常组(Ⅰ组)、心肌损伤组(Ⅱ组)和心肌梗死组(Ⅲ组),分析各组H-FABP、CK-MB、cTnI含量的变化,并应用ROC曲线分析H-FABP诊断术后急性心肌梗死的诊断截断点和应用价值.结果 Ⅲ组的H-FABP水平显著高于Ⅱ组及Ⅰ组(P<0.01),H-FABP峰值出现时间早(人ICU 2 h即达到高峰),维持时间短(入ICU 4 h即开始下降),术后1天回到基线水平.经ROC曲线检验,以H-FABP 22μg/L为心肌梗死的诊断截断点,入ICU即刻诊断灵敏度为90.9%,特异性为77.1%.入ICU 2 h的H-FABP值灵敏度为72.7%,特异性为75.0%.结论 H-FABP有助于OPCAB术后心肌梗死的早期快速诊断.%Objective To evaluate the early diagnostic value of Heart-type fatty acid-binding protein(H-FABP) for myocardial infarction in patients post off-pump coronary artery bypass (OPCAB).Methods Between March 2009 and July 2009,59 patients had been undergone OPCAB for the first time.They were divided into 3 groups (normal group,myocardial injury group and myocardial infarction group) by myocardial-bound creatiue kinase (CK-MB) 、cardiac troponio Ⅰ (cTnI) 、electrocardiogram (ECG) and echocardiogram.Serial blood samples were taken during perioperation to quantify blood levels of H-FABP,CK-MB,cTnI.Results The average H-FABP value for the patients in the myocardial infarction group is higher than the others ( P < 0.01 ).H-FABP reached the peak valve at 2 hours and decreased at 4 hours after the patients arrived at ICU.H-FABP got back to the baseline one day postoperation.Receiver operating characteristic curves( ROC curve) demonstrated that H-FABP had greater diagnostic

  6. Value of Urine Liver-Type Fatty Acid Binding Proteins in the Early Diagnosis of Acute Kidney Injury in Critically Ill Patients%肝型脂肪酸结合蛋白在重症患者急性肾损伤早期诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    黄云芳; 陈文莉; 方珣

    2011-01-01

    目的:探讨尿肝型脂肪酸结合蛋白(L-FABP)在重症患者急性肾损伤(AKI)中的早期诊断价值。方法:以我院收治的危重症患者为观察对象,按照阿姆斯特丹AKI诊断标准,将5d内符合诊断标准的AKI患者纳入AKI组(12例),对照组(12例)由匹配的非AKI患者构成。每24 h收集尿标本,持续5d。ELISA法检测尿L-FABP水平。以受试者工作特征曲线评价L-FABP对AKI的诊断作用。结果:与AKI诊断前3d比较,AKI诊断前2d及1d患者尿L-FABP均明显增高(P均<0. 05),但尿N-乙酰-β-D氨基葡萄糖苷酶(NAG)及血肌酐(Scr)无明显改变(P均>0.05);观察期间对照组尿L-FABP、NAG、Scr均无明显变化(P均>0.05)。AKI诊断前3d尿L-FABP、NAG、Scr对AKI均无诊断作用;AKI诊断前2d及1d尿L-FABP对AKI具有早期诊断作用,而NAG、Scr无早期诊断作用。结论:尿L-FABP对重症患者AKI具有较高的敏感性和特异性,可能具有AKI早期诊断价值。%Objective: To investigate the value of urinary liver-type fatty acid binding proteins (L-FABP) in the early diagnosis of acute kidney injury (AKI) in critically ill patients. Methods: Critically ill patients were divided into the AKI group ( n=12) and non-AKI group (n=12). Blood and urinary samples were collected daily for five days. The samples were used to determine serum creatinine(Scr) , N-acetyl-β-D-glucosaminidase (NAG), as well as urinary L-FABP. Standard statistic analysis was used along with receiver operating characteristic curve analysis to evaluate the diagnose value. Results: There were no significant differences in clinical parameters between non-AKI (n=14) and AKI (n = 12) groups. As compared with the levels obtained three days before the diagnosis of AKI, the urinary L-FABP levels in the AKI group increased significantly (P0. 05). The levels of urinary L-FABP, Scr and NAG had no significant changes in the control group (all P> 0.05). Conclusion; Urinary L

  7. Changes and clinical value of heart-type fatty acid binding protein in patients with acute hypertensive cerebral hemorrhage%急性高血压脑出血患者血清h-FABP水平变化及其临床应用价值

    Institute of Scientific and Technical Information of China (English)

    杨文东

    2012-01-01

    目的 通过观察急性高血压脑出血患者血清心脏型脂肪酸结合蛋白(h-FABP)水平变化,探讨其临床检测价值.方法 血清h-FABP采用双抗体夹心酶联免疫一步法定量检测;cTnI采用固相酶联免疫吸附实验(ELISA);CK-MB采用免疫抑制法测定HT5"H〗结果 急性高血压脑出血患者组血清h-FABP水平显著高于对照组(P<0.01),大量出血者及意识不清者血清h-FABP水平分别显著高于小量出血者及意识清醒者(P<0.01);血清h-FABP阳性率显著高于血清cTnI、CK-MB及心电图的阳性率(P<0.01);死亡率为25.5%(28/110),血清h-FABP、cTnI、CK-MB及心电图异常组的死亡率显著高于正常组(P<0.01);血清h-FABP预测发生死亡具有高的敏感性和阴性预测值,特异性和准确度较低,但心电图具有较高的特异性(64.5%)和准确度(69.1%).结论 血清h-FABP定量测定可作为判断急性高血压脑出血病情轻重及评价发生意外的1项客观指标,联合心电图监测临床价值更高.%Objective To understand the clinical value of heart-type fatty acid binding protein (h-FABP) in patients with acute hypertensive cerebral hemorrhage(AHCE) through the variation analysis of its serum level. Methods Serum level of h-FABP was determined by enzyme-linked immunosorbent one-step quantitative detection, cardiac troponin I(cTnl) was detected by solid-phase enzyme-linked immunosorbent assay (ELISA) and isoenzyme MB of creatine kinase(CK-MB) was assayed by immunosuppression assay. Results The h-FABP level in(AHCE) group was significantly higher than healthy control group(P<0. 01) and that in AHCE patients with massive haemorrhage and unconsciousness was significantly higher than in patients with small heamorrhage and consciousness. The positive rate of h-FABP was significantly higher than cTnI,CK-MB and electrocardiogram(P<0. 01). The mortality rate in patients, with abnormality of serum level of h-FABP,cTnl and CK-MB and ECG, was higher than patients

  8. 慢性肾脏病心肌损害与心型脂肪酸结合蛋白及心肌钙蛋白的相关性分析%Correlation Analysis of Heart Type Fatty Acid Binding Protein and Cardiac Troponin with Myocardial Damage in Chronic Kidney Disease

    Institute of Scientific and Technical Information of China (English)

    谢瑜; 沈颖; 罗惠民; 周晓萍; 江勇

    2015-01-01

    分析心型脂肪酸结合蛋白(HFABP)及心肌钙蛋白(cTnI)对慢性肾脏病(CKD)患者缺血性心肌损害的评估应用价值.选取非透析的慢性肾脏病患者,进行腺苷负荷心肌灌注显像检查,同时检测 HFABP、cTnI,并与腺苷负荷试验结果进行对比分析,明确 HFABP 及 cTnI 对缺血性心肌损害的评估价值.结果发现 HFABP 与 eGFR 负相关,与 CREA、BUN 正相关,cTnI 与 IVST、LVPWT 正相关,有31.1%的患者腺苷负荷心肌灌注显像试验阳性,HFABP 在腺苷负荷试验阳性组及阴性组患者间的差异无统计学意义,cTnI 的差异有统计学意义,腺苷负荷试验阳性结果与HFABP 不相关(r =0.041,P =0.654),与 cTnI 正相关(r =0.649,P <0.01).结果表明:HFABP受肾小球滤过率的影响较大,不是反映慢性肾脏病患者缺血性心脏损害的理想指标,cTnI 不受年龄和肾功能的直接影响,是腺苷负荷心肌灌注缺损的独立危险因素,腺苷负荷核素心肌灌注显像是评估 CKD 患者冠状动脉疾病的有效手段.%The ischemic myocardial damage evaluation value of heart type fatty acid binding protein and cardiac troponin I in CKD patients is explored in this paper.Adenosine stress myocardial perfusion imaging is performed to all patients whose levels of HFABP and cTnI are also measured and compared with adenosine stress test results to assess the ischemic myocardial damage evaluation value of HFABP and cTnI.It is observed that HFABP is negatively correlated with eGFR,and positively correlated to CREA and BUN,and that cTnI is positive corre-lated with IVST and LVPWT.31.1% patients have positive results in adenosine stress test,the positive results being positively correlated with cTnI(r =0.649,P <0.01),and having no correlation with HFABP (r =0.041, P =0.654).The results show that HFABP is strongly influenced by glomerular filtration rate,and thus not an i-deal index of

  9. 心型脂肪酸结合蛋白、肌钙蛋白Ⅰ与脑卒中继发性肺栓塞的关系%Association between heart-type fatty acid binding protein, cardiac tro-poninⅠand stroke-associated pulmonary embolism

    Institute of Scientific and Technical Information of China (English)

    韩芳; 张伟东; 廖晓凌; 王拥军

    2014-01-01

    Objective To investigate the diagnosis and prognostic value of heart-type fatty acid binding protein com-bined cardiac troponin Ⅰ in stroke-associated pulmonary embolism patients. Methods 150 patients with stroke-asso-ciated pulmonary embolism (study group) and 150 patients of stroke without pulmonary embolism (control group) from January 2011 to April 2014 in Luhe Hospital of Tongzhou District in Beijing City were selected in this study. The H-FABP and cardiac troponin Ⅰ of patients in two groups before treatment and those of the study group after treatment were detected and compared. Results The levels of plasma H-FABP and cardiac troponin Ⅰ of patients before treat-ment in study group [(9.52±2.67), (0.15±0.09) μg/L ] were higher than those of the control group [(3.87±2.96), (0.05±0.03) μg/L], the differences were statistically significant (P<0.05).After treatment, the levels of plasma H-FABP and cardiac troponinⅠ in study group [(5.51±1.97), (0.08±0.03) μg/L] were decreased than pretreatment, the differences were statistically significant (P<0.05). Conclusion The level of H-FABP and cardiac troponinⅠ increasing obviously in stroke-associated pulmonary embolism, and the detection of the two indexs can be helpful for the disease diagnosis and the access of short-time prognosis.%目的:探讨心型脂肪酸结合蛋白(H-FABP)联合肌钙蛋白Ⅰ(cTnⅠ)对脑卒中继发性肺栓塞患者早期诊断及判断预后的价值。方法选取2011年1月~2014年4月北京市通州区潞河医院收治的150例脑卒中继发性肺栓塞患者(研究组)及单纯脑卒中患者150例(对照组)。检测并比较治疗前两组及研究组治疗前后H-FABP、cTnⅠ水平。结果治疗前研究组H-FABP [(9.52±2.67)μg/L]及cTnⅠ[(0.15±0.09)μg/L]水平明显高于对照组[(3.87±2.96)、(0.05±0.03)μg/L],差异均有统计学意义(P<0.05);治疗后研究组患者血浆H-FABP、cTnⅠ水平分别为(5.51±1.97)、(0.08±0.03)

  10. 脂肪细胞型脂肪酸结合蛋白对冠心病危险程度预测价值的研究%Study on Predictive Value of Adipocyte Fatty Acid-binding Protein for Coronary Heart Disease Risk Degree

    Institute of Scientific and Technical Information of China (English)

    王峰; 刘帮助

    2013-01-01

    目的 探讨脂肪细胞型脂肪酸结合蛋白(A-FABP)表达在冠心病危险程度预测中的价值,为其防治提供依据.方法 回顾性分析经过冠状动脉造影确诊为冠心病观察组76例、同期26例阴性对照组患者的血清A-FABP表达水平、平板运动试验Duke评分,揭示A-FABP表达与冠心病危险程度之间的相关性.结果 A-FABP在冠心病观察组表达水平显著高于对照组(P <0.001),在多支病变、双支病变中A-FABP表达水平高于单支病变(P<0.05);A-FABP表达水平与Duke评分、冠状动脉病变支数、总胆固醇呈正相关,与高密度脂蛋白胆固醇水平呈负相关(P<0.05).结论 A-FABP表达与冠心病的发病及病变程度密切相关,可能对冠心病的危险程度具有一定的预测价值.%Objective To explore the predictive value of adipocyte fatty acid-binding protein (A-FABP)expression for coronary heart disease,providing guidance for the prevention and treatment.Methods A-FABP expression level and Duke score in observation group of 76 patients after coronary angiography diagnosed as coronary heart disease and 26 cases of negative controls were retrospectively analyzed to reveal the correlation between the risk degree of coronary heart disease and A-FABP expression.Results A-FABP expression level in patients with coronary heart disease was significantly higher than in the control group(P <0.001).A-FABP expression level in multi-and double-vessel lesions group were significantly higher than in single-vessel lesion and the control group(P < 0.05).A-FABP expression level was positively correlated with Duke score,coronary artery lesions and total cholesterol,and is negatively correlated with high density lipoprotein cholesterol levels(P < 0.05).Conclusion A-FABP expression is closely related with the onset and severity of coronary artery disease,and may have some predictive value for the risk degree of coronary heart disease.

  11. 血浆脑钠肽及脂肪酸结合蛋白水平与慢性收缩性心力衰竭关系的探讨%Investigation of the relationships among plasma B type natriuretic peptide,fatty acid binding protein and chronic congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    曹磊

    2011-01-01

    目的 测定慢性收缩性心力衰竭(CHF)患者的血浆脑钠肽(BNP)及血清脂肪酸结合蛋白(FABP)水平,探讨血浆BNP及血清FABP对CHF诊断及心功能评估的价值.方法 选择住院CHF患者60例,其中NYHA I级12例,II级18例,III级20例,IV级10例;原发疾病:冠心病30例,瓣膜性心脏病9例,扩张型心肌病10例,高血压性心脏病11例.另纳入20例健康体检者为健康对照组,分别测定BNP及FABP浓度,评价心功能.结果 CHF组血浆BNP及血清FABP水平显著高于健康对照组(PNYHA III级>NYHA II级,P均40%患者(P0.05).BNP与FABP呈正相关(r=0.801,P<0.01),两者与LVEF呈负相关(r=-0.718,r=-0.881,P<0.01).结论 血浆BNP及血清FABP测定对CHF的诊断和心功能的分级及预后判断都有重要的临床价值.%Objective To determine the plasma B type natriuretic peptide ( BNP ) and fatty acid binding protein ( FABP ) levels in patients with chronic heart failure ( CHF ), and to investigate the value of plasma BNP and FABP in diagnose of patients with chronic heart failure and in assessment of cardiac function. Methods There were 60 cases of CHF, according to NYHA classification, 12 cases were in degree of Ⅰ, 18 cases were Ⅱ, 20 were Ⅲ, 10 cases in IV. Primary disease:30 cases with CHD,9 cases with valvular heart disease,10 cases with dilated cardiomyopathy, 11 cases with hypertensive heart disease. The plasma BNP and FABP concentration in these 60 patients with chronic heart failure and 20 controls were determined, cardiac function assessment was conducted. Results Level of plasma BNP and FABP in CHF group were significantly higher than that of the control group( P < 0.01 ); and with the increase of degree of heart failure, plasma BNP and FABP levels gradually increased( NYHA Ⅳ > NYHA Ⅲ > NYHA Ⅱ, P < 0.01 ), meanwhile patients with LVEF ≤40% significantly higher than patients with LVEF > 40% ( P < 0.01 ). BNP was positively correlated with FABP( r = 0. 801, P < 0

  12. 吉非罗齐对游离脂肪酸和脂肪型脂肪酸结合蛋白在血脂异常兔中影响%Influence of gemfibrozil on levels of adipocyte fatty acid-binding protein in serum of dyslipidemia rabbits

    Institute of Scientific and Technical Information of China (English)

    谷祥任; 吴洁; 杜克炜

    2011-01-01

    Objective To observe the effects of gemfibrozil on serum free fatty acid(FFA) concentration and adipocyte fatty acid- binding protein(AFABP) secretion by adipose tissue from hypercholesterolemia rabbits. Methods Fifteen male New Zealand white rabbits were randomly divided into three groups. ①Control group was fed with normal diet for 12 weeks;②high cholesterol group was fed with high cholesterol group diet for 12 weeks;③gemfibrozil group was fed with same cholesterol diet for eight weeks supplemented with gemfibrozil 200 mg · kg-1 · d-1 for 4 weeks.Each group had five rabbits. FFA and AFABP concentrations in serum and adipose tissue culture supernatant were measured by enzyme-linked immunosorbent assay(ELISA). Adipose tissue was harvested for reverse transcriptionpolymerase chain reaction(RT-PCR) studies. Results After 8 and 12 weeks,rabbits from high cholesterol group and gemfibrozil group showed higher serum levels of total cholesterol, low density lipoprotein cholesterol and FFA than those of control group( P <0. 01). Gemfibrozil treatment significantly decreased body mass of rabbits in the twelfth week than in the eighth week ( P <0. 05). AFABP concentrations in serum and in culture supernatants of adipose tissue were decreased in gemfibrozil group compared with high-cholesterol group at the end of the twelfth week ( P < 0.05). The mRNA levels of AFABP in adipose tissue were increased in high cholesterol group and gemfibrozil group compared with control group ( P < 0. 05); but the mRNA levels of AFABP in adipose tissue was decreased in gemfibrozil group compared with high-cholesterol group( P <0.05). Conclusion The study indicated that gemfibrozil reduced body mass and reduced FFA and AFABP serum concentration and adipose tissue secretion ot hypereholesterolemia rabbits. These effects might be of significance for the treatment of atherosclerosis and of obesity prevention.%目的 现察吉非罗齐短期干预对高胆固醇血症兔血清游

  13. 肠脂肪酸结合蛋白在肺炎合并胃肠功能损伤患儿血清中的变化及意义%Change in serum intestinal fatty acid binding protein and its significance in children with pneumonia and gastrointestinal injury

    Institute of Scientific and Technical Information of China (English)

    范晓蕾; 李海英; 陈晓昕; 谢垒; 王怀立

    2016-01-01

    目的:探讨肠脂肪酸结合蛋白(IFABP)在社区获得性肺炎患儿血清中的变化及与胃肠功能损伤的相关性。方法选择2015年1月至10月的社区获得性肺炎患儿82例(轻症34例,重症48例),根据小儿危重病例评分(PCIS)将重症肺炎患儿分为非危重组(25例)和危重组(23例);另选取体检的健康儿童30例作为对照组。采用酶联免疫吸附法检测血清 IFABP 浓度,并对重症肺炎患儿进行急性胃肠损伤(AGI)分级。比较各组间血清 IFABP 浓度的差异,并对 IFABP 与 AGI 分级和 PCIS 进行相关性分析。结果重症肺炎血清 IFABP 浓度均高于对照组和轻症肺炎组(均 P<0.01),轻度肺炎组血清 IFABP 浓度亦明显高于对照组(P<0.01)。危重组血清 IFABP 浓度高于非危重组(P<0.01)。AGI 1~4级组血清 IFABP 均高于对照组(P<0.01),而且随着 AGI 级别的增高,血清 IFABP 浓度也逐渐增高,差异有统计学意义(P<0.01)。IFABP 与 AGI 分级呈正相关(P<0.01);与 PCIS 呈负相关(P<0.01)。结论肺炎患儿血清 IFABP 均有所增高,血清 IFABP 可以作为肺炎患儿合并胃肠损伤早期诊断和病情评估的敏感指标。%Objective To study the change in serum intestinal fatty acid binding protein (IFABP) in children with pneumonia and its correlation with gastrointestinal injury. Methods A total of 82 children with community-acquired pneumonia who were treated from January to October, 2015 were enrolled, among whom 34 had mild pneumonia and 48 had severe pneumonia. According to pediatric critical illness score (PCIS), the children with severe pneumonia were further divided into non-critical group (25 patients) and critical group (23 patients). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group. ELISA was used to measure serum IFABP level, and the acute gastrointestinal injury (AGI

  14. 心型脂肪酸结合蛋白在急性心肌梗死早期诊断价值的研究%Clinical value of heart-type fatty acid binding protein in the diagnosis of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    周晓茜; 蔡英; 于萍; 朱琛颖; 刘学波

    2013-01-01

    Objective To investigate the value of heart - type fatty acid binding protein (H -FABP) in the early diagnosis of acute myocardial infarction ( AMI). Methods 68 patients admitted to hospital with acute chest pain were selected in this study, and were divided into unstable angina pectoris (UAP) group and acute myocardial infarction (AMI)group according to the clinical diagnosis including ECG and the results of coronary arteriography. Serum H - FABP concentrations were tested by using ELISA method at 3 h ( H - FABP3) and 6 h ( H - FABP6) after the chest pain. The sensitivity, specificity, positive predictive value, negative predictive value were compared with hsTnT and CK -MB. Results Serum H - FABP3 and H - FABP6 concentrations were significantly higher in group AMI than in group UAP ( P < 0. 05 ). The sensitivity, specificity, positive predictive value, negative predictive value of H - FABP3 in the diagnosis of AMI were 87.0% , 81.8% , 90. 9% , 75.0% , while in H - FABP6 were 95.7% 、90. 9% 、95. 7% 、90.9% . The data of H - FABP6 were significantly higher than those of HABP3 except positive predictive value(P <0. 05) ; Further, the sensitivity and negative predictive value of H - FABP were significantly higher than those of hsTnT and CK - MB (P < 0. 05). Conclusion The serum H - FABP concentrations of patients were significantly increased at the early stage of AMI. The sensitivity and specificity of H - FABP in the early diagnosis of AMI were significantly higher than those of hsTnT and CK - MB.%目的 探讨心型脂肪酸结合蛋白(H-FABP)在急性心肌梗死(AMI)早期的诊断价值.方法 选择急诊胸痛可疑心肌梗死入院患者68例,根据患者的临床症状、心电图及冠状动脉造影结果将患者分为不稳定型心绞痛组(UAP组,共22例)和AMI组(共46例).分别在患者胸痛发生后3h和6h抽取静脉血5 mL,ELISA法定量测定血清H-FABP浓度.分别计算H-FABP在AMI诊断中的敏感度、特异度、阳性预测值及

  15. 脂肪细胞型脂肪酸结合蛋白疫苗对高脂喂养雌鼠体重和糖耐量的影响%Effect of Vaccination Against Adipocyte Fatty Acid Binding Protein on Body Weight and Glucose Tolerance in Female Mice with High-Fat Diet

    Institute of Scientific and Technical Information of China (English)

    金昕晔; 邹大进

    2012-01-01

    目的:构建能诱导出针对脂肪细胞型脂肪酸结合蛋白(FABP4)特异性中和抗体的疫苗,为高脂诱导下肥胖和胰岛素抵抗的防治新途径提供理论和实验依据.方法:野生型C57BL/6J雌鼠随机分为疫苗组(n=10,高脂饲养)、佐剂组(n=10,高脂饲养)和空白对照组(n=10,普通饲养),分别予以皮下注射生物合成的FABP4蛋白、佐剂和磷酸盐缓冲液,观察比较各组抗体滴度、安全耐受性和体重、摄食量、空腹血糖、胰岛素抵抗指数(HOMA-IR)、糖耐量实验血糖曲线下面积(AUC)等指标.结果:疫苗组小鼠产生了高滴度的FABP4特异性抗体,并于第3轮加强免疫后达到平衡状态.首次免疫16周后,疫苗组小鼠体重高于空白对照组,但明显低于佐剂组(P<0.05);日平均摄食量高于空白对照组(P<0.05),与佐剂组无差异(P>0.05);空腹血糖、HOMA-IR、腹腔葡萄糖耐量实验AUC均明显低于佐剂组(P<0.05),与对照组无统计学差异(P>0.05).结论:以FABP4作为抗原免疫小鼠,可产生高滴度特异性抗体IgG,有效降低高脂喂养野生型雌性小鼠体重、空腹血糖、HOMA-IR和血糖AUC等指标,为高脂诱导的肥胖和胰岛素抵抗的治疗提供了新的途径和初步证据,可进行深入研究.%Objective: To construct vaccine against adipocyte fatty acid binding protein(FABP4) in order to give theoretical and experimental evidence on prevention and cure of high-fat-induced obesity and insulin resistance. Methods: 30 wild-type female C57BL/6J mice were randomly divided into vaccine group(VG, n=10, with high-fat diet), adjuvant group(AG, n=10, with high-fat diet) and control group(CG, n=10, with normal diet), and were sub-cutaneously injected with biosynthetic FABP4, adjuvant, and phosphate buffered solution, respectively. Several indexes were observed, including antibody titers, security and tolerance, body weight, food intake, fasting blood glucose, homeostasis model of assessment

  16. Value of urinary liver-type fatty acid binding protein in prediction of renal function progression in patients with chronic glomerulonephritis%尿肝型脂肪酸结合蛋白预测慢性肾小球肾炎进展的价值

    Institute of Scientific and Technical Information of China (English)

    徐维佳; 李佳琳; 王琴; 施蓓莉; 牟姗; 倪兆慧

    2012-01-01

    Objective To evaluate the value of urinary liver-type fatty acid binding protein (L-FABP)as a biomarker in prediction of renal function progression in patients with chronic glomerulonephritis (CGN). Methods A total of 123 patients with newly diagnosed CGN by renal biopsy in Shanghai Renji Hospital between 2004 January and 2005 December were enrolled in the study,Twenty-eight healthy subjects were used as control group.Urine samples were collected before biopsy and treatment,and urinary L-FABP was measured by ELISA.The patients with follow-up every three months for 5 years were divided into progressive group and nonprogressive group.The progression of kidney function impairment was defined as a reduction of GFR ≥ 5 ml·min-1·(1.73 m2)-1·year-1 during follow-up.The risk factors of progressive renal function were evaluated and the Spearman correlation analysis was performed to find out the prognostic indicator of renal function deterioration. Results Urinary L-FABP level of CGN patients was significantly higher than that of healthy control group (P<0.01).Urinary L-FABP in CGN patients was negatively correlated with eGFR (r=-0.565,P<0.01) and positively correhted with proteinuria (r=0.501,P<0.01) and Scr (r=0.601,P<0.01).Kaplan-Meier analysis showed that urinary L-FABP excretion>76.58 μg/g·cr predicted progression of renal function.The AUC of urinary L-FABP for prognosis of CGN progression was 0.95,with 87.5% of sensitivity and 90.5%of specificity at the cutoff value of 119.8 μg/g·cr,which revealed its great value of predicting the prognosis of CGN patients. Conclusion Urinary L-FABP can be a novel biomarker of evaluation for renal injury and early progressive renal function deterioration in patients with CGN.%目的 评估尿肝型脂肪酸结合蛋白(L-FABP)预测慢性肾小球肾炎(CGN)病情进展的临床价值.方法 前瞻性入选2004年1月至2005年12月期间在我院行肾穿刺活检明确病理诊断的原发性CGN患者123

  17. Value of serum liver fatty acid-binding protein in monitoring of hepatic function after the ischemia-reperfusion injury%血清肝型脂肪酸结合蛋白在大鼠肝脏缺血再灌注损伤的早期诊断价值

    Institute of Scientific and Technical Information of China (English)

    门贺伟; 杨龙; 张荣信; 薛振毅; 蔡金贞; 张雅敏

    2012-01-01

    Objective To investigate the diagnostic value and significance of serum liver fatty acid-binding protein (L-FABP) in hepatic ischemia-reperfusion injury in rat.Methods Male Wistar rats were randomly divided into three groups:sham operation group (group A) ; reperfusion after 15 min of ischemia group (group B) ; reperfusion after 30 min of ischemia group (group C).Each group was divided into 6 subgroups based on the time of reperfusion (15 min,1 h,3 h,6 h,1 d,3 d).The model of hepatic ischemia-reperfusion injury was established,the level of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and L-FABP were tested at each time point and the expression of L-FABP was tested by Immunohistochemical Fluorescence.The pathological changes observed in the liver and evaluated the changes by Suzuki's scoring system.Results Compared with group A,the changes of serum L-FABP:increased after 15 min of reperfusion [(0.57 ± 0.14) μg/L,P < 0.05],reached the peak after 3 h of reperfusion [(1.70 ± 0.26) μg/L,P < 0.05] and returned to normal at 3 d [(0.16 ± 0.05) μg/L,P >0.05] ; the changes of serum ALT and AST:no significant increase after 15min of reperfusion,reach the top at 6h and the level was still higher than normal at 3 d (P < 0.05) ; L-FABP in liver tissue:the expression was decreased after 15min of reperfusion (0.148 ± 0.047,P < 0.05),reached to the trough at 3 h (0.071 ± 0.019,P < 0.05) and returned to normal at 3 d (0.142 ± 0.047,P > 0.05).Compared with group B,the level of serum L-FABP,AST and ALT in group C were significandy increased at each time point (P < 0.05),and the expression of L-FABP was significantly decreased (P < 0.05),the pathological changes were significantly worse.Conclusion Compared with the traditional indicator of liver function (ALT,AST),L-FABP is the more sensitive indicator to monitor the hepatic ischemia-reperfusion injury,and it consistents with the changes in the liver tissue pathology.%目的 探讨血清

  18. The change of serum fatty acid binding protein and its clinical significance in patients with hepatitis C%血清脂肪酸结合蛋白在丙肝患者中的表达变化及临床意义研究

    Institute of Scientific and Technical Information of China (English)

    毛长庚; 聂亚英; 刘建湘; 肖创清

    2015-01-01

    目的 研究丙肝患者血液中肝型脂肪酸结合酶( L-FABPs)与肝炎活动程度的关系,探讨L-FABPs对丙肝患者肝炎程度的提示和诊断价值. 方法 选取2010年5月至2014年5月于本院就诊并被确诊为慢性丙型肝炎的患者48例(丙肝组)和30名健康人(对照组) ,进行实验室和肝脏活组织检查. 分析并评价相关指标对丙肝患者肝炎程度的诊断价值.结果 丙肝患者的ALT、AST、CRP、MPV和L-FABPs水平均高于健康对照组(P<0. 01);轻度肝炎组患者血清中ALT、AST、L-FABPs明显低于中重度肝炎患者(P<0. 05). 相关分析显示,L-FABPs水平与ALT、AST呈正相关(r=0. 430,P=0. 012;r=0. 337,P=0. 028). 绘制受试者工作曲线,L-FABPs对轻度肝炎患者的诊断曲线下面积为0. 827(95%CI为0. 727~0. 926,P<0. 01),高于AST和ALT对轻度肝炎的诊断曲线下面积(0. 760,0. 775). 当L-FABPs的诊断阈值为12. 6 g/L时,诊断的灵敏度为77%,特异性为87%,假阳性率为13%,假阴性率为23%. 结论 血清L-FABPs的水平随着丙肝肝炎程度的增加而升高,对轻度肝炎的诊断的灵敏度和特异性优于ALT和AST,是追踪随访丙肝患者肝损伤的良好指标,值得临床推广使用.%Objective To detect the change of serum fatty acid binding protein( L-FABPs) in patients with hepatitis C,and to investi-gate the diagnostic value of L-FABPs. Methods 48 hepatitis C patients and 30 healthy controls were selected in this study. Serum bi-ochemical test,and serum L-FABPs were assessed. Results The serum levels of ALT,AST,CRP,MPV and L-FABPs in hepatitis C patients were significantly higher than those of healthy controls(P<0. 01). ALT,AST and L-FABPs in moderate and severe chronic hepatitis patients were significantly higher than those of mild patients(P<0. 05). The serum levels of L-FABPs was positive correlated with ALT(r=0. 430,P=0. 012) and AST (r=0. 337,P=0. 028). Receiver operating characteristic (ROC) curves were used to e-valuate the diagnosis

  19. 心脏型脂肪酸结合蛋白在早期诊断老年人急性心肌梗死中的应用价值%The value of heart-type fatty acid binding protein in the early diagnosis of acute myocardial infarction in elderly patients

    Institute of Scientific and Technical Information of China (English)

    唐江; 方臻飞; 何毅; 郭书红

    2013-01-01

    Objective To investigate the diagnostic value of heart-type fatty acid binding protein (H-FABP) versus cardiac trofonin I (cTnI) and creatinekinase-MB (CK-MB) in early diagnosis of acute myocardial infarction (AMI) in elderly patients.Methods 67 patients with acute chest pain were selceted sequentially and divided into AMI group (n=30) and non-AMI group (n=37).Plasma H-FABP level was rapidly detected by using colloidal gold reagent plate and solid phase immunochromatographic assay for qualitative determination within and after 6 hours of AMI onset.Plasma levels of cTnI and CK-MB were determined within and after 6 hours of onset.The diagnositic value of H-FABP,cTnI and CK-MB in AMI was compared within and after 6 hours of onset.Results The sensitivity of H-FABP was better than that of cTnI and CK-MB within 6 hours of onset (93.3% vs.46.6%,23.3%,both P<0.05).The negative predictive value of H-FABP was better than that of cTnI and CK-MB within 6 hours of onset (94.7% vs.69.8%,61.1%,both P< 0.05) While,positive predictive value and specificity were basically the same between H-FABP,versus cTnI and CK-MB.H-FABP and cTnI levels had significant differences between AMI and non AMI group after 6 hours of onset (all P<0.05).Plasma levels of cTnl and CK-MB were higher after 6 hours than within6 hours [cTnI (4.10±1.79) mg/L vs.(1.45±1.31) mg/L,CK MB(180.52± 158.70) U/L vs.(20.02± 7.97) U/L,both P<0.05].Conclusions As compared with cTnI and CK-MB,within 6 hours after AMI onset,H-FABP as a new myocardial necrosis marker has higher sensitivity,specificity,positive and negative predictive values in the diagnosis of AMI.While,after 6 hours of AMI onset,H-FABP has the same diagnostic value as cTnI and CK-MB.%目的 探讨心脏型脂肪酸结合蛋白(H-FABP)、肌钙蛋白(cTnI)、肌酸激酶同工酶(CKMB)在老年人的急性心肌梗死(AMI)中早期诊断价值. 方法 序贯选择2012年9月至2013年1月67例急性胸痛

  20. 血清脂肪细胞型脂肪酸结合蛋白及脂联素水平与冠心病的相关性%Association between adipocyte fatty acid binding proteins/adiponectin and coronary artery stenosis

    Institute of Scientific and Technical Information of China (English)

    金静; 彭道泉; 龚浩; 赵水平; 宁小晖; 李松林; 王淑慧

    2010-01-01

    Objective To observe the relationship between serum and monocyte-derivedmacrophages secreted adipocyte fatty acid binding protein(A-FABP), adiponectin(or A-FABP/adiponectin ratio)and coronary artery disease. Methods Three hundred and forty subjects underwent coronary angiography(CAG)were classified into CAD group(n = 211)and non-CAD group(n = 129)according to the CAG results. The severity of coronary artery stenosis was assessed by the numbers of involved coronary artery branches and the sum of the Gensini scores. Fasting venous blood was collected from all subjects and peripheral monocytes were isolated from 20 subjects(10 selected from each group with age-, gender-, and BMI-matched). Peripheral blood monocytes were obtained and stimulated into macrophages with PMA, cell culture supernatant was collected. The concentration of serum/supernatant A-FABP and adiponectin levels were assayed by enzyme-linked immunosorbent assays. Results(1)A-FABP levels tendend to be higher in CAD patients compared to non-CAD subjects[18. 3(13.2,22. 8)μg/L vs. 16. 4(13.5,20. 4)μg/L,P = 0. 088]. The concentration of adiponectin in CAD group was significantly lower than those in non-CAD group[13.9(9.8,17.1)mg/L vs. 19.7(14.5,27.6)mg/L,P <0.05].(2)The A-FABP levels increased and the adiponectin levels decreased as the number of stenotic vessels increased. Gensini scores were positively correlated with serum A-FABP(r = 0. 120, P = 0.043)and inversely correlated with adiponectin(r = - 0. 405, P = 0. 007).(3)The difference in A-FABP/adiponectin ratio was moreprominent between subjects with CAD and subjects without CAD[(1.51 ±0. 79)μg/mg vs.(0. 89 ±0. 30)μg/mg, P < 0. 01]and there was a stronger positive correlation of Gensini score to A-FABP/adiponectin ratio(r =0. 531, P =0. 000).(4)Monocyte-derived-macrophages from patients with CAD had higher A-FABP/adiponectin ratio than that in patients without CAD[(0. 51 ± 0. 19)μg/mg vs.(0. 36 ± 0. 11)μg/mg, P < 0. 05]. Conclusions

  1. Prognostic values of heart-type fatty acid-binding protein and D-dimer level in plasma in acute pulmonary embolism patients%心肌型脂肪酸结合蛋白联合血浆D-二聚体对肺栓塞预后评估的临床意义

    Institute of Scientific and Technical Information of China (English)

    陶琳; 杨毅

    2015-01-01

    ObjectiveTo evaluate the clinical value of heart-type fatty acid-binding protein (H-FABP) and D-dimer in assessing the prognosis of acute pulmonary embolism (APE). MethodsTotaly 120 APE patients were hospitalized from January 2011 to December 2014 and enroled in this study. The plasma H-FABP and D-dimer level were measured by enzyme-linked immunosorbent assay. The APE patients were divided three groups including low-risk, middle-risk and high-risk group by European heart association new guidelines. According to the clinical prognosis, the APE patients were divided into survival and death group. The H-FABP and D-dimer level in different groups and the relationship with the prognosis were assessed.ResultsWith the increased severity in patients, the H-FABP and D-dimer level were significantly elevated (P<0.05); the H-FABP and D-dimer level were significantly higher in death group as compared with survival group (P<0.05). The H-FABP and D-dimer level were positively correlated (r=0.693,P=0.000). ROC curves analysis results showed that the area under curve of H-FABP was 0.845 (95%CI: 0.752-0.918), and optimal operating point (OOP) was 8.65 µg/L, which had 81.24% sensitivity and 84.14% specificity; ACU of D-dimer was 0.832 (95%CI: 0.728-0.899), and OOP was 1.25 mg/L, which had 83.72% sensitivity and 82.65% specificity.Conclusion The H-FABP and D-dimer can effectively assess severity and prognosis of APE patients, meanwhile, it provide an objective basis for the clinical individual treatment and reducing the mortality rate of APE patients.%目的:探讨心肌型脂肪酸结合蛋白(H-FABP )联合血浆 D-二聚体在评价急性肺栓塞(APE)患者预后中的临床价值。方法选取本院2011年1月至2014年12月确诊的APE患者120例为研究对象,采用酶联免疫吸附法分别测定外周血H-FABP及D-二聚体浓度。根据病情严重程度将APE患者分为低危组、中危组及高危组;根据临床转归,分为存活组和死亡组

  2. Heart-type fatty acid binding protein for the assessment of the short-term prognosis in acute pulmonary embolism patients with hemodynamic stability on admission%心脏型脂肪酸结合蛋白对人院时血流动力学稳定的急性肺栓塞患者短期预后的评估

    Institute of Scientific and Technical Information of China (English)

    陈勇; 刘双; 郭伟; 王增智

    2013-01-01

    目的 探讨心脏型脂肪酸结合蛋白(H-FABP)对入院时血流动力学稳定的急性肺栓塞患者短期预后评估的临床意义.方法 筛选2009年12月至2010年12月在北京安贞医院就诊并被确诊的入院时血流动力学稳定的急性肺栓塞患者156例,其中符合纳入标准90例,男37例,女53例,平均年龄(61.1±14.6)岁,留取溶栓或抗凝前的外周静脉血标本,应用双抗体夹心酶联免疫吸附法测定H-FABP浓度,非均相免疫法测定肌钙蛋白Ⅰ(cTnI)、N-末端脑钠肽前体(NT-proBNP)浓度,所有患者随访30 d,根据随访结果分为复杂临床过程组(7例)和简单临床过程组(83例),结果采用Mann-Whitney U检验、x2检验、x2检验的连续性校正及logistic回归进行分析.结果 复杂临床过程组H-FABP水平高于简单临床过程组(U =54.000,P<0.01);ROC曲线获得H-FABP的最佳预后截值为7 μg/L,H-FABP、cTnI和NT-proBNP三者之间AUC比较差异无统计学意义;单变量logistic回归分析发现H-FABP≥6 μg,/L、心率≥106次/min和晕厥(均P<0.01)可预测血流动力学稳定的急性肺栓塞患者短期不良预后;多变量logistic回归分析发现仅H-FABP≥6 μg/L和晕厥(均P<0.05)仍是独立预测因素;cTnI或NT-proBNP联合H-FABP可提高对血流动力学稳定的急性肺栓塞患者治疗30 d的预测价值.结论 单独应用H-FABP或H-FABP联合其他临床资料,可对入院时血流动力学稳定的急性肺栓塞患者治疗30 d的预后进行评估,H-FABP作为预后评估可能优于cTnI和NT-proBNP.%Objective To explore the clinical value of heart-type fatty acid binding protein (H-FABP)for the assessment of the short-term prognosis in acute pulmonary embolism (APE)patients with hemodynamic stability on admission.Method A total of 156 APE patients with hemodynamic stability on admission were hospitalized in Beijing Anzhen hospital from December 2009 to December 2010,and the final study population comprised 90

  3. 慢性心力衰竭患者心型脂肪酸结合蛋白与超敏C-反应蛋白的变化及其相关性%The relationship of heart-type fatty acid binding protein and high-sensitivity C-reactive protein in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    李洁琪; 李晓翔; 吴立荣; 方颖; 李屏

    2009-01-01

    Objective To examine clinical significance and relativity of heart-type fatty acid binding protein (H-FABP) and high-sensitivity C-reactive protein (hs-CRP) in patients with chronic heart failure. Methods Ser-um concentrations of H-FABP and hs-CRP were measured in 60 patients with chronic heart failure and 30 control subjects. Left ventricular ejection fraction (LVEF) was examined by Doppler echocardio graphic in all subjects. Re-sults Serum concentrations of H-FABP and hs-CRP were higher in patients with chronic heart failure than in con-trol subjects[(6.11±1.49)μg/L vs (4.24±1.40)μg/L,and (12.77±3.65)mg/L vs(4.85±1.35) mg/L,t=5.746 and 7.543,P<0.01] but LVEF was lower in patients with chronic heart failure than in control subjects [(42.13±6.55) % vs (61.50±3.89) %,t=-14.902,P<0.01]. In CHF subgroups,H-FABP and hs-CRP lev-el increased with advancing NYHA class (F=26.288 and 351.784,P<0.01) but LVEF decreased (F=252.834,P<0.01). The serum H-FABP concentrations had a positive correlation with serum hs-CRP concentrations (r=0.801,P<0.01),and a negative correlation with LVEF (r=-0.718,P<0.01) ;serum hs-CRP concentrations had a negative correlation with LVEF(r=-0.881,P<0.01). Conclusion Serum H-FABP and hs-CRP levels are in-creased with the worsening of CHF. H-FABP and hs-CRP level are pnsitiviely related. The quantitative determination of serum concentrations of H-FABP and hs-CRP is valuable for risk stratification in patients with chronic heart fail-ure.%目的 观察慢性心力衰竭(CHF)患者血清心型脂肪酸结合蛋白(H-FABP)和超敏C-反应蛋白(hs-CRP)的浓度变化,并探讨其相关性及临床意义.方法 选择不同心功能级别的CHF患者60例及同期健康体检者30例,测定其血清H-FABP及hs-CRP的浓度,同时用彩色多普勒超声测定左心室射血分数(LVEF).结果 CHF组H-FABP[(6.11±1.49)μg/L]及ks-CRP[(12.77±3.65)mg/L]的浓度均较对照组[分别为(4.24±1.40)μg/L和(4.85±1.35)mg/L]升高(t值分别为5

  4. 对称性肢端角化病皮损中脂肪酸结合蛋白5及二氢硫辛酰胺脱氢酶表达%Expressions of fatty acid binding-protein 5 and dihydrolipoamide dehydrogenase in skin lesions of symmetrical acrokeratoderma

    Institute of Scientific and Technical Information of China (English)

    杨珮珮; 彭晶; 于作忠; 施歌; 黎兆军; 张国学; 樊翌明

    2015-01-01

    Objective To investigate the expressions of fatty acid-binding protein 5 (FABP5)and dihydroli-poamide dehydrogenase(DLD)in skin lesions of symmetrical acrokeratoderma(SAK), and to explore their significance. Methods Biopsy specimens were obtained from skin lesions on the wrists and perilesional skin of 9 patients with SAK, and from normal skin in the wrists of 9 healthy volunteers (control group). Reverse transcription PCR (RT-PCR)and immunohistochemical staining were performed to measure the expressions of FABP5 and DLD in these specimens. Results RT-PCR showed no significant differences in the mRNA expressions of FABP5 or DLD between lesional, perilesional and normal control skin specimens(both P > 0.05). Immunohistochemically, there was a significant increase in the extent and intensity of staining for FABP5 in SAK lesions. Concretely speaking, FABP5 was strongly expressed in the stratum corneum, granular and spinous layers in SAK lesions, but weakly expressed in the stratum corneum, granular and spinous layers in perilesional skin, and only in spinous and basal layers in normal control skin. The expression of DLD decreased in SAK lesions, and was observed only in the stratum corneum and spinous layer in a few cases of SAK. However, the full-thickness epidermis stained positive for DLD in perilesional skin, with the nuclei and cytoplasm both stained deep brown. Conclusion The overexpression of FABP5 in SAK lesions may participate in dysdifferentiation of keratinocytes, while the down-regulation of DLD expression suggests an imbalance in energy metabolism.%目的:探讨脂肪酸结合蛋白5(FABP5)及二氢硫辛酰胺脱氢酶(DLD)在对称性肢端角化病中的表达和意义。方法收集9例对称性肢端角化病患者腕部皮损及其周围皮肤活检标本,9例健康人腕部皮肤为对照,用逆转录 PCR(RT-PCR)及免疫组化法检测 FABP5及 DLD 表达水平。结果 RT-PCR 显示,FABP5 mRNA 及 DLD mRNA 表达在对称性

  5. Sequence Characterization, Tissue-specific Expression and Polymorphism of the Porcine(Sus scrofa) Liver-type Fatty Acid Binding Protein Gene%猪L-FABP基因的克隆、表达特征及遗传多态性研究

    Institute of Scientific and Technical Information of China (English)

    姜延志; 李学伟; 杨光希

    2006-01-01

    In this study, the full-length cDNA of porcine liver-type fatty acid binding protein gene (L-FABP) was obtained by the rapid amplification of cDNA ends (RACE). The nucleotide sequence and the predicted protein sequence share a high sequence identity with their mammalian counterparts. Semi-quantitative RT-PCR revealed that porcine L-FABP gene is expressed in all twelve tissues studied, but a transcript is more abundant in liver and small intestine than in other tissues. The part genomic DNA of the porcine L-FABP gene was amplified by PCR. The coding region of the pig L-FABP gene is organized in four exons and spans an approximate 2.62 kb genomic region. Comparative sequencing of four pig breeds revealed a C→T single nucleotide polymorphism (SNP) within exon 2. The allele and genotype frequencies differed significantly between indigenous Chinese Zang, Dahe,and Yanan pigs with higher frequencies of allele C and genotype CC and Yorkshire pigs with higher frequencies of allele T and genotype TT (P < 0.01). The association analysis suggested that the C→T polymorphism was associated with intramuscular fat content, indicating that the SNP is a potential molecular marker for intramuscular fat content.%FABPs属于脂结合蛋白超家族成员,是一类分子量较小而对脂肪酸有高亲和力的蛋白质,广泛存在于脊椎动物和非脊椎动物的细胞质中.FABPs担当细胞内脂肪酸的运输任务,它们与脂肪酸结合将其运输到脂肪酸氧化的位置、脂肪酸脂化成甘油三醋或磷脂的位置,或者进入细胞核内发挥其可能的调控功能.因此FABPs对脂类代谢具有重要的调控作用.本研究把L-FABP基因作为影响猪肌内脂肪含量的候选基因.为此,利用cDNA末端快速扩增(RACE)和PCR技术,克隆到猪肝脏型脂肪酸结合蛋白基因(L-FABP)的全长cDNA序列(GenBank登录号:AY960623)和部分基因组序列(GenBank登录号:DQ182323).猪L-FABP基因的cDNA序列全长518 bp,该

  6. The clinical significance of heart type fatty acid-binding protein in diagnosis of acute myocardial infarction%心型脂肪酸结合蛋白在诊断急性心肌梗死中的临床意义

    Institute of Scientific and Technical Information of China (English)

    丁柳美; 唐钧; 倪培华

    2011-01-01

    Objective To study the diagnostic significance of heart type fatty acid-binding protein (H-FABP) in acute myocardial infarction(AMI).Methods H-FABP,cardiac troponin I(cTnI) and creatine kinase (CK)-MB mase were detected in 78 patients with AMI, 52 patients with unstable angina(UA) ,65 patients with stable angina(SA) and 70 healthy controls by double antibody sandwich enzyme-linked immunosorbent assay.32 blood samples were collected within 2 h after AMI occurrence, and 46 blood samples were collected after AMI occurrence more than 2 h.Their H-FABP levels were detected and compared with cTnI.The diagnostic significance was analyzed.Results The levels of H-FABP, CKMB mass and cTnI of AMI group [( 78.12 ± 23.78 ) μg/L, ( 9.48 ± 2.68 ) μg/L and ( 10.12 ± 3.45 ) ng/mL]were significantly higher than those of UA group [( 18.67 ± 7.45 ) μg/L, (0.56 ± 0.11 ) μg/L and (0.21 ± 0.12) ng/mL], SA group [(2.98 ± 1.65) μg/L,(0.22 ±0.08) μg/L and (0.08 ±0.06)ng/mL]and control group [(2.32 ± 1.12) μg/L,(0.20 ±0.09)μg/L and < 0.022 ng/mL](P < 0.05).H-FABP,CK-MB mass and cTnI of UA group were significantly higher than those of SA group and control group ( P < 0.05 ).The H-FABP, CK-MB mass and cTnI levels had no difference between SA group and control group ( P > 0.05 ).The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of H-FABP in AMI diagnosis were 84.89% ,98.8% ,85.89% ,93.24% and 75.14% ,which were higher than CK-MB mass (50.11% ,89.12% ,78.54% ,80.12% and 50.78% ) and cTnI(60.22% ,93.23% ,80.34%,86.45% and 60.56% ) respectively.In the 32 cases' blood collected within 2 h, the positive rate of H-FABP (65.63%)was higher than that of cTnl ( 18.75% ) ( P < 0.05 ).In the 46 cases' blood collected after more than 2h, the positive rate of H-FABP (97.83%) had no statistical difference with that of cTnI (89.13% ) (P > 0.05).Conclusions H-FABP has good sensitivity and

  7. Association between codon 54 polymorphism of intestinal fatty acid-binding protein 2 gene and plasma lipids in middle-aged and old populations%中老年人群小肠脂肪酸结合蛋白FABP2基因54位密码子多态性与血脂水平的关系

    Institute of Scientific and Technical Information of China (English)

    常晓彤; 王振辉; 侯丽娟; 李彪英; 董明纲; 李桂喜

    2008-01-01

    背景:有研究表明,在不同人群中,突变型54T FABP2与血脂障碍以及代谢综合征的其他特征相关.目的: 调查中老年人群小肠脂肪酸结合蛋白FABP2基因多态性频率分布,分析突变型54T FABP2基因与血脂水平的关系.设计:病例-对照分析.单位: 河北北方学院生物化学教研室和解放军第二五一医院检验科.对象:选择2003-10/2005-04在解放军第二五一医院体检中心进行体检的中老年人469名,男217名,平均年龄(56±10)岁;女252名,平均年龄(55±13)岁.除外肝、肾功能异常者,相互间无血缘关系;患者均对本实验均知情同意.实验已经医院伦理委员会批准.方法:①空腹12 h后,采用全自动生化仪(Olympus AU 6400)测定血浆总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白AⅠ、载脂蛋白B水平.②采集空腹静脉血1mL,枸橼酸钠抗凝,分离白细胞,蛋白酶K消化,酚/氯仿抽提基因组DNA.采用PCR-限制性片段长度多态性技术检测各组基因型分布频率.主要观察指标:①血脂水平.②FABP2 54位点基因型分布频率.结果:①频率分布:男性54A/T FABP2基因型频率分布为A/A0.48,A/T 0.42,T/T0.10;女性为A/A0.44,A/T0.46,T/T 0.10.男性和女性突变型54T等位基因频率分别为0.31,0.33.男女间频率分布情况比较,差异无显著性意义(P > 0.05).②血脂:男性,54T等位基因携带者血浆低密度脂蛋白胆固醇、载脂蛋白B高于54A等位基因携带者,差异有显著性意义(P < 0.05);女性,54T等位基因携带者血浆总胆固醇、低密度脂蛋白胆固醇高于54A等位基因携带者,差异有显著性意义(P < 0.05).结论:在中老年人群中,FABP2基因多态性频率分布与性别无关;54T FABP2基因携带者有高血脂特征.%BACKGROUND: Studies have shown that alanine (A) to threonine (T) substitution at codon 54 of intestinal fatty acid-binding protein (FABP2) in different populations

  8. The Value of Heart Fatty Acid Binding Protein in Early Diagnosis of Kawasaki Disease with Myocardial Ischemia%心肌脂肪酸结合蛋白在川崎病心肌缺血损伤早期诊断中的应用价值

    Institute of Scientific and Technical Information of China (English)

    段庆宁

    2013-01-01

    目的:探讨心肌脂肪酸结合蛋白(h-FABP)在川崎病患儿心肌缺血损伤早期诊断中的应用价值。方法分别测定54例川崎病患儿在急性期、亚急性期、恢复期的h-FABP,并选择50例健康患儿为对照组。应用SPSS13.0软件对结果进行统计学分析。结果川崎病患儿各期h-FABP水平均明显高于对照组(P<0.05)。结论h-FABP可作为川崎病心肌缺血损伤早期判断指标。%Objective To investigate the value of heart fat y acid binding protein in early diagnosis of kawasaki disease (KD) complicated with myocardial ischemia. Methods Heart fat y acid binding protein (h-FABP) levels were measured in acute stage, subacute stage and recovery stage of KD Patients, and 50 healthy controls as wel .The results were analyzed by statistical package for the social science 13.0 (SPSS 13.0). Results The h-FABP levels of al stages in KD were obviously higher than control group (P<0.05). Conclusion H-FABP can be used in early diagnosis of myocardial ischemia in KD.

  9. Crystal structure of axolotl (Ambystoma mexicanum) liver bile acid-binding protein bound to cholic and oleic acid.

    Science.gov (United States)

    Capaldi, Stefano; Guariento, Mara; Perduca, Massimiliano; Di Pietro, Santiago M; Santomé, José A; Monaco, Hugo L

    2006-07-01

    The family of the liver bile acid-binding proteins (L-BABPs), formerly called liver basic fatty acid-binding proteins (Lb-FABPs) shares fold and sequence similarity with the paralogous liver fatty acid-binding proteins (L-FABPs) but has a different stoichiometry and specificity of ligand binding. This article describes the first X-ray structure of a member of the L-BABP family, axolotl (Ambystoma mexicanum) L-BABP, bound to two different ligands: cholic and oleic acid. The protein binds one molecule of oleic acid in a position that is significantly different from that of either of the two molecules that bind to rat liver FABP. The stoichiometry of binding of cholate is of two ligands per protein molecule, as observed in chicken L-BABP. The cholate molecule that binds buried most deeply into the internal cavity overlaps well with the analogous bound to chicken L-BABP, whereas the second molecule, which interacts with the first only through hydrophobic contacts, is more external and exposed to the solvent.

  10. MECP2 Duplication Syndrome

    DEFF Research Database (Denmark)

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients...... and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy...... condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were...

  11. Predicting nucleic acid binding interfaces from structural models of proteins.

    Science.gov (United States)

    Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael

    2012-02-01

    The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. Copyright © 2011 Wiley Periodicals, Inc.

  12. Association of the heart fatty acid-binding protein gene with quality of carcass and meat traits in pigs Associação entre o gene da proteína de ligação de ácidos graxos - coração com características de carcaça e qualidade da carne em suínos

    Directory of Open Access Journals (Sweden)

    F.C. Figueiredo

    2008-04-01

    Full Text Available The heart fatty acid-binding protein (HFABP gene was sequenced in parental animals of a F2 crossing of boars of the Brazilian native Piau breed with commercial sows (Landrace x Large White Pietrain. Primers used for PCR were designed to amplify four exons of the gene. The PCR products were sequenced and compared with the GenBank sequences. Differences between the generated sequences and the GenBank sequences were observed for both genetic groups. A total of 246 F2 animals were genotyped using the Hinf I restriction enzyme. Two genotypes were identified, 198 being animals HH and 48 Hh. The Hinf I SNP was significantly associated with weights of loin (bone-in (PO gene da proteína de ligação de ácidos graxos - coração foi seqüenciado em animais parentais de um cruzamento F2 entre varrões da raça nativa brasileira Piau e fêmeas comerciais (Landrace x Large White x Pietrain. Os primers utilizados na reação em cadeia da polimerase foram desenhados para amplificarem os quatro éxons do gene. Os fragmentos amplificados foram seqüenciados e comparados com a seqüência do gene depositada no GenBank. Foram observadas divergências entre as seqüências geradas e as do GenBank para ambos os grupos genéticos. Foram genotipados 246 animais F2 utilizando-se a enzima Hinf I. Dois genótipos foram identificados, sendo 198 animais HH e 48 animais Hh. O polimorfismo apresentou efeito sobre o peso total do carré (P<0,05, o peso da papada (P<0,05, o peso do filezinho (P<0,10 e o peso dos rins (P<0,01. Os resultados indicam que o gene da H-FABP apresenta potencial para aplicação em programas de seleção assistida por marcadores moleculares em suínos.

  13. Retinoic acid binding protein in normal and neopolastic rat prostate.

    Science.gov (United States)

    Gesell, M S; Brandes, M J; Arnold, E A; Isaacs, J T; Ueda, H; Millan, J C; Brandes, D

    1982-01-01

    Sucrose density gradient analysis of cytosol from normal and neoplastic rat prostatic tissues exhibited a peak of (3H) retinoic acid binding in the 2S region, corresponding to the cytoplasmic retinoic acid binding protein (cRABP). In the Fisher-Copenhagen F1 rat, cRABP was present in the lateral lobe, but could not be detected in the ventral nor in the dorsal prostatic lobes. Four sublines of the R-3327 rat prostatic tumor contained similar levels of this binding protein. The absence of cRABP in the normal tissue of origin of the R-3327 tumor, the rat dorsal prostate, and reappearance in the neoplastic tissues follows a pattern described in other human and animal tumors. The occurrence of cRABP in the well-differentiated as well as in the anaplastic R-3327 tumors in which markers which reflect a state of differentiation and hormonal regulation, such as androgen receptor, 5 alpha reductase, and secretory acid phosphatase are either markedly reduced or absent, points to cRABP as a marker of malignant transformation.

  14. Effect of rt-PA intravenous thrombolytic therapy on serum levels of neuro-specific endolase, C-reactive protein and fatty acid binding protein in patients with early cerebral infarction%rt-PA静脉溶栓对脑梗死早期患者血清神经特异性烯醇酶、C反应蛋白及脂肪酸结合蛋白水平影响研究

    Institute of Scientific and Technical Information of China (English)

    彭道勇; 王晓东; 王茂湘; 范铁平; 邓勇; 王苏平

    2015-01-01

    目的:探讨rt-PA静脉溶栓对脑梗死早期患者血清神经特异性烯醇酶( NSE)、C反应蛋白( CRP)及脂肪酸结合蛋白水平( FABP)的影响。方法收集大连市中心医院收治的急性脑海梗死患者54例,随机分为对照组和实验组,每组27例,2组均给予降低颅内压、改善循环、营养脑细胞常规治疗,对照组在此基础上给予低分子肝素钙注射液5000 U皮下注射,1次/12 h,连续7 d ;实验组在对照组基础上,给予注射用阿替普酶( rt-PA)溶栓治疗,连续7 d,治疗结束后,对所有患者的NSE、CRP及FABP水平进行检测。结果与对照组治疗后比较,实验组患者血清CRP、NSE和FABP水平显著降低(P<0.05)。结论 rt-PA静脉溶栓能够显著降低脑梗死早期患者血清NSE、CRP及FABP水平,改善患者预后,对临床有指导意义。%Objective To analyse effect of rt-PA intravenous thrombolytic therapy on serum levels of neuro-specific endolase, C-reactive protein and fatty acid binding protein in patients with early cerebral infarction.Methods 54 patients who were diagnosed with early acute cerebral infarction in Dalian Municipal Central Hospital were collected.All patients were randomly divided into experimental group and control group,27 cases in each group.Two groups were given conventional treatment,such as reduction of intracranial pressure,improve circulation and nutrition brain cells.Control group was given low molecular weight heparin calcium injection 5000U, one times per 12 h for 7 consecutive days, and experimental group was given rt-PA intravenous thrombolytic therapy on the basis of the control group for 7 consecutive days, post-treatment,the serum levels of NSE, CRP and FABP were detected in all patients.Results Compared with control group post-treatment, the serum CRP,NSE and FABP level was lower in experimental group ( P<0.05).Conclusions The rt-PA intravenous thrombolytic therapy can

  15. Obstructive Sleep Apena Hypopnea Syndrome in Relation to Serum Adipocyte Fatty Acid-Binding Protein:A Comparative Study between Xinjiang Uygur and Han Ethnic Groups%新疆维汉民族阻塞性睡眠呼吸暂停低通气综合征患者血清脂肪细胞型脂肪酸结合蛋白水平比较研究

    Institute of Scientific and Technical Information of China (English)

    夏宇; 武玉刚; 哈依努尔; 胡昕; 叶红

    2012-01-01

    Objective To investigate the relation between obstructive sleep apnea hypopnea syndrome ( OSAHS ) and fasting serum adipocyte fatty - acid binding protein (A - FABP ) in Xinjiang Uygur and Han ethnic groups. Methods A total of 120 ( 60 from each ethnic group ) male patients were randomly selected from those diagnosed as having OSAHS by polysomnogra-phy ( PSG ) in our hospital. Another 104 men ( 52 from each ethnic group ) without OSAHS were randomly selected as the control groups from the health checkup subjects. The serum A - FABP level of subjects in the four groups was measured with ELISA. Results The serum A - FABP level of OSAHS patients was positively correlated with the neck circumference, waist circumference , abdominal circumference, apnea hypopnea index ( AHI ), body mass index ( BMI ), and the longest apnea time ( Tmax ) ( P <0. 01 ), and was negatively correlated with the lowest oxygen saturation ( LSaO2 ) ( P <0. 01 ). The BMI and A - FABP of the OSAHS patients were higher than that of the subjects in the control groups ( P < 0. 05 ). The serum A - FABP level of the OSAHS patients in Uygur group was significantly higher than that of the Han group ( P < 0. 01 ). Conclusion OSAHS may cause the increase of fasting serum A - FABP. Further studies are needed to investigate the discrepancy of fasting serum A - FABP levels of Uygur and Han OSAHS patients.%目的 探讨新疆维汉民族阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者空腹血清脂肪细胞型脂肪酸结合蛋白(A-FABP)水平变化.方法 采取完全随机方法抽取经多道睡眠描记术(PSG)监测确诊为OSAHS的维族及汉族患者各60例,并选取维族及汉族各52例健康体检者作为对照组,测定两组血清A-FABP水平及其他指标.结果 OSAHS患者的血清A-FABP水平与其颈围、腰围、腹围、睡眠呼吸暂停低通气指数(AHI)、体质指数(BMI)、最长呼吸暂停时间均呈正相关(P<0.01),与最低血氧饱和度呈负相关(P<0

  16. Plant Genome Duplication Database.

    Science.gov (United States)

    Lee, Tae-Ho; Kim, Junah; Robertson, Jon S; Paterson, Andrew H

    2017-01-01

    Genome duplication, widespread in flowering plants, is a driving force in evolution. Genome alignments between/within genomes facilitate identification of homologous regions and individual genes to investigate evolutionary consequences of genome duplication. PGDD (the Plant Genome Duplication Database), a public web service database, provides intra- or interplant genome alignment information. At present, PGDD contains information for 47 plants whose genome sequences have been released. Here, we describe methods for identification and estimation of dates of genome duplication and speciation by functions of PGDD.The database is freely available at http://chibba.agtec.uga.edu/duplication/.

  17. 饲粮脂肪水平对冬毛期银狐生长性能、体脂肪酸组成及空肠中小肠型脂肪酸结合蛋白表达的影响%Effects of Dietary Fat Level on Growth Performance, Body Fatty acid Composition and the Expression of Intestinal Fatty Acid Binding Protein in Jejunum of Silver Foxes during Winter Fur-Growing Period

    Institute of Scientific and Technical Information of China (English)

    张婷; 钟伟; 罗婧; 周宁; 黄健; 王卓; 孙皓然; 樊燕燕; 李光玉

    2015-01-01

    为研究饲粮脂肪水平对冬毛期银狐生长性能、体脂肪酸组成及空肠中小肠脂肪酸结合蛋白( I-FABP)表达的影响,选取145日龄、体重相近的健康雄性银狐50只,随机分成5组(每组10个重复,每个重复1只) ,分别饲喂含10%、12%、16%、20%、24%混合油脂(鸡油:豆油=1:1)的试验饲粮,试验饲粮实测脂肪水平分别为12. 85%( A 组)、14. 71%( B 组)、18. 72%( C 组)、22.23%( D组)、26.11%( E组). 预试期为15 d,正试期为75 d. 结果显示:1)饲粮脂肪水平显著影响冬毛期银狐的平均日采食量( ADFI) ( P0.05). 3)饲粮脂肪水平对银狐皮下腹部脂肪中SFA、MUFA和PUFA的比例无显著影响( P>0.05). 4)随饲粮脂肪水平的升高,空肠中I-FABP mRNA的相对表达量呈上升趋势,表现为E组显著高于A、B、C组(P0.05) . 3) Dietary fat level had no significant effects on the proportion of SFA, MUFA and PUFA of subcutaneous fat of silver foxes ( P>0.05) . 4) The relative expression of I-FABP mRNA in jejunum was in-creased with the dietary fat level increasing, and it showed that group E was significantly higher than groups A, B and C ( P<0.05) . In conclusion, the silver foxes have the best growth performance when fed diets with 18.72% fat during winter fur-growing period;body fatty acid composition of silver foxes reflect the dietary fat-ty acid composition, the fatty acid composition of intermuscular fat is affected by dietary fat level, while the fatty acid composition of subcutaneous fat is stable;moreover, increasing dietary fat level can improve the ex-pression of I-FABP in jejunum of silver foxes during winter fur-growing period.

  18. 川崎病心型脂肪酸结合蛋白及血小板活化因子的变化及临床意义%Serum heart-type fatty acid-binding protein and platelet activating factor levels in Kawasaki disease and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    洪泽; 孙兴珍

    2011-01-01

    46例川崎病患儿(观察组)根据超声心动图结果分为冠状动脉损伤(CAL)组19例和非冠状动脉损伤(NCAL)组27例,另选择正常健康者50例为对照组.检测所有对象的心型脂肪酸结合蛋白(h-FABP)、血小板活化因子(PAF)、肌钙蛋白Ⅰ及肌酸磷酸激酶同工酶等.结果显示,观察组h-FABP、肌钙蛋白Ⅰ水平和阳性率均显著高于对照组(P<0.05),两组间肌酸磷酸激酶同工酶水平和阳性率比较差异无统计学意义(P>0.05),观察组h-FABP阳性率显著高于肌钙蛋白Ⅰ和肌酸磷酸激酶同工酶阳性率(P<0.05),PAF水平及血小板、中性粒细胞计数显著高于对照组(P<0.05);CAL组h-FABP、PAF水平显著高于NCAL组(P<0.05).提示,h-FABP和PAF对预测川崎病患儿冠状动脉病变有重要的临床价值.%Forty six children with Kawasaki disease (observer group) were classified as coronary artery lesions (CAL) subgroup (19 cases) and non-coronary artery lesions (NCAL) subgroup (27 cases)according to echocardiography; 50 healthy children served as control group.Serum heart-type fatty acidbinding protein (h-FABP), platelet activating factor (PAF), cardiac tropnin Ⅰ (cTnI) and creatine kinase isoenzyme MB (CK-MB) levels of all subjects were detected.The results showed that the h-FABP and cTnI levels and positive rate in observer group were higher those in control group (P < 0.05 ), while there were no differences in CK-MB level and positive rate between two groups ( P > 0.05 ).The h-FABP positive rate in observation group was higher than the positive rates of cTnI and CK-MB (P <0.05).The PAF level, PLT and polymorphonuclear neutrophil count in observer group were higher than those in control group ( P <0.05).The h-FABP and PAF levels in CAL subgroup were higher than those in NCAL subgroup (P <0.05).The results suggest that serum h-FABP and PAF can be used as diagnostic indicators for Kawasaki disease complicated with coronary artery lesions.

  19. 卡维地洛与比索洛尔对心力衰竭患者心功能及心型脂肪结合蛋白、脑钠肽的影响%Effect of Carvedilol and Bisoprolol on the Changes of Heart Type Fatty Acid Binding Protein and Brain Natri-uretic Peptide in Patients with Congestive Heart Failure

    Institute of Scientific and Technical Information of China (English)

    张海涛; 邵辉; 王兴宏; 董秋立; 王忠明

    2015-01-01

    OBJECTIVE:To observe the changes of heart type fatty binding protein (H-FABP) and brain natriuretic peptide (BNP)when carvedilol and bisoprolol in the treatment of elderly patients with chronic heart failure(CHF). METHODS:110 CHF patients were randomly assigned into carvedilol group and bisoprolol group (n=55). Carvedilol group was given carvedilol 3.125 mg,bid,doubling dose every 2 weeks to reach target dose 25mg or maximum tolerant dose;bisoprolol group was given bisoprolol 1.25 mg,qd,doubling dose every 2 weeks to reach target dose 10 mg or maximum tolerant dose. Treatment course lasted for 6 months. Clinical effective rate of 2 groups were observed after treatment. Echocardiography was used to measure the changes of LVEDD,LVEF,SBP and DBP before and after treatment. The plasma concentration of BNP and H-FABP were measured by radio-immunoassay. RESULTS:After treatment,total effective rate of carvedilol group(96.4%)was higher than that of bisoprolol group (89.2%),with statistical significance(P<0.05). Compared with before treatment,the levels of LVEDD,LVEF,BNP,H-FABP, SBP and DBP in 2 groups were all decreased significantly after treatment,with statistical significance (P<0.01 or P<0.05). CON-CLUSIONS:Both carvedilol and bisoprolol can significantly improve cardiac function,but carvedilol efficacy is more significant. At the same time,significant decrease of H-FABP before and after treatment indicate that H-FABP can be used as a reliable index of heart failure treatment effect.%目的:观察卡维地洛与比索洛尔对老年心力衰竭(CHF)患者心功能及心型脂肪结合蛋白(H-FABP)、脑钠肽(BNP)水平的影响。方法:选取CHF患者110例,按随机数字表法分为卡维地洛组和比索洛尔组,各55例。卡维地洛组患者给予卡维地洛3.125 mg,bid,每2周剂量加倍,直至达目标靶剂量25 mg或耐受最大剂量;比索洛尔组患者给予比索洛尔1.25 mg,qd,每2周剂量加

  20. Duplication in DNA Sequences

    Science.gov (United States)

    Ito, Masami; Kari, Lila; Kincaid, Zachary; Seki, Shinnosuke

    The duplication and repeat-deletion operations are the basis of a formal language theoretic model of errors that can occur during DNA replication. During DNA replication, subsequences of a strand of DNA may be copied several times (resulting in duplications) or skipped (resulting in repeat-deletions). As formal language operations, iterated duplication and repeat-deletion of words and languages have been well studied in the literature. However, little is known about single-step duplications and repeat-deletions. In this paper, we investigate several properties of these operations, including closure properties of language families in the Chomsky hierarchy and equations involving these operations. We also make progress toward a characterization of regular languages that are generated by duplicating a regular language.

  1. Mesangial cell-derived tumor necrosis factor α up-regulates the expression of tubular liver type fatty acid binding-protein and its renoprotective role in IgA nephropathy%系膜细胞源性肿瘤坏死因子α上调IgA肾病肾小管肝型脂肪酸结合蛋白的表达及其肾脏保护作用

    Institute of Scientific and Technical Information of China (English)

    佐楠; 栗霄立; 王力宁; 李子龙; 王均; 冯江敏; 马健飞; 范秋灵; 姚丽

    2011-01-01

    Objective To explore the mechanism of up-regulation of tubular liver-type fatty acid binding-protein (L-FABP) in IgA nephropathy (IgAN) and its renoprotective role.Methods Murine mesangial cells (MCs) from primary cell culture were cultured with aggregated IgA (AIgA) (10 to 250 mg/L) for 48 hours. The supernatant after culture was collected as AIgA-MC medium. Murine proximal tubular cell line (mProx) stably expressing human L-FABP (hL-FABP) by transfection (mProx-L) were cultured with AIgA, AIgA-MC medium and /or neutralizing anti-TNF-α antibody and recombinant murine TNF-α, respectively. AIgA-MC medium (AIgA final concentration was 25 mg/L) was cultured with mProx and mProx-L cells. The mRNA expressions of hL-FABP and MCP-1 of the cells were detected by real-time PCR. The protein expressions of hL-FABP and 4-HNE of the cells were detected by Western blotting. Results (1) The hL-FABP mRNA and protein expression stimulated by AIgA-MC medium was significantly higher as compared to AIgA (P<0.01). (2) Pre-incubation of neutralizing anti-TNF-α antibody (final concentration was 1 and 5 mg/L) with mProx-L cells could significantly suppress the up-regulation of hL-FABP protein expression induced by AlgA-MC medium (P<0.05 and P<0.01).(3) Recombinant murine TNF-α (final concentration was 50 and 250 ng/L) also induced a significant up-regulation of hL-FABP expression (P<0.01). (4) After the stimulation of AIgA-MC medium, both 4-HNE protein expression and MCP-1 mRNA expression were significantly suppressed in mProx-L cells compared to those of mProx cells (P <0.05 and P<0.01). Conclusion Mesangial cell-derived TNF-α can induce up-regulation of tubular L-FABP expression. Overexpression of tubular L-FABP may lessen the progression of IgAN by reducing oxidative stress and inflammatory mediators.%目的 探讨体外近曲小管肝型脂肪酸结合蛋白(L-FABP)在IgA肾病(IgAN)中的上调机制及其对肾脏的保护作用.方法 原代培养的小鼠系膜

  2. Nucleic acid binding and other biomedical properties of artificial oligolysines

    Directory of Open Access Journals (Sweden)

    Roviello GN

    2016-11-01

    Full Text Available Giovanni N Roviello,1 Caterina Vicidomini,1 Vincenzo Costanzo,1 Valentina Roviello2 1CNR Istituto di Biostrutture e Bioimmagini, Via Mezzocannone site and Headquarters, 2Centro Regionale di Competenza (CRdC Tecnologie, Via Nuova Agnano, Napoli, Italy Abstract: In the present study, we report the interaction of an artificial oligolysine (referred to as AOL realized in our laboratory with targets of biomedical importance. These included polyinosinic acid (poly rI and its complex with polycytidylic acid (poly I:C, RNAs with well-known interferon-inducing ability, and double-stranded (ds DNA. The ability of the peptide to bind both single-stranded poly rI and ds poly I:C RNAs emerged from our circular dichroism (CD and ultraviolet (UV studies. In addition, we found that AOL forms complexes with dsDNA, as shown by spectroscopic binding assays and UV thermal denaturation experiments. These findings are encouraging for the possible use of AOL in biomedicine for nucleic acid targeting and oligonucleotide condensation, with the latter being a key step preceding their clinical application. Moreover, we tested the ability of AOL to bind to proteins, using serum albumin as a model protein. We demonstrated the oligolysine–protein binding by CD experiments which suggested that AOL, positively charged under physiological conditions, binds to the protein regions rich in anionic residues. Finally, the morphology characterization of the solid oligolysine, performed by scanning electron microscopy, showed different crystal forms including cubic-shaped crystals confirming the high purity of AOL. Keywords: nucleic acid binding, polyinosinic acid, double-stranded nucleic acids, oligolysine, circular dichroism

  3. On-line flow displacement immunoassay for fatty acid-binding protein

    NARCIS (Netherlands)

    Kaptein, WA; Korf, J; Yang, M; Glatz, JFC; Renneberg, R

    1998-01-01

    In standard displacement flow immunoassays the analyte in the sample creates an active dissociation of labelled antigens (or antigen homologues) from an antigen binding site of an immobilized antibody, after which the labelled substance is measured downstream. Such systems have been described for mo

  4. Urine liver fatty acid binding protein and chronic kidney disease progression

    DEFF Research Database (Denmark)

    Khatir, Dinah S; Bendtsen, Mette D; Birn, Henrik

    2017-01-01

    , regarding progression of chronic kidney disease (CKD). In a prospective study design a cohort of 74 stage 3-4 CKD patients (age 61 ± 13 years) were included. Glomerular filtration ratio (GFR, (51)Cr-EDTA-clearance), 24-hour ambulatory BP, 24-hour urinary albumin/creatinine ratio (UAC) and urinary L...

  5. Expression and Characterization of Human Heart Type Fatty Acid Binding Protein in Pichia Pastoris

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    H-FABP is regarded as a tissue-specific protein existing only in myocardial cells. It is released from the cardiac tissue and gets into the plasma when a heart attack occurs; the myocardial infarction is a good case in point. As a result, the detection of H-FABP will be an early and important biomarker for the disease concerned. The objective of the study is to prepare the recombinant H-FABP by aeukaryotic expression system, pichia, to produce the protein mimicking natural H-FABP, as an immunogen for the production of the specific antibody. A gene fragment encoding H-FABP was cloned in the expressing vector pPICZα, after sequencing. The recombinant plasmid was transformed into the competent cells of the X-33 strain by means of electroporation. The expression of the target peptide indueed by methanol was screened by means of Western blotting, with the available MAb( Clone 6B6 ). Highly expressive engineer strains were obtained. The production of recombinant H-FABP under induction was about 0.7 g/L, with an Mr of 14.5 kDa and recognized by a commercially available MAb (Clone 6B6). The recombinant vector was successfully constructed. Following this, H-FABP was expressed in X-33, and it would become the source of the preparation of specific antibodies, to develop diagnostic kits.

  6. Role of Fatty Acid Binding Protein 5 (FABP5) in Breast Cancer Progression and Metastasis

    Science.gov (United States)

    2013-04-01

    al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 2002;21:2000–8. 16. Allavena P, Sica A, Solinas G, Porta...17. Sica A, Allavena P, Mantovani A. Cancer related inflammation: the macrophage connection. Cancer Lett 2008;267:204–15. 18. Pollard JW. Tumour...Allavena P, Sica A. Role of tumor- associated macrophages in tumor progression and invasion. Cancer Metastasis Rev 2006;25:315–22. 39. Nicolini A

  7. A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs

    OpenAIRE

    Miao, Zhichao; Westhof, Eric

    2015-01-01

    Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i) the definition of nucleic acid binding sites; ii) the training and test datasets; iii) the algorithmic methods for the prediction strategies; iv) the performance measures and v) the distribution and avail...

  8. A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs.

    OpenAIRE

    Zhichao Miao; Eric Westhof

    2015-01-01

    Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i) the definition of nucleic acid binding sites; ii) the training and test datasets; iii) the algorithmic methods for the prediction strategies; iv) the performance measures and v) the distribution and avail...

  9. Comparative analysis of the sialic acid binding activity of four different IBV strains

    OpenAIRE

    2009-01-01

    Abstract Avian infectious bronchitis virus (IBV) is a major pathogen in commercial poultry flocks. Recently we demonstrated, that sialic acid serves as a receptor determinant for IBV on the tracheal epithelium. Here we compared the IBV strains Beaudette, 4/91, Italy02, and QX for their sialic acid binding properties. We demonstrate that sialic acid binding is important for the infection of primary chicken kidney cells and the tracheal epithelium by all four strains. There were only...

  10. In Vitro Bile Acid Binding Capacities of Red Leaf Lettuce and Cruciferous Vegetables.

    Science.gov (United States)

    Yang, Isabelle F; Jayaprakasha, Guddadarangavvanahally K; Patil, Bhimanagouda S

    2017-09-13

    In the present study, we tested the bile acid binding capacity of red leaf lettuce, red cabbage, red kale, green kale, and Brussels sprouts through in vitro digestion process by simulating mouth, gastric, and intestinal digestion using six bile acids at physiological pH. Green and red kale exhibited significantly higher (86.5 ± 2.9 and 89.7 ± 0.9%, respectively) bile acid binding capacity compared to the other samples. Further, three different compositions of bile acids were tested to understand the effect on different health conditions. To predict the optimal dose for bile acid binding, we established a logistic relationship between kale dose and bile acid binding capacity. The results indicated that kale showed significantly higher bile acid binding capacity (82.5 ± 2.9% equivalent to 72.06 mg) at 1.5 g sample and remained constant up to 2.5 g. In addition, minimally processed (microwaved 3 min or steamed 8 min) green kale showed significantly enhanced bile acid binding capacity (91.1 ± 0.3 and 90.2 ± 0.7%, respectively) compared to lyophilized kale (85.5 ± 0.24%). Among the six bile acids tested, kale preferentially bound hydrophobic bile acids chenodeoxycholic acid and deoxycholic acid. Therefore, regular consumption of kale, especially minimally processed kale, can help excrete more bile acids and, thus, may lower the risk of hypercholesterolemia.

  11. A Duplicate Construction Experiment.

    Science.gov (United States)

    Bridgeman, Brent

    This experiment was designed to assess the ability of item writers to construct truly parallel tests based on a "duplicate-construction experiment" in which Cronbach argues that if the universe description and sampling are ideally refined, the two independently constructed tests will be entirely equivalent, and that within the limits of item…

  12. Near Duplicate Document Detection Survey

    Directory of Open Access Journals (Sweden)

    Bassma S. Alsulami

    2012-04-01

    Full Text Available Search engines are the major breakthrough on the web for retrieving the information. But List of retrieved documents contains a high percentage of duplicated and near document result. So there is the need to improve the performance of search results. Some of current search engine use data filtering algorithm which can eliminate duplicate and near duplicate documents to save the users’ time and effort. The identification of similar or near-duplicate pairs in a large collection is a significant problem with wide-spread applications. In this paper survey present an up-to-date review of the existing literature in duplicate and near duplicate detection in Web

  13. Gastric, pancreatic, and ureteric duplication

    Directory of Open Access Journals (Sweden)

    Chattopadhyay Anindya

    2010-01-01

    Full Text Available We report a case of an 8-month-old, asymptomatic child who was incidentally detected to have two cystic structures in the abdomen. Surgical exploration revealed a gastric and pancreatic duplication cyst along with a blind-ending duplication of the right ureter. Excision of the duplications was relatively straightforward, and the child made an uneventful recovery. This constellation of duplications has not been reported before.

  14. An Introduction to Duplicate Detection

    CERN Document Server

    Nauman, Felix

    2010-01-01

    With the ever increasing volume of data, data quality problems abound. Multiple, yet different representations of the same real-world objects in data, duplicates, are one of the most intriguing data quality problems. The effects of such duplicates are detrimental; for instance, bank customers can obtain duplicate identities, inventory levels are monitored incorrectly, catalogs are mailed multiple times to the same household, etc. Automatically detecting duplicates is difficult: First, duplicate representations are usually not identical but slightly differ in their values. Second, in principle

  15. The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus

    Directory of Open Access Journals (Sweden)

    Enjuanes Luis

    2011-09-01

    Full Text Available Abstract Background Transmissible gastroenteritis virus (TGEV has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity. Methods The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results. Results Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3 deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time. Conclusions Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.

  16. In Vitro bile acid binding of kale, mustard greens, broccoli, cabbage and green bell pepper improves with microwave cooking

    Science.gov (United States)

    Bile acid binding potential of foods and food fractions has been related to lowering the risk of heart disease and that of cancer. Sautéing or steam cooking has been observed to significantly improve bile acid binding of green/leafy vegetables. It was hypothesized that microwave cooking could impr...

  17. Diverse roles of the nucleic acid binding protein KHSRP in cell differentiation and disease

    Science.gov (United States)

    Briata, Paola; Bordo, Domenico; Puppo, Margherita; Gorlero, Franco; Rossi, Martina; Bizzozzero, Nora Perrone; Gherzi, Roberto

    2015-01-01

    The single-stranded nucleic acid binding protein KHSRP (KH-Type Splicing Regulatory Protein) modulates RNA life and gene expression at various levels. KHSRP controls important cellular functions as different as proliferation, differentiation, metabolism and response to infectious agents. We summarize and discuss experimental evidence providing a potential link between changes in KHSRP expression/function and human diseases including neuromuscular disorders, obesity, type II diabetes, and cancer. PMID:26708421

  18. Analysis of Duplicate Genes in Soybean

    Institute of Scientific and Technical Information of China (English)

    C.M. Cai; K.J. Van; M.Y. Kim; S.H. Lee

    2007-01-01

    @@ Gene duplication is a major determinant of the size and gene complement of eukaryotic genomes (Lockton and Gaut, 2005). There are a number of different ways in which duplicate genes can arise (Sankoff, 2001), but the most spectacular method of gene duplication may be whole genome duplication via polyploidization.

  19. Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins

    DEFF Research Database (Denmark)

    Madsen, Peder; Rasmussen, H H; Leffers, H

    1992-01-01

    as MRP 14, L1, or calprotectin; calgranulin A or MRP 8; and cystatin A or stefin A. Here, we have cloned and sequenced the cDNA (clone 1592) encoding a new member of this group of low-molecular-weight proteins [isoelectric focusing (IEF) SSP 3007 in the keratinocyte 2D gel protein database] that we have...

  20. Partial 1q Duplications and Associated Phenotype

    Science.gov (United States)

    Morris, Marcos L.M.; Baroneza, José E.; Teixeira, Patricia; Medina, Cristina T.N.; Cordoba, Mara S.; Versiani, Beatriz R.; Roese, Liege L.; Freitas, Erika L.; Fonseca, Ana C.S.; dos Santos, Maria C.G.; Pic-Taylor, Aline; Rosenberg, Carla; Oliveira, Silviene F.; Ferrari, Iris; Mazzeu, Juliana F.

    2016-01-01

    Duplications of the long arm of chromosome 1 are rare. Distal duplications are the most common and have been reported as either pure trisomy or unbalanced translocations. The paucity of cases with pure distal 1q duplications has made it difficult to delineate a partial distal trisomy 1q syndrome. Here, we report 2 patients with overlapping 1q duplications detected by G-banding. Array CGH and FISH were performed to characterize the duplicated segments, exclude the involvement of other chromosomes and determine the orientation of the duplication. Patient 1 presents with a mild phenotype and carries a 22.5-Mb 1q41q43 duplication. Patient 2 presents with a pure 1q42.13qter inverted duplication of 21.5 Mb, one of the smallest distal 1q duplications ever described and one of the few cases characterized by array CGH, thus contributing to a better characterization of distal 1q duplication syndrome. PMID:27022331

  1. Distinct roles of urinary liver-type fatty acid-binding protein in non-diabetic patients with anemia.

    Directory of Open Access Journals (Sweden)

    Naohiko Imai

    Full Text Available Various stresses including ischemia are known to up-regulate renal L-FABP gene expression and increase the urinary excretion of L-FABP. In diabetic patients with anemia, the urinary excretion of L-FABP is significantly increased. We studied the clinical significance of urinary L-FABP and its relationship with anemia in non-diabetic patients.A total of 156 patients were studied in this retrospective cross-sectional analysis. The associations between anemia and urinary L-FABP levels, and the predictors of urinary L-FABP levels in non-diabetic patients were evaluated.Urinary L-FABP levels were significantly higher in patients with anemia compared to those in patients without anemia. Similarly, the urinary L-FABP levels were significantly higher in patients with albuminuria compared to those in patients without albuminuria. Urinary L-FABP levels correlated with urinary albumin-to-creatinine ratios, estimated glomerular filtration rates, body mass index, and hemoglobin levels. Multivariate linear regression analysis determined that hemoglobin levels (β = -0.249, P = 0.001 and urinary albumin-to-creatinine ratios (β = 0.349, P < 0.001 were significant predictors of urinary L-FABP levels.Urinary L-FABP is strongly associated with anemia in non-diabetic patients.

  2. HUMAN LIVER FATTY ACID BINDING PROTEIN (L-FABP) T94A VARIANT ALTERS STRUCTURE, STABILITY, AND INTERACTION WITH FIBRATES

    OpenAIRE

    Martin, Gregory G.; McIntosh, Avery L.; Huang, Huan; Gupta, Shipra; Atshaves, Barbara P.; Landrock, Kerstin K.; Landrock, Danilo; Kier, Ann B.; Schroeder, Friedhelm

    2013-01-01

    Although the human L-FABP T94A variant arises from the most commonly occurring SNP in the entire FABP family, there is a complete lack of understanding regarding the role of this polymorphism in human disease. It has been hypothesized that the T94A substitution results in complete loss of ligand binding ability and function analogous to L-FABP gene ablation. This possibility was addressed using recombinant human WT T94T and T94A variant L-FABP and cultured primary human hepatocytes. Non-conse...

  3. Clinical study on intestinal fatty acid binding protein and the endotoxin in early diagnosis of intestinal barrier dysfunction

    Institute of Scientific and Technical Information of China (English)

    孔令尚

    2013-01-01

    Objective To screen the high specific and sensitivemonitoring indications in the diagnosis of intestinal barrier dysfunction.Methods A total of 70 critical patients with intestinal barrier dysfunction and acute physiology

  4. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels

    Directory of Open Access Journals (Sweden)

    Bhattacharjee Rakesh

    2010-02-01

    Full Text Available Abstract Introduction Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity. Methods A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65 and non-obese (NOB. Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135, corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped. Results Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values. Conclusions Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.

  5. Recent Advances in Nucleic Acid Binding Aspects of Berberine Analogs and Implications for Drug Design.

    Science.gov (United States)

    Bhowmik, Debipreeta; Kumar, Gopinatha Suresh

    2016-01-01

    Berberine is one of the most widely known alkaloids belonging to the protoberberine group exhibiting myriad therapeutic properties. The anticancer potency of berberine appears to derive from its multiple actions including strong interaction with nucleic acids exhibiting adenine-thymine base pair specificity, inhibition of the enzymes topoisomerases and telomerases, and stabilizing the quadruplex structures. It was realized that the development of berberine as a potential anticancer agent necessitates enhancing its nucleic acid binding efficacy through appropriate structural modifications. More recently a number of such approaches have been attempted in various laboratories with great success. Several derivatives have been synthesized mostly with substitutions at the 8, 9 and 13 positions of the isoquinoline chromophore, and studied for enhanced nucleic acid binding activity. In this article, we present an up to date review of the details of the interaction of berberine and several of its important synthetic 8, 9 and 13 substituted derivatives with various nucleic acid structures reported recently. These studies provide interesting knowledge on the mode, mechanism, sequence and structural specificity of the binding of berberine derivatives and correlate structural and energetic aspects of the interaction providing better understanding of the structure- activity relations for designing and development of berberine based therapeutic agents with higher efficacy and therapeutic potential.

  6. A Large-Scale Assessment of Nucleic Acids Binding Site Prediction Programs.

    Directory of Open Access Journals (Sweden)

    Zhichao Miao

    2015-12-01

    Full Text Available Computational prediction of nucleic acid binding sites in proteins are necessary to disentangle functional mechanisms in most biological processes and to explore the binding mechanisms. Several strategies have been proposed, but the state-of-the-art approaches display a great diversity in i the definition of nucleic acid binding sites; ii the training and test datasets; iii the algorithmic methods for the prediction strategies; iv the performance measures and v the distribution and availability of the prediction programs. Here we report a large-scale assessment of 19 web servers and 3 stand-alone programs on 41 datasets including more than 5000 proteins derived from 3D structures of protein-nucleic acid complexes. Well-defined binary assessment criteria (specificity, sensitivity, precision, accuracy… are applied. We found that i the tools have been greatly improved over the years; ii some of the approaches suffer from theoretical defects and there is still room for sorting out the essential mechanisms of binding; iii RNA binding and DNA binding appear to follow similar driving forces and iv dataset bias may exist in some methods.

  7. Intrathoracic enteric foregut duplication cyst.

    Directory of Open Access Journals (Sweden)

    Birmole B

    1994-10-01

    Full Text Available A one month old male child presented with respiratory distress since day 10 of life. There was intercostal retraction and decreased air entry on the right side. Investigations revealed a well defined cystic mass in the posterior mediastinum with vertebral anomalies, the cyst was excised by posterolateral thoracotomy. Histopathology revealed it to be an enteric foregut duplication cyst.

  8. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    Science.gov (United States)

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-08-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-binding activity. No hybridization was detected in RNA extracted from ovary, spleen, kidney, or liver, which contain relatively low levels of cellular retinoic acid-binding protein activity. Analysis of genomic clones isolated from an EcoRI bovine genomic library demonstrated that the bovine cellular retinoic acid-binding protein gene is composed of four exons and three introns. Two putative promoter sequences were identified in the cloned 5' sequence of the gene.

  9. The inhibition of anti-DNA binding to DNA by nucleic acid binding polymers.

    Directory of Open Access Journals (Sweden)

    Nancy A Stearns

    Full Text Available Antibodies to DNA (anti-DNA are the serological hallmark of systemic lupus erythematosus (SLE and can mediate disease pathogenesis by the formation of immune complexes. Since blocking immune complex formation can attenuate disease manifestations, the effects of nucleic acid binding polymers (NABPs on anti-DNA binding in vitro were investigated. The compounds tested included polyamidoamine dendrimer, 1,4-diaminobutane core, generation 3.0 (PAMAM-G3, hexadimethrine bromide, and a β-cylodextrin-containing polycation. As shown with plasma from patients with SLE, NABPs can inhibit anti-DNA antibody binding in ELISA assays. The inhibition was specific since the NABPs did not affect binding to tetanus toxoid or the Sm protein, another lupus autoantigen. Furthermore, the polymers could displace antibody from preformed complexes. Together, these results indicate that NABPs can inhibit the formation of immune complexes and may represent a new approach to treatment.

  10. Autopolyploidy genome duplication preserves other ancient genome duplications in Atlantic salmon (Salmo salar)

    Science.gov (United States)

    Davidson, William S.

    2017-01-01

    Salmonids (e.g. Atlantic salmon, Pacific salmon, and trouts) have a long legacy of genome duplication. In addition to three ancient genome duplications that all teleosts are thought to share, salmonids have had one additional genome duplication. We explored a methodology for untangling these duplications from each other to better understand them in Atlantic salmon. In this methodology, homeologous regions (paralogous/duplicated genomic regions originating from a whole genome duplication) from the most recent genome duplication were assumed to have duplicated genes at greater density and have greater sequence similarity. This assumption was used to differentiate duplicated gene pairs in Atlantic salmon that are either from the most recent genome duplication or from earlier duplications. From a comparison with multiple vertebrate species, it is clear that Atlantic salmon have retained more duplicated genes from ancient genome duplications than other vertebrates--often at higher density in the genome and containing fewer synonymous mutations. It may be that polysomic inheritance is the mechanism responsible for maintaining ancient gene duplicates in salmonids. Polysomic inheritance (when multiple chromosomes pair during meiosis) is thought to be relatively common in salmonids compared to other vertebrate species. These findings illuminate how genome duplications may not only increase the number of duplicated genes, but may also be involved in the maintenance of them from previous genome duplications as well. PMID:28241055

  11. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    OpenAIRE

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-01-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-bindin...

  12. Congenital duplication of the gallbladder.

    Science.gov (United States)

    Safioleas, Michael C; Papavassiliou, Vassilios G; Moulakakis, Konstantinos G; Angouras, Dimitrios C; Skandalakis, Panagiotis

    2006-03-01

    Duplication of the gallbladder is a rare congenital anomaly of the biliary system. In this article, two cases of gallbladder duplication are presented. The first case is a patient with double gallbladder and concomitant choledocholithiasis. The probable diagnosis of double gallbladder was made preoperatively by computed tomography. The patient underwent a successful open cholecystectomy and common bile duct exploration. In the second case, two cystic formations in the place of gallbladder are demonstrated with ultrasound scan in a woman with acute cholecystitis. At surgery, two gallbladders were found. A brief review of epidemiology and anatomy of double gallbladder is included, along with a discussion of the difficulties in diagnosis and treatment of this condition.

  13. Yeast genome duplication was followed by asynchronous differentiation of duplicated genes

    DEFF Research Database (Denmark)

    Langkjær, Rikke Breinhold; Cliften, P.F.; Johnston, M.

    2003-01-01

    Gene redundancy has been observed in yeast, plant and human genomes, and is thought to be a consequence of whole-genome duplications(1-3). Baker's yeast, Saccharomyces cerevisiae, contains several hundred duplicated genes(1). Duplication(s) could have occurred before or after a given speciation. ...

  14. AMID: autonomous modeler of intragenic duplication.

    Science.gov (United States)

    Kummerfeld, Sarah K; Weiss, Anthony S; Fekete, Alan; Jermiin, Lars S

    2003-01-01

    Intragenic duplication is an evolutionary process where segments of a gene become duplicated. While there has been much research into whole-gene or domain duplication, there have been very few studies of non-tandem intragenic duplication. The identification of intragenically replicated sequences may provide insight into the evolution of proteins, helping to link sequence data with structure and function. This paper describes a tool for autonomously modelling intragenic duplication. AMID provides: identification of modularly repetitive genes; an algorithm for identifying repeated modules; and a scoring system for evaluating the modules' similarity. An evaluation of the algorithms and use cases are presented.

  15. Genomic evidence for adaptation by gene duplication.

    Science.gov (United States)

    Qian, Wenfeng; Zhang, Jianzhi

    2014-08-01

    Gene duplication is widely believed to facilitate adaptation, but unambiguous evidence for this hypothesis has been found in only a small number of cases. Although gene duplication may increase the fitness of the involved organisms by doubling gene dosage or neofunctionalization, it may also result in a simple division of ancestral functions into daughter genes, which need not promote adaptation. Hence, the general validity of the adaptation by gene duplication hypothesis remains uncertain. Indeed, a genome-scale experiment found similar fitness effects of deleting pairs of duplicate genes and deleting individual singleton genes from the yeast genome, leading to the conclusion that duplication rarely results in adaptation. Here we contend that the above comparison is unfair because of a known duplication bias among genes with different fitness contributions. To rectify this problem, we compare homologous genes from the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. We discover that simultaneously deleting a duplicate gene pair in S. cerevisiae reduces fitness significantly more than deleting their singleton counterpart in S. pombe, revealing post-duplication adaptation. The duplicates-singleton difference in fitness effect is not attributable to a potential increase in gene dose after duplication, suggesting that the adaptation is owing to neofunctionalization, which we find to be explicable by acquisitions of binary protein-protein interactions rather than gene expression changes. These results provide genomic evidence for the role of gene duplication in organismal adaptation and are important for understanding the genetic mechanisms of evolutionary innovation.

  16. Chromosome I duplications in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    McKim, K.S.; Rose, A.M. (Univ. of British Columbia, Vancouver (Canada))

    1990-01-01

    We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left half of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.

  17. Tubular Colonic Duplication Presenting as Rectovestibular Fistula.

    Science.gov (United States)

    Karkera, Parag J; Bendre, Pradnya; D'souza, Flavia; Ramchandra, Mukunda; Nage, Amol; Palse, Nitin

    2015-09-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in about 15% of all gastrointestinal duplications. Double termination of tubular colonic duplication in the perineum is even more uncommon. We present a case of a Y-shaped tubular colonic duplication which presented with a rectovestibular fistula and a normal anus. Radiological evaluation and initial exploration for sigmoidostomy revealed duplicated colons with a common vascular supply. Endorectal mucosal resection of theduplicated distal segment till the colostomy site with division of the septum of the proximal segment and colostomy closure proved curative without compromise of the continence mechanism. Tubular colonic duplication should always be ruled out when a diagnosis of perineal canal is considered in cases of vestibular fistula alongwith a normal anus.

  18. Steam Cooking Significantly Improves in Vitro Bile Acid Binding of Beets, Eggplant, Asparagus, Carrots, Green Beans and Cauliflower

    Science.gov (United States)

    The relative healthful potential of cooked beets, okra, eggplant, asparagus, carrots, green beans, cauliflower and turnips was evaluated by determining their in vitro bile acid binding using a mixture of bile acids secreted in human bile at a duodenal physiological pH of 6.3. Six treatments and two...

  19. Duplicability of self-interacting human genes.

    LENUS (Irish Health Repository)

    Pérez-Bercoff, Asa

    2010-01-01

    BACKGROUND: There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. RESULTS: We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD) or small-scale duplication (SSD), and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. CONCLUSIONS: Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.

  20. Narrow, duplicated internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, T. [Servico de Neurorradiologia, Hospital Garcia de Orta, Avenida Torrado da Silva, 2801-951, Almada (Portugal); Shayestehfar, B. [Department of Radiology, UCLA Oliveview School of Medicine, Los Angeles, California (United States); Lufkin, R. [Department of Radiology, UCLA School of Medicine, Los Angeles, California (United States)

    2003-05-01

    A narrow internal auditory canal (IAC) constitutes a relative contraindication to cochlear implantation because it is associated with aplasia or hypoplasia of the vestibulocochlear nerve or its cochlear branch. We report an unusual case of a narrow, duplicated IAC, divided by a bony septum into a superior relatively large portion and an inferior stenotic portion, in which we could identify only the facial nerve. This case adds support to the association between a narrow IAC and aplasia or hypoplasia of the vestibulocochlear nerve. The normal facial nerve argues against the hypothesis that the narrow IAC is the result of a primary bony defect which inhibits the growth of the vestibulocochlear nerve. (orig.)

  1. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    Energy Technology Data Exchange (ETDEWEB)

    Gangi Setty, Thanuja [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Cho, Christine [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Govindappa, Sowmya [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Apicella, Michael A. [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Ramaswamy, S., E-mail: ramas@instem.res.in [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India)

    2014-07-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

  2. Polymorphic Nucleic Acid Binding of Bioactive Isoquinoline Alkaloids and Their Role in Cancer

    Directory of Open Access Journals (Sweden)

    Motilal Maiti

    2010-01-01

    Full Text Available Bioactive alkaloids occupy an important position in applied chemistry and play an indispensable role in medicinal chemistry. Amongst them, isoquinoline alkaloids like berberine, palmatine and coralyne of protoberberine group, sanguinarine of the benzophenanthridine group, and their derivatives represent an important class of molecules for their broad range of clinical and pharmacological utility. In view of their extensive occurrence in various plant species and significantly low toxicities, prospective development and use of these alkaloids as effective anticancer agents are matters of great current interest. This review has focused on the interaction of these alkaloids with polymorphic nucleic acid structures (B-form, A-form, Z-form, HL-form, triple helical form, quadruplex form and their topoisomerase inhibitory activity reported by several research groups using various biophysical techniques like spectrophotometry, spectrofluorimetry, thermal melting, circular dichroism, NMR spectroscopy, electrospray ionization mass spectroscopy, viscosity, isothermal titration calorimetry, differential scanning calorimetry, molecular modeling studies, and so forth, to elucidate their mode and mechanism of action for structure-activity relationships. The DNA binding of the planar sanguinarine and coralyne are found to be stronger and thermodynamically more favoured compared to the buckled structure of berberine and palmatine and correlate well with the intercalative mechanism of sanguinarine and coralyne and the partial intercalation by berberine and palmatine. Nucleic acid binding properties are also interpreted in relation to their anticancer activity.

  3. Staphylococcus aureus immunodominant surface antigen B is a cell-surface associated nucleic acid binding protein

    Directory of Open Access Journals (Sweden)

    Cerca Nuno

    2009-03-01

    Full Text Available Abstract Background Staphylococcus aureus immunodominant surface antigen B (IsaB elicits an immune response during septicemia and is generally classified as a virulence factor, but its biological function remains completely undefined. In an attempt to identify staphylococcal RNA-binding proteins, we designed an RNA Affinity Chromatography assay and subsequently isolated IsaB. Results Western analysis indicated that IsaB was both secreted and cell-surface associated. Gel Shift analysis confirmed the RNA binding activity but revealed that IsaB bound to any nucleic acid without sequence specificity. IsaB exhibited the highest affinity for double-stranded DNA followed by single-stranded DNA and RNA. Because extracellular DNA has been shown to play a role in biofilm formation, we investigated the biofilm-forming capacity of an isogenic isaB deletion mutant but we found that IsaB did not contribute to biofilm formation under any conditions tested. Conclusion IsaB is an extracellular nucleic acid binding protein, with little to no sequence specificity, but its role in virulence remains unclear.

  4. Current approach to male infertility treatment: sperm selection procedure based on hyaluronic acid binding ability

    Directory of Open Access Journals (Sweden)

    A. V. Zobova

    2015-01-01

    Full Text Available Intracytoplasmic sperm injection into an oocyte is widely used throughout the world in assisted reproductive technologies programs in the presence of male infertility factor. However, this approach can allow selection of a single sperm, which is carrying different types of pathologies. Minimizing of any potential risks, entailing the occurrence of abnormalities in the embryos development (apoptosis, fragmentation of embryos, alterations in gene expression, aneuploidies is a very important condition for reducing the potential negative consequences resulting the manipulation with gametes. Processes that could be influenced by the embryologist must be fulfilled in safe and physiological way as much as it is possible. Data of numerous publications reporting about the positive effects of using the technology of sperm selection by hyaluronic acid binding, let make a conclusion about the high prospects of this approach in the treatment of male infertility by methods of in vitro fertilization. The selection of sperm with improved characteristics, which determine the maturity and genetic integrity, provides an opportunity to improve the parameters of pre-implantation embryogenesis, having thus a positive effect on clinical outcomes of assisted reproductive technologies programs.

  5. DNA Methylation of Cellular Retinoic Acid-Binding Proteins in Cervical Cancer

    Science.gov (United States)

    Arellano-Ortiz, Ana L.; Salcedo-Vargas, Mauricio; Vargas-Requena, Claudia L.; López-Díaz, José A.; De la Mora-Covarrubias, Antonio; Silva-Espinoza, Juan C.; Jiménez-Vega, Florinda

    2016-01-01

    This study determined the methylation status of cellular retinoic acid-binding protein (CRABP) gene promoters and associated them with demographic characteristics, habits, and the presence of human papilloma virus (HPV) in patients with cervical cancer (CC), low and high squamous intraepithelial lesions, and no intraepithelial lesion. Women (n = 158) were selected from the Colposcopy Clinic of Sanitary Jurisdiction II in Ciudad Juarez, Chihuahua, Mexico. Demographic characteristics and habit information were collected. Cervical biopsy and endocervical scraping were used to determine methylation in promoter regions by methylation-specific polymerase chain reaction technique. We found hemi-methylation patterns in the promoter regions of CRABP1 and CRABP2; there was 28.5% hemi-methylation in CRABP1 and 7.0% in that of CRABP2. Methylation in CRABP1 was associated with age (≥35 years, P = 0.002), family history of cancer (P = 0.032), the presence of HPV-16 (P = 0.013), and no alcohol intake (P = 0.035). These epigenetic changes could be involved in the CC process, and CRABP1 has the potential to be a predictive molecular marker of retinoid therapy response. PMID:27867303

  6. Detecting long tandem duplications in genomic sequences

    Directory of Open Access Journals (Sweden)

    Audemard Eric

    2012-05-01

    Full Text Available Abstract Background Detecting duplication segments within completely sequenced genomes provides valuable information to address genome evolution and in particular the important question of the emergence of novel functions. The usual approach to gene duplication detection, based on all-pairs protein gene comparisons, provides only a restricted view of duplication. Results In this paper, we introduce ReD Tandem, a software using a flow based chaining algorithm targeted at detecting tandem duplication arrays of moderate to longer length regions, with possibly locally weak similarities, directly at the DNA level. On the A. thaliana genome, using a reference set of tandem duplicated genes built using TAIR,a we show that ReD Tandem is able to predict a large fraction of recently duplicated genes (dS  Conclusions ReD Tandem allows to identify large tandem duplications without any annotation, leading to agnostic identification of tandem duplications. This approach nicely complements the usual protein gene based which ignores duplications involving non coding regions. It is however inherently restricted to relatively recent duplications. By recovering otherwise ignored events, ReD Tandem gives a more comprehensive view of existing evolutionary processes and may also allow to improve existing annotations.

  7. The combinatorics of tandem duplication trees.

    Science.gov (United States)

    Gascuel, Olivier; Hendy, Michael D; Jean-Marie, Alain; McLachlan, Robert

    2003-02-01

    We developed a recurrence relation that counts the number of tandem duplication trees (either rooted or unrooted) that are consistent with a set of n tandemly repeated sequences generated under the standard unequal recombination (or crossover) model of tandem duplications. The number of rooted duplication trees is exactly twice the number of unrooted trees, which means that on average only two positions for a root on a duplication tree are possible. Using the recurrence, we tabulated these numbers for small values of n. We also developed an asymptotic formula that for large n provides estimates for these numbers. These numbers give a priori probabilities for phylogenies of the repeated sequences to be duplication trees. This work extends earlier studies where exhaustive counts of the numbers for small n were obtained. One application showed the significance of finding that most maximum-parsimony trees constructed from repeat sequences from human immunoglobins and T-cell receptors were tandem duplication trees. Those findings provided strong support to the proposed mechanisms of tandem gene duplication. The recurrence relation also suggests efficient algorithms to recognize duplication trees and to generate random duplication trees for simulation. We present a linear-time recognition algorithm.

  8. SNBRFinder: A Sequence-Based Hybrid Algorithm for Enhanced Prediction of Nucleic Acid-Binding Residues.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Yang

    Full Text Available Protein-nucleic acid interactions are central to various fundamental biological processes. Automated methods capable of reliably identifying DNA- and RNA-binding residues in protein sequence are assuming ever-increasing importance. The majority of current algorithms rely on feature-based prediction, but their accuracy remains to be further improved. Here we propose a sequence-based hybrid algorithm SNBRFinder (Sequence-based Nucleic acid-Binding Residue Finder by merging a feature predictor SNBRFinderF and a template predictor SNBRFinderT. SNBRFinderF was established using the support vector machine whose inputs include sequence profile and other complementary sequence descriptors, while SNBRFinderT was implemented with the sequence alignment algorithm based on profile hidden Markov models to capture the weakly homologous template of query sequence. Experimental results show that SNBRFinderF was clearly superior to the commonly used sequence profile-based predictor and SNBRFinderT can achieve comparable performance to the structure-based template methods. Leveraging the complementary relationship between these two predictors, SNBRFinder reasonably improved the performance of both DNA- and RNA-binding residue predictions. More importantly, the sequence-based hybrid prediction reached competitive performance relative to our previous structure-based counterpart. Our extensive and stringent comparisons show that SNBRFinder has obvious advantages over the existing sequence-based prediction algorithms. The value of our algorithm is highlighted by establishing an easy-to-use web server that is freely accessible at http://ibi.hzau.edu.cn/SNBRFinder.

  9. Fatty acids - trans fatty acids

    Science.gov (United States)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  10. Sialic Acid Binding Properties of Soluble Coronavirus Spike (S1 Proteins: Differences between Infectious Bronchitis Virus and Transmissible Gastroenteritis Virus

    Directory of Open Access Journals (Sweden)

    Christine Winter

    2013-07-01

    Full Text Available The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV and the spike protein of infectious bronchitis virus (IBV. Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.

  11. Partial Duplication of Chromosome 8p

    African Journals Online (AJOL)

    rme

    The partial chromosome 8p duplication is a rare syndrome and is ... clinical and cytogenetic data of 5 Arab patients with de novo inversion duplication of 8p. ... characterized by Fluorescent in situ ... thick lower lips, down turned angles of mouth ...

  12. Duodenal duplication cyst identified with MRCP

    Energy Technology Data Exchange (ETDEWEB)

    Carbognin, G.; Guarise, A.; Biasiutti, C.; Pagnotta, N.; Procacci, C. [Department of Radiology, University Hospital ' G.B. Rossi' , Verona (Italy)

    2000-08-01

    We report a case of a stalked cystic duodenal duplication. The lesion, hyperintense on T2-weighted GRE images, maintained the signal intensity after oral administration of a negative contrast agent (Lumirem, Guerbet, Aulnay-Sous-Bois, France), confirming its independence from the duodenal lumen. To our knowledge, this is the first demonstration of duodenal duplication by means of MR cholangiopancreatography. (orig.)

  13. Bilateral duplication of the internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Weon, Young Cheol; Kim, Jae Hyoung; Choi, Sung Kyu [Seoul National University College of Medicine, Department of Radiology, Seoul National University Bundang Hospital, Seongnam-si (Korea); Koo, Ja-Won [Seoul National University College of Medicine, Department of Otolaryngology, Seoul National University Bundang Hospital, Seongnam-si (Korea)

    2007-10-15

    Duplication of the internal auditory canal is an extremely rare temporal bone anomaly that is believed to result from aplasia or hypoplasia of the vestibulocochlear nerve. We report bilateral duplication of the internal auditory canal in a 28-month-old boy with developmental delay and sensorineural hearing loss. (orig.)

  14. Current incidence of duplicate publication in otolaryngology.

    Science.gov (United States)

    Cheung, Veronique Wan Fook; Lam, Gilbert O A; Wang, Yun Fan; Chadha, Neil K

    2014-03-01

    Duplicate publication--deemed highly unethical--is the reproduction of substantial content in another article by the same authors. In 1999, Rosenthal et al. identified an 8.5% incidence of duplicate articles in two otolaryngology journals. We explored the current incidence in three otolaryngology journals in North America and Europe. Retrospective literature review. Index articles in 2008 in Archives of Otolaryngology-Head and Neck Surgery, Laryngoscope, and Clinical Otolaryngology were searched using MEDLINE. Potential duplicate publications in 2006 through 2010 were identified using the first, second, and last authors' names. Three authors independently investigated suspected duplicate publications--classifying them by degree of duplication. Of 358 index articles screened, 75 (20.9%) had 119 potential duplicates from 2006 to 2010. Full review of these 119 potential duplicates revealed a total of 40 articles with some form of redundancy (33.6% of the potential duplicates) involving 27 index articles (7.5% of 358 index articles); one (0.8%) "dual" publication (identical or nearly identical data and conclusions to the index article); three (2.5%) "suspected" dual publications (less than 50% new data and same conclusions); and 36 (30.3%) publications with "salami-slicing" (portion of the index article data repeated) were obtained. Further analysis compared the likelihood of duplicate publication by study source and subspecialty within otolaryngology. The incidence of duplicate publication has not significantly changed over 10 years. "Salami-slicing" was a concerning practice, with no cross-referencing in 61% of these cases. Detecting and eliminating redundant publications is a laborious task, but it is essential in upholding the journal quality and research integrity. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Duplicated Ižnternal Juguler Vein

    Directory of Open Access Journals (Sweden)

    Ahmet Kirbas

    2014-03-01

    Full Text Available    Duplicated internal juguler vein (DIJV is a rare anomaly and reported incidence is 0.4 % in the literature. A 45-year-old female patient was referred to our hospital because of non pulsatile neck swelling. The magnetic resonance image (MRI showed left IJVs divided at the angles of the mandible running anterior to the common carotid artery until anterior mediastinal level. Clinicians should be aware of the rare possibility of duplicated IJVs in patients presenting with neck swelling. The development of imaging technics have revealed more cases of duplicated internal juguler vein.

  16. Nature and management of duplicate medication alerts

    NARCIS (Netherlands)

    Heringa, Mette; Floor, Annemieke; Meijer, Willemijn M.; De Smet, Peter A G M; Bouvy, Marcel L.|info:eu-repo/dai/nl/153182210

    2015-01-01

    OBJECTIVE: To investigate the nature of duplicate medication (DM) alerts, their management by community pharmacists, and potential characteristics of DM alerts that lead to interventions by pharmacists. METHODS: Observational study in 53 community pharmacies. Each pharmacist registered the nature

  17. Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells.

    Science.gov (United States)

    Mitchell, Ryan W; On, Ngoc H; Del Bigio, Marc R; Miller, Donald W; Hatch, Grant M

    2011-05-01

    The blood-brain barrier (BBB), formed by the brain capillary endothelial cells, provides a protective barrier between the systemic blood and the extracellular environment of the CNS. Passage of fatty acids from the blood to the brain may occur either by diffusion or by proteins that facilitate their transport. Currently several protein families have been implicated in fatty acid transport. The focus of the present study was to identify the fatty acid transport proteins (FATPs) expressed in the brain microvessel endothelial cells and characterize their involvement in fatty acid transport across an in vitro BBB model. The major fatty acid transport proteins expressed in human brain microvessel endothelial cells (HBMEC), mouse capillaries and human grey matter were FATP-1, -4 and fatty acid binding protein 5 and fatty acid translocase/CD36. The passage of various radiolabeled fatty acids across confluent HBMEC monolayers was examined over a 30-min period in the presence of fatty acid free albumin in a 1 : 1 molar ratio. The apical to basolateral permeability of radiolabeled fatty acids was dependent upon both saturation and chain length of the fatty acid. Knockdown of various fatty acid transport proteins using siRNA significantly decreased radiolabeled fatty acid transport across the HBMEC monolayer. Our findings indicate that FATP-1 and FATP-4 are the predominant fatty acid transport proteins expressed in the BBB based on human and mouse expression studies. While transport studies in HBMEC monolayers support their involvement in fatty acid permeability, fatty acid translocase/CD36 also appears to play a prominent role in transport of fatty acids across HBMEC.

  18. Distal Xq duplication and functional Xq disomy

    Directory of Open Access Journals (Sweden)

    Schluth-Bolard Caroline

    2009-02-01

    Full Text Available Abstract Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq. Clinical manifestations widely vary depending on the gender of the patient and on the gene content of the duplicated segment. Prevalence of Xq duplications remains unknown. About 40 cases of Xq28 functional disomy due to cytogenetically visible rearrangements, and about 50 cases of cryptic duplications encompassing the MECP2 gene have been reported. The most frequently reported distal duplications involve the Xq28 segment and yield a recognisable phenotype including distinctive facial features (premature closure of the fontanels or ridged metopic suture, broad face with full cheeks, epicanthal folds, large ears, small and open mouth, ear anomalies, pointed nose, abnormal palate and facial hypotonia, major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and proneness to infections. Xq duplications may be caused either by an intrachromosomal duplication or an unbalanced X/Y or X/autosome translocation. In XY males, structural X disomy always results in functional disomy. In females, failure of X chromosome dosage compensation could result from a variety of mechanisms, including an unfavourable pattern of inactivation, a breakpoint separating an X segment from the X-inactivation centre in cis, or a small ring chromosome. The MECP2 gene in Xq28 is the most important dosage-sensitive gene responsible for the abnormal phenotype in duplications of distal Xq. Diagnosis is based on clinical features and is confirmed by CGH array techniques. Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X. The recurrence risk is significant if a structural rearrangement is present in one of the parent, the most frequent situation being that of an intrachromosomal duplication inherited from the mother. Prenatal diagnosis is performed by

  19. Fatty Liver

    Science.gov (United States)

    ... Abbreviations Weights & Measures ENGLISH View Professional English Deutsch Japanese Espaniol Find information on medical topics, symptoms, drugs, ... inside liver cells. Just consuming a high-fat diet does not result in fatty liver. Rarely, fat ...

  20. 48 CFR 1331.205-70 - Duplication of effort.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Duplication of effort....205-70 Duplication of effort. The Department will not pay any costs for work that is duplicative of..., Duplication of Effort, in all cost-reimbursement, time and materials, and labor hour solicitations...

  1. 44 CFR 204.62 - Duplication and recovery of assistance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Duplication and recovery of... Administration § 204.62 Duplication and recovery of assistance. (a) Duplication of benefits. We provide supplementary assistance under the Stafford Act, which generally may not duplicate benefits received by...

  2. Do Children Think that Duplicating the Body also Duplicates the Mind?

    Science.gov (United States)

    Hood, Bruce; Gjersoe, Nathalia L.; Bloom, Paul

    2012-01-01

    Philosophers use hypothetical duplication scenarios to explore intuitions about personal identity. Here we examined 5- to 6-year-olds' intuitions about the physical properties and memories of a live hamster that is apparently duplicated by a machine. In Study 1, children thought that more of the original's physical properties than episodic…

  3. A conserved segmental duplication within ELA.

    Science.gov (United States)

    Brinkmeyer-Langford, C L; Murphy, W J; Childers, C P; Skow, L C

    2010-12-01

    The assembled genomic sequence of the horse major histocompatibility complex (MHC) (equine lymphocyte antigen, ELA) is very similar to the homologous human HLA, with the notable exception of a large segmental duplication at the boundary of ELA class I and class III that is absent in HLA. The segmental duplication consists of a ∼ 710 kb region of at least 11 repeated blocks: 10 blocks each contain an MHC class I-like sequence and the helicase domain portion of a BAT1-like sequence, and the remaining unit contains the full-length BAT1 gene. Similar genomic features were found in other Perissodactyls, indicating an ancient origin, which is consistent with phylogenetic analyses. Reverse-transcriptase PCR (RT-PCR) of mRNA from peripheral white blood cells of healthy and chronically or acutely infected horses detected transcription from predicted open reading frames in several of the duplicated blocks. This duplication is not present in the sequenced MHCs of most other mammals, although a similar feature at the same relative position is present in the feline MHC (FLA). Striking sequence conservation throughout Perissodactyl evolution is consistent with a functional role for at least some of the genes included within this segmental duplication.

  4. A novel cold-regulated cold shock domain containing protein from scallop Chlamys farreri with nucleic acid-binding activity.

    Directory of Open Access Journals (Sweden)

    Chuanyan Yang

    Full Text Available BACKGROUND: The cold shock domain (CSD containing proteins (CSDPs are one group of the evolutionarily conserved nucleic acid-binding proteins widely distributed in bacteria, plants, animals, and involved in various cellular processes, including adaptation to low temperature, cellular growth, nutrient stress and stationary phase. METHODOLOGY: The cDNA of a novel CSDP was cloned from Zhikong scallop Chlamys farreri (designated as CfCSP by expressed sequence tag (EST analysis and rapid amplification of cDNA ends (RACE approach. The full length cDNA of CfCSP was of 1735 bp containing a 927 bp open reading frame which encoded an N-terminal CSD with conserved nucleic acids binding motif and a C-terminal domain with four Arg-Gly-Gly (RGG repeats. The CSD of CfCSP shared high homology with the CSDs from other CSDPs in vertebrate, invertebrate and bacteria. The mRNA transcripts of CfCSP were mainly detected in the tissue of adductor and also marginally detectable in gill, hepatopancreas, hemocytes, kidney, mantle and gonad of healthy scallop. The relative expression level of CfCSP was up-regulated significantly in adductor and hemocytes at 1 h and 24 h respectively after low temperature treatment (P<0.05. The recombinant CfCSP protein (rCfCSP could bind ssDNA and in vitro transcribed mRNA, but it could not bind dsDNA. BX04, a cold sensitive Escherichia coli CSP quadruple-deletion mutant, was used to examine the cold adaptation ability of CfCSP. After incubation at 17°C for 120 h, the strain of BX04 containing the vector pINIII showed growth defect and failed to form colonies, while strain containing pINIII-CSPA or pINIII-CfCSP grew vigorously, indicating that CfCSP shared a similar function with E. coli CSPs for the cold adaptation. CONCLUSIONS: These results suggest that CfCSP is a novel eukaryotic cold-regulated nucleic acid-binding protein and may function as an RNA chaperone in vivo during the cold adaptation process.

  5. Impact of L-FABP and glucose on polyunsaturated fatty acid induction of PPARα-regulated β-oxidative enzymes

    OpenAIRE

    Petrescu, Anca D.; Huang, Huan; Martin, Gregory G.; McIntosh, Avery L.; Storey, Stephen M.; Landrock, Danilo; Kier, Ann B.; Schroeder, Friedhelm

    2012-01-01

    Liver fatty acid binding protein (L-FABP) is the major soluble protein that binds very-long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) in hepatocytes. However, nothing is known about L-FABP's role in n-3 PUFA-mediated peroxisome proliferator activated receptor-α (PPARα) transcription of proteins involved in long-chain fatty acid (LCFA) β-oxidation. This issue was addressed in cultured primary hepatocytes from wild-type, L-FABP-null, and PPARα-null mice with these major findings: 1) PUF...

  6. Infected colonic duplication: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hye Seon; Lee, Young Hwan; Kang, Eugene; Oh, Yeon Kyun; Yun, Ki Jung [Wonkwang Univ. School of Medicine and Hospital, Iksan (Korea, Republic of)

    2012-09-15

    An enteric duplication is a relatively common congenital anomaly, which is rarely complicated by infection. We report the radiologic findings including ultrasound, barium enema and computed tomography (CT) of an infected colonic duplication that was confirmed by pathology. This case demonstrated a complex hypoechoic cystic mass with a thick wall and septa in the left lower quadrant of abdomen and increased the color flow on the Color Doppler ultrasonography. On CT images, the cystic mass contained multiple enhancing septa, infiltrated to the mesocolon and displaced the adjacent bowels. On exploration, a large cystic mass with an abscess attached to the mesocolic border adhering to the small bowel was found.

  7. Nucleic acid-binding glycoproteins which solubilize nucleic acids in dilute acid: re-examination of the Ustilago maydis glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Unrau, P.; Champ, D.R.; Young, J.L.; Grant, C.E.

    1980-01-01

    Holloman reported the isolation from Ustilago maydis of a glycoprotein which prevented the precipitation of nucleic acids in cold 5% trichloroacetic acid. Two glycoprotein fractions from U. maydis with this nucleic acid-solubilizing activity were isolated in our laboratory using improved purification procedures. The activity was not due to nuclease contamination. The glycoproteins are distinguished by: their ability to bind to concanavalin A-Sepharose; their differential binding to double- and single-stranded deoxyribonucleic acid, and to ribonucleic acid; their molecular weights (46,000 and 69,000); and the relative amounts present in growing versus nongrowing cells. Both fractions required sulfhydryl-reducing conditions for optimal yields, specific activity, and stability. Nucleic acid binding was cooperative, the minimum number of glycoproteins required to make a native T7 DNA molecule soluble in dilute acid being estimated at 2 and 15, respectively.

  8. Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein Implicated in Cytotoxin Accumulation.

    Science.gov (United States)

    Ehara, Haruhiko; Makino, Marie; Kodama, Koichiro; Konoki, Keiichi; Ito, Takuhiro; Sekine, Shun-ichi; Fukuzawa, Seketsu; Yokoyama, Shigeyuki; Tachibana, Kazuo

    2015-07-06

    Okadaic acid (OA) is a marine polyether cytotoxin that was first isolated from the marine sponge Halichondria okadai. OA is a potent inhibitor of protein serine/threonine phosphatases (PP) 1 and 2A, and the structural basis of phosphatase inhibition has been well investigated. However, the role and mechanism of OA retention in the marine sponge have remained elusive. We have solved the crystal structure of okadaic acid binding protein 2.1 (OABP2.1) isolated from H. okadai; it has strong affinity for OA and limited sequence homology to other proteins. The structure revealed that OABP2.1 consists of two α-helical domains, with the OA molecule deeply buried inside the protein. In addition, the global fold of OABP2.1 was unexpectedly similar to that of aequorin, a jellyfish photoprotein. The presence of structural homologues suggested that, by using similar protein scaffolds, marine invertebrates have developed diverse survival systems adapted to their living environments.

  9. Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.

    Science.gov (United States)

    Nelson, Cara H; Peng, Chi-Chi; Lutz, Justin D; Yeung, Catherine K; Zelter, Alex; Isoherranen, Nina

    2016-08-01

    Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.

  10. Tsetse salivary gland proteins 1 and 2 are high affinity nucleic acid binding proteins with residual nuclease activity.

    Directory of Open Access Journals (Sweden)

    Guy Caljon

    Full Text Available Analysis of the tsetse fly salivary gland EST database revealed the presence of a highly enriched cluster of putative endonuclease genes, including tsal1 and tsal2. Tsal proteins are the major components of tsetse fly (G. morsitans morsitans saliva where they are present as monomers as well as high molecular weight complexes with other saliva proteins. We demonstrate that the recombinant tsetse salivary gland proteins 1&2 (Tsal1&2 display DNA/RNA non-specific, high affinity nucleic acid binding with K(D values in the low nanomolar range and a non-exclusive preference for duplex. These Tsal proteins exert only a residual nuclease activity with a preference for dsDNA in a broad pH range. Knockdown of Tsal expression by in vivo RNA interference in the tsetse fly revealed a partially impaired blood digestion phenotype as evidenced by higher gut nucleic acid, hematin and protein contents.

  11. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice

    DEFF Research Database (Denmark)

    Fentz, Joachim; Kjøbsted, Rasmus; Birk, Jesper B.;

    2015-01-01

    The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα md......) and FABPpm (plasma membrane fatty acid binding protein) (by ∼17-40%), together with fully abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser(237) phosphorylation during contraction/exercise in AMPKα mdKO mice, may impair FA transport capacity and FA transport protein translocation...

  12. Esophageal duplication and congenital esophageal stenosis.

    Science.gov (United States)

    Trappey, A Francois; Hirose, Shinjiro

    2017-04-01

    Esophageal duplication and congenital esophageal stenosis (CES) may represent diseases with common embryologic etiologies, namely, faulty tracheoesophageal separation and differentiation. Here, we will re-enforce definitions for these diseases as well as review their embryology, diagnosis, and treatment. Copyright © 2017. Published by Elsevier Inc.

  13. Metabolic Adaptation after Whole Genome Duplication

    NARCIS (Netherlands)

    Hoek, M.J.A. van; Hogeweg, P.

    2009-01-01

    Whole genome duplications (WGDs) have been hypothesized to be responsible for major transitions in evolution. However, the effects of WGD and subsequent gene loss on cellular behavior and metabolism are still poorly understood. Here we develop a genome scale evolutionary model to study the dynamics

  14. Fetal cyst reveling retroperitoneal enteric duplication

    Directory of Open Access Journals (Sweden)

    Imene Dahmane Ayadi

    2017-01-01

    Full Text Available Retroperitoneum is a very uncommon site of enteric duplication (ED. We report a new case of retroperitoneal ED cyst suspected in utero. Prenatal ultrasound showed an abdominal cystic mass. Noncommunicating retroperitoneal ED cyst measuring 70 mm × 30 mm was resected. Histopathologic examination confirmed the diagnosis.

  15. Gastric Duplication Cyst Causing Gastric Outlet Obstruction

    Directory of Open Access Journals (Sweden)

    Muna Al Shehi

    2012-07-01

    Full Text Available This is a case report of a newborn baby with gastric duplication cyst presented with non-bilious vomiting and upper abdominal distension. The diagnosis was suspected clinically and established by ultrasonography and computed tomography. The cyst was completely excised with uneventful recovery.

  16. Organising European technical documentation to avoid duplication.

    Science.gov (United States)

    Donawa, Maria

    2006-04-01

    The development of comprehensive accurate and well-organised technical documentation that demonstrates compliance with regulatory requirements is a resource-intensive, but critically important activity for medical device manufacturers. This article discusses guidance documents and method of organising technical documentation that may help avoid costly and time-consuming duplication.

  17. Incomplete urethral duplication in an adult male.

    LENUS (Irish Health Repository)

    Davis, N F

    2012-09-01

    Urethral duplication is a rare congenital anomaly with less than 200 cases reported. It predominantly occurs in males and is nearly always diagnosed in childhood or adolescence. It is defined as a complete second passage from the bladder to the dorsum of the penis or as an accessory pathway that ends blindly on the dorsal or ventral surface.

  18. Decomposition of Parallel Copies with Duplication

    Directory of Open Access Journals (Sweden)

    G. N. Purohit

    2012-05-01

    Full Text Available SSA form is becoming more popular in the context of JIT compilation since it allows the compiler to perform important optimizations like common sub-expression elimination or constant propagation without the drawbacks of keeping huge data structures in memory or requiring a lot of computing power. The recent approach of SSA-based register allocation performs SSA elimination after register allocation. F. Bouchez et al. proposed parallel copy motion to prevent the splitting of edges when going out of colored SSA by moving the code that should be assigned to the edges to a more convenient place. Duplications in parallel copies pose some problems when moving them. In this paper an approach has been developed to decompose parallel copies so that duplications can be handled separately and parallel copies can be easily moved away without duplication. A simple and elegant application is moving duplicated copies out of critical edges. This is often beneficial compared to the alternative splitting the edge.

  19. Our experience with unusual gastrointestinal tract duplications in infants

    Directory of Open Access Journals (Sweden)

    Bilal Mirza

    2014-01-01

    Full Text Available Background: Classical duplications may present along any part of gastrointestinal tract (GIT from mouth to anus. Atypical or unusual rare varieties of GIT duplications may also occur, but with different anatomical features. Materials and Methods: We reviewed our 5-year record (February 2008-January 2013 to describe clinical profile of unusual GIT duplications in neonates and small infants. Results: Three patients with atypical variety of GIT duplications were managed in our department during this tenure. Two were females and one male. Age was ranged between 11 days and 2 months. All patients presented with massive abdominal distension causing respiratory embarrassment in two of them. In all patients, the pre-operative differential diagnoses also included GIT duplication cysts. Computerized tomography (CT scan showed single huge cyst in one and multiple cysts in two patients. In one patient the CT scan also depicted a thoracic cyst in relation to posterior mediastinum. At operation, one patient had colonic tubular duplication cyst along with another isolated duplication cyst, the second case had a tubular duplication cyst of ileum with its segmental dilatation, and in the third case two isolated duplications were found. Duplication cysts were excised along with mucosal stripping in one patient, cyst excision and intestinal resection and anastomosis in one patient, and only cysts excision in one. All patients did well post-operatively. Conclusion: We presented unusual GIT duplications. These duplications are managed on similar lines as classical duplications with good prognosis when dealt early.

  20. Presentation and Surgical Management of Duodenal Duplication in Adults

    Directory of Open Access Journals (Sweden)

    Caroline C. Jadlowiec

    2015-01-01

    Full Text Available Duodenal duplications in adults are exceedingly rare and their diagnosis remains difficult as symptoms are largely nonspecific. Clinical presentations include pancreatitis, biliary obstruction, gastrointestinal bleeding from ectopic gastric mucosa, and malignancy. A case of duodenal duplication in a 59-year-old female is presented, and her treatment course is reviewed with description of combined surgical and endoscopic approach to repair, along with a review of historic and current recommendations for management. Traditionally, gastrointestinal duplications have been treated with surgical resection; however, for duodenal duplications, the anatomic proximity to the biliopancreatic ampulla makes surgical management challenging. Recently, advances in endoscopy have improved the clinical success of cystic intraluminal duodenal duplications. Despite these advances, surgical resection is still recommended for extraluminal tubular duplications although combined techniques may be necessary for long tubular duplications. For duodenal duplications, a combined approach of partial excision combined with mucosal stripping may offer advantage.

  1. Duplication cysts: Diagnosis, management, and the role of endoscopic ultrasound.

    Science.gov (United States)

    Liu, Roy; Adler, Douglas G

    2014-07-01

    Gastrointestinal tract duplication cysts are rare congenital gastrointestinal malformation in young patients and adults. They consist of foregut duplication cysts, small bowel duplication cysts, and large bowel duplication cysts. Endoscopic ultrasound (EUS) has been widely used as a modality for the evaluation and diagnosis of duplication cysts. EUS is the diagnostic tool of choice to investigate duplication cysts since it can distinguish between solid and cystic lesions. The question of whether or not to perform EUS-fine needle aspiration (EUS-FNA) on a lesion suspected of being a duplication cyst is controversial as these lesions can become infected with significant consequences, although EUS-FNA is often required to obtain a definitive diagnosis and to rule out more ominous lesions. This manuscript will review the literature on duplication cysts throughout the body and will also focus on the role of EUS and FNA with regards to these lesions.

  2. Localization of the cellular retinoic acid binding protein (CRABP) gene relative to the acute promyelocytic leukemia-associated breakpoint on human chromosome 15

    NARCIS (Netherlands)

    A.H.M. Geurts van Kessel (Ad); H. de Leeuw (H.); E.J. Dekker (E.); J.M. Rijks (Jolianne); N. Spurr (N.); A.M. Ledbetter (Andrew M.); E. Kootwijk (E.); M.J. Vaessen (Marie-Josée)

    1991-01-01

    textabstractA human genomic fragment comprising the cellular retinoic acid binding protein (CRABP) gene was isolated. By using a panel of somatic cell hybrids, this gene could be assigned to human chromosome 15. Subsequently, a possible involvement of the CRABP gene in translocation (15;17) (q22;q11

  3. Fermentation of liquid coproducts and liquid compound diets: Part 2. Effects on pH, acid-binding capacity, organic acids and ethanol during a 6-day period

    NARCIS (Netherlands)

    Scholten, R.H.J.; Rijnen, M.M.J.A.; Schrama, J.W.; Boer, H.; Peet-Schwering, van der C.M.C.; Hartog, den L.A.; Vesseur, P.C.

    2001-01-01

    The effects of a 6-day storage period on changes in pH, acid-binding capacity, level of organic acids and ethanol of three liquid coproducts [liquid wheat starch (LWS), mashed potato steam peel (PSP) and cheese whey (CW)] and two liquid compound diets [liquid grower diet (LGD) and liquid finisher

  4. Common Variants of the Liver Fatty Acid Binding Protein Gene Influence the Risk of Type 2 Diabetes and Insulin Resistance in Spanish Population

    Science.gov (United States)

    Mansego, Maria Luisa; Martínez, Fernando; Martínez-Larrad, Maria Teresa; Zabena, Carina; Rojo, Gemma; Morcillo, Sonsoles; Soriguer, Federico; Martín-Escudero, Juan Carlos; Serrano-Ríos, Manuel; Redon, Josep; Chaves, Felipe Javier

    2012-01-01

    Summary The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated. Methods 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model. Results One polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population. Conclusions The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians. PMID:22396741

  5. Common variants of the liver fatty acid binding protein gene influence the risk of type 2 diabetes and insulin resistance in Spanish population.

    Directory of Open Access Journals (Sweden)

    Maria Luisa Mansego

    Full Text Available SUMMARY: The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated. METHODS: 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes. DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model. RESULTS: One polymorphism (rs2197076 and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population. CONCLUSIONS: The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians.

  6. Skeletal muscle metabolic characteristics before and after energy restriction in human obesity: fibre type, enzymatic beta-oxidative capacity and fatty acid-binding protein content.

    NARCIS (Netherlands)

    Kempen, K.P.G.; Saris, W.H.M.; Kuipers, H.; Glatz, J.F.; van der Vusse, G.J.

    1998-01-01

    University of Maastricht, Maastricht, The Netherlands. BACKGROUND: Skeletal muscle has the ability to adapt as result of dietary, hormonal or pharmacological interventions affecting energy metabolism. The aim of the present study was to investigate the effects of energy restriction on skeletal muscl

  7. Liver-type fatty acid-binding protein and lipid transport%肝型脂肪酸结合蛋白与脂类转运

    Institute of Scientific and Technical Information of China (English)

    张虎; 朱金玲; 张玉萍; 罗佳滨

    2008-01-01

    肝型脂肪酸结合蛋白(L-FABP)是脂肪酸结合蛋白(FABPs)家族成员之一,与其他成员结构和功能方面有相同之处又有区别.L-FABP主要表达于肝脏组织和小肠,介导脂肪酸及多种疏水基团转运,涉及多种疾病的发病机制.多年来其转运机制备受关注,研究方法从体外到体内,从细胞分子水平到基因沉默动物水平.虽然L-FABP的转运机制研究越来越深入,但是仍需要进一步加强基础研究,揭示其调控脂类转运的机制.本文主要对L-FABP的特性、结构及体内研究现状作一综述.

  8. Liver - fatty acid binding protein and renal disease%肝型脂肪酸结合蛋白(L-FABP)与肾脏疾病

    Institute of Scientific and Technical Information of China (English)

    孔祥雷; 许冬梅

    2008-01-01

    脂肪酸结合蛋白(FABPs)属于脂结合蛋白(lipid-binding proteins)超家族中的一类,根据其组织的特异性分布,可分为肝型(L-FABP)、小肠型(I-FABP)、心肌型(H-FABP)等9种.目前国外研究L-FABP在肾脏疾病中具有重要的意义,国内尚无报道,本文就L-FABP在肾脏疾病中的研究进展做一简要综述.

  9. 心型脂肪酸结合蛋白与急性脑梗死%Heart Fatty Acid Binding Protein and Acute Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    邱晨红; 赵中; 董万利

    2007-01-01

    脂肪酸结合蛋白(FABP)是一种小分子胞内脂肪酸结合蛋白,与细胞生长、基因表达、离子通道的功能有关.细胞缺血损伤时,可发生胞内FABP渗漏.业已证实,脑梗死超早期可出现血清FABP水平增高.文章综述了FABP的生物学功能和在缺血性脑损伤中的表达机制.

  10. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample) proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group) bred as either high- or low-capacity runners (HCR and LCR, respectively) that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897) and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5). Sixteen proteins were significantly (p ion (551.21 m/z) of the doubly-charged peptide SLGVGFATR (454.19 m/z) of residues 23-31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater (p = 0.0095) in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study) finding FABPH abundance was 2.23-fold greater (p = 0.0396) in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  11. THE ASSOCIATION OF Ala54Thr VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN GENE WITH GENERAL AND REGIONAL ADIPOSE TISSUE DEPOTS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective. To ascertain the relationship between the Ala54Thr variation of FABP2 gene and general as well as regional adipose tissue depots.Subjects. 165 subjects, in which 86 were subjects with normal glucose tolerance (NGT) [age 54.45±9.80, male/female 1.05,body mass index (BMI)26.48±4.01] and 79 were subjects with non-insulin-dependent diabetes mellitus (NIDDM)(age 55.86±10.00,male/female 1.08,BMI 26.75±3.30).Design and measurements. An association study of FABP2-Ala54Thr variation detected by PCR/HhaI digestion with general and regional adipose tissue depots determined by BMI and magnetic resonance imaging [abdominal subcutaneous and visceral adipose tissue area (SA and VA) and femoral subcutaneous adipose tissue area (FA)].Results. The geneotype and allele frequencies of FABP2-Ala54Thr variation in Chinese were quite close to the frequencies in American Caucasians and Pima Indians reported in the literature. Significant difference in genotype frequency distribution was observed between FA subgroups comparisons (FA≥75cm2 versus FA<75cm2)in NIDDM subjects (X2=11.460,P=0.003),with significantly increased in Thr54-carrier[Thr54(+)]genotype frequency and Thr54 allele frequency in NIDDM subject with FA<75cm2(odd ratio for genotype was 4.62,X2=10.112,P=0.001;and for allele=2.36,X2=5.379,P=0.020).The FA in NIDDM-Thr54(+)subgroup was significantly lower than that in subjects with NIDDM-Thr54(-)sugroup(61.19±21.51cm2 versus 75.36±31.70cm2,P=0.021). Stepwise regression analysis revealed that FABP2-Thr54 genotype variation was an independent factor contributing to the variation of FA in NIDDM(P=0.003).Conclusion. FABP2 is associated with regional adipose tissue depot.The decreased femoral subcutaneous adipose tissue depot in NIDDM subjects is related to FABP2-Thr54 variant.

  12. Increase in Skin Autofluorescence and Release of Heart-Type Fatty Acid Binding Protein in Plasma Predicts Mortality of Hemodialysis Patients

    NARCIS (Netherlands)

    Arsov, Stefan; Trajceska, Lada; van Oeveren, Wim; Smit, Andries J.; Dzekova, Pavlina; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Graaff, Reindert

    2013-01-01

    Advanced glycation end-products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1-year increase in skin autofluorescence (DAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients.

  13. Structure of a fatty acid-binding protein from Bacillus subtilis determined by sulfur-SAD phasing using in-house chromium radiation

    DEFF Research Database (Denmark)

    Nan, Jie; Zhou, Yanfeng; Yang, Cheng

    2009-01-01

    Sulfur single-wavelength anomalous dispersion (S-SAD) and halide-soaking methods are increasingly being used for ab initio phasing. With the introduction of in-house Cr X-ray sources, these methods benefit from the enhanced anomalous scattering of S and halide atoms, respectively. Here, these met......Sulfur single-wavelength anomalous dispersion (S-SAD) and halide-soaking methods are increasingly being used for ab initio phasing. With the introduction of in-house Cr X-ray sources, these methods benefit from the enhanced anomalous scattering of S and halide atoms, respectively. Here......) were located using standard methods. The anomalous scattering of some of the BsDegV S atoms and Br atoms was weak, thus neither sulfurs nor bromides could be used alone for structure determination using the collected data. When all 17 heavy-atom sites were used for SAD phasing, an easily interpretable...

  14. Value of heart-type fatty acid-binding protein (H-FABP) for emergency department patients with suspected acute coronary syndrome.

    Science.gov (United States)

    Banu, Karakus Yilmaz; Niyazi, Ozüçelik Doğaç; Erdem, Cevik; Dpekçi Afşin, Doğan Hatice; Ozlem, Uzun; Yasemin, Celik; Afsin, Ipekci

    2014-09-01

    The aim of this study is testing the value of H-FABP in the early diagnosis of ACS alone or with routinely used biomarkers such as myoglobin, CK-MB, and cTn I in patients who admitted to emergency department (ED) with complaint of chest pain and suspected acute coronary syndrome. This prospective and cross-sectional study was performed at the Emergency Department of University hospital between June 2009 and September 2010. Patients who were admitted with chest pain within first 48 hours and suspected ACS were enrolled to the study. Blood samples were taken for CK-MB, myoglobin, cTnI and H-FABP The patients were divided into two groups (ACS and non ACS). Statistical analyse were used for relation of biomarkers with diagnosis of ACS. A 66 patients were included to the study. H-FAPB values were positive in 15.2% patients. When H-FABP was added to routinely used biomarkers in the diagnosis of ACS, increasing was observed in all sensitivity, specificity, PPV and NPV values. However, this increase was not statistically significant. H-FABP did not provide any significant change in early diagnosis and exclusion of ACS diagnosis when used either alone or combination with routinely used biomarkers.

  15. The increase of fatty acid-binding protein aP2 in overweight and obese children: interactions with dietary fat and impact on measures of subclinical inflammation

    NARCIS (Netherlands)

    Aeberli, I.; Beljean, N.; Lehmann, R.; I'Allemand, D.; Spinas, G.A.; Zimmermann, M.B.

    2008-01-01

    In adults, circulating aP2 may link obesity, inflammation and the metabolic syndrome, but there are few data in children. Experimental models support that dietary factors, particularly dietary fat, may be major determinants of phenotype. OBJECTIVE: The aim of this study was to investigate, in normal

  16. Case report: Antenatal MRI diagnosis of esophageal duplication cyst.

    Science.gov (United States)

    Rangasami, Rajeswaran; Chandrasekharan, Anupama; Archana, Lal; Santhosh, Joseph

    2009-02-01

    Esophageal duplication cysts are classified as a subgroup of foregut duplication cysts. They are very rare and are predominantly detected in children. Antenatal detection is very rare. We report a case of an esophageal duplication cyst that was accurately identified antenatally by USG and MRI.

  17. Unilateral Pulmonary Agenesis and Gastric Duplication Cyst: A Rare Association

    OpenAIRE

    Amir Halilbasic; Fahrija Skokic; Nesad Hotic; Edin Husaric; Gordana Radoja; Selma Muratovic; Nermina Dedic; Meliha Halilbasic

    2013-01-01

    Lung agenesis and gastric duplication cysts are both rare congenital anomalies. Gastric duplication cysts can present with nausea, vomiting, hematemesis, or vague abdominal pain. Unilateral pulmonary agenesis can present with respiratory distress which usually occurs due to retention of bronchial secretions and inflammations. We report the unique case of right pulmonary agenesis associated with gastric duplication cyst.

  18. Unilateral Pulmonary Agenesis and Gastric Duplication Cyst: A Rare Association

    Directory of Open Access Journals (Sweden)

    Amir Halilbasic

    2013-01-01

    Full Text Available Lung agenesis and gastric duplication cysts are both rare congenital anomalies. Gastric duplication cysts can present with nausea, vomiting, hematemesis, or vague abdominal pain. Unilateral pulmonary agenesis can present with respiratory distress which usually occurs due to retention of bronchial secretions and inflammations. We report the unique case of right pulmonary agenesis associated with gastric duplication cyst.

  19. Effect of Duplicate Genes on Mouse Genetic Robustness: An Update

    Directory of Open Access Journals (Sweden)

    Zhixi Su

    2014-01-01

    Full Text Available In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD. Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.

  20. 48 CFR 1352.231-71 - Duplication of effort.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Duplication of effort. 1352.231-71 Section 1352.231-71 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CLAUSES... Duplication of effort. As prescribed in 48 CFR 1331.205-70, insert the following clause: Duplication of...

  1. Genetics Home Reference: 7q11.23 duplication syndrome

    Science.gov (United States)

    ... Health Conditions 7q11.23 duplication syndrome 7q11.23 duplication syndrome Enable Javascript to view the expand/collapse ... PDF Open All Close All Description 7q11.23 duplication syndrome is a condition that can cause a ...

  2. Rationality of Cross-System Data Duplication: A Case Study

    NARCIS (Netherlands)

    Hordijk, Wiebe; Wieringa, Roel; Pernici, Barbara

    2010-01-01

    Duplication of data across systems in an organization is a problem because it wastes effort and leads to inconsistencies. Researchers have proposed several technical solutions but duplication still occurs in practice. In this paper we report on a case study of how and why duplication occurs in a lar

  3. 38 CFR 10.52 - Duplication of payments prohibited.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Duplication of payments prohibited. 10.52 Section 10.52 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUSTED COMPENSATION Payments § 10.52 Duplication of payments prohibited. Duplication of payments...

  4. 47 CFR 80.467 - Duplication of VHF service.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Duplication of VHF service. 80.467 Section 80... STATIONS IN THE MARITIME SERVICES Public Coast Stations Use of Telephony § 80.467 Duplication of VHF service. No duplication of service areas as determined by subpart P of this part will be permitted...

  5. Genetics Home Reference: 22q11.2 duplication

    Science.gov (United States)

    ... Home Health Conditions 22q11.2 duplication 22q11.2 duplication Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description 22q11.2 duplication is a condition caused by an extra copy ...

  6. 47 CFR 76.1508 - Network non-duplication.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Network non-duplication. 76.1508 Section 76... MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Open Video Systems § 76.1508 Network non-duplication. (a... regarding the exercise of network non-duplication rights immediately available to all appropriate...

  7. 47 CFR 76.122 - Satellite network non-duplication.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Satellite network non-duplication. 76.122... MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Network Non-duplication Protection, Syndicated Exclusivity and Sports Blackout § 76.122 Satellite network non-duplication. (a) Upon receiving notification pursuant...

  8. Recognition of intermediate functionality by acyl carrier protein over a complete cycle of fatty acid biosynthesis.

    Science.gov (United States)

    Płoskoń, Eliza; Arthur, Christopher J; Kanari, Amelia L P; Wattana-amorn, Pakorn; Williams, Christopher; Crosby, John; Simpson, Thomas J; Willis, Christine L; Crump, Matthew P

    2010-07-30

    It remains unclear whether in a bacterial fatty acid synthase (FAS) acyl chain transfer is a programmed or diffusion controlled and random action. Acyl carrier protein (ACP), which delivers all intermediates and interacts with all synthase enzymes, is the key player in this process. High-resolution structures of intermediates covalently bound to an ACP representing each step in fatty acid biosynthesis have been solved by solution NMR. These include hexanoyl-, 3-oxooctanyl-, 3R-hydroxyoctanoyl-, 2-octenoyl-, and octanoyl-ACP from Streptomyces coelicolor FAS. The high-resolution structures reveal that the ACP adopts a unique conformation for each intermediate driven by changes in the internal fatty acid binding pocket. The binding of each intermediate shows conserved structural features that may ensure effective molecular recognition over subsequent rounds of fatty acid biosynthesis. 2010 Elsevier Ltd. All rights reserved.

  9. Duplication Cyst of the Sigmoid Colon

    Directory of Open Access Journals (Sweden)

    Bastian Domajnko

    2009-01-01

    Full Text Available A 21-year-old male with developmental delay presented with abdominal pain of two days' duration. He was afebrile and his abdomen was soft with mild diffuse tenderness. There were no peritoneal signs. Plain x-ray demonstrated a large air-filled structure in the right upper quadrant. Computed tomography of the abdomen revealed a 9×8 cm structure adjacent to the hepatic flexure containing an air-fluid level. It did not contain oral contrast and had no apparent communication with the colon. At operation, the cystic lesion was identified as a duplication cyst of the sigmoid colon that was adherent to the right upper quadrant. The cyst was excised with a segment of the sigmoid colon and a stapled colo-colostomy was performed. Recovery was uneventful. Final pathology was consistent with a duplication cyst of the sigmoid colon. The cyst was attached to the colon but did not communicate with the lumen.

  10. Identifying Tracks Duplicates via Neural Network

    CERN Document Server

    Sunjerga, Antonio; CERN. Geneva. EP Department

    2017-01-01

    The goal of the project is to study feasibility of state of the art machine learning techniques in track reconstruction. Machine learning techniques provide promising ways to speed up the pattern recognition of tracks by adding more intelligence in the algorithms. Implementation of neural network to process of track duplicates identifying will be discussed. Different approaches are shown and results are compared to method that is currently in use.

  11. Pseudomyxoma Peritonei Originating from an Intestinal Duplication

    Directory of Open Access Journals (Sweden)

    Julie Lemahieu

    2013-01-01

    Full Text Available Alimentary tract duplications are rare congenital anomalies. They most often become symptomatic in childhood and rarely undergo malignant transformation. Pseudomyxoma peritonei (PMP is an equally uncommon condition, most frequently originating from a primary appendiceal mucinous neoplasm. We report an extremely unusual case of PMP arising from an intestinal duplication. A 67-year-old woman presented with vague upper abdominal pain, and, unexpectedly, explorative laparoscopy revealed diffuse jelly-like peritoneal implants. The histopathological diagnosis of a low-grade PMP or “disseminated peritoneal adenomucinosis” was made. At that moment, no primary tumor was found. During later surgery, a cystic lesion located in the mesentery of the small bowel could be resected. Histologically, the cyst wall clearly showed the concentric layering of a normal bowel wall. The mucosa, however, displayed a diffuse low-grade villous adenoma. We concluded that this histological picture was most consistent with a small intestinal duplication, containing a low-grade villous adenoma. The adenoma caused a mucocele, which subsequently leaked or ruptured, giving rise to noninvasive mucinous peritoneal implants or low-grade PMP, also known as “disseminated peritoneal adenomucinosis” (DPAM.

  12. Pseudomyxoma peritonei originating from an intestinal duplication.

    Science.gov (United States)

    Lemahieu, Julie; D'Hoore, André; Deloose, Stijn; Sciot, Raf; Moerman, Philippe

    2013-01-01

    Alimentary tract duplications are rare congenital anomalies. They most often become symptomatic in childhood and rarely undergo malignant transformation. Pseudomyxoma peritonei (PMP) is an equally uncommon condition, most frequently originating from a primary appendiceal mucinous neoplasm. We report an extremely unusual case of PMP arising from an intestinal duplication. A 67-year-old woman presented with vague upper abdominal pain, and, unexpectedly, explorative laparoscopy revealed diffuse jelly-like peritoneal implants. The histopathological diagnosis of a low-grade PMP or "disseminated peritoneal adenomucinosis" was made. At that moment, no primary tumor was found. During later surgery, a cystic lesion located in the mesentery of the small bowel could be resected. Histologically, the cyst wall clearly showed the concentric layering of a normal bowel wall. The mucosa, however, displayed a diffuse low-grade villous adenoma. We concluded that this histological picture was most consistent with a small intestinal duplication, containing a low-grade villous adenoma. The adenoma caused a mucocele, which subsequently leaked or ruptured, giving rise to noninvasive mucinous peritoneal implants or low-grade PMP, also known as "disseminated peritoneal adenomucinosis" (DPAM).

  13. Structural basis for the assembly and nucleic acid binding of the TREX-2 transcription-export complex.

    Science.gov (United States)

    Ellisdon, Andrew M; Dimitrova, Lyudmila; Hurt, Ed; Stewart, Murray

    2012-02-19

    The conserved TREX-2 transcription-export complex integrates transcription and processing of many actively transcribed nascent mRNAs with the recruitment of export factors at nuclear pores and also contributes to transcriptional memory and genomic stability. We report the crystal structure of the Sac3-Thp1-Sem1 segment of Saccharomyces cerevisiae TREX-2 that interfaces with the gene expression machinery. Sac3-Thp1-Sem1 forms a previously uncharacterized PCI-domain complex characterized by the juxtaposition of Sac3 and Thp1 winged helix domains, forming a platform that mediates nucleic acid binding. Our structure-guided mutations support the idea that the Thp1-Sac3 interaction is an essential requirement for mRNA binding and for the coupling of transcription and processing to mRNP assembly and export. These results provide insight into how newly synthesized transcripts are efficiently transferred from TREX-2 to the principal mRNA export factor, and they reveal how Sem1 stabilizes PCI domain-containing proteins and promotes complex assembly.

  14. Crystal structure and nucleic acid-binding activity of the CRISPR-associated protein Csx1 of Pyrococcus furiosus.

    Science.gov (United States)

    Kim, Young Kwan; Kim, Yeon-Gil; Oh, Byung-Ha

    2013-02-01

    In many prokaryotic organisms, chromosomal loci known as clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (CAS) genes comprise an acquired immune defense system against invading phages and plasmids. Although many different Cas protein families have been identified, the exact biochemical functions of most of their constituents remain to be determined. In this study, we report the crystal structure of PF1127, a Cas protein of Pyrococcus furiosus DSM 3638 that is composed of 480 amino acids and belongs to the Csx1 family. The C-terminal domain of PF1127 has a unique β-hairpin structure that protrudes out of an α-helix and contains several positively charged residues. We demonstrate that PF1127 binds double-stranded DNA and RNA and that this activity requires an intact β-hairpin and involve the homodimerization of the protein. In contrast, another Csx1 protein from Sulfolobus solfataricus P2 that is composed of 377 amino acids does not have the β-hairpin structure and exhibits no DNA-binding properties under the same experimental conditions. Notably, the C-terminal domain of these two Csx1 proteins is greatly diversified, in contrast to the conserved N-terminal domain, which appears to play a common role in the homodimerization of the protein. Thus, although P. furiosus Csx1 is identified as a nucleic acid-binding protein, other Csx1 proteins are predicted to exhibit different individual biochemical activities. Copyright © 2012 Wiley Periodicals, Inc.

  15. Techno-functional properties and in vitro bile acid-binding capacities of tamarillo (Solanum betaceum Cav.) hydrocolloids.

    Science.gov (United States)

    Gannasin, Sri Puvanesvari; Adzahan, Noranizan Mohd; Mustafa, Shuhaimi; Muhammad, Kharidah

    2016-04-01

    Hydrocolloids were extracted from seed mucilage and the pulp fractions from red tamarillo (Solanum betaceum Cav.) mesocarp, and characterisation of their techno-functional properties and in vitro bile acid-binding capacities was performed. The seed mucilage hydrocolloids that were extracted, using either 1% citric acid (THC) or water (THW), had a good foaming capacity (32-36%), whereas the pulp hydrocolloids that were extracted, using 72% ethanol (THE) or 20mM HEPES buffer (THH), had no foaming capacity. The pulp hydrocolloid, however, possessed high oil-holding and water-holding capacities in the range of 3.3-3.6 g oil/g dry sample and 25-27 g water/g dry sample, respectively. This enabled the pulp hydrocolloid to entrap more bile acids (35-38% at a hydrocolloid concentration of 2%) in its gelatinous network in comparison to commercial oat fibre and other hydrocolloids studied. The exceptional emulsifying properties (80-96%) of both hydrocolloids suggest their potential applications as food emulsifiers and bile acid binders.

  16. Purification of Two Novel Sugar Acid-binding Lectins from Haplomitrium Mnioides (bryophyte, Plantae) and their Preliminary Characterization.

    Science.gov (United States)

    Masuzaki, Hiroaki; Hosono, Masahiro; Nitta, Kazuo

    2017-01-01

    Two novel sugar acid-binding lectins were purified from Haplomitrium mnioides (Lindb.) Schust. using a procedure consisting of ammonium sulfate precipitation, G-50 gel filtration, hydroxyapatite chromatography, and HW-50 gel filtration. We reported their partial physicochemical properties: molecular weight, affinity for carbohydrates and organic acids, pH stability, and dependence of their hemagglutination activity on metal ions. We also determined their N-terminal amino acid sequences. H. mnioides lectins (HMLs) were monomers (one with a molecular weight of approximately 27 kDa, and the other with a molecular weight of approximately 105 kDa) under both nonreducing and reducing conditions. They were named HML27 and HML105, respectively. Both HMLs had an affinity for N-acetylneuraminic acid, D-glucuronic acid, D-glucaric acid, bovine submaxillary mucin, heparin, and organic acids, such as citrate, 2-oxoglutaric acid, and D-2-hydroxyglutarate. Furthermore, HML27 had an affinity for α-D-galacturonic acid, D-malate, L-malate, and pyruvate, while HML105 had an affinity for D-gluconic acid. HML27 and HML105 are novel plant lectins: they have an affinity for sugar acids and organic acids and specifically recognize the carboxyl group, and there is no homology between their N-terminal amino acid sequences and those of the previously described lectins and agglutinins.

  17. Perforated ileal duplication cyst with haemorrhagic pseudocyst formation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Im Kyung; Kim, Bong Soo; Kim, Heung Chul; Lee, In Sun; Hwang, Woo Chul [Department of Radiology, College of Medicine, Hallym University (Korea); Namkung, Sook [Department of Radiology, College of Medicine, Hallym University (Korea); Department of Radiology, Chuncheon Sacred Heart Hospital, 153 Kyo-dong, Chuncheon, Kangwon-do, 200-704 (Korea)

    2003-07-01

    Duplication cysts of the gastrointestinal tract are rare congenital abnormalities. Ectopic gastric mucosa, which can be found in duplications, may cause peptic ulceration, gastrointestinal bleeding or perforation. We report a 1-year-old boy with a perforated ileal duplication cyst with haemorrhagic pseudocyst formation caused by peptic ulceration of the duplication cyst. It presented a snowman-like appearance consisting of a small, thick-walled, true enteric cyst and a large, thin-walled haemorrhagic pseudocyst on US and CT. It is an unusual manifestation of a duplication cyst, which has not been reported in the English language literature. (orig.)

  18. Molecular trajectories leading to the alternative fates of duplicate genes.

    Directory of Open Access Journals (Sweden)

    Michael Marotta

    Full Text Available Gene duplication generates extra gene copies in which mutations can accumulate without risking the function of pre-existing genes. Such mutations modify duplicates and contribute to evolutionary novelties. However, the vast majority of duplicates appear to be short-lived and experience duplicate silencing within a few million years. Little is known about the molecular mechanisms leading to these alternative fates. Here we delineate differing molecular trajectories of a relatively recent duplication event between humans and chimpanzees by investigating molecular properties of a single duplicate: DNA sequences, gene expression and promoter activities. The inverted duplication of the Glutathione S-transferase Theta 2 (GSTT2 gene had occurred at least 7 million years ago in the common ancestor of African great apes and is preserved in chimpanzees (Pan troglodytes, whereas a deletion polymorphism is prevalent in humans. The alternative fates are associated with expression divergence between these species, and reduced expression in humans is regulated by silencing mutations that have been propagated between duplicates by gene conversion. In contrast, selective constraint preserved duplicate divergence in chimpanzees. The difference in evolutionary processes left a unique DNA footprint in which dying duplicates are significantly more similar to each other (99.4% than preserved ones. Such molecular trajectories could provide insights for the mechanisms underlying duplicate life and death in extant genomes.

  19. Production of Medium Chain Fatty Acids by Yarrowia lipolytica: Combining Molecular Design and TALEN to Engineer the Fatty Acid Synthase.

    Science.gov (United States)

    Rigouin, Coraline; Gueroult, Marc; Croux, Christian; Dubois, Gwendoline; Borsenberger, Vinciane; Barbe, Sophie; Marty, Alain; Daboussi, Fayza; André, Isabelle; Bordes, Florence

    2017-06-21

    Yarrowia lipolytica is a promising organism for the production of lipids of biotechnological interest and particularly for biofuel. In this study, we engineered the key enzyme involved in lipid biosynthesis, the giant multifunctional fatty acid synthase (FAS), to shorten chain length of the synthesized fatty acids. Taking as starting point that the ketoacyl synthase (KS) domain of Yarrowia lipolytica FAS is directly involved in chain length specificity, we used molecular modeling to investigate molecular recognition of palmitic acid (C16 fatty acid) by the KS. This enabled to point out the key role of an isoleucine residue, I1220, from the fatty acid binding site, which could be targeted by mutagenesis. To address this challenge, TALEN (transcription activator-like effector nucleases)-based genome editing technology was applied for the first time to Yarrowia lipolytica and proved to be very efficient for inducing targeted genome modifications. Among the generated FAS mutants, those having a bulky aromatic amino acid residue in place of the native isoleucine at position 1220 led to a significant increase of myristic acid (C14) production compared to parental wild-type KS. Particularly, the best performing mutant, I1220W, accumulates C14 at a level of 11.6% total fatty acids. Overall, this work illustrates how a combination of molecular modeling and genome-editing technology can offer novel opportunities to rationally engineer complex systems for synthetic biology.

  20. Nuclear magnetic resonance structure of the nucleic acid-binding domain of severe acute respiratory syndrome coronavirus nonstructural protein 3.

    Science.gov (United States)

    Serrano, Pedro; Johnson, Margaret A; Chatterjee, Amarnath; Neuman, Benjamin W; Joseph, Jeremiah S; Buchmeier, Michael J; Kuhn, Peter; Wüthrich, Kurt

    2009-12-01

    The nuclear magnetic resonance (NMR) structure of a globular domain of residues 1071 to 1178 within the previously annotated nucleic acid-binding region (NAB) of severe acute respiratory syndrome coronavirus nonstructural protein 3 (nsp3) has been determined, and N- and C-terminally adjoining polypeptide segments of 37 and 25 residues, respectively, have been shown to form flexibly extended linkers to the preceding globular domain and to the following, as yet uncharacterized domain. This extension of the structural coverage of nsp3 was obtained from NMR studies with an nsp3 construct comprising residues 1066 to 1181 [nsp3(1066-1181)] and the constructs nsp3(1066-1203) and nsp3(1035-1181). A search of the protein structure database indicates that the globular domain of the NAB represents a new fold, with a parallel four-strand beta-sheet holding two alpha-helices of three and four turns that are oriented antiparallel to the beta-strands. Two antiparallel two-strand beta-sheets and two 3(10)-helices are anchored against the surface of this barrel-like molecular core. Chemical shift changes upon the addition of single-stranded RNAs (ssRNAs) identified a group of residues that form a positively charged patch on the protein surface as the binding site responsible for the previously reported affinity for nucleic acids. This binding site is similar to the ssRNA-binding site of the sterile alpha motif domain of the Saccharomyces cerevisiae Vts1p protein, although the two proteins do not share a common globular fold.

  1. Mechanistic studies for the role of cellular nucleic-acid-binding protein (CNBP) in regulation of c-myc transcription.

    Science.gov (United States)

    Chen, Siqi; Su, Lijuan; Qiu, Jun; Xiao, Nannan; Lin, Jing; Tan, Jia-Heng; Ou, Tian-Miao; Gu, Lian-Quan; Huang, Zhi-Shu; Li, Ding

    2013-10-01

    Guanine-rich sequence of c-myc nuclease hypersensitive element (NHE) III1 is known to fold in G-quadruplex and subsequently serves as a transcriptional silencer. Cellular nucleic-acid-binding protein (CNBP), a highly conserved zinc-finger protein with multiple biological functions, could bind to c-myc NHE III1 region, specifically to the single strand G-rich sequence. In the present study, a variety of methods, including cloning, expression and purification of protein, EMSA, CD, FRET, Ch-IP, RNA interference, luciferase reporter assay, SPR, co-immunoprecipitation, and co-transfection, were applied to investigate the mechanism for the role of CNBP in regulating c-myc transcription. We found that human CNBP specifically bound to the G-rich sequence of c-myc NHE III1 region both in vitro and in cellulo, and subsequently promoted the formation of G-quadruplex. CNBP could induce a transient decrease followed by an increase in c-myc transcription in vivo. The interaction of CNBP with NM23-H2 was responsible for the increase of c-myc transcription. Based on above experimental results, a new mechanism, involving G-quadruplex related CNBP/NM23-H2 interaction, for the regulation of c-myc transcription was proposed. These findings indicated that the regulation of c-myc transcription through NHE III1 region might be governed by mechanisms involving complex protein-protein interactions, and suggested a new possibility of CNBP as a potential anti-cancer target based on CNBP's biological function in c-myc transcription. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Bile acid binding resin prevents fat accumulation through intestinal microbiota in high-fat diet-induced obesity in mice.

    Science.gov (United States)

    Kusumoto, Yukie; Irie, Junichiro; Iwabu, Kaho; Tagawa, Hirotsune; Itoh, Arata; Kato, Mari; Kobayashi, Nana; Tanaka, Kumiko; Kikuchi, Rieko; Fujita, Masataka; Nakajima, Yuya; Morimoto, Kohkichi; Sugizaki, Taichi; Yamada, Satoru; Kawai, Toshihide; Watanabe, Mitsuhiro; Oike, Yuichi; Itoh, Hiroshi

    2017-06-01

    Bile acid binding resin (BAR) absorbs intestinal bile acids, and improves obesity and metabolic disorders, but the precise mechanism remains to be clarified. Recent findings reveal that obesity is associated with skewed intestinal microbiota. Thus, we investigated the effect of BAR on intestinal microbiota and the role of microbiota in the prevention of obesity in high-fat diet-induced obesity in mice. Male Balb/c mice were fed a low-fat diet (LFD), high-fat diet (HFD), or HFD with BAR (HFD+BAR), and then metabolic parameters, caecal microbiota, and metabolites were investigated. The same interventions were conducted in germ-free and antibiotic-treated mice. The frequency of Clostridium leptum subgroup was higher in both HFD-fed and HFD+BAR-fed mice than in LFD-fed mice. The frequency of Bacteroides-Prevotella group was lower in HFD-fed mice than in LFD-fed mice, but the frequency was higher in HFD+BAR-fed mice than in HFD-fed mice. Caecal propionate was lower in HFD-fed mice than in LFD-fed mice, and higher in HFD+BAR-fed mice than in HFD-fed mice. HFD+BAR-fed mice showed lower adiposity than HFD-fed mice, and the reduction was not observed in germ-free or antibiotic-treated mice. Colonized germ-free mice showed a reduction in adiposity by BAR administration. Energy expenditure was lower in HFD-fed mice and higher in HFD+BAR-fed mice, but the increments induced by administration of BAR were not observed in antibiotic-treated mice. Modulation of intestinal microbiota by BAR could be a novel therapeutic approach for obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Siglec-15, a member of the sialic acid-binding lectin, is a novel regulator for osteoclast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Hiruma, Yoshiharu, E-mail: hiruma.yoshiharu.hy@daiichisankyo.co.jp [Biological Research Laboratories, Daiichi Sankyo Co. Ltd., Tokyo 134-8630 (Japan); Hirai, Takehiro [Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo Co. Ltd., Tokyo 134-8630 (Japan); Tsuda, Eisuke [Biological Research Laboratories, Daiichi Sankyo Co. Ltd., Tokyo 134-8630 (Japan)

    2011-06-10

    Highlights: {yields} Siglec-15 was identified as a gene overexpressed in giant cell tumor. {yields} Siglec-15 mRNA expression increased in association with osteoclast differentiation. {yields} Polyclonal antibody to Siglec-15 inhibited osteoclast differentiation in vitro. -- Abstract: Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells derived from monocyte/macrophage-lineage precursors and are critically responsible for bone resorption. In giant cell tumor of bone (GCT), numerous TRAP-positive multinucleated giant cells emerge and severe osteolytic bone destruction occurs, implying that the emerged giant cells are biologically similar to osteoclasts. To identify novel genes involved in osteoclastogenesis, we searched genes whose expression pattern was significantly different in GCT from normal and other bone tumor tissues. By screening a human gene expression database, we identified sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) as one of the genes markedly overexpressed in GCT. The mRNA expression level of Siglec-15 increased in association with osteoclast differentiation in cultures of mouse primary unfractionated bone marrow cells (UBMC), RAW264.7 cells of the mouse macrophage cell line and human osteoclast precursors (OCP). Treatment with polyclonal antibody to mouse Siglec-15 markedly inhibited osteoclast differentiation in primary mouse bone marrow monocyte/macrophage (BMM) cells stimulated with receptor activator of nuclear factor {kappa}B ligand (RANKL) or tumor necrosis factor (TNF)-{alpha}. The antibody also inhibited osteoclast differentiation in cultures of mouse UBMC and RAW264.7 cells stimulated with active vitamin D{sub 3} and RANKL, respectively. Finally, treatment with polyclonal antibody to human Siglec-15 inhibited RANKL-induced TRAP-positive multinuclear cell formation in a human OCP culture. These results suggest that Siglec-15 plays an important role in osteoclast differentiation.

  4. SANCTIONING DUPLICATION IN ADMINISTRATIVE AND PENAL AREAS

    Directory of Open Access Journals (Sweden)

    José Manuel Cabrera Delgado

    2014-12-01

    Full Text Available This article provides a first approach from the point of view of jurisprudence, to the recurring problem of concurrency sanctions in cases where further intervention of the courts has become necessary for administrative action. In this regard, the main judgments of both the Constitutional Court and the Supreme Court is, that have shaped the decisions that must be applied from the administrative level, in particular by educational inspectors, when it is foreseeable that it can produce a duplication of disciplinary procedures in the two areas, penal and administrative.

  5. Gene duplication as a major force in evolution

    Indian Academy of Sciences (India)

    Santoshkumar Magadum; Urbi Banerjee; Priyadharshini Murugan; Doddabhimappa Gangapur; Rajasekar Ravikesavan

    2013-04-01

    Gene duplication is an important mechanism for acquiring new genes and creating genetic novelty in organisms. Many new gene functions have evolved through gene duplication and it has contributed tremendously to the evolution of developmental programmes in various organisms. Gene duplication can result from unequal crossing over, retroposition or chromosomal (or genome) duplication. Understanding the mechanisms that generate duplicate gene copies and the subsequent dynamics among gene duplicates is vital because these investigations shed light on localized and genomewide aspects of evolutionary forces shaping intra-specific and inter-specific genome contents, evolutionary relationships, and interactions. Based on whole-genome analysis of Arabidopsis thaliana, there is compelling evidence that angiosperms underwent two whole-genome duplication events early during their evolutionary history. Recent studies have shown that these events were crucial for creation of many important developmental and regulatory genes found in extant angiosperm genomes. Recent studies also provide strong indications that even yeast (Saccharomyces cerevisiae), with its compact genome, is in fact an ancient tetraploid. Gene duplication can provide new genetic material for mutation, drift and selection to act upon, the result of which is specialized or new gene functions. Without gene duplication the plasticity of a genome or species in adapting to changing environments would be severely limited. Whether a duplicate is retained depends upon its function, its mode of duplication, (i.e. whether it was duplicated during a whole-genome duplication event), the species in which it occurs, and its expression rate. The exaptation of preexisting secondary functions is an important feature in gene evolution, just as it is in morphological evolution.

  6. Analysis of recent segmental duplications in the bovine genome

    Directory of Open Access Journals (Sweden)

    Li Congjun

    2009-12-01

    Full Text Available Abstract Background Duplicated sequences are an important source of gene innovation and structural variation within mammalian genomes. We performed the first systematic and genome-wide analysis of segmental duplications in the modern domesticated cattle (Bos taurus. Using two distinct computational analyses, we estimated that 3.1% (94.4 Mb of the bovine genome consists of recently duplicated sequences (≥ 1 kb in length, ≥ 90% sequence identity. Similar to other mammalian draft assemblies, almost half (47% of 94.4 Mb of these sequences have not been assigned to cattle chromosomes. Results In this study, we provide the first experimental validation large duplications and briefly compared their distribution on two independent bovine genome assemblies using fluorescent in situ hybridization (FISH. Our analyses suggest that the (75-90% of segmental duplications are organized into local tandem duplication clusters. Along with rodents and carnivores, these results now confidently establish tandem duplications as the most likely mammalian archetypical organization, in contrast to humans and great ape species which show a preponderance of interspersed duplications. A cross-species survey of duplicated genes and gene families indicated that duplication, positive selection and gene conversion have shaped primates, rodents, carnivores and ruminants to different degrees for their speciation and adaptation. We identified that bovine segmental duplications corresponding to genes are significantly enriched for specific biological functions such as immunity, digestion, lactation and reproduction. Conclusion Our results suggest that in most mammalian lineages segmental duplications are organized in a tandem configuration. Segmental duplications remain problematic for genome and assembly and we highlight genic regions that require higher quality sequence characterization. This study provides insights into mammalian genome evolution and generates a valuable

  7. RBscore&NBench: a high-level web server for nucleic acid binding residues prediction with a large-scale benchmarking database.

    Science.gov (United States)

    Miao, Zhichao; Westhof, Eric

    2016-07-08

    RBscore&NBench combines a web server, RBscore and a database, NBench. RBscore predicts RNA-/DNA-binding residues in proteins and visualizes the prediction scores and features on protein structures. The scoring scheme of RBscore directly links feature values to nucleic acid binding probabilities and illustrates the nucleic acid binding energy funnel on the protein surface. To avoid dataset, binding site definition and assessment metric biases, we compared RBscore with 18 web servers and 3 stand-alone programs on 41 datasets, which demonstrated the high and stable accuracy of RBscore. A comprehensive comparison led us to develop a benchmark database named NBench. The web server is available on: http://ahsoka.u-strasbg.fr/rbscorenbench/.

  8. Inhibitors of Fatty Acid Synthesis Induce PPAR α -Regulated Fatty Acid β -Oxidative Genes: Synergistic Roles of L-FABP and Glucose.

    Science.gov (United States)

    Huang, Huan; McIntosh, Avery L; Martin, Gregory G; Petrescu, Anca D; Landrock, Kerstin K; Landrock, Danilo; Kier, Ann B; Schroeder, Friedhelm

    2013-01-01

    While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase inhibitor) prevent lipid accumulation by inhibiting fatty acid synthesis, the mechanism of action is not simply accounted for by inhibition of the enzymes alone. Liver fatty acid binding protein (L-FABP), a mediator of long chain fatty acid signaling to peroxisome proliferator-activated receptor- α (PPAR α ) in the nucleus, was found to bind TOFA and its activated CoA thioester, TOFyl-CoA, with high affinity while binding C75 and C75-CoA with lower affinity. Binding of TOFA and C75-CoA significantly altered L-FABP secondary structure. High (20 mM) but not physiological (6 mM) glucose conferred on both TOFA and C75 the ability to induce PPAR α transcription of the fatty acid β -oxidative enzymes CPT1A, CPT2, and ACOX1 in cultured primary hepatocytes from wild-type (WT) mice. However, L-FABP gene ablation abolished the effects of TOFA and C75 in the context of high glucose. These effects were not associated with an increased cellular level of unesterified fatty acids but rather by increased intracellular glucose. These findings suggested that L-FABP may function as an intracellular fatty acid synthesis inhibitor binding protein facilitating TOFA and C75-mediated induction of PPAR α in the context of high glucose at levels similar to those in uncontrolled diabetes.

  9. Development of a Novel Nonradiometric Assay for Nucleic Acid Binding to TDP-43 Suitable for High-Throughput Screening Using AlphaScreen® Technology

    OpenAIRE

    Cassel, Joel A.; Blass, Benjamin E.; Reitz, Allen B.; Pawlyk, Aaron C.

    2010-01-01

    TAR DNA binding protein 43 (TDP-43) is a nucleic acid binding protein that is associated with the pathology of cystic fibrosis and neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar dementia. We have developed a robust, quantitative, nonradiometric high-throughput assay measuring oligonucleotide binding to TDP-43 using AlphaScreen® technology. Biotinylated single-stranded TAR DNA (bt-TAR-32) and 6 TG repeats (bt-TG6) bound with high affinity to TDP-43, w...

  10. The Duplicate-Replacement System: An Alternative Method of Handling Book Duplicates.

    Science.gov (United States)

    Clement, Russell T.

    This report studied the alternative method of using book duplicates as replacement copies for worn or missing stack items. The simple operational procedure which is proposed and evaluated could be adapted to virtually any library setting. When tested in Brigham Young University's Lee Library, it was found that such a procedure cost an estimated…

  11. FT Duplication Coordinates Reproductive and Vegetative Growth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Chuan-Yu [Mississippi State University (MSU); Adams, Joshua P. [Mississippi State University (MSU); Kim, Hyejin [Mississippi State University (MSU); No, Kyoungok [Mississippi State University (MSU); Ma, Caiping [Oregon State University, Corvallis; Strauss, Steven [Oregon State University, Corvallis; Drnevich, Jenny [University of Illinois, Urbana-Champaign; Wickett, Norman [Pennsylvania State University; Vandervelde, Lindsay [Mississippi State University (MSU); Ellis, Jeffrey D. [Mississippi State University (MSU); Rice, Brandon [Mississippi State University (MSU); Gunter, Lee E [ORNL; Tuskan, Gerald A [ORNL; Brunner, Amy M. [Virginia Polytechnic Institute and State University (Virginia Tech); Page, Grier P. [RTI International; Carlson, John E. [Pennsylvania State University; DePamphilis, Claude [Pennsylvania State University; Luthe, Dawn S. [Pennsylvania State University; Yuceer, Cetin [Mississippi State University (MSU)

    2011-01-01

    Annual plants grow vegetatively at early developmental stages and then transition to the reproductive stage, followed by senescence in the same year. In contrast, after successive years of vegetative growth at early ages, woody perennial shoot meristems begin repeated transitions between vegetative and reproductive growth at sexual maturity. However, it is unknown how these repeated transitions occur without a developmental conflict between vegetative and reproductive growth. We report that functionally diverged paralogs FLOWERING LOCUS T1 (FT1) and FLOWERING LOCUS T2 (FT2), products of whole-genome duplication and homologs of Arabidopsis thaliana gene FLOWERING LOCUS T (FT), coordinate the repeated cycles of vegetative and reproductive growth in woody perennial poplar (Populus spp.). Our manipulative physiological and genetic experiments coupled with field studies, expression profiling, and network analysis reveal that reproductive onset is determined by FT1 in response to winter temperatures, whereas vegetative growth and inhibition of bud set are promoted by FT2 in response to warm temperatures and long days in the growing season. The basis for functional differentiation between FT1 and FT2 appears to be expression pattern shifts, changes in proteins, and divergence in gene regulatory networks. Thus, temporal separation of reproductive onset and vegetative growth into different seasons via FT1 and FT2 provides seasonality and demonstrates the evolution of a complex perennial adaptive trait after genome duplication.

  12. Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2.

    Science.gov (United States)

    Fukushi, Daisuke; Yamada, Kenichiro; Nomura, Noriko; Naiki, Misako; Kimura, Reiko; Yamada, Yasukazu; Kumagai, Toshiyuki; Yamaguchi, Kumiko; Miyake, Yoshishige; Wakamatsu, Nobuaki

    2014-04-01

    Xq28 duplication syndrome including MECP2 is a neurodevelopmental disorder characterized by axial hypotonia at infancy, severe intellectual disability, developmental delay, mild characteristic facial appearance, epilepsy, regression, and recurrent infections in males. We identified a Japanese family of Xq28 duplications, in which the patients presented with cerebellar ataxia, severe constipation, and small feet, in addition to the common clinical features. The 488-kb duplication spanned from L1CAM to EMD and contained 17 genes, two pseudo genes, and three microRNA-coding genes. FISH and nucleotide sequence analyses demonstrated that the duplication was tandem and in a forward orientation, and the duplication breakpoints were located in AluSc at the EMD side, with a 32-bp deletion, and LTR50 at the L1CAM side, with "tc" and "gc" microhomologies at the duplication breakpoints, respectively. The duplicated segment was completely segregated from the grandmother to the patients. These results suggest that the duplication was generated by fork-stalling and template-switching at the AluSc and LTR50 sites. This is the first report to determine the size and nucleotide sequences of the duplicated segments at Xq28 of three generations of a family and provides the genotype-phenotype correlation of the patients harboring the specific duplicated segment.

  13. Seasonal upregulation of catabolic enzymes and fatty acid transporters in the flight muscle of migrating hoary bats, Lasiurus cinereus.

    Science.gov (United States)

    McGuire, Liam P; Fenton, M Brock; Guglielmo, Christopher G

    2013-06-01

    The high energy density of fat, and limited capacity for carbohydrate storage suggest that migrating bats should fuel endurance flights with fat, as observed in migrating birds. Yet, cursorial mammals are unable to support high intensity exercise with fat stores. We hypothesized that migratory bats and birds have converged on similar physiological mechanisms to fuel endurance flight with fat. We predicted bats would seasonally upregulate fatty acid transport and oxidation pathways when migration demands were high. We studied seasonal variation in mitochondrial oxidative enzyme activities and fatty acid transport protein expression in the flight muscle of hoary bats (Lasiurus cinereus). Carnitine palmitoyl transferase, 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activity increased during migration. There were no changes in expression of fatty acid translocase or plasma membrane fatty acid binding protein. Heart-type fatty acid binding protein expression increased 5-fold in migrating females, but did not vary seasonally in males. An aerial insectivore lifestyle, and the coincidence of migration and pregnancy may explain differences in transporter expression compared to previously studied birds. Overall, our results are consistent with seasonal upregulation of lipid metabolism and aerobic capacity, and confirm that migration poses distinct physiological challenges for bats. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. RECTAL DUPLICATION CYST IN PREVIOUS ANORECTAL MALFORMATION AND DOWN SYNDROME

    Directory of Open Access Journals (Sweden)

    A. Burgio

    2012-12-01

    Full Text Available Gastrointestinal (GI tract duplications are rare congenital malformations. Most of them occur in the ileum and only 1-5%, of all duplication, were in the rectum. Different clinical features including chronic constipation, rectal prolapsed or polips. We report on a 4-years-old girl with Down syndrome and anorectal malformation (ARM who was found to have a rectal duplication cyst.

  15. Cholecystitis of a duplicated gallbladder complicated by a cholecystoenteric fistula

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Brady K. [University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY (United States); Chess, Mitchell A. [University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY (United States); Advanced Imaging, Batavia, NY (United States)

    2009-04-15

    Gallbladder duplications are uncommon anatomic variants that are sometimes mistaken for other entities on imaging. We present a surgically confirmed case of cholecystitis in a ductular-type duplicated gallbladder complicated by the formation of an inflammatory fistula to the adjacent duodenum. Both US and magnetic resonance cholangiopancreatography were performed preoperatively, in addition to intraoperative cholangiography, which confirmed the presence of a duplicated gallbladder. (orig.)

  16. Colonic duplication in an adult mimicking a tumor of pancreas

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Duplications of the alimentary tract are uncommon congenital malformations that can present diagnostic difficulties.We report a rare case of a cystic colonic duplication in a female adult.Preoperative investigations were suggestive of pancreatic tumor.The diagnosis was established based on the histopathological examination of the resected specimen.We concluded that,though uncommon,intestinal duplication should be considered in differential diagnosis of abdominal mass.

  17. Duplicate inferior vena cava filters: more is not always better.

    Science.gov (United States)

    Katyal, Anup; Javed, Muhammad Ali

    2016-01-01

    Duplication of the inferior vena cava (IVC) has been reported in literature. This achieves clinical significance in the setting of lower extremity venous thromboembolism with a contraindication for anticoagulation. We describe a case of lower extremity deep vein thrombosis with duplicate IVC. Anticoagulation was contraindicated in this case leading to successful treatment with double IVC filters. We conducted a PubMed search for all current English language published literature, where filters were placed in the presence of duplicate IVC. We suggest that patients with deep vein thrombosis should have an accurate assessment of venous anatomy before IVC filter placement. Duplication of IVC, although rare, should be considered as this has management implications.

  18. MR Imaging Findings in Xp21.2 Duplication Syndrome

    Science.gov (United States)

    Whitehead, Matthew T; Helman, Guy; Gropman, Andrea L

    2016-01-01

    Xp21.2 duplication syndrome is a rare genetic disorder of undetermined prevalence and clinical relevance. As the use of chromosomal microarray has become first line for the work-up of childhood developmental delay, more gene deletions and duplications have been recognized. To the best of our knowledge, the imaging findings of Xp21.2 duplication syndrome have not been reported. We report a case of a 33 month-old male referred for developmental delay that was found to have an Xp21.2 duplication containing IL1RAPL1 and multiple midline brain malformations.

  19. Special Issue: Gene Conversion in Duplicated Genes

    Directory of Open Access Journals (Sweden)

    Hideki Innan

    2011-06-01

    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  20. Duplicación apendicular Appendicular duplication

    Directory of Open Access Journals (Sweden)

    Fidel Taquechel Barreto

    2011-09-01

    Full Text Available El apéndice cecal es un órgano pródigamente estudiado, debido a la gran frecuencia con que se producen inflamaciones agudas en él, no obstante, son menos conocidas las anomalías congénitas que resultan en una duplicación apendicular, por ser esta una entidad rara. Se presenta un caso de una paciente que se interviene quirúrgicamente por una apendicitis aguda, en la cual se encontró otro apéndice cecal. Se realiza discusión y revisión del tema.Cecal appendix is much studied organ due to the high frequency of its acute inflammations, however, the congenital anomalies are less associated resulting in a appendicular duplication because of it is a rare entity. This is the case of a female patient operated on due to acute appendicitis founding another cecal appendix.

  1. Benchmarking Transcriptome Quantification Methods for Duplicated Genes in Xenopus laevis.

    Science.gov (United States)

    Kwon, Taejoon

    2015-01-01

    Xenopus is an important model organism for the study of genome duplication in vertebrates. With the full genome sequence of diploid Xenopus tropicalis available, and that of allotetraploid X. laevis close to being finished, we will be able to expand our understanding of how duplicated genes have evolved. One of the key features in the study of the functional consequence of gene duplication is how their expression patterns vary across different conditions, and RNA-seq seems to have enough resolution to discriminate the expression of highly similar duplicated genes. However, most of the current RNA-seq analysis methods were not designed to study samples with duplicate genes such as in X. laevis. Here, various computational methods to quantify gene expression in RNA-seq data were evaluated, using 2 independent X. laevis egg RNA-seq datasets and 2 reference databases for duplicated genes. The fact that RNA-seq can measure expression levels of similar duplicated genes was confirmed, but long paired-end reads are more informative than short single-end reads to discriminate duplicated genes. Also, it was found that bowtie, one of the most popular mappers in RNA-seq analysis, reports significantly smaller numbers of unique hits according to a mapping quality score compared to other mappers tested (BWA, GSNAP, STAR). Calculated from unique hits based on a mapping quality score, both expression levels and the expression ratio of duplicated genes can be estimated consistently among biological replicates, demonstrating that this method can successfully discriminate the expression of each copy of a duplicated gene pair. This comprehensive evaluation will be a useful guideline for studying gene expression of organisms with genome duplication using RNA-seq in the future.

  2. Overexpression of Fatty-Acid-β-Oxidation-Related Genes Extends the Lifespan of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Shin-Hae Lee

    2012-01-01

    Full Text Available A better understanding of the aging process is necessary to ensure that the healthcare needs of an aging population are met. With the trend toward increased human life expectancies, identification of candidate genes affecting the regulation of lifespan and its relationship to environmental factors is essential. Through misexpression screening of EP mutant lines, we previously isolated several genes extending lifespan when ubiquitously overexpressed, including the two genes encoding the fatty-acid-binding protein and dodecenoyl-CoA delta-isomerase involved in fatty-acid β-oxidation, which is the main energy resource pathway in eukaryotic cells. In this study, we analyzed flies overexpressing the two main components of fatty-acid β-oxidation, and found that overexpression of fatty-acid-β-oxidation-related genes extended the Drosophila lifespan. Furthermore, we found that the ability of dietary restriction to extend lifespan was reduced by the overexpression of fatty-acid-β-oxidation-related genes. Moreover, the overexpression of fatty-acid-β-oxidation-related genes enhanced stress tolerance to oxidative and starvation stresses and activated the dFOXO signal, indicating translocation to the nucleus and transcriptional activation of the dFOXO target genes. Overall, the results of this study suggest that overexpression of fatty-acid-β-oxidation-related genes extends lifespan in a dietary-restriction-related manner, and that the mechanism of this process may be related to FOXO activation.

  3. Chlorophyll-derived fatty acids regulate expression of lipid metabolizing enzymes in liver - a nutritional opportunity

    Directory of Open Access Journals (Sweden)

    Wolfrum Christian

    2001-01-01

    Full Text Available Nutritional values of fatty acid classes are normally discussed on the basis of their saturated, monounsaturated and polyunsaturated structures with implicit understanding that they are straight-chain. Here we focus on chlorophyll-derived phytanic and pristanic acids that are minor isoprenoid branched-chain lipid constituents in food, but of unknown nutritional value. After describing the enzyme machinery that degrades these nutrient fatty acids in the peroxisome, we show by the criteria of a mouse model and of a human cell culture model that they induce with high potency expression of enzymes responsible for beta-oxidation of straight-chain fatty acids in the peroxisome. We summarize present mechanistic knowledge on fatty acid signaling to the nucleus, which involves protein/protein contacts between peroxisome proliferator activated receptor (PPAR and fatty acid binding protein (FABP. In this signaling event the branched-chain fatty acids are the most effective ones. Finally, on the basis of this nutrient-gene interaction we discuss nutritional opportunities and therapeutic aspects of the chlorophyll-derived fatty acids.

  4. Analysis of Ligand Binding Specificity of Chicken Liver Basic Fatty Acid Binding Protein (Lb-FABP)and Liver Fatty Acid Binding Protein (L-FABP)%鸡肝脏基础型脂肪酸结合蛋白和肝脏脂肪酸结合蛋白配基结合特性分析

    Institute of Scientific and Technical Information of China (English)

    赵玉芳; 冷丽; 王守志; 张慧; 王宇祥; 王启贵; 李辉

    2013-01-01

    为探讨鸡肝脏基础型脂肪酸结合蛋白(Lb-FABP)和肝脏脂肪酸结合蛋白(L-FABP)蛋白的配基结合属性,诱导表达并利用Glutathione Sepharose 4B亲和层析纯化了鸡的GST/Lb-FABP和GST/L-FABP融合蛋白,得到的GST/Lb-FABP和GST/L-FABP融合蛋白大小分别为38 ku和40 ku.将鸡的Lb-FABP和L-FABP分别与1,8-ANS探针结合,结果显示Lb-FABP和L-FABP均表现出对荧光探针的较强结合能力;为进一步测定棕榈酸、花生四烯酸、油酸、胆汁酸和维甲酸这5种配体与Lb-FABP和L-FABP结合的特异性和亲合力,使用这些脂质分子与1,8-ANS探针进行置换分析,结果表明鸡Lb-FABP与维甲酸结合能力最强,而L-FABP与油酸的结合能力最强.本研究结果为深入探究Lb-FABP和L-FABP的生物学功能提供了良好的基础.

  5. A rare case of congenital Y-type urethral duplication

    Directory of Open Access Journals (Sweden)

    Charu Tiwari

    2015-11-01

    Full Text Available Duplication of urethra is a rare congenital anomaly. We report a case of Y-type of urethral duplication with the accessory urethra arising from posterior urethra and opening in the perineum. The orthotopic urethra was normal. The accessory urethral tract was cored, transfixed and divided. At 1 year of follow-up, the patient has no urinary complaints

  6. Gene duplication models for directed networks with limits on growth

    Science.gov (United States)

    Enemark, Jakob; Sneppen, Kim

    2007-11-01

    Background: Duplication of genes is important for evolution of molecular networks. Many authors have therefore considered gene duplication as a driving force in shaping the topology of molecular networks. In particular it has been noted that growth via duplication would act as an implicit means of preferential attachment, and thereby provide the observed broad degree distributions of molecular networks. Results: We extend current models of gene duplication and rewiring by including directions and the fact that molecular networks are not a result of unidirectional growth. We introduce upstream sites and downstream shapes to quantify potential links during duplication and rewiring. We find that this in itself generates the observed scaling of transcription factors for genome sites in prokaryotes. The dynamical model can generate a scale-free degree distribution, p(k)\\propto 1/k^{\\gamma } , with exponent γ = 1 in the non-growing case, and with γ>1 when the network is growing. Conclusions: We find that duplication of genes followed by substantial recombination of upstream regions could generate features of genetic regulatory networks. Our steady state degree distribution is however too broad to be consistent with data, thereby suggesting that selective pruning acts as a main additional constraint on duplicated genes. Our analysis shows that gene duplication can only be a main cause for the observed broad degree distributions if there are also substantial recombinations between upstream regions of genes.

  7. Dynamic Delayed Duplicate Detection for External Memory Model Checking

    DEFF Research Database (Denmark)

    Evangelista, Sami

    2008-01-01

    Duplicate detection is an expensive operation of disk-based model checkers. It consists of comparing some potentially new states, the candidate states, to previous visited states. We propose a new approach to this technique called dynamic delayed duplicate detection. This one exploits some typical...

  8. Penile shaft sinus: A sequalae of circumcision in urethral duplication

    Directory of Open Access Journals (Sweden)

    Lukman O Abdur-Rahman

    2009-01-01

    Full Text Available Urethral duplication (UD is rare congenital anomalies with varied presentation. Careful clinical evaluation of children by specialist would enhance diagnosis, adequate management and reduce occurrence of complication. We present a 12-year-old boy with chronic post circumcision ventral penile sinus that was successfully managed for urethral duplication.

  9. 44 CFR 206.191 - Duplication of benefits.

    Science.gov (United States)

    2010-10-01

    ... individuals and families. (b) Government policy. (1) Federal agencies providing disaster assistance under the... duplication of benefits, according to the general policy guidance of the Federal Emergency Management Agency... disaster relief agencies establish and follow policies and procedures to prevent and remedy duplication...

  10. 42 CFR 457.626 - Prevention of duplicate payments.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Prevention of duplicate payments. 457.626 Section... Payments to States § 457.626 Prevention of duplicate payments. (a) General rule. No payment shall be made... CFR 144.103, which is not part of, or wholly owned by, a governmental entity. Prompt payment...

  11. 40 CFR 25.13 - Coordination and non-duplication.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS UNDER THE RESOURCE CONSERVATION AND RECOVERY ACT, THE SAFE DRINKING WATER ACT, AND THE CLEAN WATER ACT § 25.13 Coordination and non-duplication. The public participation activities and materials that... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Coordination and non-duplication....

  12. 10 CFR 7.21 - Cost of duplication of documents.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Cost of duplication of documents. 7.21 Section 7.21 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.21 Cost of duplication of documents. Copies of the records, reports, transcripts, minutes, appendices, working papers, drafts, studies, agenda, or...

  13. MECP2 duplication: possible cause of severe phenotype in females.

    Science.gov (United States)

    Scott Schwoerer, Jessica; Laffin, Jennifer; Haun, Joanne; Raca, Gordana; Friez, Michael J; Giampietro, Philip F

    2014-04-01

    MECP2 duplication syndrome, originally described in 2005, is an X-linked neurodevelopmental disorder comprising infantile hypotonia, severe to profound intellectual disability, autism or autistic-like features, spasticity, along with a variety of additional features that are not always clinically apparent. The syndrome is due to a duplication (or triplication) of the gene methyl CpG binding protein 2 (MECP2). To date, the disorder has been described almost exclusively in males. Female carriers of the duplication are thought to have no or mild phenotypic features. Recently, a phenotype for females began emerging. We describe a family with ∼290 kb duplication of Xq28 region that includes the MECP2 gene where the proposita and affected family members are female. Twin sisters, presumed identical, presented early with developmental delay, and seizures. Evaluation of the proposita at 25 years of age included microarray comparative genomic hybridization (aCGH) which revealed the MECP2 gene duplication. The same duplication was found in the proposita's sister, who is more severely affected, and the proband's mother who has mild intellectual disability and depression. X-chromosome inactivation studies showed significant skewing in the mother, but was uninformative in the twin sisters. We propose that the MECP2 duplication caused for the phenotype of the proband and her sister. These findings support evidence for varied severity in some females with MECP2 duplications.

  14. 29 CFR 1912.4 - Avoidance of duplication.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Avoidance of duplication. 1912.4 Section 1912.4 Labor... (CONTINUED) ADVISORY COMMITTEES ON STANDARDS Organizational Matters § 1912.4 Avoidance of duplication. No... advisory committee established under section 7(b) of the Act....

  15. Evolution after whole-genome duplication: a network perspective.

    Science.gov (United States)

    Zhu, Yun; Lin, Zhenguo; Nakhleh, Luay

    2013-11-06

    Gene duplication plays an important role in the evolution of genomes and interactomes. Elucidating how evolution after gene duplication interplays at the sequence and network level is of great interest. In this work, we analyze a data set of gene pairs that arose through whole-genome duplication (WGD) in yeast. All these pairs have the same duplication time, making them ideal for evolutionary investigation. We investigated the interplay between evolution after WGD at the sequence and network levels and correlated these two levels of divergence with gene expression and fitness data. We find that molecular interactions involving WGD genes evolve at rates that are three orders of magnitude slower than the rates of evolution of the corresponding sequences. Furthermore, we find that divergence of WGD pairs correlates strongly with gene expression and fitness data. Because of the role of gene duplication in determining redundancy in biological systems and particularly at the network level, we investigated the role of interaction networks in elucidating the evolutionary fate of duplicated genes. We find that gene neighborhoods in interaction networks provide a mechanism for inferring these fates, and we developed an algorithm for achieving this task. Further epistasis analysis of WGD pairs categorized by their inferred evolutionary fates demonstrated the utility of these techniques. Finally, we find that WGD pairs and other pairs of paralogous genes of small-scale duplication origin share similar properties, giving good support for generalizing our results from WGD pairs to evolution after gene duplication in general.

  16. 47 CFR 61.73 - Duplication of rates or regulations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Duplication of rates or regulations. 61.73 Section 61.73 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Duplication of rates or regulations. A carrier concurring in schedules of another carrier must not...

  17. 49 CFR 24.3 - No duplication of payments.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false No duplication of payments. 24.3 Section 24.3 Transportation Office of the Secretary of Transportation UNIFORM RELOCATION ASSISTANCE AND REAL PROPERTY ACQUISITION FOR FEDERAL AND FEDERALLY-ASSISTED PROGRAMS General § 24.3 No duplication of payments. No...

  18. Testing of duplicate rinse aliquots for presence of Salmonella

    Science.gov (United States)

    Testing of chicken carcass rinses for Salmonella prevalence is often performed in duplicate because of the potential importance of the results, but anecdotal reports indicate that duplicate samples often disagree. This might be due to normal variation in microbiological methods or to the testing of...

  19. Two cases of the caudal duplication anomaly including a discordant monozygotic twin

    NARCIS (Netherlands)

    Kroes, HY; Takahashi, M; Zijlstra, RJ; Baert, JALL; Kooi, KA; Hofstra, RMW; van Essen, AJ

    2002-01-01

    We present two unrelated patients with various duplications in the caudal region. One patient presented with a duplication of the distal spine from L4, left double ureter, duplication of the vagina and cervix, and duplication of the distal colon. The second patient was diagnosed with a duplication

  20. Two cases of the caudal duplication anomaly including a discordant monozygotic twin

    NARCIS (Netherlands)

    Kroes, HY; Takahashi, M; Zijlstra, RJ; Baert, JALL; Kooi, KA; Hofstra, RMW; van Essen, AJ

    2002-01-01

    We present two unrelated patients with various duplications in the caudal region. One patient presented with a duplication of the distal spine from L4, left double ureter, duplication of the vagina and cervix, and duplication of the distal colon. The second patient was diagnosed with a duplication o

  1. Detection of tandam duplications and implications for linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matise, T.C.; Weeks, D.E. (Univ. of Pittsburgh, PA (United States)); Chakravarti, A. (Case Western Reserve Univ., Cleveland, OH (United States)); Patel, P.I.; Lupski, J.R. (Baylor College of Medicine, Houston, TX (United States)); Nelis, E.; Timmerman, V.; Van Broeckhoven, C. (Univ. of Antwerp (Belgium))

    1994-06-01

    The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, the authors studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. They demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, they devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. They tested their methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, the method detected 96% of duplicated markers (with a false-positive rate of 5%). On the CMT1A data the method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A. 18 refs., 5 figs., 6 tabs.

  2. Histone modification pattern evolution after yeast gene duplication

    Directory of Open Access Journals (Sweden)

    Zou Yangyun

    2012-07-01

    Full Text Available Abstract Background Gene duplication and subsequent functional divergence especially expression divergence have been widely considered as main sources for evolutionary innovations. Many studies evidenced that genetic regulatory network evolved rapidly shortly after gene duplication, thus leading to accelerated expression divergence and diversification. However, little is known whether epigenetic factors have mediated the evolution of expression regulation since gene duplication. In this study, we conducted detailed analyses on yeast histone modification (HM, the major epigenetics type in this organism, as well as other available functional genomics data to address this issue. Results Duplicate genes, on average, share more common HM-code patterns than random singleton pairs in their promoters and open reading frames (ORF. Though HM-code divergence between duplicates in both promoter and ORF regions increase with their sequence divergence, the HM-code in ORF region evolves slower than that in promoter region, probably owing to the functional constraints imposed on protein sequences. After excluding the confounding effect of sequence divergence (or evolutionary time, we found the evidence supporting the notion that in yeast, the HM-code may co-evolve with cis- and trans-regulatory factors. Moreover, we observed that deletion of some yeast HM-related enzymes increases the expression divergence between duplicate genes, yet the effect is lower than the case of transcription factor (TF deletion or environmental stresses. Conclusions Our analyses demonstrate that after gene duplication, yeast histone modification profile between duplicates diverged with evolutionary time, similar to genetic regulatory elements. Moreover, we found the evidence of the co-evolution between genetic and epigenetic elements since gene duplication, together contributing to the expression divergence between duplicate genes.

  3. X-ray structure of Pur-alpha reveals a Whirly-like fold and an unusual nucleic-acid binding surface.

    Science.gov (United States)

    Graebsch, Almut; Roche, Stéphane; Niessing, Dierk

    2009-11-03

    The PUR protein family is a distinct and highly conserved class that is characterized by its sequence-specific RNA- and DNA-binding. Its best-studied family member, Pur-alpha, acts as a transcriptional regulator, as host factor for viral replication, and as cofactor for mRNP localization in dendrites. Pur-alpha-deficient mice show severe neurologic defects and die after birth. Nucleic-acid binding by Pur-alpha is mediated by its central core region, for which no structural information is available. We determined the x-ray structure of residues 40 to 185 from Drosophila melanogaster Pur-alpha, which constitutes a major part of the core region. We found that this region contains two almost identical structural motifs, termed "PUR repeats," which interact with each other to form a PUR domain. DNA- and RNA-binding studies confirmed that PUR domains are indeed functional nucleic-acid binding domains. Database analysis show that PUR domains share a fold with the Whirly class of nucleic-acid binding proteins. Structural analysis combined with mutational studies suggest that a PUR domain binds nucleic acids through two independent surface regions involving concave beta-sheets. Structure-based sequence alignment revealed that the core region harbors a third PUR repeat at its C terminus. Subsequent characterization by small-angle x-ray scattering (SAXS) and size-exclusion chromatography indicated that PUR repeat III mediates dimerization of Pur-alpha. Surface envelopes calculated from SAXS data show that the Pur-alpha dimer consisting of repeats I to III is arranged in a Z-like shape. This unexpected domain organization of the entire core domain of Pur-alpha has direct implications for ssDNA/ssRNA and dsDNA binding.

  4. Novel Duplicate Address Detection with Hash Function.

    Science.gov (United States)

    Song, GuangJia; Ji, ZhenZhou

    2016-01-01

    Duplicate address detection (DAD) is an important component of the address resolution protocol (ARP) and the neighbor discovery protocol (NDP). DAD determines whether an IP address is in conflict with other nodes. In traditional DAD, the target address to be detected is broadcast through the network, which provides convenience for malicious nodes to attack. A malicious node can send a spoofing reply to prevent the address configuration of a normal node, and thus, a denial-of-service attack is launched. This study proposes a hash method to hide the target address in DAD, which prevents an attack node from launching destination attacks. If the address of a normal node is identical to the detection address, then its hash value should be the same as the "Hash_64" field in the neighboring solicitation message. Consequently, DAD can be successfully completed. This process is called DAD-h. Simulation results indicate that address configuration using DAD-h has a considerably higher success rate when under attack compared with traditional DAD. Comparative analysis shows that DAD-h does not require third-party devices and considerable computing resources; it also provides a lightweight security resolution.

  5. Omega-3 Fatty Acids

    Science.gov (United States)

    Omega-3 fatty acids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the ... the blood in people with very high triglycerides. Omega-3 fatty acids are in a class of ...

  6. Omega-6 Fatty Acids

    Science.gov (United States)

    Omega-6 fatty acids are types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of omega-6 fatty acids are found in black currant ...

  7. Duplicated laboratory tests: evaluation of a computerized alert intervention abstract.

    Science.gov (United States)

    Bridges, Sharon A; Papa, Linda; Norris, Anne E; Chase, Susan K

    2014-01-01

    Redundant testing contributes to reductions in healthcare system efficiency. The purpose of this study was to: (1) determine if the use of a computerized alert would reduce the number and cost of duplicated Acute Hepatitis Profile (AHP) laboratory tests and (2) assess what patient, test, and system factors were associated with duplication. This study used a quasi-experimental pre- and post-test design to determine the proportion of duplication of the AHP test before and after implementation of a computerized alert intervention. The AHP test was duplicated if the test was requested again within 15 days of the initial test being performed and the result present in the medical record. The intervention consisted of a computerized alert (pop-up window) that indicated to the clinician that the test had recently been ordered. A total of 674 AHP tests were performed in the pre-intervention period and 692 in the postintervention group. In the pre-intervention period, 53 (7.9%) were duplicated and in postintervention, 18 (2.6%) were duplicated (ptests (p≤.001). Implementation of computerized alerts may be useful in reducing duplicate laboratory tests and improving healthcare system efficiency.

  8. Immunoglobulin and fatty acids

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...

  9. Foregut duplication cysts of the stomach with respiratory epithelium

    Institute of Scientific and Technical Information of China (English)

    Theodosios Theodosopoulos; Athanasios Marinis; Konstantinos Karapanos; Georgios Vassilikostas; Nikolaos Dafnios; Lazaros Samanides; Eleni Carvounis

    2007-01-01

    Gastrointestinal duplication is a congenital rare disease entity. Gastric duplication cysts seem to appear even more rarely. Herein, two duplications cysts of the stomach in a 46 year-old female patient are presented.Abdominal computed tomography demonstrated a cystic lesion attached to the posterior aspect of the gastric fundus, while upper gastrointestinal endoscopy was negative. An exploratory laparotomy revealed a non-communicating cyst and a smaller similar cyst embedded in the gastrosplenic ligament. Excision of both cysts along with the spleen was performed and pathology reported two smooth muscle coated cysts with a pseudostratified ciliated epithelial lining (respiratory type).

  10. Methods, apparatus and system for selective duplication of subtasks

    Energy Technology Data Exchange (ETDEWEB)

    Andrade Costa, Carlos H.; Cher, Chen-Yong; Park, Yoonho; Rosenburg, Bryan S.; Ryu, Kyung D.

    2016-03-29

    A method for selective duplication of subtasks in a high-performance computing system includes: monitoring a health status of one or more nodes in a high-performance computing system, where one or more subtasks of a parallel task execute on the one or more nodes; identifying one or more nodes as having a likelihood of failure which exceeds a first prescribed threshold; selectively duplicating the one or more subtasks that execute on the one or more nodes having a likelihood of failure which exceeds the first prescribed threshold; and notifying a messaging library that one or more subtasks were duplicated.

  11. Benchmarks for measurement of duplicate detection methods in nucleotide databases.

    Science.gov (United States)

    Chen, Qingyu; Zobel, Justin; Verspoor, Karin

    2017-01-08

    Duplication of information in databases is a major data quality challenge. The presence of duplicates, implying either redundancy or inconsistency, can have a range of impacts on the quality of analyses that use the data. To provide a sound basis for research on this issue in databases of nucleotide sequences, we have developed new, large-scale validated collections of duplicates, which can be used to test the effectiveness of duplicate detection methods. Previous collections were either designed primarily to test efficiency, or contained only a limited number of duplicates of limited kinds. To date, duplicate detection methods have been evaluated on separate, inconsistent benchmarks, leading to results that cannot be compared and, due to limitations of the benchmarks, of questionable generality. In this study, we present three nucleotide sequence database benchmarks, based on information drawn from a range of resources, including information derived from mapping to two data sections within the UniProt Knowledgebase (UniProtKB), UniProtKB/Swiss-Prot and UniProtKB/TrEMBL. Each benchmark has distinct characteristics. We quantify these characteristics and argue for their complementary value in evaluation. The benchmarks collectively contain a vast number of validated biological duplicates; the largest has nearly half a billion duplicate pairs (although this is probably only a tiny fraction of the total that is present). They are also the first benchmarks targeting the primary nucleotide databases. The records include the 21 most heavily studied organisms in molecular biology research. Our quantitative analysis shows that duplicates in the different benchmarks, and in different organisms, have different characteristics. It is thus unreliable to evaluate duplicate detection methods against any single benchmark. For example, the benchmark derived from UniProtKB/Swiss-Prot mappings identifies more diverse types of duplicates, showing the importance of expert curation, but

  12. Finding all sorting tandem duplication random loss operations

    DEFF Research Database (Denmark)

    Bernt, Matthias; Chen, Kuan Yu; Chen, Ming Chiang

    2011-01-01

    A tandem duplication random loss (TDRL) operation duplicates a contiguous segment of genes, followed by the random loss of one copy of each of the duplicated genes. Although the importance of this operation is founded by several recent biological studies, it has been investigated only rarely from...... a theoretical point of view. Of particular interest are sorting TDRLs which are TDRLs that, when applied to a permutation representing a genome, reduce the distance towards another given permutation. The identification of sorting genome rearrangement operations in general is a key ingredient of many algorithms...

  13. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Anna Garbelli

    Full Text Available DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication.

  14. A motif unique to the human DEAD-box protein DDX3 is important for nucleic acid binding, ATP hydrolysis, RNA/DNA unwinding and HIV-1 replication.

    Science.gov (United States)

    Garbelli, Anna; Beermann, Sandra; Di Cicco, Giulia; Dietrich, Ursula; Maga, Giovanni

    2011-05-12

    DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication.

  15. Surface plasmon resonance-enhanced fluorescence implementation of a single-step competition assay: demonstration of fatty acid measurement using an anti-fatty acid monoclonal antibody and a Cy5-labeled fatty acid.

    Science.gov (United States)

    Vareiro, Margarida M L M; Tranchant, Isabelle; Maplin, Sandra; Zak, Kris; Gani, M M; Slevin, Christopher J; Hailes, Helen C; Tabor, Alethea B; Cameron, Petra J; Jenkins, A Toby A; Williams, David E

    2008-06-15

    The development of a single-step, separation-free method for measurement of low concentrations of fatty acid using a surface plasmon resonance-enhanced fluorescence competition assay with a surface-bound antibody is described. The assay behavior was unexpectedly complex. A nonlinear coverage-dependent self-quenching of emission from surface-bound fluorescent label was deduced from the response kinetics and attributed to a surface plasmon-mediated energy transfer between adsorbed fluorophores, modified by the effects of plasmon interference. Principles of assay design to avoid complications from such effects are discussed. An anti-fatty acid mouse monoclonal antibody reacting to the alkyl chain was prepared and supported on a gold chip at a spacing appropriate for surface-plasmon field-enhanced fluorescence spectroscopy (SPEFS), by applying successively a self-assembled biotinylated monolayer, then streptavidin, then biotinylated protein A, and then the antibody, which was crosslinked to the protein A. Synthesis of a fluorescently (Cy5) tagged C-11 fatty acid is reported. SPEFS was used to follow the kinetics of the binding of the labeled fatty acid to the antibody, and to implement a competition assay with free fatty acid (undecanoic acid), sensitive at the 1 microM scale, a sensitivity limit caused by the low affinity of antibodies for free fatty acids, rather than the SPEFS technique itself. Free fatty acid concentration in human serum is in the range 0.1-1mM, suggesting that this measurement approach could be applied in a clinical diagnostic context. Finally, a predictive, theoretical model of fatty acid binding was developed that accounted for the observed "overshoot" kinetics.

  16. Attack Vulnerability of Network with Duplication-Divergence Mechanism

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We study the attack vulnerability of network with duplication-divergence mechanism. Numerical results have shown that the duplication-divergence network with larger retention probability a is more robust against target attack relatively. Furthermore, duplication-divergence network is broken down more quickly than its counterpart BA network under target attack. Such result is consistent with the fact of WWW and Internet networks under target attack. So duplication-divergence model is a more realistic one for us to investigate the characteristics of the world wide web in future. We also observe that the exponent 7 of degree distribution and average degree are important parameters of networks, reflecting the performance of networks under target attack. Our results are helpful to the research on the security of network.

  17. Noncommunicating isolated enteric duplication cyst in the abdomen ...

    African Journals Online (AJOL)

    review of the literature. Hyun-Young Kim, Soo-Hong ... Keywords: abdomen, children, duplication, isolated, noncommunicating. Department of ... He also had a fever with a body ... unknown origin is observed in the abdominal cavity in children.

  18. Complete duplication of bladder and urethra: a case report.

    Science.gov (United States)

    Esham, W; Holt, H A

    1980-05-01

    A case of complete duplication of the bladder and urethra in a girl is reported, demonstrating outlet obstruction in the bladder on the left side. Associated anomalies and pertinent literature are reviewed.

  19. Profiling of gene duplication patterns of sequenced teleost genomes: evidence for rapid lineage-specific genome expansion mediated by recent tandem duplications

    Directory of Open Access Journals (Sweden)

    Lu Jianguo

    2012-06-01

    Full Text Available Abstract Background Gene duplication has had a major impact on genome evolution. Localized (or tandem duplication resulting from unequal crossing over and whole genome duplication are believed to be the two dominant mechanisms contributing to vertebrate genome evolution. While much scrutiny has been directed toward discerning patterns indicative of whole-genome duplication events in teleost species, less attention has been paid to the continuous nature of gene duplications and their impact on the size, gene content, functional diversity, and overall architecture of teleost genomes. Results Here, using a Markov clustering algorithm directed approach we catalogue and analyze patterns of gene duplication in the four model teleost species with chromosomal coordinates: zebrafish, medaka, stickleback, and Tetraodon. Our analyses based on set size, duplication type, synonymous substitution rate (Ks, and gene ontology emphasize shared and lineage-specific patterns of genome evolution via gene duplication. Most strikingly, our analyses highlight the extraordinary duplication and retention rate of recent duplicates in zebrafish and their likely role in the structural and functional expansion of the zebrafish genome. We find that the zebrafish genome is remarkable in its large number of duplicated genes, small duplicate set size, biased Ks distribution toward minimal mutational divergence, and proportion of tandem and intra-chromosomal duplicates when compared with the other teleost model genomes. The observed gene duplication patterns have played significant roles in shaping the architecture of teleost genomes and appear to have contributed to the recent functional diversification and divergence of important physiological processes in zebrafish. Conclusions We have analyzed gene duplication patterns and duplication types among the available teleost genomes and found that a large number of genes were tandemly and intrachromosomally duplicated, suggesting

  20. Effects of different fatty acid chain lengths on fatty acid oxidation-related protein expression levels in rat skeletal muscles.

    Science.gov (United States)

    Ishizawa, Rie; Masuda, Kazumi; Sakata, Susumu; Nakatani, Akira

    2015-01-01

    Skeletal muscles can adapt to dietary interventions that affect energy metabolism. Dietary intake of medium-chain fatty acids (MCFAs) enhances mitochondrial oxidation of fatty acids (FAO) in type IIa skeletal muscle fibers. However, the effect of MCFAs diet on mitochondrial or cytoplasmic FAO-related protein expression levels in different types of muscle fibers remains unclear. This study aims to examine the effects of a high-fat diet, containing MCFAs, on mitochondrial enzyme activities and heart-type fatty acid-binding protein (H-FABP) levels in different types of skeletal muscle fibers. Five-week-old male Wistar rats were assigned to one of the following three dietary conditions: standard chow (SC, 12% of calories from fat), high-fat MCFA, or high-fat long-chain fatty acids (LCFAs) diet (60% of calories from fat for both). The animals were provided food and water ad libitum for 4 weeks, following which citrate synthase (CS) activity and H-FABP concentration were analyzed. The epididymal fat pads (EFP) were significantly smaller in the MCFA group than in the LCFA group (p increase in CS activity compared with that observed in SC-fed controls in all types of skeletal muscle fibers (triceps, surface portion of gastrocnemius (gasS), deep portion of gastrocnemius (gasD), and soleus; p increase the expression of the mitochondrial enzyme CS, but not that of H-FABP, in both fast- and slow-twitch muscle fibers, suggesting that H-FABP expression is dependent on the chain length of fatty acids in the cytoplasm of skeletal muscles cells.

  1. Duplicate Appendix With Acute Ruptured Appendicitis: A Case Report

    OpenAIRE

    Nazir, Sharique; Bulanov, Alex; Ilyas, Mohammed Iyoob Mohammed; Jabbour, Ibrahim I.; Griffith, Larry

    2015-01-01

    Duplication of the appendix is a rare congenital anomaly that, in adults, is most often found incidentally during surgery for other reasons. Appendicitis in the duplicated appendix is very rare and has been reported less than 10 times in the medical literature. We describe a 33-year-old woman with worsening periumbilical pain, nausea, vomiting, and fever. Physical examination showed localized peritonitis in the right lower quadrant. She had an elevated white blood cell count with neutrophilia...

  2. Gene duplication in the genome of parasitic Giardia lamblia

    Directory of Open Access Journals (Sweden)

    Flores Roberto

    2010-02-01

    Full Text Available Abstract Background Giardia are a group of widespread intestinal protozoan parasites in a number of vertebrates. Much evidence from G. lamblia indicated they might be the most primitive extant eukaryotes. When and how such a group of the earliest branching unicellular eukaryotes developed the ability to successfully parasitize the latest branching higher eukaryotes (vertebrates is an intriguing question. Gene duplication has long been thought to be the most common mechanism in the production of primary resources for the origin of evolutionary novelties. In order to parse the evolutionary trajectory of Giardia parasitic lifestyle, here we carried out a genome-wide analysis about gene duplication patterns in G. lamblia. Results Although genomic comparison showed that in G. lamblia the contents of many fundamental biologic pathways are simplified and the whole genome is very compact, in our study 40% of its genes were identified as duplicated genes. Evolutionary distance analyses of these duplicated genes indicated two rounds of large scale duplication events had occurred in G. lamblia genome. Functional annotation of them further showed that the majority of recent duplicated genes are VSPs (Variant-specific Surface Proteins, which are essential for the successful parasitic life of Giardia in hosts. Based on evolutionary comparison with their hosts, it was found that the rapid expansion of VSPs in G. lamblia is consistent with the evolutionary radiation of placental mammals. Conclusions Based on the genome-wide analysis of duplicated genes in G. lamblia, we found that gene duplication was essential for the origin and evolution of Giardia parasitic lifestyle. The recent expansion of VSPs uniquely occurring in G. lamblia is consistent with the increment of its hosts. Therefore we proposed a hypothesis that the increment of Giradia hosts might be the driving force for the rapid expansion of VSPs.

  3. Modeling protein network evolution under genome duplication and domain shuffling

    Directory of Open Access Journals (Sweden)

    Isambert Hervé

    2007-11-01

    Full Text Available Abstract Background Successive whole genome duplications have recently been firmly established in all major eukaryote kingdoms. Such exponential evolutionary processes must have largely contributed to shape the topology of protein-protein interaction (PPI networks by outweighing, in particular, all time-linear network growths modeled so far. Results We propose and solve a mathematical model of PPI network evolution under successive genome duplications. This demonstrates, from first principles, that evolutionary conservation and scale-free topology are intrinsically linked properties of PPI networks and emerge from i prevailing exponential network dynamics under duplication and ii asymmetric divergence of gene duplicates. While required, we argue that this asymmetric divergence arises, in fact, spontaneously at the level of protein-binding sites. This supports a refined model of PPI network evolution in terms of protein domains under exponential and asymmetric duplication/divergence dynamics, with multidomain proteins underlying the combinatorial formation of protein complexes. Genome duplication then provides a powerful source of PPI network innovation by promoting local rearrangements of multidomain proteins on a genome wide scale. Yet, we show that the overall conservation and topology of PPI networks are robust to extensive domain shuffling of multidomain proteins as well as to finer details of protein interaction and evolution. Finally, large scale features of direct and indirect PPI networks of S. cerevisiae are well reproduced numerically with only two adjusted parameters of clear biological significance (i.e. network effective growth rate and average number of protein-binding domains per protein. Conclusion This study demonstrates the statistical consequences of genome duplication and domain shuffling on the conservation and topology of PPI networks over a broad evolutionary scale across eukaryote kingdoms. In particular, scale

  4. Inferring angiosperm phylogeny from EST data with widespread gene duplication

    OpenAIRE

    Sanderson, Michael J.; McMahon, Michelle M.

    2007-01-01

    Background Most studies inferring species phylogenies use sequences from single copy genes or sets of orthologs culled from gene families. For taxa such as plants, with very high levels of gene duplication in their nuclear genomes, this has limited the exploitation of nuclear sequences for phylogenetic studies, such as those available in large EST libraries. One rarely used method of inference, gene tree parsimony, can infer species trees from gene families undergoing duplication and loss, bu...

  5. [Respiratory insufficiency due to duplications of the oesophagus].

    Science.gov (United States)

    Luoma, Reijo

    2015-01-01

    Duplications of the oesophagus are uncommon congenital malformations with possible occurrence in any part of the gastrointestinal tract. The duplications may be cysts, diverticula or tubular-shaped. Cysts may even occur further away from the gastrointestinal tract, not necessarily having contact with it. I present a patient case, in which a 13-month-old child was brought to the emergency room due to gradually increasing dyspnea. The child made a full recovery after the surgical procedure.

  6. Gene and genome duplication in Acanthamoeba polyphaga Mimivirus.

    Science.gov (United States)

    Suhre, Karsten

    2005-11-01

    Gene duplication is key to molecular evolution in all three domains of life and may be the first step in the emergence of new gene function. It is a well-recognized feature in large DNA viruses but has not been studied extensively in the largest known virus to date, the recently discovered Acanthamoeba polyphaga Mimivirus. Here, I present a systematic analysis of gene and genome duplication events in the mimivirus genome. I found that one-third of the mimivirus genes are related to at least one other gene in the mimivirus genome, either through a large segmental genome duplication event that occurred in the more remote past or through more recent gene duplication events, which often occur in tandem. This shows that gene and genome duplication played a major role in shaping the mimivirus genome. Using multiple alignments, together with remote-homology detection methods based on Hidden Markov Model comparison, I assign putative functions to some of the paralogous gene families. I suggest that a large part of the duplicated mimivirus gene families are likely to interfere with important host cell processes, such as transcription control, protein degradation, and cell regulatory processes. My findings support the view that large DNA viruses are complex evolving organisms, possibly deeply rooted within the tree of life, and oppose the paradigm that viral evolution is dominated by lateral gene acquisition, at least in regard to large DNA viruses.

  7. A novel duplicate images detection method based on PLSA model

    Science.gov (United States)

    Liao, Xiaofeng; Wang, Yongji; Ding, Liping; Gu, Jian

    2012-01-01

    Web image search results usually contain duplicate copies. This paper considers the problem of detecting and clustering duplicate images contained in web image search results. Detecting and clustering the duplicate images together facilitates users' viewing. A novel method is presented in this paper to detect and cluster duplicate images by measuring similarity between their topics. More specifically, images are viewed as documents consisting of visual words formed by vector quantizing the affine invariant visual features. Then a statistical model widely used in text domain, the PLSA(Probabilistic Latent Semantic Analysis) model, is utilized to map images into a probabilistic latent semantic space. Because the main content remains unchanged despite small digital alteration, duplicate images will be close to each other in the derived semantic space. Based on this, a simple clustering process can successfully detect duplicate images and cluster them together. Comparing to those methods based on comparison between hash value of visual words, this method is more robust to the visual feature level alteration posed on the images. Experiments demonstrates the effectiveness of this method.

  8. Duplicate publication rate decline in Korean medical journals.

    Science.gov (United States)

    Kim, Soo Young; Bae, Chong-Woo; Hahm, Chang Kok; Cho, Hye Min

    2014-02-01

    The purpose of this study was to examine trends in duplicate publication in Korean medical articles indexed in the KoreaMed database from 2004 to 2009, before and after a campaign against scientific misconduct launched by the Korean Association of Medical Journal Editors in 2006. The study covered period from 2007 to 2012; and 5% of the articles indexed in KoreaMed were retrieved by random sampling. Three authors reviewed full texts of the retrieved articles. The pattern of duplicate publication, such as copy, salami slicing (fragmentation), and aggregation (imalas), was also determined. Before the launching ethics campaign, the national duplication rate in medical journals was relatively high: 5.9% in 2004, 6.0% in 2005, and 7.2% in 2006. However, duplication rate steadily declined to 4.5% in 2007, 2.8% in 2008, and 1.2 % in 2009. Of all duplicated articles, 53.4% were classified as copies, 27.8% as salami slicing, and 18.8% as aggregation (imalas). The decline in duplicate publication rate took place as a result of nationwide campaigns and monitoring by KoreaMed and KoreaMed Synapse, starting from 2006.

  9. Mechanisms involved in the selective transfer of long chain polyunsaturted fatty acids to the fetus

    Directory of Open Access Journals (Sweden)

    Alfonso eGil-Sánchez

    2011-09-01

    Full Text Available The concentration of long chain polyunsaturated fatty acid (LCPUFA in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA during gestation and development of the cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is that of maternal origin. Both in vitro and human in vivo studies using labelled fatty acids have shown the preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts and even re-esterified and stored in lipid droplets (LD. Although trophoblast cells are not specialized in lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA synthetases and adipophilin or other enzymes related with lipolysis, modifying their rate of placental transfer and metabolization. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge on the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process.

  10. Mutational dynamics of murine angiogenin duplicates

    Directory of Open Access Journals (Sweden)

    Fares Mario A

    2010-10-01

    Angiogenin in vertebrates and highlight the plasticity of this protein after gene duplication. Our results suggest functional divergence among mAng paralogs. This puts forward mAng as a good system candidate for testing functional plasticity of such an important protein while stresses caution when using mouse as a model to infer the consequences of mutations in the single Ang copy of humans.

  11. Role of computed tomography in oesophageal duplications. Report of two cases; Duplications oesophagiennes: place de la tomodensitometrie

    Energy Technology Data Exchange (ETDEWEB)

    Jouini, S.; Menif, E.; Azaiez, N.; Ben Hajel, H.; Cheikh, I.; Ben Ammar, A.; Sellami, M.; Ben Jaafar, M. [Hopital La Rabta, Tunis (Tunisia)

    1995-12-31

    The authors present two cases of esophageal duplication: tubular in one case and cystic in the other. This rare anomaly was identified in both cases by CT scan. A review of literature is proposed. (authors). 22 refs., 10 figs.

  12. Crystallization and preliminary X-ray diffraction analysis of the sialic acid-binding domain (VP8*) of porcine rotavirus strain CRW-8

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Stacy A. [Institute for Glycomics, Griffith University (Gold Coast Campus) PMB 50, Gold Coast Mail Centre, Queensland 9726 (Australia); Holloway, Gavan; Coulson, Barbara S. [Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010 (Australia); Szyczew, Alex J.; Kiefel, Milton J.; Itzstein, Mark von; Blanchard, Helen, E-mail: h.blanchard@griffith.edu.au [Institute for Glycomics, Griffith University (Gold Coast Campus) PMB 50, Gold Coast Mail Centre, Queensland 9726 (Australia)

    2005-06-01

    The sialic acid-binding domain (VP8*) component of the porcine CRW-8 rotavirus spike protein has been overexpressed in E. coli, purified and co-crystallized with an N-acetylneuraminic acid derivative. X-ray diffraction data have been collected to 2.3 Å, which has enabled determination of the structure by molecular replacement. Rotavirus recognition and attachment to host cells involves interaction with the spike protein VP4 that projects outwards from the surface of the virus particle. An integral component of these spikes is the VP8* domain, which is implicated in the direct recognition and binding of sialic acid-containing cell-surface carbohydrates and facilitates subsequent invasion by the virus. The expression, purification, crystallization and preliminary X-ray diffraction analysis of VP8* from porcine CRW-8 rotavirus is reported. Diffraction data have been collected to 2.3 Å resolution, enabling the determination of the VP8* structure by molecular replacement.

  13. Duplication and maintenance of the Myb genes of vertebrate animals

    Directory of Open Access Journals (Sweden)

    Colin J. Davidson

    2012-11-01

    Gene duplication is an important means of generating new genes. The major mechanisms by which duplicated genes are preserved in the face of purifying selection are thought to be neofunctionalization, subfunctionalization, and increased gene dosage. However, very few duplicated gene families in vertebrate species have been analyzed by functional tests in vivo. We have therefore examined the three vertebrate Myb genes (c-Myb, A-Myb, and B-Myb by cytogenetic map analysis, by sequence analysis, and by ectopic expression in Drosophila. We provide evidence that the vertebrate Myb genes arose by two rounds of regional genomic duplication. We found that ubiquitous expression of c-Myb and A-Myb, but not of B-Myb or Drosophila Myb, was lethal in Drosophila. Expression of any of these genes during early larval eye development was well tolerated. However, expression of c-Myb and A-Myb, but not of B-Myb or Drosophila Myb, during late larval eye development caused drastic alterations in adult eye morphology. Mosaic analysis implied that this eye phenotype was cell-autonomous. Interestingly, some of the eye phenotypes caused by the retroviral v-Myb oncogene and the normal c-Myb proto-oncogene from which v-Myb arose were quite distinct. Finally, we found that post-translational modifications of c-Myb by the GSK-3 protein kinase and by the Ubc9 SUMO-conjugating enzyme that normally occur in vertebrate cells can modify the eye phenotype caused by c-Myb in Drosophila. These results support a model in which the three Myb genes of vertebrates arose by two sequential duplications. The first duplication was followed by a subfunctionalization of gene expression, then neofunctionalization of protein function to yield a c/A-Myb progenitor. The duplication of this progenitor was followed by subfunctionalization of gene expression to give rise to tissue-specific c-Myb and A-Myb genes.

  14. Anti-HIV Ⅰ/Ⅱ Activity and Molecular Cloning of a Novel Mannose/Sialic Acid-binding Lectin from Rhizome of Polygonatum cyrtonema Hua

    Institute of Scientific and Technical Information of China (English)

    Jie AN; Jin-Ku BAO; Jin-Zhi LIU; Chuan-Fang WU; Jian LI; Lei DAI; Els Van DAMME; Jan BALZARINI; Erik De CLERCQ; Fang CHEN

    2006-01-01

    The anti-human immunodeficiency virus (HIV) Ⅰ/Ⅱ activity of a mannose and sialic acid binding lectin isolated from rhizomes of Polygonatum cyrtonema Hua was elucidated by comparing its HIV infection inhibitory activity in MT-4 and CEM cells with that of other mannose-binding lectins (MBLs). The anti-HIV activity of Polygonatum cyrtonema Hua lectin (PCL) was 10- to 100-fold more potent than other tested MBLs, but without significant cytotoxicity towards MT-4 or CEM cells. To amplify cDNA of PCL by 3'/5'-rapid amplification of cDNA ends (RACE), the 30 amino acids of N-terminal were determined by sequencing and the degenerate oligonucleotide primers were designed. The full-length cDNA of PCL contained 693 bp with an open reading frame encoding a precursor protein of 160 amino acid residues, consisting of a 28-residue signal peptide, a 22-residue C-terminal cleavage peptide and a 110-residue mature polypeptide which contained three tandemly arranged subdomains with an obvious sequence homology to the monocot MBL. However, only one active mannose-binding site (QDNVY) was found in subdomain Ⅰ of PCL, that of subdomain Ⅱ and Ⅲ changed to HNNVY and PDNVY, respectively. There was no intron in PCL, which was in good agreement with other monocot MBLs. Molecular modeling of PCL indicated that its three-dimen-sional structure resembles that of the snowdrop agglutinin. By docking, an active sialic acid-binding site was found in PCL. The instabilization of translation initiation region (TIR) in mRNA of PCL benefits its high expression in rhizomes.

  15. Cellular nucleic acid binding protein binds G-rich single-stranded nucleic acids and may function as a nucleic acid chaperone.

    Science.gov (United States)

    Armas, Pablo; Nasif, Sofía; Calcaterra, Nora B

    2008-02-15

    Cellular nucleic acid binding protein (CNBP) is a small single-stranded nucleic acid binding protein made of seven Zn knuckles and an Arg-Gly rich box. CNBP is strikingly conserved among vertebrates and was reported to play broad-spectrum functions in eukaryotic cells biology. Neither its biological function nor its mechanisms of action were elucidated yet. The main goal of this work was to gain further insights into the CNBP biochemical and molecular features. We studied Bufo arenarum CNBP (bCNBP) binding to single-stranded nucleic acid probes representing the main reported CNBP putative targets. We report that, although bCNBP is able to bind RNA and single-stranded DNA (ssDNA) probes in vitro, it binds RNA as a preformed dimer whereas both monomer and dimer are able to bind to ssDNA. A systematic analysis of variant probes shows that the preferred bCNBP targets contain unpaired guanosine-rich stretches. These data expand the knowledge about CNBP binding stoichiometry and begins to dissect the main features of CNBP nucleic acid targets. Besides, we show that bCNBP presents a highly disordered pre