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Sample records for human acyltransferase activity

  1. Enzymatic characterization of a human acyltransferase activity.

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    Akihiko Ozawa

    Full Text Available Non-histone protein acylation is increasingly recognized as an important posttranslational modification, but little is known as to the biochemical properties of protein serine acylating enzymes.We here report that we have identified a metal-stimulated serine octanoyltransferase activity in microsomes from human erythroleukemic (HEL cells. The HEL acylating enzyme was linear with respect to time and protein, exhibited a neutral pH optimum (stimulated by cobalt and zinc, and inhibited by chelating reagents. Hydroxylamine treatment removed most, but not all, of the attached radioactivity. A salt extract of microsomal membranes contained the major portion of enzyme activity, indicating that this acyltransferase is not an integral membrane protein. Sucrose density fractionation showed that the acyltransferase activity is concentrated in the endoplasmic reticulum. In competition experiments, the acyltransferase was well inhibited by activated forms of fatty acids containing at least eight to fourteen carbons, but not by acetyl CoA. The zinc-stimulated HEL acyltransferase did not octanoylate proenkephalin, proopiomelanocortin, His-tagged proghrelin, or proghrelin lacking the amino-terminal His-tag stub of Gly-Ala-Met. The peptides des-acyl ghrelin and ACTH were also not acylated; however, des-acyl ghrelin containing the N-terminal tripeptide Gly-Ala-Met was acylated. Mutagenesis studies indicated a requirement for serine five residues from the amino terminus, reminiscent of myristoyl transferase, but not of ghrelin acylation. However, recombinant myristoyl transferase could not recapitulate the hydroxylamine sensitivity, zinc-stimulation, nor EDTA inhibition obtained with HEL acyltransferase, properties preserved in the HEL cell enzyme purified through four sequential chromatographic steps.In conclusion, our data demonstrate the presence of a zinc-stimulated acyltransferase activity concentrated in the endoplasmic reticulum in HEL cells which is likely

  2. Reduction of dietary saturated fatty acids correlates with increased plasma lecithin cholesterol acyltransferase activity in humans.

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    Bérard, A M; Dabadie, H; Palos-Pinto, A; Dumon, M-F; Darmon, M

    2004-06-01

    Increased HDL-cholesterol (HDL-C) concentrations have been associated with lower coronary heart disease risk. On the other hand, dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids that are substrates of lecithin cholesterol acyltransferase (LCAT), an important enzyme in HDL metabolism. The purpose of this study was to examine the association between the saturated fatty acid (SFA) intake and LCAT activity. An interventional study was performed in a monk community of 25 men. A French monk community, South West of France. The basal diet of the study cohort contained SFA in a proportion of 13.5% of their total energy intake (TEI). They were submitted to two experimental isocaloric diets containing either 8.4% of the TEI in SFA (diet A) or 11% (diet B), each lasting 5 weeks. The elevation of SFA in diet B was mainly obtained by decreasing carbohydrates. The only significant difference among total fats between diets A and B was the myristic acid content (0.6 and 1.2% of TEI, respectively). The elevation in SFA in diet B resulted in a significant increase of HDL-C (P<0.04), while plasma apo A-I concentration and LCAT activity both decreased (P<0.02). Altogether, these results are consistent with a negative effect of SFA on reverse cholesterol transport.

  3. Human plasma lecithin-cholesterol acyltransferase

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  4. Molecular Cloning and Characterization of a Novel Human Glycine-N-acyltransferase Gene GLYATL1, Which Activates Transcriptional Activity of HSE Pathway

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    Long Yu

    2007-05-01

    Full Text Available The glycine-N-acyltransferase (GLYAT is well known to be involved in thedetoxification of endogenous and exogenous xenobiotic acyl-CoA's in mammals.Unfortunately, the knowledge about the gene encoding GLYAT is very limited. Here wereport a novel gene encoding a GLYAT member, designated as GLYATL1, which was1546 base pairs in length and contained an open reading frame (ORF encoding apolypeptide of 302 amino acids. GLYATL1 was a split gene that was consisted of 7 exonsand 6 introns and mapped to chromosome 11q12.1. The expression of GLYATL1 could befound in liver, kidney, pancreas, testis, ovary and stomach among 18 human tissues by RT-PCR analysis. Subcellular localization of myc-tagged GLYATL1 fusion protein revealedthat GLYATL1 was distributed primarily in the cytoplasm of COS-7 cells. Furthermore,through the pathway profiling assay, the GLYATL1 protein was found to activate HSEsignaling pathway in a dose-dependent manner when overexpressed in HEK293T cells.

  5. Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation

    International Nuclear Information System (INIS)

    Yu, Jung Hwan; Lee, Yoo Jeong; Kim, Hyo Jung; Choi, Hyeonjin; Choi, Yoonjeong; Seok, Jo Woon; Kim, Jae-woo

    2015-01-01

    Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans. - Highlights: • PPARγ promotes MGAT1 expression in human primary hepatocytes. • PPARγ directly regulates MGAT1 promoter activity. • Human MGAT1 promoter has at least two PPARγ-binding elements. • Inhibition of MGAT1 expression attenuates hepatic lipid accumulation in humans

  6. Monoacylglycerol O-acyltransferase 1 is regulated by peroxisome proliferator-activated receptor γ in human hepatocytes and increases lipid accumulation

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    Yu, Jung Hwan [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Lee, Yoo Jeong [Division of Metabolic Disease, Center for Biomedical Sciences, National Institutes of Health, Cheongwon-gun, Chungbuk 363-951 (Korea, Republic of); Kim, Hyo Jung; Choi, Hyeonjin [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Choi, Yoonjeong; Seok, Jo Woon [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Kim, Jae-woo, E-mail: japol13@yuhs.ac [Department of Biochemistry and Molecular Biology, Integrated Genomic Research Center for Metabolic Regulation, Institute of Genetic Science, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 120-752 (Korea, Republic of); Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2015-05-08

    Monoacylglycerol O-acyltransferase (MGAT) is an enzyme that is involved in triglyceride synthesis by catalyzing the formation of diacylglycerol from monoacylglycerol and fatty acyl CoAs. Recently, we reported that MGAT1 has a critical role in hepatic TG accumulation and that its suppression ameliorates hepatic steatosis in a mouse model. However, the function of MGAT enzymes in hepatic lipid accumulation has not been investigated in humans. Unlike in rodents, MGAT3 as well as MGAT1 and MGAT2 are present in humans. In this study, we evaluated the differences between MGAT subtypes and their association with peroxisome proliferator-activated receptor γ (PPARγ), a regulator of mouse MGAT1 expression. In human primary hepatocytes, basal expression of MGAT1 was lower than that of MGAT2 or MGAT3, but was strongly induced by PPARγ overexpression. A luciferase assay as well as an electromobility shift assay revealed that human MGAT1 promoter activity is driven by PPARγ by direct binding to at least two regions of the promoter in 293T and HepG2 cells. Moreover, siRNA-mediated suppression of MGAT1 expression significantly attenuated lipid accumulation by PPARγ overexpression in HepG2 cells, as evidenced by oil-red-O staining. These results suggest that human MGAT1 has an important role in fatty liver formation as a target gene of PPARγ, and blocking MGAT1 activity could be an efficient therapeutic way to reduce nonalcoholic fatty liver diseases in humans. - Highlights: • PPARγ promotes MGAT1 expression in human primary hepatocytes. • PPARγ directly regulates MGAT1 promoter activity. • Human MGAT1 promoter has at least two PPARγ-binding elements. • Inhibition of MGAT1 expression attenuates hepatic lipid accumulation in humans.

  7. Discovery and characterization of inhibitors of human palmitoyl acyltransferases.

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    Ducker, Charles E; Griffel, Lindsay K; Smith, Ryan A; Keller, Staci N; Zhuang, Yan; Xia, Zuping; Diller, John D; Smith, Charles D

    2006-07-01

    The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for high-throughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening.

  8. Comparison of human plasma low- and high-density lipoproteins as substrates for lecithin: cholesterol acyltransferase.

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    Barter, P J; Hopkins, G J; Gorjatschko, L

    1984-01-17

    A recent observation that lecithin: cholesterol acyltransferase (EC 2.3.1.43) interacts with both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in human plasma is in apparent conflict with an earlier finding that the purified enzyme, while highly reactive with isolated HDL, was only minimally reactive with LDL. There is evidence, however, that lecithin: cholesterol acyltransferase may exist physiologically as a component of a complex with other proteins and that studies with the isolated enzyme may therefore provide misleading results. Consequently, interactions of the enzyme with isolated human lipoproteins have been re-examined in incubations containing lecithin: cholesterol acyltransferase as a component of human lipoprotein-free plasma in which a physiologically active complex of the enzyme with other proteins may have been preserved. In this system there was a ready esterification of the free cholesterol associated with both LDL and HDL-subfraction 3 (HDL3) in reactions that obeyed typical enzyme-saturation kinetics. For a given preparation of lipoprotein-free plasma the Vmax values with LDL and with HDL3 were virtually identical. The apparent Km for free cholesterol associated with HDL3 was 5.6 X 10(-5) M, while for that associated with LDL it was 4.1 X 10(-4) M. This implied that, in terms of free cholesterol concentration, the affinity of HDL3 for lecithin: cholesterol acyltransferase was about 7-times greater than that of LDL. When expressed in terms of lipoprotein particle concentration, however, it was apparent that the affinity of LDL for the enzyme was considerably greater than that of HDL3. When the lipoprotein fractions were equated in terms of lipoprotein surface area, the apparent affinities of the two fractions for the enzyme were found to be comparable.

  9. Structure of a bacterial toxin-activating acyltransferase.

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    Greene, Nicholas P; Crow, Allister; Hughes, Colin; Koronakis, Vassilis

    2015-06-09

    Secreted pore-forming toxins of pathogenic Gram-negative bacteria such as Escherichia coli hemolysin (HlyA) insert into host-cell membranes to subvert signal transduction and induce apoptosis and cell lysis. Unusually, these toxins are synthesized in an inactive form that requires posttranslational activation in the bacterial cytosol. We have previously shown that the activation mechanism is an acylation event directed by a specialized acyl-transferase that uses acyl carrier protein (ACP) to covalently link fatty acids, via an amide bond, to specific internal lysine residues of the protoxin. We now reveal the 2.15-Å resolution X-ray structure of the 172-aa ApxC, a toxin-activating acyl-transferase (TAAT) from pathogenic Actinobacillus pleuropneumoniae. This determination shows that bacterial TAATs are a structurally homologous family that, despite indiscernible sequence similarity, form a distinct branch of the Gcn5-like N-acetyl transferase (GNAT) superfamily of enzymes that typically use acyl-CoA to modify diverse bacterial, archaeal, and eukaryotic substrates. A combination of structural analysis, small angle X-ray scattering, mutagenesis, and cross-linking defined the solution state of TAATs, with intermonomer interactions mediated by an N-terminal α-helix. Superposition of ApxC with substrate-bound GNATs, and assay of toxin activation and binding of acyl-ACP and protoxin peptide substrates by mutated ApxC variants, indicates the enzyme active site to be a deep surface groove.

  10. Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

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    Hiramine, Yasushi; Tanabe, Toshizumi

    2011-06-01

    Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

  11. Purification of peroxisomal acyl-CoA: dihydroxyacetonephosphate acyltransferase from human placenta

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    Ofman, R.; Wanders, R. J.

    1994-01-01

    The peroxisomal enzyme acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT) was extracted from human placental membranes using CHAPS as a detergent in the presence of 1 M KCl. Prior to assay dipalmitoylphosphatidylcholine was added to the sample as eluted from the various columns in order to

  12. Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

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    Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

    2016-01-01

    Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

  13. New insights into the catalytic mechanism of human glycine N-acyltransferase.

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    van der Sluis, Rencia; Ungerer, Vida; Nortje, Carla; A van Dijk, Alberdina; Erasmus, Elardus

    2017-11-01

    Even though the glycine conjugation pathway was one of the first metabolic pathways to be discovered, this pathway remains very poorly characterized. The bi-substrate kinetic parameters of a recombinant human glycine N-acyltransferase (GLYAT, E.C. 2.3.1.13) were determined using the traditional colorimetric method and a newly developed HPLC-ESI-MS/MS method. Previous studies analyzing the kinetic parameters of GLYAT, indicated a random Bi-Bi and/or ping-pong mechanism. In this study, the hippuric acid concentrations produced by the GLYAT enzyme reaction were analyzed using the allosteric sigmoidal enzyme kinetic module. Analyses of the initial rate (v) against substrate concentration plots, produced a sigmoidal curve (substrate activation) when the benzoyl-CoA concentrations was kept constant, whereas the plot with glycine concentrations kept constant, passed through a maximum (substrate inhibition). Thus, human GLYAT exhibits mechanistic kinetic cooperativity as described by the Ferdinand enzyme mechanism rather than the previously assumed Michaelis-Menten reaction mechanism. © 2017 Wiley Periodicals, Inc.

  14. The Role of Lecithin: Retinol Acyltransferase (LRAT)-Mediated Esterification of Vitamin A in Regulating Human Breast Cancer Cell Proliferation and Differentiation

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    2007-04-01

    involved in thetranscriptional regulation of the human LRAT gene. 15. SUBJECT TERMS Breast cancer, lecithin : Retinol Acyltransferase (LRAT...R.R., Nanus, D.M., Scherr, D.S., and Gudas, L.J. 2004. Reduced lecithin : retinol acyltransferase expression correlates with increased pathologic...Solubilization and partial characterization of lecithin -retinol acyltransferase from rat liver. J Nutr Biochem 2: 503-511. Isogai, M., Chiantore, M.V., Haque

  15. Activities of acyl-CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT) in microsomal preparations of developing sunflower and safflower seeds.

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    Banaś, Walentyna; Sanchez Garcia, Alicia; Banaś, Antoni; Stymne, Sten

    2013-06-01

    The last step in triacylglycerols (TAG) biosynthesis in oil seeds, the acylation of diacylglycerols (DAG), is catalysed by two types of enzymes: the acyl-CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). The relative contribution of these enzymes in the synthesis of TAG has not yet been defined in any plant tissue. In the presented work, microsomal preparations were obtained from sunflower and safflower seeds at different stages of development and used in DGAT and PDAT enzyme assays. The ratio between PDAT and DGAT activity differed dramatically between the two different species. DGAT activities were measured with two different acyl acceptors and assay methods using two different acyl-CoAs, and in all cases the ratio of PDAT to DGAT activity was significantly higher in safflower than sunflower. The sunflower DGAT, measured by both methods, showed significant higher activity with 18:2-CoA than with 18:1-CoA, whereas the opposite specificity was seen with the safflower enzyme. The specificities of PDAT on the other hand, were similar in both species with 18:2-phosphatidylcholine being a better acyl donor than 18:1-PC and with acyl groups at the sn-2 position utilised about fourfold the rate of the sn-1 position. No DAG:DAG transacylase activity could be detected in the microsomal preparations.

  16. Role of low density lipoprotein in the activation of plasma lysolecithin acyltransferase activity. Effect of chemical and enzymatic modifications of the lipoprotein on enzyme activity.

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    Subbaiah, P V; Chen, C H; Bagdade, J D; Albers, J J

    1985-01-01

    The effect of various chemical and enzymatic modifications of low density lipoprotein (LDL) on its ability to activate the isolated human plasma lysolecithin acyltransferase (LAT) was studied. Removal of all lipids from LDL resulted in the complete loss of LAT activation. Removal of only neutral lipids by extraction with heptane retained up to 50% of the original activity, which was not increased further by reconstitution of the LDL with the extracted lipids. Hydrolysis of the diacylphosphoglycerides of the LDL with phospholipases resulted in complete loss of LAT activation which was partially restored by the addition of egg lecithin. Hydrolysis of more than 4% of LDL protein by trypsin led to a linear decrease in activity with complete loss of activity occurring when about 25% of the LDL protein is hydrolyzed. Modification of the arginine groups of LDL reversibly inhibited the activation of LAT. Modification of lysine residues of LDL by acetylation, acetoacetylation or succinylation also abolished its ability to activate lysolecithin acylation.

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

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

    1986-02-12

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

  18. Effect of γ irradiation on the activity of lecithin-cholesterol acyltransferase in plasma of the rat

    International Nuclear Information System (INIS)

    Dousset, N.; Douste-Blazy, L.

    1975-01-01

    Plasma cholesterol and lecithin-cholesterol-acyl-transferase activity are studied in irradiated rats. Ionizing radiations cause an increase of cholesterol levels in plasma, concerning mainly ester fraction. Lecithin-cholesterol-acyltransferase activity in plasma of irradiated rats is lowered 48 hours after exposure. This decreased rate of LCAT is probably the consequence of the post-irradiation hypercholesterolemia [fr

  19. Lysophosphatidic acid acyltransferase β (LPAATβ promotes the tumor growth of human osteosarcoma.

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    Farbod Rastegar

    2010-12-01

    Full Text Available Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2 in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated.Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma.Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially attractive given the availability of selective

  20. Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice

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    Manzini, S.; Pinna, C.; Busnelli, M.; Cinquanta, P.; Rigamonti, E.; Ganzetti, G.S.; Dellera, F.; Sala, A.; Calabresi, L.; Franceschini, G.; Parolini, C.; Chiesa, G.

    2015-01-01

    Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcatwt) and LCAT knockout (LcatKO) mice exposed to noradrenaline showed reduced contractility in LcatKO mice (P < 0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in LcatKO mice (P < 0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in LcatKO mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcatwt and LcatKO mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity. PMID:26254103

  1. Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

    Science.gov (United States)

    Manzini, S; Pinna, C; Busnelli, M; Cinquanta, P; Rigamonti, E; Ganzetti, G S; Dellera, F; Sala, A; Calabresi, L; Franceschini, G; Parolini, C; Chiesa, G

    2015-11-01

    Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity. Copyright © 2015. Published by Elsevier Inc.

  2. Membrane topology of hedgehog acyltransferase.

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    Matevossian, Armine; Resh, Marilyn D

    2015-01-23

    Hedgehog acyltransferase (Hhat) is a multipass transmembrane enzyme that mediates the covalent attachment of the 16-carbon fatty acid palmitate to the N-terminal cysteine of Sonic Hedgehog (Shh). Palmitoylation of Shh by Hhat is critical for short and long range signaling. Knowledge of the topological organization of Hhat transmembrane helices would enhance our understanding of Hhat-mediated Shh palmitoylation. Bioinformatics analysis of transmembrane domains within human Hhat using 10 different algorithms resulted in highly consistent predictions in the C-terminal, but not in the N-terminal, region of Hhat. To empirically determine the topology of Hhat, we designed and exploited Hhat constructs containing either terminal or 12 different internal epitope tags. We used selective permeabilization coupled with immunofluorescence as well as a protease protection assay to demonstrate that Hhat contains 10 transmembrane domains and 2 re-entrant loops. The invariant His and highly conserved Asp residues within the membrane-bound O-acyltransferase (MBOAT) homology domain are segregated on opposite sides of the endoplasmic reticulum membrane. The localization of His-379 on the lumenal membrane surface is consistent with a role for this invariant residue in catalysis. Analysis of the activity and stability of the Hhat constructs revealed that the C-terminal MBOAT domain is especially sensitive to manipulation. Moreover, there was remarkable similarity in the overall topological organization of Hhat and ghrelin O-acyltransferase, another MBOAT family member. Knowledge of the topological organization of Hhat could serve as an important tool for further design of selective Hhat inhibitors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Castor diacylglycerol acyltransferase type1(DGAT1)displays greater activity with diricinolein than Arabidopsis DGAT1

    Science.gov (United States)

    Castor oil contains the hydroxy fatty acid ricinoleate as a major (90%) component. The diacylglycerol acyltransferase (DGAT) carries out the final reaction step in the biosynthesis of triacylglycerol, the principal constituent of seed oil, and has been considered to be the step that controls the oil...

  4. LECITHIN: CHOLESTEROL ACYLTRANSFERASE ACTIVITY IS DECREASED IN TYPE 2 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    A. Ghanei

    2007-09-01

    Full Text Available Lecithin cholesterol acyltransferase (LCAT plays a major role in the removal of free cholesterol from tissues via assisting HDL-C maturation, and its activity has been proposed as the main indicator of HDL-C function. The aim of the study was to measure LCAT activity in type 2 diabetic patients and to elucidate whether LCAT is associated with metabolic control, and insulin resistance. A case-control study was conducted in Imam Khomeini Hospital during 2006, recruiting 45 type 2 diabetes mellitus patients and 45 healthy subjects. Cases and controls were matched regarding gender, age and body mass index (BMI. FBS, lipid profile, LCAT activity, HbA1C, insulin were measured and insulin resistance (HOMA-IRwas calculated for both patients and controls. The studied variables were then compared between the two groups, and the association of LCAT activity with any of the variables was examined. Twenty-five subjects were female and 20 male both among patients and controls. Mean age of diabetics was 49.9 yrs (range, 40-64, and of controls 51.1 yrs (range, 39-64. FBS, HbA1C, HOMA-IR and TG in patients were significantly higher than controls, and HDL-C in controls was significantly higher than patients. LCAT activity of patients (73 9.1 µmol/L/h was significantly lower than that in controls (88 4.5 µmol/L/h (p<0.001. LCAT activity had significant inverse correlations with HbA1C and duration of diabetes. After multilinear regression analysis in patients, LCAT activity was only correlated with HbA1C level (ß= -0.9, p<0.001. LCAT activity had no significant association with HDL-C and HOMA-IR in any of the groups."nLCAT activity is significantly decreased in patients with type 2 diabetes compared with healthy controls, and has an inverse correlation with the magnitude of hyperglycemia.

  5. Altered regulation of lipid biosynthesis in a mutant of Arabidopsis deficient in chloroplast glycerol-3-phosphate acyltransferase activity

    International Nuclear Information System (INIS)

    Kunst, L.; Browse, J.; Somerville, C.

    1988-01-01

    The leaf membrane lipids of many plant species, including Arabidopsis thaliana (L.) Heynh., are synthesized by two complementary pathways that are associated with the chloroplast and the endoplasmic reticulum. By screening directly for alterations in lipid acyl-group composition, the authors have identified several mutants of Arabidopsis that lack the plastid pathway because of a deficiency in activity of the first enzyme in the plastid pathway of glycerolipid synthesis, acyl-ACP:sn-glycerol-3-phosphate acyltransferase. The lesion results in an increased synthesis of lipids by the cytoplasmic pathway that largely compensates for the loss of the plastid pathway and provides nearly normal amounts of all the lipids required for chloroplast biogenesis. However, the fatty acid composition of the leaf membrane lipids of the mutants is altered because the acyltransferases associated with the two pathways normally exhibit different substrate specificities. The remarkable flexibility of the system provides an insight into the nature of the regulatory mechanisms that allocate lipids for membrane biogenesis

  6. Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids.

    Science.gov (United States)

    Subbaiah, P V; Liu, M

    1996-05-31

    Oxidation of lipoproteins results in the formation of several polar phospholipids with pro-inflammatory and pro-atherogenic properties. To examine the possible role of lecithin/cholesterol acyltransferase (LCAT) in the metabolism of these oxidized phospholipids, we oxidized whole plasma with either Cu(2+) or a free-radical generator, and determined the various activities of LCAT. Oxidation caused a reduction in plasma phosphatidylcholine (PC), an increase in a short-chain polar PC (SCP-PC), and an inhibition of the transfer of long-chain acyl groups to cholesterol (LCAT activity) or to lyso PC (lysolecithin acyltransferase (LAT) I activity). However, the transfer of short-chain acyl groups from SCP-PC to lyso PCLAT II activity) was stimulated several fold, in direct correlation with the degree of oxidation. LAT II activity was not stimulated by oxidation in LCAT-deficient plasma, showing that it is carried out by LCAT. Oxidized normal plasma exhibited low LCAT activity even in the presence of exogenous proteoliposome substrate, indicating that the depletion of substrate PC was not responsible for the loss of activity. Oxidation of isolated LDL or HDL abolished their ability to support LCAT and LAT I activities of exogenous enzyme, but promoted the LAT II activity. Purified LCAT lost its LCAT and LAT I functions, but not its LAT II function, when oxidized in vitro. These results show that while oxidation of plasma causes a loss of LCAT's ability to transfer long-chain acyl groups, its ability to transfer short-chain acyl groups, from SCP-PC is retained, and even stimulated, suggesting that LCAT may have a physiological role in the metabolism of oxidized PC in plasma.

  7. Lysophosphatidylcholine acyltransferase1 overexpression promotes oral squamous cell carcinoma progression via enhanced biosynthesis of platelet-activating factor.

    Science.gov (United States)

    Shida-Sakazume, Tomomi; Endo-Sakamoto, Yosuke; Unozawa, Motoharu; Fukumoto, Chonji; Shimada, Ken; Kasamatsu, Atsushi; Ogawara, Katsunori; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2015-01-01

    The relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown. We investigated LPCAT1 expression and its functional mechanism in OSCCs. We analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines. Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status. We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression. LPCAT1 mRNA and protein were up-regulated significantly (poral keratinocytes. Immunohistochemistry showed significantly (poral cancer.

  8. Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT) is associated with anorexia nervosa.

    Science.gov (United States)

    Müller, Timo D; Tschöp, Matthias H; Jarick, Ivonne; Ehrlich, Stefan; Scherag, Susann; Herpertz-Dahlmann, Beate; Zipfel, Stefan; Herzog, Wolfgang; de Zwaan, Martina; Burghardt, Roland; Fleischhaker, Christian; Klampfl, Karin; Wewetzer, Christoph; Herpertz, Stephan; Zeeck, Almut; Tagay, Sefik; Burgmer, Markus; Pfluger, Paul T; Scherag, André; Hebebrand, Johannes; Hinney, Anke

    2011-05-01

    The gastrointestinal peptide hormone ghrelin promotes food intake and increases body weight and adiposity through activation of the growth hormone secretagogue receptor (GHSR1a). To promote its biological action ghrelin is acylated at its serine 3 residue by the recently discovered ghrelin O-acyltransferase (GOAT, a.k.a. membrane-bound O-acyltransferase 4, MBOAT4). Plasma levels of total and acyl-ghrelin are negatively correlated with body-mass-index (BMI); as lower the BMI as higher plasma levels of total and acylated ghrelin and vice versa. Accordingly, plasma levels of total and acyl-ghrelin are elevated in patients with anorexia nervosa (AN) and decline upon weight regain. The importance of the endogenous Goat/ghrelin system in the neuroendocrine adaptation to fasting was recently highlighted by the observation that acyl-ghrelin mediated elevation of growth hormone (GH) release prevents starvation induced hypoglycemia in Goat(-/-) mice. The aim of this study was to test if genetic variation of GOAT is implicated in the etiology of AN. We therefore assessed association of 6 tagging single nucleotide polymorphisms (tagSNPs), which were predicted to cover 96% the common genetic variability of GOAT plus 50 kb of the 5' and 3' flanking region, in 543 German patients with AN and 612 German normal and underweight healthy controls. Based on a recessive mode of inheritance we observed some evidence for association of the G/G genotype at SNP rs10096097 with AN (nominal two-sided p = 0.031). Based on our results we conclude that genetic variation in GOAT might be implicated in the etiology of AN. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Lysophosphatidic acid activates peroxisome proliferator activated receptor-γ in CHO cells that over-express glycerol 3-phosphate acyltransferase-1.

    Directory of Open Access Journals (Sweden)

    Cliona M Stapleton

    2011-04-01

    Full Text Available Lysophosphatidic acid (LPA is an agonist for peroxisome proliferator activated receptor-γ (PPARγ. Although glycerol-3-phosphate acyltransferase-1 (GPAT1 esterifies glycerol-3-phosphate to form LPA, an intermediate in the de novo synthesis of glycerolipids, it has been assumed that LPA synthesized by this route does not have a signaling role. The availability of Chinese Hamster Ovary (CHO cells that stably overexpress GPAT1, allowed us to analyze PPARγ activation in the presence of LPA produced as an intracellular intermediate. LPA levels in CHO-GPAT1 cells were 6-fold higher than in wild-type CHO cells, and the mRNA abundance of CD36, a PPARγ target, was 2-fold higher. Transactivation assays showed that PPARγ activity was higher in the cells that overexpressed GPAT1. PPARγ activity was enhanced further in CHO-GPAT1 cells treated with the PPARγ ligand troglitazone. Extracellular LPA, phosphatidic acid (PA or a membrane-permeable diacylglycerol had no effect, showing that PPARγ had been activated by LPA generated intracellularly. Transient transfection of a vector expressing 1-acylglycerol-3-phosphate acyltransferase-2, which converts endogenous LPA to PA, markedly reduced PPARγ activity, as did over-expressing diacylglycerol kinase, which converts DAG to PA, indicating that PA could be a potent inhibitor of PPARγ. These data suggest that LPA synthesized via the glycerol-3-phosphate pathway can activate PPARγ and that intermediates of de novo glycerolipid synthesis regulate gene expression.

  10. Plasma lecithin : cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men

    NARCIS (Netherlands)

    Dullaart, R. P. F.; Perton, F.; Kappelle, P.J.W.H.; de Vries, R.; Sluiter, W. J.; van Tol, A.

    Lecithin:cholesterol acyltransferase (LCAT) is instrumental in high-density lipoprotein (HDL) maturation, but high LCAT levels do not predict low cardiovascular risk. LCAT may affect antioxidative or anti-inflammatory properties of HDL We determined the relationship of plasma high-sensitivity

  11. A Novel Human Ghrelin Variant (In1-Ghrelin) and Ghrelin-O-Acyltransferase Are Overexpressed in Breast Cancer: Potential Pathophysiological Relevance

    Science.gov (United States)

    Gahete, Manuel D.; Córdoba-Chacón, José; Hergueta-Redondo, Marta; Martínez-Fuentes, Antonio J.; Kineman, Rhonda D.; Moreno-Bueno, Gema

    2011-01-01

    The human ghrelin gene, which encodes the ghrelin and obestatin peptides, contains 5 exons (Ex), with Ex1-Ex4 encoding a 117 amino-acid (aa) preproprotein that is known to be processed to yield a 28-aa (ghrelin) and/or a 23-aa (obestatin) mature peptides, which possess biological activities in multiple tissues. However, the ghrelin gene also encodes additional peptides through alternative splicing or post-translational modifications. Indeed, we previously identified a spliced mRNA ghrelin variant in mouse (In2-ghrelin-variant), which is regulated in a tissue-dependent manner by metabolic status and may thus be of biological relevance. Here, we have characterized a new human ghrelin variant that contains Ex0-1, intron (In) 1, and Ex2 and lacks Ex3-4. This human In1-ghrelin variant would encode a new prepropeptide that conserves the first 12aa of native-ghrelin (including the Ser3-potential octanoylation site) but has a different C-terminal tail. Expression of In1-variant was detected in 22 human tissues and its levels were positively correlated with those of ghrelin-O-acyltransferase (GOAT; p = 0.0001) but not with native-ghrelin expression, suggesting that In1-ghrelin could be a primary substrate for GOAT in human tissues. Interestingly, levels of In1-ghrelin variant expression in breast cancer samples were 8-times higher than those of normal mammary tissue, and showed a strong correlation in breast tumors with GOAT (p = 0.0001), ghrelin receptor-type 1b (GHSR1b; p = 0.049) and cyclin-D3 (a cell-cycle inducer/proliferation marker; p = 0.009), but not with native-ghrelin or GHSR1a expression. Interestingly, In1-ghrelin variant overexpression increased basal proliferation of MDA-MB-231 breast cancer cells. Taken together, our results provide evidence that In1-ghrelin is a novel element of the ghrelin family with a potential pathophysiological role in breast cancer. PMID:21829727

  12. Identification of a botanical inhibitor of intestinal diacylglyceride acyltransferase 1 activity via in vitro screening and a parallel, randomized, blinded, placebo-controlled clinical trial.

    Science.gov (United States)

    Velliquette, Rodney A; Grann, Kerry; Missler, Stephen R; Patterson, Jennifer; Hu, Chun; Gellenbeck, Kevin W; Scholten, Jeffrey D; Randolph, R Keith

    2015-01-01

    Diacylglyceride acyltransferase 1 (DGAT1) is the enzyme that adds the final fatty acid on to a diacylglyceride during triglyceride (TG) synthesis. DGAT1 plays a key role in the repackaging of dietary TG into circulating TG rich chylomicrons. A growing amount of research has indicated that an exaggerated postprandial circulating TG level is a risk indicator for cardiovascular and metabolic disorders. The aim of this research was to identify a botanical extract that inhibits intestinal DGAT1 activity and attenuates postprandial hypertriglyceridemia in overweight and obese humans. Twenty individual phytochemicals and an internal proprietary botanical extract library were screened with a primary cell-free DGAT1 enzyme assay that contained dioleoyl glycerol and palmitoleoyl Coenzyme A as substrates plus human intestinal microsomes as the DGAT1 enzyme source. Botanical extracts with IC50 values botanical extracts were then evaluated in a parallel, double-blind, placebo-controlled clinical trial. Ninety healthy, overweight and obese participants were randomized to receive 2 g daily of placebo or individual botanical extracts (the investigational product) for seven days. Serum TG levels were measured before and after consuming a high fat meal (HFM) challenge (0.354 L drink/shake; 77 g fat, 25 g carbohydrate and 9 g protein) as a marker of intestinal DGAT1 enzyme activity. Phenolic acids (i.e., gallic acid) and polyphenols (i.e., cyanidin) abundantly found in nature appeared to inhibit DGAT1 enzyme activity in vitro. Four polyphenolic rich botanical extracts were identified from in vitro evaluation in both cell-free and cellular model systems: apple peel extract (APE), grape extract (GE), red raspberry leaf extract (RLE) and apricot/nectarine extract (ANE) (IC50 = 1.4, 5.6, and 10.4 and 3.4 μg/mL, respectively). In the seven day clinical trial, compared to placebo, only GE significantly reduced the baseline subtracted change in serum TG AUC following

  13. Four new compounds isolated from Psoralea corylifolia and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

    Science.gov (United States)

    Lin, Xin; Li, Ban-Ban; Zhang, Le; Li, Hao-Ze; Meng, Xiao; Jiang, Yi-Yu; Lee, Hyun-Sun; Cui, Long

    2018-05-14

    A new bakuchiol compound Δ 11 -12-hydroxy-12-dimethyl bakuchiol (1), a new flavanone compound 2(S)-6-methoxy-7- hydroxymethylene-4'-hydroxyl-flavanone (8), and two new isoflavanone compounds 4',7-dihydroxy-3'-(6"β-hydroxy-3″,7″-dimethyl-,2″,7″-dibutenyl)-geranylisoflavone (9) and 4',7-dihydroxy-3'-(7″-hydroxy-7″-methyl-2″,5″-dibutenyl)-geranylisoflavone (10) together with eight known compounds (2-7, 11, 12) were isolated from the P. corylifolia. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2. Among them, compounds 3, 9 and 10 were found to exhibit selective inhibitory activity on DGAT1 with IC 50 values ranging from 93.7 ± 1.3 to 96.2 ± 1.1 μM. Compound 1 showed inhibition activity on DGAT1 with IC 50 values 73.4 ± 1.3 μM and inhibition of DGAT2 with IC 50 value 121.1 ± 1.3 μM. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Simplified procedure for the in vitro assay of the initial linear rate of the reaction of lecithin-cholesterol acyltransferase in human serum

    International Nuclear Information System (INIS)

    Mahadevan, V.; Soloff, L.A.

    1985-01-01

    A simple sensitive method for the determination of the initial rate of the reaction of lecithin-cholesterol acyltransferase by equilibrating [ 3 H]cholesterol with unesterified cholesterol of human serum is described. The resulting serum is incubated for various time periods at 37 degrees C and the increase of the label in the cholesterol ester fraction is measured. The labeling is effected by a fids at 37 degrees C and the increase of the label in the cholesterol ester fraction is measured. The labeling is effected by a filter paper method in which a paper strip containing the labeled cholesterol is placed in serum at 4 degrees C, thereby preventing the formation of labeled cholesterol esters by the action of the enzyme. The rate of the reaction was linear up to 30 min

  15. Four new sesqui-lignans isolated from Acanthopanax senticosus and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

    Science.gov (United States)

    Li, Jia-Lin; Li, Na; Lee, Hyun-Sun; Xing, Shan-Shan; Qi, Shi-Zhou; Tuo, Zhen-Dong; Zhang, Le; Li, Ban-Ban; Chen, Jian-Guang; Cui, Long

    2016-03-01

    Four new sesqui-lignans, (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (1), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',3″-dihydroxy-3,5,3',5',4″-pentamethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (2), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-3',4″-dihydroxy-3,5,4',5″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (3) and acanthopanax A (7) together with three known compounds (4-6) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 1-6 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 61.1 ± 1.3 to 97.7 ± 1.1 μM and compound 7 showed selective inhibition of DGAT2 with IC50 value 93.2 ± 1.2. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Glycerophosphate/Acylglycerophosphate Acyltransferases

    Directory of Open Access Journals (Sweden)

    Atsushi Yamashita

    2014-11-01

    Full Text Available Acyl-CoA:glycerol-3-phosphate acyltransferase (GPAT and acyl-CoA: 1-acyl-glycerol-3-phosphate acyltransferase (AGPAT are involved in the de novo synthesis of triacylglycerol (TAG and glycerophospholipids. Many enzymes belonging to the GPAT/AGPAT family have recently been identified and their physiological or pathophysiological roles have been proposed. The roles of GPAT/AGPAT in the synthesis of TAG and obesity-related diseases were revealed through the identification of causative genes of these diseases or analyses of genetically manipulated animals. Recent studies have suggested that some isoforms of GPAT/AGPAT family enzymes are involved in the fatty acid remodeling of phospholipids. The enzymology of GPAT/AGPAT and their physiological/ pathological roles in the metabolism of glycerolipids have been described and discussed in this review.

  17. Phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamines by Ca2+-dependent N-acyltransferase.

    Science.gov (United States)

    Hussain, Zahir; Uyama, Toru; Kawai, Katsuhisa; Binte Mustafiz, Smriti Sultana; Tsuboi, Kazuhito; Araki, Nobukazu; Ueda, Natsuo

    2018-05-01

    N-acyl-phosphatidylethanolamine (NAPE) is known to be a precursor for various bioactive N-acylethanolamines including the endocannabinoid anandamide. NAPE is produced in mammals through the transfer of an acyl chain from certain glycerophospholipids to phosphatidylethanolamine (PE) by Ca 2+ -dependent or -independent N-acyltransferases. The ε isoform of mouse cytosolic phospholipase A 2 (cPLA 2 ε) was recently identified as a Ca 2+ -dependent N-acyltransferase (Ca-NAT). In the present study, we first showed that two isoforms of human cPLA 2 ε function as Ca-NAT. We next purified both mouse recombinant cPLA 2 ε and its two human orthologues to examine their catalytic properties. The enzyme absolutely required Ca 2+ for its activity and the activity was enhanced by phosphatidylserine (PS). PS enhanced the activity 25-fold in the presence of 1 mM CaCl 2 and lowered the EC 50 value of Ca 2+ >8-fold. Using a PS probe, we showed that cPLA 2 ε largely co-localizes with PS in plasma membrane and organelles involved in the endocytic pathway, further supporting the interaction of cPLA 2 ε with PS in living cells. Finally, we found that the Ca 2+ -ionophore ionomycin increased [ 14 C]NAPE levels >10-fold in [ 14 C]ethanolamine-labeled cPLA 2 ε-expressing cells while phospholipase A/acyltransferase-1, acting as a Ca 2+ -independent N-acyltransferase, was insensitive to ionomycin for full activity. In conclusion, PS potently stimulated the Ca 2+ -dependent activity and human cPLA 2 ε isoforms also functioned as Ca-NAT. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Two bifunctional enzymes from the marine protist Thraustochytrium roseum: biochemical characterization of wax ester synthase/acyl-CoA:diacylglycerol acyltransferase activity catalyzing wax ester and triacylglycerol synthesis.

    Science.gov (United States)

    Zhang, Nannan; Mao, Zejing; Luo, Ling; Wan, Xia; Huang, Fenghong; Gong, Yangmin

    2017-01-01

    Triacylglycerols (TAGs) and wax esters (WEs) are important neutral lipids which serve as energy reservoir in some plants and microorganisms. In recent years, these biologically produced neutral lipids have been regarded as potential alternative energy sources for biofuel production because of the increased interest on developing renewable and environmentally benign alternatives for fossil fuels. In bacteria, the final step in TAG and WE biosynthetic pathway is catalyzed by wax ester synthase/acyl coenzyme A (acyl-CoA):diacylglycerol acyltransferase (WS/DGAT). This bifunctional WS/DGAT enzyme is also a key enzyme in biotechnological production of liquid WE via engineering of plants and microorganisms. To date, knowledge about this class of biologically and biotechnologically important enzymes is mainly from biochemical characterization of WS/DGATs from Arabidopsis, jojoba and some bacteria that can synthesize both TAGs and WEs intracellularly, whereas little is known about WS/DGATs from eukaryotic microorganisms. Here, we report the identification and characterization of two bifunctional WS/DGAT enzymes (designated TrWSD4 and TrWSD5) from the marine protist Thraustochytrium roseum . Both TrWSD4 and TrWSD5 comprise a WS-like acyl-CoA acyltransferase domain and the recombinant proteins purified from Escherichia coli Rosetta (DE3) have substantial WS and lower DGAT activity. They exhibit WS activity towards various-chain-length saturated and polyunsaturated acyl-CoAs and fatty alcohols ranging from C 10 to C 18 . TrWSD4 displays WS activity with the lowest K m value of 0.14 μM and the highest k cat / K m value of 1.46 × 10 5  M -1  s -1 for lauroyl-CoA (C 12:0 ) in the presence of 100 μM hexadecanol, while TrWSD5 exhibits WS activity with the lowest K m value of 0.96 μM and the highest k cat / K m value of 9.83 × 10 4  M -1  s -1 for decanoyl-CoA (C 10:0 ) under the same reaction condition. Both WS/DGAT enzymes have the highest WS activity at 37 and 47

  19. Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

    NARCIS (Netherlands)

    J.A. Beentjes; A. van Tol (Arie); W.J. Sluiter (Wim); R.P.F. Dullaart (Robin)

    2000-01-01

    textabstractThe effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are

  20. Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

    OpenAIRE

    Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

    1994-01-01

    Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosph...

  1. Hepatic regulation of platelet-activating factor acetylhydrolase and lecithin:cholesterol acyltransferase biliary and plasma output in rats exposed to bacterial lipopolysaccharide.

    Science.gov (United States)

    Svetlov, S I; Sturm, E; Olson, M S; Crawford, J M

    1999-07-01

    Normal rat bile contains secretory platelet-activating factor acetylhydrolase (PAF-AH), the enzyme capable of hydrolyzing the inflammatory mediator platelet-activating factor (PAF), and phospholipids containing oxidized truncated fatty acids. Because lecithin:cholesterol acyltransferase (LCAT) possesses intrinsic PAF-AH-like activity, it also may represent a potential anti-inflammatory enzyme. The behavior of PAF-AH and LCAT in hepatobiliary inflammatory responses in vivo has not been characterized. We therefore investigated the biliary and plasma secretion and pharmacological characteristics of these enzymes in rats subjected to intraportal bacterial endotoxin exposure (lipopolysaccharide [LPS], Escherichia coli, 055:B5). Portal vein LPS infusion (1 mg/kg, bolus) resulted in a maximal 4- to 5-fold increase in bile PAF-AH-specific activity with a gradual decline to baseline by 18 hours. Biliary PAF-AH hydrolyzed also the truncated sn-2-succinoyl and sn-2-glutaroyl analogs of PAF, indicating a broader activity of PAF-AH in bile toward byproducts of glycerophospholipid peroxidation. Plasma PAF-AH activity was not altered 5 hours after LPS injection compared with saline injection, but it was significantly elevated 18 hours after endotoxin exposure. The levels of LCAT in bile were low and declined to nearly undetectable values by 5 hours after cannulation in both control and LPS-exposed rats. Plasma LCAT activity was significantly increased after 5 hours and decreased 18 hours after LPS injection. In summary, hepatic exposure to endotoxin results in a rapid increase in biliary secretion of PAF-AH followed by elevation of LCAT and PAF-AH levels in plasma. We propose that biliary secretion of PAF-AH may be involved in the hepatic response to endotoxic insult by counteracting potential inflammatory damage in the biliary tree and gastrointestinal tract, whereas plasma increases in LCAT and PAF-AH may promote elimination of excess PAF and oxidized phospholipids in the

  2. Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats.

    Science.gov (United States)

    Benaicheta, Nora; Labbaci, Fatima Z; Bouchenak, Malika; Boukortt, Farida O

    2016-01-14

    Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats.

  3. Effect of growth hormone replacement therapy on plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

    NARCIS (Netherlands)

    Beentjes, JAM; van Tol, A; Sluiter, WJ; Dullaart, RPF

    The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, We unknown. We carried out a 6 mouths study in 24

  4. Acute and chronic effects of a 24-hour intravenous triglyceride emulsion challenge on plasma lecithin : cholesterol acyltransferase, phospholipid transfer protein, and cholesteryl ester transfer protein activities

    NARCIS (Netherlands)

    Riemens, SC; Van Tol, A; Sluiter, WJ; Dullaart, RPF

    Lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), and cholesteryl ester transfer protein (CETP) are key factors in remodeling of high density lipoproteins (HDL) and triglyceride-rich lipoproteins. We examined the effect of a large, 24 h intravenous fat load on plasma

  5. Synthetic triterpenoid inhibition of human ghrelin O-acyltransferase: Involvement of a functionally required cysteine provides mechanistic insight into ghrelin acylation

    OpenAIRE

    McGovern-Gooch, Kayleigh R.; Mahajani, Nivedita S.; Garagozzo, Ariana; Schramm, Anthony J.; Hannah, Lauren G.; Sieburg, Michelle A.; Chisholm, John D.; Hougland, James L.

    2017-01-01

    The peptide hormone ghrelin plays a key role in regulating hunger and energy balance within the body. Ghrelin signaling presents a promising and unexploited target for development of small-molecule therapeutics to treat obesity, diabetes, and other health conditions. Inhibition of ghrelin O-acyltransferase (GOAT), which catalyzes an essential octanoylation step in ghrelin maturation, offers a potential avenue for controlling ghrelin signaling. Through screening a small molecule library, we ha...

  6. Attenuation of hedgehog acyltransferase-catalyzed sonic Hedgehog palmitoylation causes reduced signaling, proliferation and invasiveness of human carcinoma cells

    DEFF Research Database (Denmark)

    Konitsiotis, Antonios D; Chang, Shu-Chun; Jovanović, Biljana

    2014-01-01

    ) cell line PANC-1 and transfected HEK293a cells Hhat localized to the endoplasmic reticulum. siRNA knockdown showed that Hhat is required for Sonic hedgehog (Shh) palmitoylation, for its assembly into high molecular weight extracellular complexes and for functional activity. Hhat knockdown inhibited Hh...

  7. Lipid Oxidation in Carriers of Lecithin: Cholesterol Acyltransferase Gene Mutations

    NARCIS (Netherlands)

    Holleboom, Adriaan G.; Daniil, Georgios; Fu, Xiaoming; Zhang, Renliang; Hovingh, G. Kees; Schimmel, Alinda W.; Kastelein, John J. P.; Stroes, Erik S. G.; Witztum, Joseph L.; Hutten, Barbara A.; Tsimikas, Sotirios; Hazen, Stanley L.; Chroni, Angeliki; Kuivenhoven, Jan Albert

    2012-01-01

    Objective-Lecithin:cholesterol acyltransferase (LCAT) has been shown to play a role in the depletion of lipid oxidation products, but this has so far not been studied in humans. In this study, we investigated processes and parameters relevant to lipid oxidation in carriers of functional LCAT

  8. Lipid Oxidation in Carriers of Lecithin : Cholesterol Acyltransferase Gene Mutations

    NARCIS (Netherlands)

    Holleboom, Adriaan G.; Daniil, Georgios; Fu, Xiaoming; Zhang, Renliang; Hovingh, G. Kees; Schimmel, Alinda W.; Kastelein, John J. P.; Stroes, Erik S. G.; Witztum, Joseph L.; Hutten, Barbara A.; Tsimikas, Sotirios; Hazen, Stanley L.; Chroni, Angeliki; Kuivenhoven, Jan Albert

    2012-01-01

    OBJECTIVE: Lecithin:cholesterol acyltransferase (LCAT) has been shown to play a role in the depletion of lipid oxidation products, but this has so far not been studied in humans. In this study, we investigated processes and parameters relevant to lipid oxidation in carriers of functional LCAT

  9. Role of lecithin-cholesterol acyltransferase in the metabolism of oxidized phospholipids in plasma: studies with platelet-activating factor-acetyl hydrolase-deficient plasma.

    Science.gov (United States)

    Subramanian, V S; Goyal, J; Miwa, M; Sugatami, J; Akiyama, M; Liu, M; Subbaiah, P V

    1999-07-09

    To determine the relative importance of platelet-activating factor-acetylhydrolase (PAF-AH) and lecithin-cholesterol acyltransferase (LCAT) in the hydrolysis of oxidized phosphatidylcholines (OXPCs) to lyso-phosphatidylcholine (lyso-PC), we studied the formation and metabolism of OXPCs in the plasma of normal and PAF-AH-deficient subjects. Whereas the loss of PC following oxidation was similar in the deficient and normal plasmas, the formation of lyso-PC was significantly lower, and the accumulation of OXPC was higher in the deficient plasma. Isolated LDL from the PAF-AH-deficient subjects was more susceptible to oxidation, and stimulated adhesion molecule synthesis in endothelial cells, more than the normal LDL. Oxidation of 16:0-[1-14C]-18:2 PC, equilibrated with plasma PC, resulted in the accumulation of labeled short- and long-chain OXPCs, in addition to the labeled aqueous products. The formation of the aqueous products decreased by 80%, and the accumulation of short-chain OXPC increased by 110% in the deficient plasma, compared to the normal plasma, showing that PAF-AH is predominantly involved in the hydrolysis of the truncated OXPCs. Labeled sn-2-acyl group from the long-chain OXPC was not only hydrolyzed to free fatty acid, but was preferentially transferred to diacylglycerol, in both the normal and deficient plasmas. In contrast, the acyl group from unoxidized PC was transferred only to cholesterol, showing that the specificity of LCAT is altered by OXPC. It is concluded that, while PAF-AH carries out the hydrolysis of mainly truncated OXPCs, LCAT hydrolyzes and transesterifies the long-chain OXPCs.

  10. High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol

    Science.gov (United States)

    Sethi, Amar A.; Sampson, Maureen; Warnick, Russell; Muniz, Nehemias; Vaisman, Boris; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Remaley, Alan T.

    2016-01-01

    BACKGROUND We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors. METHODS Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women ≥735 mg/L; men ≥619 mg/L) or low HDL-C (n = 42; women ≤387 mg/L; men ≤341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay. RESULTS Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) μmol · L−1 · h−1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) μmol · L−1 · h−1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P < 0.0001). CONCLUSIONS IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease. PMID:20511449

  11. Characterization of reconstituted partially purified glycerophosphate acyltransferase from Escherichia coli

    NARCIS (Netherlands)

    Kessels, J.M.M.; Bosch, H. van den

    1982-01-01

    A modification of the method of Snider and Kennedy (J. Bacteriol. (1977) 130, 1072–1083) was worked out to solubilize sn-glycero-3-phosphate acyltransferase from whole cells by Triton X-100. The solubilized preparation was used for a systematic study of the reconstitution of enzymatic activity as

  12. Concerted elevation of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin.

    Science.gov (United States)

    Meegalla, Rupalie L; Billheimer, Jeffrey T; Cheng, Dong

    2002-11-01

    Glucose and insulin are anabolic signals which upregulate the transcriptions of a series of lipogenic enzymes to convert excess carbohydrate into triglycerides for efficient energy storage. These enzymes include ATP-citrate lyase (ACL), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (G3PA). Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) is important to synthesize fatty acids into triglycerides. Two DGATs from different gene families have recently been identified. In the current study, we report that glucose preferentially enhances DGAT1 mRNA expression, whereas insulin specifically increases the level of DGAT2 mRNA. Treatment of adipocytes with glucose and insulin together results in higher DGAT activity in the membrane than cells treated with either of the agents alone, indicating that glucose and insulin have additive effect on DGAT activation. In mice treated with fast/refeeding protocol, DGAT2 mRNA decreased upon fasting and was replenished upon refeeding in adipose tissue and liver. This pattern of change was not observed for DGAT1. Inasmuch as DGAT1 mRNA is less abundant in liver, we suggest that DGAT1 is more involved in fat absorption in the intestine and in basal level triglyceride synthesis in adipose tissue where it is more highly expressed. In contrast, DGAT2 is more likely to play important roles in assembly of de novo synthesized fatty acids into VLDL particles in the liver.

  13. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves lecithin: cholesterol acyltransferase activity in rats fed enriched-cholesterol diet.

    Science.gov (United States)

    Zidan, Y; Bouderbala, S; Djellouli, F; Lacaille-Dubois, M A; Bouchenak, M

    2014-10-15

    The effects of Portulaca oleracea (Po) lyophilized aqueous extract were determined on the serum high-density lipoproteins (HDL2 and HDL3) amounts and composition, as well as on lecithin: cholesterol acyltansferase (LCAT) activity. Male Wistar rats (n = 12) were fed on 1% cholesterol-enriched diet for 10 days. After this phase, hypercholesterolemic rats (HC) were divided into two groups fed the same diet supplemented or not with Portulaca oleracea (Po-HC) (0.5%) for four weeks. Serum total cholesterol (TC) and triacylglycerols (TG), and liver TG values were respectively 1.6-, 1.8-, and 1.6-fold lower in Po-HC than in HC group. Cholesterol concentrations in LDL-HDL1, HDL2, and HDL3 were respectively 1.8, 1.4-, and 2.4-fold decreased in Po-HC group. HDL2 and HDL3 amounts, which were the sum of apolipoproteins (apos), TG, cholesteryl esters (CE), unesterified cholesterol (UC), and phospholipids (PL) contents, were respectively 4.5-fold higher and 1.2-fold lower with Po treatment. Indeed, enhanced LCAT activity (1.2-fold), its cofactor-activator apo A-I (2-fold) and its reaction product HDL2-CE (2.1-fold) were observed, whereas HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) were 1.2- and 2.4-fold lower. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves reverse cholesterol transport in rat fed enriched-cholesterol diet, contributing to anti-atherogenic effects. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Comparative genomics and proteomics of vertebrate diacylglycerol acyltransferase (DGAT), acyl CoA wax alcohol acyltransferase (AWAT) and monoacylglycerol acyltransferase (MGAT).

    Science.gov (United States)

    Holmes, Roger S

    2010-03-01

    BLAT (BLAST-Like Alignment Tool) analyses of the opossum (Monodelphis domestica) and zebrafish (Danio rerio) genomes were undertaken using amino acid sequences of the acylglycerol acyltransferase (AGAT) superfamily. Evidence is reported for 8 opossum monoacylglycerol acyltransferase-like (MGAT) (E.C. 2.3.1.22) and diacylglycerol acyltransferase-like (DGAT) (E.C. 2.3.1.20) genes and proteins, including DGAT1, DGAT2, DGAT2L6 (DGAT2-like protein 6), AWAT1 (acyl CoA wax alcohol acyltransferase 1), AWAT2, MGAT1, MGAT2 and MGAT3. Three of these genes (AWAT1, AWAT2 and DGAT2L6) are closely localized on the opossum X chromosome. Evidence is also reported for six zebrafish MGAT- and DGAT-like genes, including two DGAT1-like genes, as well as DGAT2-, MGAT1-, MGAT2- and MGAT3-like genes and proteins. Predicted primary, secondary and transmembrane structures for the opossum and zebrafish MGAT-, AWAT- and DGAT-like subunits and the intron-exon boundaries for genes encoding these enzymes showed a high degree of similarity with other members of the AGAT superfamily, which play major roles in triacylglyceride (DGAT), diacylglyceride (MGAT) and wax ester (AWAT) biosynthesis. Alignments of predicted opossum, zebrafish and other vertebrate DGAT1, DGAT2, other DGAT2-like and MGAT-like amino acid sequences with known human and mouse enzymes demonstrated conservation of residues which are likely to play key roles in catalysis, lipid binding or in maintaining structure. Phylogeny studies of the human, mouse, opossum, zebrafish and pufferfish MGAT- and DGAT-like enzymes indicated that the common ancestors for these genes predated the appearance of bony fish during vertebrate evolution whereas the AWAT- and DGAT2L6-like genes may have appeared more recently prior to the appearance of marsupial and eutherian mammals. Copyright 2009 Elsevier Inc. All rights reserved.

  15. Esterification of all-trans-retinol in normal human epithelial cell strains and carcinoma lines from oral cavity, skin and breast: reduced expression of lecithin:retinol acyltransferase in carcinoma lines.

    Science.gov (United States)

    Guo, X; Ruiz, A; Rando, R R; Bok, D; Gudas, L J

    2000-11-01

    When exogenous [(3)H]retinol (vitamin A) was added to culture medium, normal human epithelial cells from the oral cavity, skin, lung and breast took up and esterified essentially all of the [(3)H]retinol within a few hours. As shown by [(3)H]retinol pulse-chase experiments, normal epithelial cells then slowly hydrolyzed the [(3)H]retinyl esters to [(3)H]retinol, some of which was then oxidized to [(3)H]retinoic acid (RA) over a period of several days. In contrast, cultured normal human fibroblasts and human umbilical vein endothelial cells (HUVEC) did not esterify significant amounts of [(3)H]retinol; this lack of [(3)H]retinol esterification was correlated with a lack of expression of lecithin:retinol acyltransferase (LRAT) transcripts in normal fibroblast and HUVEC strains. These results indicate that normal, differentiated cell types differ in their ability to esterify retinol. Human carcinoma cells (neoplastically transformed epithelial cells) of the oral cavity, skin and breast did not esterify much [(3)H]retinol and showed greatly reduced LRAT expression. Transcripts of the neutral, bile salt-independent retinyl ester hydrolase and the bile salt-dependent retinyl ester hydrolase were undetectable in all of the normal cell types, including the epithelial cells. These experiments suggest that retinoid-deficiency in the tumor cells could develop because of the lack of retinyl esters, a storage form of retinol.

  16. Soybean oil biosynthesis: role of diacylglycerol acyltransferases.

    Science.gov (United States)

    Li, Runzhi; Hatanaka, Tomoko; Yu, Keshun; Wu, Yongmei; Fukushige, Hirotada; Hildebrand, David

    2013-03-01

    Diacylglycerol acyltransferase (DGAT) catalyzes the acyl-CoA-dependent acylation of sn-1,2-diacylglycerol to form seed oil triacylglycerol (TAG). To understand the features of genes encoding soybean (Glycine max) DGATs and possible roles in soybean seed oil synthesis and accumulation, two full-length cDNAs encoding type 1 diacylglycerol acyltransferases (GmDGAT1A and GmDGAT1B) were cloned from developing soybean seeds. These coding sequences share identities of 94 % and 95 % in protein and DNA sequences. The genomic architectures of GmDGAT1A and GmDGAT1B both contain 15 introns and 16 exons. Differences in the lengths of the first exon and most of the introns were found between GmDGAT1A and GmDGAT1B genomic sequences. Furthermore, detailed in silico analysis revealed a third predicted DGAT1, GmDGAT1C. GmDGAT1A and GmDGAT1B were found to have similar activity levels and substrate specificities. Oleoyl-CoA and sn-1,2-diacylglycerol were preferred substrates over vernoloyl-CoA and sn-1,2-divernoloylglycerol. Both transcripts are much more abundant in developing seeds than in other tissues including leaves, stem, roots, and flowers. Both soybean DGAT1A and DGAT1B are highly expressed at developing seed stages of maximal TAG accumulation with DGAT1B showing highest expression at somewhat later stages than DGAT1A. DGAT1A and DGAT1B show expression profiles consistent with important roles in soybean seed oil biosynthesis and accumulation.

  17. Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

    Science.gov (United States)

    Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

    1994-11-08

    Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosphoglycan (IPG) mediator, prepared from beef liver, bypassed this defect and comparably activated G3PAT in cell-free adipocyte preparations of both diabetic GK and control rats. A myo-inositol-containing IPG mediator did not activate G3PAT. Relative to control adipocytes, labeling of GPI by [3H]glucosamine was diminished by 50% and insulin failed to stimulate GPI hydrolysis in GK adipocytes. In contrast to GPI-dependent G3PAT activation, insulin-stimulated hexose transport was intact in adipocytes and soleus and gastrocnemius muscles of the GK rat, as was insulin-induced activation of mitogen-activated protein kinase and protein kinase C. We conclude that (i) chiro-inositol-containing IPG mediator activates G3PAT during insulin action, (ii) diabetic GK rats have a defect in synthesizing or releasing functional chiro-inositol-containing IPG, and (iii) defective IPG-regulated intracellular glucose metabolism contributes importantly to insulin resistance in diabetic GK rats.

  18. Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion.

    Science.gov (United States)

    Casaschi, Adele; Rubio, Brent K; Maiyoh, Geoffrey K; Theriault, Andre G

    2004-10-01

    The purpose of the present study was to examine the role of taxifolin, a plant flavonoid, on several aspects involving apolipoprotein B (apoB) secretion and triglyceride (TG) availability in HepG2 cells. Taxifolin was shown by ELISA to markedly reduce apoB secretion under basal and lipid-rich conditions up to 63% at 200 micromol/L. As to the mechanism underlying this effect, we examined whether taxifolin exerted its effect by limiting TG availability in the microsomal lumen essential for lipoprotein assembly. Taxifolin was shown to inhibit microsomal TG synthesis by 37% and its subsequent transfer into the lumen (-26%). The reduction in synthesis was due to a decrease in diacylglycerol acyltransferase (DGAT) activity (-35%). The effect on DGAT activity was found to be non-competitive and non-transcriptional in nature. Both DGAT-1 and DGAT-2 mRNA expression remained essentially unchanged suggesting the point of regulation may be at the post-transcriptional level. Evidence is accumulating that microsomal triglyceride transfer protein (MTP) is also involved in determining the amount of lumenal TG available for lipoprotein assembly and secretion. Taxifolin was shown to inhibit this enzyme by 41%. Whether the reduction in TG accumulation in the microsomal lumen is predominantly due to DGAT and/or MTP activity remains to be addressed. In summary, taxifolin reduced apoB secretion by limiting TG availability via DGAT and MTP activity.

  19. A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics

    Directory of Open Access Journals (Sweden)

    Kirsten Tschapalda

    2016-06-01

    Full Text Available Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened >320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1, a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests.

  20. Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Eudes, Aymerick [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mouille, Maxence [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Robinson, David S. [Joint BioEnergy Institute, Emeryville, CA (United States); Benites, Veronica T. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); San Francisco State Univ., San Francisco, CA (United States); Wang, George [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Roux, Lucien [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Ecole Polytechnique Federale de Lausanne, Lausanne (Switzerland); Tsai, Yi-Lin [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Baidoo, Edward E. K. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Chiu, Tsan-Yu [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Heazlewood, Joshua L. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); The Univ. of Melbourne, Melbourne, VIC (Australia); Scheller, Henrik V. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Mukhopadhyay, Aindrila [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Keasling, Jay D. [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States); Technical Univ. of Denmark, Horsholm (Denmark); Deutsch, Samuel [Joint BioEnergy Institute, Emeryville, CA (United States); Loqué, Dominique [Joint BioEnergy Institute, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. Claude Bernard Lyon 1, Villeurbanne (France)

    2016-11-21

    BAHD acyltransferases, named after the first four biochemically characterized enzymes of the group, are plant-specific enzymes that catalyze the transfer of coenzyme A-activated donors onto various acceptor molecules. They are responsible for the synthesis in plants of a myriad of secondary metabolites, some of which are beneficial for humans either as therapeutics or as specialty chemicals such as flavors and fragrances. The production of pharmaceutical, nutraceutical and commodity chemicals using engineered microbes is an alternative, green route to energy-intensive chemical syntheses that consume petroleum-based precursors. However, identification of appropriate enzymes and validation of their functional expression in heterologous hosts is a prerequisite for the design and implementation of metabolic pathways in microbes for the synthesis of such target chemicals. As a result, for the synthesis of valuable metabolites in the yeast Saccharomyces cerevisiae, we selected BAHD acyltransferases based on their preferred donor and acceptor substrates. In particular, BAHDs that use hydroxycinnamoyl-CoAs and/or benzoyl-CoA as donors were targeted because a large number of molecules beneficial to humans belong to this family of hydroxycinnamate and benzoate conjugates. The selected BAHD coding sequences were synthesized and cloned individually on a vector containing the Arabidopsis gene At4CL5, which encodes a promiscuous 4-coumarate:CoA ligase active on hydroxycinnamates and benzoates. The various S. cerevisiae strains obtained for co-expression of At4CL5 with the different BAHDs effectively produced a wide array of valuable hydroxycinnamate and benzoate conjugates upon addition of adequate combinations of donors and acceptor molecules. In particular, we report here for the first time the production in yeast of rosmarinic acid and its derivatives, quinate hydroxycinnamate esters such as chlorogenic acid, and glycerol hydroxycinnamate esters

  1. Defense Human Resources Activity > PERSEREC

    Science.gov (United States)

    Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

  2. Crystallization and preliminary X-ray analysis of the bacillaene synthase trans-acting acyltransferase PksC

    International Nuclear Information System (INIS)

    Cuskin, Fiona; Solovyova, Alexandra S.; Lewis, Richard J.; Race, Paul R.

    2011-01-01

    The expression, purification and crystallization of the trans-acting acyltransferase PksC from the bacillaene hybrid polyketide synthase/nonribosomal peptide synthetase is described. The crystals belonged to the orthorhombic space group P2 1 2 1 2 1 and diffracted to 1.44 Å resolution. The antibiotic bacillaene is biosynthesized in Bacillus subtilis by a hybrid type 1 modular polyketide synthase/nonribosomal peptide synthetase of the trans-acyltransferase (trans-AT) class. Within this system, the essential acyl-group loading activity is provided by the action of three free-standing trans-acting acyltransferases. Here, the recombinant expression, purification and crystallization of the bacillaene synthase trans-acting acyltransferase PksC are reported. A diffraction data set has been collected from a single PksC crystal to 1.44 Å resolution and the crystal was found to belong to the orthorhombic space group P2 1 2 1 2 1

  3. Identification of conserved regions and residues within Hedgehog acyltransferase critical for palmitoylation of Sonic Hedgehog.

    Directory of Open Access Journals (Sweden)

    John A Buglino

    2010-06-01

    Full Text Available Sonic hedgehog (Shh is a palmitoylated protein that plays key roles in mammalian development and human cancers. Palmitoylation of Shh is required for effective long and short range Shh-mediated signaling. Attachment of palmitate to Shh is catalyzed by Hedgehog acyltransferase (Hhat, a member of the membrane bound O-acyl transferase (MBOAT family of multipass membrane proteins. The extremely hydrophobic composition of MBOAT proteins has limited their biochemical characterization. Except for mutagenesis of two conserved residues, there has been no structure-function analysis of Hhat, and the regions of the protein required for Shh palmitoylation are unknown.Here we undertake a systematic approach to identify residues within Hhat that are required for protein stability and/or enzymatic activity. We also identify a second, novel MBOAT homology region (residues 196-234 that is required for Hhat activity. In total, ten deletion mutants and eleven point mutants were generated and analyzed. Truncations at the N- and C-termini of Hhat yielded inactive proteins with reduced stability. Four Hhat mutants with deletions within predicted loop regions and five point mutants retained stability but lost palmitoylation activity. We purified two point mutants, W378A and H379A, with defective Hhat activity. Kinetic analyses revealed alterations in apparent K(m and V(max for Shh and/or palmitoyl CoA, changes that likely explain the catalytic defects observed for these mutants.This study has pinpointed specific regions and multiple residues that regulate Hhat stability and catalysis. Our findings should be applicable to other MBOAT proteins that mediate lipid modification of Wnt proteins and ghrelin, and should serve as a model for understanding how secreted morphogens are modified by palmitoyl acyltransferases.

  4. The Role of Lecithin: Retinol Acyltransferase (LRAT) Mediated Esterification of Vitamin A in Regulating Human Breast Cancer Cell Proliferation and Differentiation

    National Research Council Canada - National Science Library

    Su, Dan

    2005-01-01

    .... Also, transgenic mice were generated in which human LRAT was ectopically expressed either in the suprabasal layer or in the basal layer of epithelial cells driven by the cytokeratin 10 promoter...

  5. Measurement of dihydroxyacetone-phosphate acyltransferase (DHAPAT) in chorionic villous samples, blood cells and cultured cells

    NARCIS (Netherlands)

    Wanders, R. J.; Ofman, R.; Romeijn, G. J.; Schutgens, R. B.; Mooijer, P. A.; Dekker, C.; van den Bosch, H.

    1995-01-01

    Dihydroxyacetone-phosphate acyltransferase (DHAPAT) is a peroxisomal enzyme catalysing the first step in ether-phospholipid biosynthesis. DHAPAT is deficient in cells from patients suffering from a variety of peroxisomal disorders. Accurate measurement of the activity of this enzyme is of great

  6. Discovery of an Orally Bioavailable Benzimidazole Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitor That Suppresses Body Weight Gain in Diet-Induced Obese Dogs and Postprandial Triglycerides in Humans.

    Science.gov (United States)

    Nakajima, Katsumasa; Chatelain, Ricardo; Clairmont, Kevin B; Commerford, Renee; Coppola, Gary M; Daniels, Thomas; Forster, Cornelia J; Gilmore, Thomas A; Gong, Yongjin; Jain, Monish; Kanter, Aaron; Kwak, Youngshin; Li, Jingzhou; Meyers, Charles D; Neubert, Alan D; Szklennik, Paul; Tedesco, Vivienne; Thompson, James; Truong, David; Yang, Qing; Hubbard, Brian K; Serrano-Wu, Michael H

    2017-06-08

    Modification of a gut restricted class of benzimidazole DGAT1 inhibitor 1 led to 9 with good oral bioavailability. The key structural changes to 1 include bioisosteric replacement of the amide with oxadiazole and α,α-dimethylation of the carboxylic acid, improving DGAT1 potency and gut permeability. Since DGAT1 is expressed in the small intestine, both 1 and 9 can suppress postprandial triglycerides during acute oral lipid challenges in rats and dogs. Interestingly, only 9 was found to be effective in suppressing body weight gain relative to control in a diet-induced obese dog model, suggesting the importance of systemic inhibition of DGAT1 for body weight control. 9 has advanced to clinical investigation and successfully suppressed postprandial triglycerides during an acute meal challenge in humans.

  7. Activation of lipoprotein lipase by lipoprotein fractions of human serum.

    Science.gov (United States)

    Bier, D M; Havel, R J

    1970-11-01

    Triglycerides in fat emulsions are hydrolyzed by lipoprotein lipase only when they are "activated" by serum lipoproteins. The contribution of different lipoprotein fractions to hydrolysis of triglycerides in soybean oil emulsion was assessed by determining the quantity of lipoprotein fraction required to give half-maximal hydrolysis. Most of the activator property of whole serum from normolipidemic, postabsorptive subjects was in high density lipoproteins. Low density lipoproteins and serum from which all lipoprotein classes were removed had little or no activity. Also, little activator was present in guinea pig serum or in very low density poor serum from an individual with lecithin:cholesterol acyltransferase deficiency, both of which are deficient in high density lipoproteins. Human very low density lipoproteins are potent activators and are much more active than predicted from their content of high density lipoprotein-protein. Per unit weight of protein, very low density lipoproteins had 13 times the activity of high density lipoproteins. These observations suggest that one or more of the major apoproteins of very low density lipoproteins, present as a minor constituent of high density lipoproteins, may be required for the activation process.

  8. Nucleotide sequence of a cDNA for branched chain acyltransferase with analysis of the deduced protein structure

    International Nuclear Information System (INIS)

    Hummel, K.B.; Litwer, S.; Bradford, A.P.; Aitken, A.; Danner, D.J.; Yeaman, S.J.

    1988-01-01

    Nucleotide sequence was determined for a 1.6-kilobase human cDNA putative for the branched chain acyltransferase protein of the branched chain α-ketoacid dehydrogenase complex. Translation of the sequence reveals an open reading frame encoding a 315-amino acid protein of molecular weight 35,759 followed by 560 bases of 3'-untranslated sequence. Three repeats of the polyadenylation signal hexamer ATTAAA are present prior to the polyadenylate tail. Within the open reading frame is a 10-amino acid fragment which matches exactly the amino acid sequence around the lipoate-lysine residue in bovine kidney branched chain acyltransferase, thus confirming the identity of the cDNA. Analysis of the deduced protein structure for the human branched chain acyltransferase revealed an organization into domains similar to that reported for the acyltransferase proteins of the pyruvate and α-ketoglutarate dehydrogenase complexes. This similarity in organization suggests that a more detailed analysis of the proteins will be required to explain the individual substrate and multienzyme complex specificity shown by these acyltransferases

  9. Functional roles of three cutin biosynthetic acyltransferases in cytokinin responses and skotomorphogenesis.

    Directory of Open Access Journals (Sweden)

    Lei Wu

    Full Text Available Cytokinins (CKs regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1, whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr. GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase with diacylglycerol acyltransferase (DGAT activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8 double mutant [defective in glycerol-3-phosphate (G3P acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1, which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis.

  10. Induction of 1-Acylglycerophosphocholine Acyltransferase Genes by Fibrates in the Liver of Rats

    OpenAIRE

    山崎, 研; 若林, 美智子; 池田, 英里香; 田中, 静代; 坂本, 武史; 光本, 篤史; 工藤, なをみ; 川嶋, 洋一

    2012-01-01

    The effect of fibrates (clofibric acid, bezafibrate and fenofibrate) on the gene expression and activity of 1-acylglycerophosphocholine acyltransferase (LPCAT) was investigated. The administration of 0.1% (w/w) clofibric acid, bezafibrate or fenofibrate in diet for 14?d to rats induced LPCAT activity in hepatic microsomes in the following order: fenofibrate>bezafibrate>clofibric acid. The LPCAT induced by fenofibrate preferred to arachidonoyl-CoA and linoleoyl-CoA to a greater extent than did...

  11. Essential oil of Pinus koraiensis leaves exerts antihyperlipidemic effects via up-regulation of low-density lipoprotein receptor and inhibition of acyl-coenzyme A: cholesterol acyltransferase.

    Science.gov (United States)

    Kim, Ji-Hyun; Lee, Hyo-Jung; Jeong, Soo-Jin; Lee, Min-Ho; Kim, Sung-Hoon

    2012-09-01

    Hyperlipidemia is an important factor to induce metabolic syndrome such as obesity, diabetes and cardiovascular diseases. Recently, some antihyperlipidemic agents from herbal medicines have been in the spotlight in the medical science field. Thus, the present study evaluated the antihyperlipidemic activities of the essential oil from the leaves of Pinus koraiensis SIEB (EOPK) that has been used as a folk remedy for heart disease. The reverse transcription polymerase chain reaction (RT-PCR) revealed that EOPK up-regulated low density lipoprotein receptor (LDLR) at the mRNA level as well as negatively suppressed the expression of sterol regulatory element-binding protein (SREBP)-1c, SREBP-2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) involved in lipid metabolism in HepG2 cells. Also, western blotting showed that EOPK activated LDLR and attenuated the expression of FAS at the protein level in the cells. Consistently, EOPK significantly inhibited the level of human acylcoenzyme A: cholesterol acyltransferase (hACAT)1 and 2 and reduced the low-density lipoprotein (LDL) oxidation activity. Furthermore, chromatography-mass spectrometry (GC-MS) analysis showed that EOPK, an essential oil mixture, contained camphene (21.11%), d-limonene (21.01%), α-pinene (16.74%) and borneol (11.52%). Overall, the findings suggest that EOPK can be a potent pharmaceutical agent for the prevention and treatment of hyperlipidemia. Copyright © 2012 John Wiley & Sons, Ltd.

  12. In vitro production of beta-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin:cholester acyltransferase, cholesterylester transfer proteins and lipoprotein lipase.

    Science.gov (United States)

    Chung, B H; Segrest, J P; Franklin, F

    1998-12-01

    As a model for the formation of beta-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoproteins in fresh plasma were interacted in vitro with endogenous lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C for 18 h resulted in (1) esterification of about 45% plasma unesterified cholesterol (UC), (2) a marked increase in cholesterylester (CE) (+129%) and a decrease in triglyceride (TG) (-45%) in VLDL, and (3) a marked increase of TG (+ 341%) with a small net decrease of CE (-3.6%) in LDL, causing a significant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (from 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCAT and CETP-reacted plasma by LpL, which hydrolyzed >90% of VLDL-TG and about 50-60% of LDL-TG, converted most of VLDL in control plasma (>85%) but less than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LDL density fraction and transformed the large, buoyant LDL in the LCAT and CETP-reacted plasma into particles smaller and denser than those in the control plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained apo B-100 and E but little or no detectable apo Cs and consisted of particles having pre-beta and beta-electrophoretic mobilities. The inhibition of LCAT during incubation of plasma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density region but lowered the extent of alteration in the size and density of LDL. The LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normolipidemic fasting plasma were less pronounced

  13. Deficiency of acyl-CoA: Dihydroxyacetone phosphate acyltransferase in patients with Zellweger (cerebro-hepato-renal) syndrome

    NARCIS (Netherlands)

    Bosch, H. van den; Schutgens, R.B.H.; Romeyn, G.J.; Wanders, R.J.A.; Schrakamp, G.; Heymans, H.S.A.

    1984-01-01

    We have recently reported on plasmalogen deficiency in tissues and fibroblasts from patients with Zellweger syndrome. In this paper we have analyzed the activity of the first enzyme in the pathway leading to plasmalogen biosynthesis, i.e. acyl-CoA: dihydroxyacetone phosphate acyltransferase in

  14. Molecular Characterization of Two Lysophospholipid:acyl-CoA Acyltransferases Belonging to the MBOAT Family in Nicotiana benthamiana.

    Directory of Open Access Journals (Sweden)

    Donghui Zhang

    Full Text Available In the remodeling pathway for the synthesis of phosphatidylcholine (PC, acyl-CoA-dependent lysophosphatidylcholine (lysoPC acyltransferase (LPCAT catalyzes the reacylation of lysoPC. A number of genes encoding LPCATs have been cloned and characterized from several plants in recent years. Using Arabidopsis and other plant LPCAT sequences to screen the genome database of Nicotiana benthamiana, we identified two cDNAs encoding the putative tobacco LPCATs (NbLPCAT1 and NbLPCAT2. Both of them were predicted to encode a protein of 463 amino acids with high similarity to LPCATs from other plants. Protein sequence features such as the presence of at least eight putative transmembrane regions, four highly conserved signature motifs and several invariant residues indicate that NbLPCATs belong to the membrane bound O-acyltransferase family. Lysophospholipid acyltransferase activity of NbLPCATs was confirmed by testing lyso-platelet-activating factor (lysoPAF sensitivity through heterologous expression of each full-length cDNA in a yeast mutant Y02431 (lca1△ disrupted in endogenous LPCAT enzyme activity. Analysis of fatty acid profiles of phospholipids from the NbLPCAT-expressing yeast mutant Y02431 cultures supplemented with polyunsaturated fatty acids suggested more incorporation of linoleic acid (18:2n6, LA and α-linolenic acid (18:3n3, ALA into PC compared to yeast mutant harbouring empty vector. In vitro enzymatic assay demonstrated that NbLPCAT1had high lysoPC acyltransferase activity with a clear preference for α-linolenoyl-CoA (18:3, while NbLPCAT2 showed a high lysophosphatidic acid (lysoPA acyltransferase activity towards α-linolenoyl-CoA and a weak lysoPC acyltransferase activity. Tissue-specific expression analysis showed a ubiquitous expression of NbLPCAT1 and NbLPCAT2 in roots, stems, leaves, flowers and seeds, and a strong expression in developing flowers. This is the first report on the cloning and characterization of lysophospholipid

  15. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .

  16. Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation.

    Science.gov (United States)

    Goyal, J; Wang, K; Liu, M; Subbaiah, P V

    1997-06-27

    Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.

  17. Human Activity in the Web

    OpenAIRE

    Radicchi, Filippo

    2009-01-01

    The recent information technology revolution has enabled the analysis and processing of large-scale datasets describing human activities. The main source of data is represented by the Web, where humans generally use to spend a relevant part of their day. Here we study three large datasets containing the information about Web human activities in different contexts. We study in details inter-event and waiting time statistics. In both cases, the number of subsequent operations which differ by ta...

  18. Diacylglycerol acyltransferase-2 (DGAT2) and monoacylglycerol acyltransferase-2 (MGAT2) interact to promote triacylglycerol synthesis.

    Science.gov (United States)

    Jin, Youzhi; McFie, Pamela J; Banman, Shanna L; Brandt, Curtis; Stone, Scot J

    2014-10-10

    Acyl CoA:1,2-diacylglycerol acyltransferase (DGAT)-2 is an integral membrane protein that catalyzes triacylglycerol (TG) synthesis using diacylglycerol and fatty acyl CoA as substrates. DGAT2 resides in the endoplasmic reticulum (ER), but when cells are incubated with fatty acids, DGAT2 interacts with lipid droplets presumably to catalyze localized TG synthesis for lipid droplet expansion. Previous studies have shown that DGAT2 interacts with proteins that synthesize its fatty acyl CoA substrates. In this study, we provide additional evidence that DGAT2 is present in a protein complex. Using a chemical cross-linker, disuccinimidyl suberate (DSS), we demonstrated that DGAT2 formed a dimer and was also part of a protein complex of ∼ 650 kDa, both in membranes and on lipid droplets. Using co-immunoprecipitation experiments and an in situ proximity ligation assay, we found that DGAT2 interacted with monoacylglycerol acyltransferase (MGAT)-2, an enzyme that catalyzes the synthesis of diacylglycerol. Deletion mutagenesis showed that the interaction with MGAT2 was dependent on the two transmembrane domains of DGAT2. No significant interaction of DGAT2 with lipin1, another enzyme that synthesizes diacylglycerol, could be detected. When co-expressed in cells, DGAT2 and MGAT2 co-localized in the ER and on lipid droplets. Co-expression also resulted in increased TG storage compared with expression of DGAT2 or MGAT2 alone. Incubating McArdle rat hepatoma RH7777 cells with 2-monoacylglycerol caused DGAT2 to translocate to lipid droplets. This also led to the formation of large cytosolic lipid droplets, characteristic of DGAT2, but not DGAT1, and indicated that DGAT2 can utilize monoacylglycerol-derived diacylglycerol. These findings suggest that the interaction of DGAT2 and MGAT2 serves to channel lipid substrates efficiently for TG biosynthesis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Diacylglycerol Acyltransferase-2 (DGAT2) and Monoacylglycerol Acyltransferase-2 (MGAT2) Interact to Promote Triacylglycerol Synthesis*

    Science.gov (United States)

    Jin, Youzhi; McFie, Pamela J.; Banman, Shanna L.; Brandt, Curtis; Stone, Scot J.

    2014-01-01

    Acyl CoA:1,2-diacylglycerol acyltransferase (DGAT)-2 is an integral membrane protein that catalyzes triacylglycerol (TG) synthesis using diacylglycerol and fatty acyl CoA as substrates. DGAT2 resides in the endoplasmic reticulum (ER), but when cells are incubated with fatty acids, DGAT2 interacts with lipid droplets presumably to catalyze localized TG synthesis for lipid droplet expansion. Previous studies have shown that DGAT2 interacts with proteins that synthesize its fatty acyl CoA substrates. In this study, we provide additional evidence that DGAT2 is present in a protein complex. Using a chemical cross-linker, disuccinimidyl suberate (DSS), we demonstrated that DGAT2 formed a dimer and was also part of a protein complex of ∼650 kDa, both in membranes and on lipid droplets. Using co-immunoprecipitation experiments and an in situ proximity ligation assay, we found that DGAT2 interacted with monoacylglycerol acyltransferase (MGAT)-2, an enzyme that catalyzes the synthesis of diacylglycerol. Deletion mutagenesis showed that the interaction with MGAT2 was dependent on the two transmembrane domains of DGAT2. No significant interaction of DGAT2 with lipin1, another enzyme that synthesizes diacylglycerol, could be detected. When co-expressed in cells, DGAT2 and MGAT2 co-localized in the ER and on lipid droplets. Co-expression also resulted in increased TG storage compared with expression of DGAT2 or MGAT2 alone. Incubating McArdle rat hepatoma RH7777 cells with 2-monoacylglycerol caused DGAT2 to translocate to lipid droplets. This also led to the formation of large cytosolic lipid droplets, characteristic of DGAT2, but not DGAT1, and indicated that DGAT2 can utilize monoacylglycerol-derived diacylglycerol. These findings suggest that the interaction of DGAT2 and MGAT2 serves to channel lipid substrates efficiently for TG biosynthesis. PMID:25164810

  20. Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors.

    Science.gov (United States)

    Lee, Kyeong; Goo, Ja-Il; Jung, Hwa Young; Kim, Minkyoung; Boovanahalli, Shanthaveerappa K; Park, Hye Ran; Kim, Mun-Ock; Kim, Dong-Hyun; Lee, Hyun Sun; Choi, Yongseok

    2012-12-15

    A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Lysophosphatidic acid acyltransferase beta regulates mTOR signaling.

    Directory of Open Access Journals (Sweden)

    Michelle A Blaskovich

    Full Text Available Lysophosphatidic acid acyltransferase (LPAAT-β is a phosphatidic acid (PA generating enzyme that plays an essential role in triglyceride synthesis. However, LPAAT-β is now being studied as an important regulator of cell growth and differentiation and as a potential therapeutic target in cancer since PA is necessary for the activity of key proteins such as Raf, PKC-ζ and mTOR. In this report we determine the effect of LPAAT-β silencing with siRNA in pancreatic adenocarcinoma cell lines. We show for the first time that LPAAT-β knockdown inhibits proliferation and anchorage-independent growth of pancreatic cancer cells. This is associated with inhibition of signaling by mTOR as determined by levels of mTORC1- and mTORC2-specific phosphorylation sites on 4E-BP1, S6K and Akt. Since PA regulates the activity of mTOR by modulating its binding to FKBP38, we explored the possibility that LPAAT-β might regulate mTOR by affecting its association with FKBP38. Coimmunoprecipitation studies of FKBP38 with mTOR show increased levels of FKBP38 associated with mTOR when LPAAT-β protein levels are knocked down. Furthermore, depletion of LPAAT-β results in increased Lipin 1 nuclear localization which is associated with increased nuclear eccentricity, a nuclear shape change that is dependent on mTOR, further confirming the ability of LPAAT-β to regulate mTOR function. Our results provide support for the hypothesis that PA generated by LPAAT-β regulates mTOR signaling. We discuss the implications of these findings for using LPAAT-β as a therapeutic target.

  2. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  3. HUMAN ACTIVITY MONITORING USING SMARTPHONE

    OpenAIRE

    TOKALA, SAI SUJIT; ROKALA, RANADEEP

    2014-01-01

    The main aim of the project is to develop an algorithm which will classify the activity performed by a human who is carrying a smart phone. The day to day life made humans very busy at work and during daily activities, mostly elderly people who are at home have an important need to monitor their activity by others when they are alone, if they are inactive for a long time without movement, or in some situations like if they have fallen down, became unconscious for sometime or seized with a car...

  4. Controlling Lipid Fluxes at Glycerol-3-phosphate Acyltransferase Step in Yeast

    Science.gov (United States)

    Marr, Nancy; Foglia, Julena; Terebiznik, Mauricio; Athenstaedt, Karin; Zaremberg, Vanina

    2012-01-01

    The ability to channel excess fatty acids into neutral lipids like triacylglycerol (TAG) is a critical strategy used by cells to maintain lipid homeostasis. Upon activation to acyl-CoA, fatty acids become readily available as substrates for acyltransferases involved in neutral lipid synthesis. Neutral lipids are then packed into organelles derived from the endoplasmic reticulum called lipid particles (LPs). The first acylation step in the de novo pathway for TAG synthesis is catalyzed by glycerol-3-phosphate acyltransferases (GPATs). Two isoforms, Gat1p/Gpt2p and Gat2p/Sct1p, are present in the yeast Saccharomyces cerevisiae. Previous evidence indicated that these enzymes contribute differentially to the synthesis of TAG in actively growing cells. In this work we studied the role of the yeast GPATs in the formation of LPs induced by a surplus of oleic acid. Yeast lacking Gat1p (but not Gat2p) were sensitive to oleate and failed to accumulate LPs induced by this unsaturated fatty acid. It is shown that oleate induces dephosphorylation of Gat1p as well as an increment in its levels. Most importantly, we identified novel Gat1p crescent structures that are formed in the presence of oleate. These structures are connected with the endoplasmic reticulum and are intimately associated with LPs. No such structures were observed for Gat2p. A crucial point of control of lipid fluxes at the GPAT step is proposed. PMID:22267742

  5. Inhibition of ghrelin o-acyltransferase attenuated lipotoxicity by inducing autophagy via AMPK–mTOR pathway

    Directory of Open Access Journals (Sweden)

    Zhang S

    2018-04-01

    Full Text Available Shaoren Zhang, Yuqing Mao, Xiaoming Fan Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai, China Background: Nonalcoholic fatty liver disease (NAFLD has been considered the most commonly occurring chronic hepatopathy in the world. Ghrelin o-acyltransferase (GOAT is an acylation enzyme which has an acylated position 3 serine on ghrelin. Recent investigation revealed that activated autophagy could attenuate liver steatosis. The aim of this study was to explore therapeutic roles that inhibit GOAT exerted in NAFLD, and its potential association with autophagy.Materials and methods: Human LO2 cells were pretreated with siRNA-GOAT to induce liver steatosis using free fatty acids (FFAs. A chronic NAFLD model was established by feeding male mice C57bl/6 with high-fat diet (HFD for 56 days with GO-CoA-Tat administrated subcutaneously. Lipid droplets were identified by Oil Red O stains. Body weight (BW of mice was measured every week. Autophagy, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, serum biochemical indicators (glucose [Glu], total cholesterol [TC], triglyceride [TG], aspartate aminotransferase [AST], alanine aminotransferase [ALT] and signaling pathway proteins of phosphorylated AMPK–mTOR were measured.Results: The TG contents of the FFA and HFD groups were decreased by the inhibition of GOAT. Among mice treated with GO-CoA-Tat and siRNA-GOAT, IL-6 and TNF-α concentrations were remarkably decreased. Indicators of liver injury such as ALT and AST were also remarkably decreased among mice treated with GO-CoA-Tat. Likewise, GO-CoA-Tat significantly reduced the BW of mice and serum TG, TC and Glu. Autophagy was induced along with reduced lipids in the cells of the FFA and HFD groups. The inhibition of GOAT upregulated autophagy via AMPK–mTOR restoration.Conclusion: These results indicate that the inhibition of GOAT attenuates lipotoxicity by autophagy stimulation via AMPK–mTOR restoration

  6. A soluble diacylglycerol acyltransferase is involved in triacylglycerol biosynthesis in the oleaginous yeast Rhodotorula glutinis.

    Science.gov (United States)

    Rani, Sapa Hima; Saha, Saikat; Rajasekharan, Ram

    2013-01-01

    The biosynthesis of triacylglycerol (TAG) occurs in the microsomal membranes of eukaryotes. Here, we report the identification and functional characterization of diacylglycerol acyltransferase (DGAT), a member of the 10 S cytosolic TAG biosynthetic complex (TBC) in Rhodotorula glutinis. Both a full-length and an N-terminally truncated cDNA clone of a single gene were isolated from R. glutinis. The DGAT activity of the protein encoded by RgDGAT was confirmed in vivo by the heterologous expression of cDNA in a Saccharomyces cerevisiae quadruple mutant (H1246) that is defective in TAG synthesis. RgDGAT overexpression in yeast was found to be capable of acylating diacylglycerol (DAG) in an acyl-CoA-dependent manner. Quadruple mutant yeast cells exhibit growth defects in the presence of oleic acid, but wild-type yeast cells do not. In an in vivo fatty acid supplementation experiment, RgDGAT expression rescued quadruple mutant growth in an oleate-containing medium. We describe a soluble acyl-CoA-dependent DAG acyltransferase from R. glutinis that belongs to the DGAT3 class of enzymes. The study highlights the importance of an alternative TAG biosynthetic pathway in oleaginous yeasts.

  7. Involvement of an octose ketoreductase and two acyltransferases in the biosynthesis of paulomycins

    Science.gov (United States)

    Li, Jine; Wang, Min; Ding, Yong; Tang, Yue; Zhang, Zhiguo; Chen, Yihua

    2016-02-01

    C-4 hydroxyethyl branched octoses have been observed in polysaccharides of several genera of gram negative bacteria and in various antibiotics produced by gram positive bacteria. The C-4 hydroxyethyl branch was proposed to be converted from C-4 acetyl branch by an uncharacterized ketoreduction step. Paulomycins (PAUs) are glycosylated antibiotics with potent inhibitory activity against gram positive bacteria and are structurally defined by its unique C-4‧ hydroxyethyl branched paulomycose moiety. A novel aldo-keto-reductase, Pau7 was characterized as the enzyme catalyzing the stereospecific ketoreduction of 7‧-keto of PAU E (1) to give the C-4‧ hydroxyethyl branched paulomycose moiety of PAU F (2). An acyltransferase Pau6 further decorates the C-4‧ hydroxyethyl branch of paulomycose moiety of 2 by attaching various fatty acyl chains to 7‧-OH to generate diverse PAUs. In addition, another acyltransferase Pau24 was proposed to be responsible for the 13-O-acetylation of PAUs.

  8. Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase

    Science.gov (United States)

    Glukhova, Alisa; Hinkovska-Galcheva, Vania; Kelly, Robert; Abe, Akira; Shayman, James A.; Tesmer, John J. G.

    2015-03-01

    Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

  9. Physical activity and human health

    Directory of Open Access Journals (Sweden)

    Paulina Wojciechowska

    2015-01-01

    Full Text Available Introduction: The dynamic development of the automotive industry, transport, and the media means that human life has become much easier. At the same time, the comfortable living conditions have decreased physical activity. Biologically conditioned, the need of activity has been minimised by the ever-increasing pace of life. As a result, it may lead to the loss of physical and mental health. Active recreation is not only an excellent source of activity, but also a source of satisfaction. Youths and adults should therefore spend their free time primarily on various forms of physical activity. Aim of the research : To evaluate the physical fitness of students who regularly practice physical exercise, those who occasionally practice, and those not practicing any form of physical activity. Material and methods : In the research we used a questionnaire of the Ruffier test and an orthostatic test. The study involved a group of 15 people aged 20–25 years. Participation in the study was entirely voluntary and anonymous. The study group consisted only of women. Results obtained from the questionnaire survey were fully reflected during exercise tests performed. Results and conclusions: Only regularly practiced physical activity has an effect on our body. Regular exercise increases our body’s physical capacity. Activity is the best means of prevention of lifestyle diseases. Youths and adults should spend their free time mainly doing various forms of physical activity.

  10. Catalytic center of lecithin:cholesterol acyltransferase: isolation and sequence of diisopropyl fluorophosphate-labeled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Park, Y.B.; Yueksel, U.G.; Gracy, R.W.; Lacko, A.G.

    1987-02-27

    Lecithin:cholesterol acyltransferase (LCAT) was purified from hog plasma and subsequently reacted with (/sup 3/H)-Diisopropyl fluorophosphate (DFP). The labeled enzyme was digested with pepsin and the peptides separated by high performance liquid chromatography (HPLC). Two radioactive peptides were isolated, subjected to automated amino acid sequencing and yielded the following data: A) Ile-Ser-Leu-Gly-Ala-Pro-Trp-Gly-Gly-Ser, and B) Tyr-Ile-Phe-Asp-x-Gly-Phe-Pro-Tyr-x-Asp-Pro-Val. Both of these sequences represent very highly conserved regions of the enzyme when compared to the sequence of human LCAT. Peptide (A) is considered to represent the catalytic center of LCAT based on comparisons with data reported in the literature.

  11. The role of acyl-CoA:diacylglycerol acyltransferase (DGAT) in energy metabolism.

    Science.gov (United States)

    Yu, Yi-Hao; Ginsberg, Henry N

    2004-01-01

    Acyl-CoA:diacylglycerol acyltransferase (DGAT, EC2.3.1.20), a key enzyme in triglyceride (TG) biosynthesis, not only participates in lipid metabolism but also influences metabolic pathways of other fuel molecules. Changes in the expression and/or activity levels of DGAT may lead to changes in systemic insulin sensitivity and energy homeostasis. The synthetic role of DGAT in adipose tissue, the liver, and the intestine, sites where endogenous levels of DGAT activity and TG synthesis are high, is relatively clear. Less clear is whether DGAT plays a mediating or preventive role in the development of ectopic lipotoxicity in tissues such as muscle and the pancreas, when their supply of free fatty acids (FFAs) exceeds their needs. Future studies with tissue-specific overexpression and/or knockout in these animal models would be expected to shed additional light on these issues.

  12. Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.

    Science.gov (United States)

    Caldo, Kristian Mark P; Acedo, Jeella Z; Panigrahi, Rashmi; Vederas, John C; Weselake, Randall J; Lemieux, M Joanne

    2017-10-01

    Diacylglycerol acyltransferase 1 (DGAT1) is an integral membrane enzyme catalyzing the final and committed step in the acyl-coenzyme A (CoA)-dependent biosynthesis of triacylglycerol (TAG). The biochemical regulation of TAG assembly remains one of the least understood areas of primary metabolism to date. Here, we report that the hydrophilic N-terminal domain of Brassica napus DGAT1 (BnaDGAT1 1-113 ) regulates activity based on acyl-CoA/CoA levels. The N-terminal domain is not necessary for acyltransferase activity and is composed of an intrinsically disordered region and a folded segment. We show that the disordered region has an autoinhibitory function and a dimerization interface, which appears to mediate positive cooperativity, whereas the folded segment of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA. Under increasing acyl-CoA levels, the binding of acyl-CoA with this noncatalytic site facilitates homotropic allosteric activation. Enzyme activation, on the other hand, is prevented under limiting acyl-CoA conditions (low acyl-CoA-to-CoA ratio), whereby CoA acts as a noncompetitive feedback inhibitor through interaction with the same folded segment. The three-dimensional NMR solution structure of the allosteric site revealed an α-helix with a loop connecting a coil fragment. The conserved amino acid residues in the loop interacting with CoA were identified, revealing details of this important regulatory element for allosteric regulation. Based on these results, a model is proposed illustrating the role of the N-terminal domain of BnaDGAT1 as a positive and negative modulator of TAG biosynthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

  13. Co-ordinate induction of hepatic mitochondrial and peroxisomal carnitine acyltransferase synthesis by diet and drugs.

    Science.gov (United States)

    Brady, P S; Marine, K A; Brady, L J; Ramsay, R R

    1989-01-01

    The present studies examined the effect of agents that induce peroxisomal and mitochondrial beta-oxidation on hepatic mitochondrial carnitine palmitoyltransferase (CPT) and peroxisomal carnitine acyltransferase [CPTs of Ramsay (1988) Biochem. J. 249, 239-245; COT of Farrell & Bieber (1983) Arch. Biochem. Biophys. 222, 123-132 and Miyazawa, Ozasa, Osumi & Hashimoto (1983) J. Biochem. 94, 529-542]. In the first studies, high fat diets containing corn oil or fish oil were used to induce peroxisomal and mitochondrial enzymes. Rats were fed one of three diets for 4 weeks: (1) low fat, with corn oil as 11% of energy (kJ); (2) high fat, with corn oil as 45% of kJ; (3) high fat, with fish oil as 45% of kJ. At the end of 4 weeks, both mitochondrial CPT and peroxisomal CPTs exhibited increases in activity, immunoreactive protein, mRNA levels and transcription rates in livers of rats fed either high-fat diet compared to the low fat diet. Riboflavin deficiency or starvation for 48 h also increased the peroxisomal CPTs mRNA. A second set of studies used the plasticizer 2-(diethylhexyl)phthalate (DEHP), 0.5% clofibrate or 1% acetylsalicylic acid (fed for 3 weeks) to alter peroxisomal and mitochondrial fatty acid oxidation. With DEHP, the mitochondrial CPT and peroxisomal CPTs activity, immunoreactive protein, mRNA levels and and transcription rate were all increased by 3-5-fold. The peroxisomal CPTs activity, immunoreactive protein, mRNA levels and transcription rate were increased 2-3-fold by clofibrate and acetylsalicylic acid, again similar to mitochondrial CPT. The results of the combined studies using both diet and drugs to cause enzyme induction suggest that the synthesis of the carnitine acyltransferases (mitochondrial CPT and peroxisomal CPTs) may be co-ordinated with each other; however, the co-ordinate regulatory factors have not yet been identified. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:2775196

  14. Evidence that Plasmodium falciparum diacylglycerol acyltransferase is essential for intraerythrocytic proliferation

    International Nuclear Information System (INIS)

    Palacpac, Nirianne Marie Q.; Hiramine, Yasushi; Seto, Shintaro; Hiramatsu, Ryuji; Horii, Toshihiro; Mitamura, Toshihide

    2004-01-01

    In triacylglycerol (TAG)-accumulating organisms, the physiological roles of diacylglycerol acyltransferase (DGAT), a principal enzyme in the major biosynthetic pathway for TAG, appear to be diverse. Apicomplexan parasite, Plasmodium falciparum, shows unique features in TAG metabolism and trafficking during intraerythrocytic development, and unlike most eukaryotes, only one open reading frame (ORF) encoding a candidate DGAT could be found in its genome. However, whether this candidate ORF encodes P. falciparum DGAT and its physiological relevance have not been assessed. Here, we demonstrate that the ORF is transcribed as a ∼3.6 kb single mRNA throughout intraerythrocytic development, markedly elevated at trophozoite, schizont, and segmented schizont, and indeed encodes a protein exhibiting DGAT activity. Further, we provide evidence that the parasite in which the ORF was disrupted via double crossover recombination cannot be enriched, implying a fundamental role of PfDGAT in intraerythrocytic proliferation

  15. Diacylglycerol acyltransferase-1 (DGAT1 inhibition perturbs postprandial gut hormone release.

    Directory of Open Access Journals (Sweden)

    Hua V Lin

    Full Text Available Diacylglycerol acyltransferase-1 (DGAT1 is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1 and peptide YY (PYY only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4 inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases.

  16. Stereochemical and positional specificity of the lipase/acyltransferase produced by Aeromonas hydrophila.

    Science.gov (United States)

    Robertson, D L; Hilton, S; Buckley, J T

    1992-06-02

    Aeromonas species secrete a glycerophospholipid-cholesterol acyltransferase (GCAT) which shares many properties with mammalian plasma lecithin-cholesterol acetyltransferase (LCAT). We have studied the stereochemical and positional specificity of GCAT against a variety of lipid substrates using NMR spectroscopy as well as other assay methods. The results show that both the primary and secondary acyl ester bonds of L-phosphatidylcholine can be hydrolyzed but only the sn-2 fatty acid can be transferred to cholesterol. The enzyme has an absolute requirement for the L configuration at the sn-2 position of phosphatidylcholine. The secondary ester bond of D-phosphatidylcholine cannot be hydrolyzed, and this lipid is not a substrate for acyl transfer. In contrast to the phospholipases, but similar to LCAT, the enzyme does not interact stereochemically with the phosphorus of phosphatidylcholine. In fact, the phosphorus is not required for enzyme activity, as GCAT will also hydrolyze monolayers of diglyceride, although at much lower rates.

  17. An in vitro fatty acylation assay reveals a mechanism for Wnt recognition by the acyltransferase Porcupine.

    Science.gov (United States)

    Asciolla, James J; Miele, Matthew M; Hendrickson, Ronald C; Resh, Marilyn D

    2017-08-18

    Wnt proteins are a family of secreted signaling proteins that play key roles in regulating cell proliferation in both embryonic and adult tissues. Production of active Wnt depends on attachment of palmitoleate, a monounsaturated fatty acid, to a conserved serine by the acyltransferase Porcupine (PORCN). Studies of PORCN activity relied on cell-based fatty acylation and signaling assays as no direct enzyme assay had yet been developed. Here, we present the first in vitro assay that accurately recapitulates PORCN-mediated fatty acylation of a Wnt substrate. The critical feature is the use of a double disulfide-bonded Wnt peptide that mimics the two-dimensional structure surrounding the Wnt acylation site. PORCN-mediated Wnt acylation was abolished when the Wnt peptide was treated with DTT, and did not occur with a linear (non-disulfide-bonded) peptide, or when the double disulfide-bonded Wnt peptide contained Ala substituted for the Ser acylation site. We exploited this in vitro Wnt acylation assay to provide direct evidence that the small molecule LGK974, which is in clinical trials for managing Wnt-driven tumors, is a bona fide PORCN inhibitor whose IC 50 for inhibition of Wnt fatty acylation in vitro closely matches that for inhibition of Wnt signaling. Side-by-side comparison of PORCN and Hedgehog acyltransferase (HHAT), two enzymes that attach 16-carbon fatty acids to secreted proteins, revealed that neither enzyme will accept the other's fatty acyl-CoA or peptide substrates. These findings illustrate the unique enzyme-substrate selectivity exhibited by members of the membrane-bound O -acyl transferase family. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. A Novel Complementation Assay for Quick and Specific Screen of Genes Encoding Glycerol-3-Phosphate Acyltransferases

    Directory of Open Access Journals (Sweden)

    Jie Lei

    2018-03-01

    Full Text Available The initial step in glycerolipid biosynthesis, especially in diverse allopolyploid crop species, is poorly understood, mainly due to the lack of an effective and convenient method for functional characterization of genes encoding glycerol-3-phosphate acyltransferases (GPATs catalyzing this reaction. Here we present a novel complementation assay for quick and specific characterization of GPAT-encoding genes. Its key design involves rational construction of yeast conditional lethal gat1Δgat2Δ double mutant bearing the heterologous Arabidopsis AtGPAT1 gene whose leaky expression under repressed conditions does not support any non-specific growth, thereby circumventing the false positive problem encountered with the system based on the gat1Δgat2Δ mutant harboring the native episomal GAT1 gene whose leaky expression appears to be sufficient for generating enough GPAT activities for the non-specific restoration of the mutant growth. A complementation assay developed based on this novel mutant enables quick phenotypic screen of GPAT sequences. A high degree of specificity of our assay was exemplified by its ability to differentiate effectively GPAT-encoding genes from those of other fatty acyltransferases and lipid-related sequences. Using this assay, we show that Arabidopsis AtGPAT1, AtGPAT5, and AtGPAT7 can complement the phosphatidate biosynthetic defect in the double mutants. Collectively, our assay provides a powerful tool for rapid screening, validation and optimization of GPAT sequences, aiding future engineering of the initial step of the triacylglycerol biosynthesis in oilseeds.

  19. Role of Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase in Oleaginous Streptomyces sp. Strain G25

    Science.gov (United States)

    Röttig, Annika; Strittmatter, Carl Simon; Schauer, Jennifer; Hiessl, Sebastian; Daniel, Rolf

    2016-01-01

    ABSTRACT Recently, we isolated a novel Streptomyces strain which can accumulate extraordinarily large amounts of triacylglycerol (TAG) and consists of 64% fatty acids (dry weight) when cultivated with glucose and 50% fatty acids (dry weight) when cultivated with cellobiose. To identify putative gene products responsible for lipid storage and cellobiose utilization, we analyzed its draft genome sequence. A single gene encoding a wax ester synthase/acyl coenzyme A (CoA):diacylglycerol acyltransferase (WS/DGAT) was identified and heterologously expressed in Escherichia coli. The purified enzyme AtfG25 showed acyltransferase activity with C12- or C16-acyl-CoA, C12 to C18 alcohols, or dipalmitoyl glycerol. This acyltransferase exhibits 24% amino acid identity to the model enzyme AtfA from Acinetobacter baylyi but has high sequence similarities to WS/DGATs from other Streptomyces species. To investigate the impact of AtfG25 on lipid accumulation, the respective gene, atfG25, was inactivated in Streptomyces sp. strain G25. However, cells of the insertion mutant still exhibited DGAT activity and were able to store TAG, albeit in lower quantities and at lower rates than the wild-type strain. These findings clearly indicate that AtfG25 has an important, but not exclusive, role in TAG biosynthesis in the novel Streptomyces isolate and suggest the presence of alternative metabolic pathways for lipid accumulation which are discussed in the present study. IMPORTANCE A novel Streptomyces strain was isolated from desert soil, which represents an extreme environment with high temperatures, frequent drought, and nutrient scarcity. We believe that these harsh conditions promoted the development of the capacity for this strain to accumulate extraordinarily large amounts of lipids. In this study, we present the analysis of its draft genome sequence with a special focus on enzymes potentially involved in its lipid storage. Furthermore, the activity and importance of the detected

  20. Cloning and characterization of an acyl-CoA-dependent diacylglycerol acyltransferase 1 (DGAT1) gene from Tropaeolum majus, and a study of the functional motifs of the DGAT protein using site-directed mutagenesis to modify enzyme activity and oil content.

    Science.gov (United States)

    Xu, Jingyu; Francis, Tammy; Mietkiewska, Elzbieta; Giblin, E Michael; Barton, Dennis L; Zhang, Yan; Zhang, Meng; Taylor, David C

    2008-10-01

    A full-length cDNA encoding a putative diacylglycerol acyltransferase 1 (DGAT1, EC 2.3.1.20) was obtained from Tropaeolum majus (garden nasturtium). The 1557-bp open reading frame of this cDNA, designated TmDGAT1, encodes a protein of 518 amino acids showing high homology to other plant DGAT1s. The TmDGAT1 gene was expressed exclusively in developing seeds. Expression of recombinant TmDGAT1 in the yeast H1246MATalpha quadruple mutant (DGA1, LRO1, ARE1, ARE2) restored the capability of the mutant host to produce triacylglycerols (TAGs). The recombinant TmDGAT1 protein was capable of utilizing a range of (14)C-labelled fatty acyl-CoA donors and diacylglycerol acceptors, and could synthesize (14)C-trierucin. Collectively, these findings confirm that the TmDGAT1 gene encodes an acyl-CoA-dependent DGAT1. In plant transformation studies, seed-specific expression of TmDGAT1 was able to complement the low TAG/unusual fatty acid phenotype of the Arabidopsis AS11 (DGAT1) mutant. Over-expression of TmDGAT1 in wild-type Arabidopsis and high-erucic-acid rapeseed (HEAR) and canola Brassica napus resulted in an increase in oil content (3.5%-10% on a dry weight basis, or a net increase of 11%-30%). Site-directed mutagenesis was conducted on six putative functional regions/motifs of the TmDGAT1 enzyme. Mutagenesis of a serine residue in a putative SnRK1 target site resulted in a 38%-80% increase in DGAT1 activity, and over-expression of the mutated TmDGAT1 in Arabidopsis resulted in a 20%-50% increase in oil content on a per seed basis. Thus, alteration of this putative serine/threonine protein kinase site can be exploited to enhance DGAT1 activity, and expression of mutated DGAT1 can be used to enhance oil content.

  1. Roles of Acyl-CoA:Diacylglycerol Acyltransferases 1 and 2 in Triacylglycerol Synthesis and Secretion in Primary Hepatocytes.

    Science.gov (United States)

    Li, Chen; Li, Lena; Lian, Jihong; Watts, Russell; Nelson, Randal; Goodwin, Bryan; Lehner, Richard

    2015-05-01

    Very low-density lipoprotein assembly and secretion are regulated by the availability of triacylglycerol. Although compelling evidence indicates that the majority of triacylglycerol in very low-density lipoprotein is derived from re-esterification of lipolytic products released by endoplasmic reticulum-associated lipases, little is known about roles of acyl-CoA:diacylglycerol acyltransferases (DGATs) in this process. We aimed to investigate the contribution of DGAT1 and DGAT2 in lipid metabolism and lipoprotein secretion in primary mouse and human hepatocytes. We used highly selective small-molecule inhibitors of DGAT1 and DGAT2, and we tracked storage and secretion of lipids synthesized de novo from [(3)H]acetic acid and from exogenously supplied [(3)H]oleic acid. Inactivation of individual DGAT activity did not affect incorporation of either radiolabeled precursor into intracellular triacylglycerol, whereas combined inactivation of both DGATs severely attenuated triacylglycerol synthesis. However, inhibition of DGAT2 augmented fatty acid oxidation, whereas inhibition of DGAT1 increased triacylglycerol secretion, suggesting preferential channeling of separate DGAT-derived triacylglycerol pools to distinct metabolic pathways. Inactivation of DGAT2 impaired cytosolic lipid droplet expansion, whereas DGAT1 inactivation promoted large lipid droplet formation. Moreover, inactivation of DGAT2 attenuated expression of lipogenic genes. Finally, triacylglycerol secretion was significantly reduced on DGAT2 inhibition without altering extracellular apolipoprotein B levels. Our data suggest that DGAT1 and DGAT2 can compensate for each other to synthesize triacylglycerol, but triacylglycerol synthesized by DGAT1 is preferentially channeled to oxidation, whereas DGAT2 synthesizes triacylglycerol destined for very low-density lipoprotein assembly. © 2015 American Heart Association, Inc.

  2. [Progress in the study on diacylgycerol acyltransferase (DGAT)-related genes].

    Science.gov (United States)

    Ma, Hai-Ming; Shi, Qi-Shun; Liu, Xiao-Chun

    2005-12-01

    Diacylgycerol Acyltransferase (DGAT) plays an important role in the formation of lipid in different tissues of biological body. DGAT catalyzes the final step in triacylglycerol (TAG) biosynthesis by converting diacylgycerol (DAG) and fatty acyl-coenzyme A (CoA) into triacylglycerol. This enzyme is coded by both DGAT1 and DGAT2. DGAT1 belongs to the gene family of cholesterol acyltransferase (ACAT). DGAT2 belongs to the gene family of monoacylgycerol acyltransferases (MGAT1). This paper reviewed the structure, location on chromosome and biological effect of DGAT-related genes. The relationship between polymorphism and performance of animal was also discussed.

  3. Generation of N-Acylphosphatidylethanolamine by Members of the Phospholipase A/Acyltransferase (PLA/AT) Family*

    Science.gov (United States)

    Uyama, Toru; Ikematsu, Natsuki; Inoue, Manami; Shinohara, Naoki; Jin, Xing-Hua; Tsuboi, Kazuhito; Tonai, Takeharu; Tokumura, Akira; Ueda, Natsuo

    2012-01-01

    Bioactive N-acylethanolamines (NAEs), including N-palmitoylethanolamine, N-oleoylethanolamine, and N-arachidonoylethanolamine (anandamide), are formed from membrane glycerophospholipids in animal tissues. The pathway is initiated by N-acylation of phosphatidylethanolamine to form N-acylphosphatidylethanolamine (NAPE). Despite the physiological importance of this reaction, the enzyme responsible, N-acyltransferase, remains molecularly uncharacterized. We recently demonstrated that all five members of the HRAS-like suppressor tumor family are phospholipid-metabolizing enzymes with N-acyltransferase activity and are renamed HRASLS1–5 as phospholipase A/acyltransferase (PLA/AT)-1–5. However, it was poorly understood whether these proteins were involved in the formation of NAPE in living cells. In the present studies, we first show that COS-7 cells transiently expressing recombinant PLA/AT-1, -2, -4, or -5, and HEK293 cells stably expressing PLA/AT-2 generated significant amounts of [14C]NAPE and [14C]NAE when cells were metabolically labeled with [14C]ethanolamine. Second, as analyzed by liquid chromatography-tandem mass spectrometry, the stable expression of PLA/AT-2 in cells remarkably increased endogenous levels of NAPEs and NAEs with various N-acyl species. Third, when NAPE-hydrolyzing phospholipase D was additionally expressed in PLA/AT-2-expressing cells, accumulating NAPE was efficiently converted to NAE. We also found that PLA/AT-2 was partly responsible for NAPE formation in HeLa cells that endogenously express PLA/AT-2. These results suggest that PLA/AT family proteins may produce NAPEs serving as precursors of bioactive NAEs in vivo. PMID:22825852

  4. Human activities threaten coral reefs

    International Nuclear Information System (INIS)

    Tveitdal, Svein; Bjoerke, Aake

    2002-01-01

    Research indicates that 58 per cent of the coral reefs of the world are threatened by human activities. Pollution and global heating represent some of the threats. Coral reefs just beneath the surface of the sea are very sensitive to temperature changes. Since 1979, mass death of coral reefs has been reported increasingly often. More than 1000 marine species live in the coral reefs, among these are one fourth of all marine species of fish. It is imperative that the coral reefs be preserved, as coastal communities all over the world depend on them as sources of food and as they are the raw materials for important medicines. The article discusses the threats to the coral reefs in general and does not single out any particular energy-related activity as the principal threat. For instance, the El-Nino phenomenon of the Pacific Ocean is probably involved in mass death of coral reefs and in the North Sea large parts of deep-water reefs have been crushed by heavy beam trawlers fishing for bottom fish

  5. A Review of Human Activity Recognition Methods

    Directory of Open Access Journals (Sweden)

    Michalis eVrigkas

    2015-11-01

    Full Text Available Recognizing human activities from video sequences or still images is a challenging task due to problems such as background clutter, partial occlusion, changes in scale, viewpoint, lighting, and appearance. Many applications, including video surveillance systems, human-computer interaction, and robotics for human behavior characterization, require a multiple activity recognition system. In this work, we provide a detailed review of recent and state-of-the-art research advances in the field of human activity classification. We propose a categorization of human activity methodologies and discuss their advantages and limitations. In particular, we divide human activity classification methods into two large categories according to whether they use data from different modalities or not. Then, each of these categories is further analyzed into sub-categories, which reflect how they model human activities and what type of activities they are interested in. Moreover, we provide a comprehensive analysis of the existing, publicly available human activity classification datasets and examine the requirements for an ideal human activity recognition dataset. Finally, we report the characteristics of future research directions and present some open issues on human activity recognition.

  6. Photoaffinity Labeling of Developing Jojoba Seed Microsomal Membranes with a Photoreactive Analog of Acyl-Coenzyme A (Acyl-CoA) (Identification of a Putative Acyl-CoA:Fatty Alcohol Acyltransferase.

    Science.gov (United States)

    Shockey, J. M.; Rajasekharan, R.; Kemp, J. D.

    1995-01-01

    Jojoba (Simmondsia chinensis, Link) is the only plant known that synthesizes liquid wax. The final step in liquid wax biosynthesis is catalyzed by an integral membrane enzyme, fatty acyl-coenzyme A (CoA):fatty alcohol acyltransferase, which transfers an acyl chain from acyl-CoA to a fatty alcohol to form the wax ester. To purify the acyltransferase, we have labeled the enzyme with a radioiodinated, photoreactive analog of acyl-CoA, 12-[N-(4-azidosalicyl)amino] dodecanoyl-CoA (ASD-CoA). This molecule acts as an inhibitor of acyltransferase activity in the dark and as an irreversible inhibitor upon exposure to ultraviolet light. Oleoyl-CoA protects enzymatic activity in a concentration-dependent manner. Photolysis of microsomal membranes with labeled ASD-CoA resulted in strong labeling of two polypeptides of 57 and 52 kD. Increasing concentrations of oleoyl-CoA reduced the labeling of the 57-kD polypeptide dramatically, whereas the labeling of the 52-kD polypeptide was much less responsive to oleoyl-CoA. Also, unlike the other polypeptide, the labeling of the 57-kD polypeptide was enhanced considerably when photolyzed in the presence of dodecanol. These results suggest that a 57-kD polypeptide from jojoba microsomes may be the acyl-CoA:fatty alcohol acyltransferase.

  7. Cloning and expression of a novel lysophospholipase which structurally resembles lecithin cholesterol acyltransferase.

    Science.gov (United States)

    Taniyama, Y; Shibata, S; Kita, S; Horikoshi, K; Fuse, H; Shirafuji, H; Sumino, Y; Fujino, M

    1999-04-02

    Lecithin cholesterol acyltransferase (LCAT) is the key enzyme in the esterification of plasma cholesterol and in the reverse cholesterol transport on high-density lipoprotein (HDL). We have found a novel LCAT-related gene among differentially expressed cDNA fragments between two types of foam cells derived from THP-1 cells, which are different in cholesterol efflux ability, using a subtractive PCR technique. The deduced 412-amino-acid sequence has 49% amino acid sequence similarity with human LCAT. In contrast to the liver-specific expression of LCAT, mRNA expression of the gene was observed mainly in peripheral tissues including kidney, placenta, pancreas, testis, spleen, heart, and skeletal muscle. The protein exists in human plasma and is probably associated with HDL. Moreover, we discovered that the recombinant protein hydrolyzed lysophosphatidylcholine (lysoPC), a proatherogenic lipid, to glycerophosphorylcholine and a free fatty acid. We have therefore named this novel enzyme LCAT-like lysophospholipase (LLPL), through which a new catabolic pathway for lysoPC on lipoproteins could be elucidated. Copyright 1999 Academic Press.

  8. Human rights education (HRE) and transnational activism

    NARCIS (Netherlands)

    Mihr, A.; Schmitz, Hans-Peter

    2007-01-01

    Transnational human rights activism occupies today a significant place in the practice and scholarship of current global affairs. This article reviews the past successes and limits of this activism and suggests Human Rights Education (HRE) as a strategic tool currently underutilized by activists and

  9. Monetary reward activates human prefrontal cortex

    International Nuclear Information System (INIS)

    Thut, G.; Roelcke, U.; Nienhusmeier, M.; Missimer, J.; Maguire, R.P.; Leenders, K.L.; Schultz, W.

    1997-01-01

    We present a rCBF PET activation study, in which we demonstrated that reward processing in humans activates a cortical-subcortical network including dorsolateral prefrontal, orbital frontal, thalamic and midbrain regions. It is suggested that, as found for non-human primates, the basal ganglia-thalamo-cortical system is implicated in reward processing. (author) 1 fig., 3 refs

  10. Brain Activity and Human Unilateral Chewing

    Science.gov (United States)

    Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

    2012-01-01

    Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

  11. Carboxypeptidase activity in human mycoplasmas.

    OpenAIRE

    Shibata, K; Watanabe, T

    1986-01-01

    Mycoplasma salivarium produced citrulline, ammonia, and ATP from N-benzoylglycyl-L-arginine. The activity was inhibited by EDTA and was therefore concluded to be due to an arginine-specific carboxypeptidase. The activity was also found to exist in M. orale, M. buccale, M. faucium, and M. hominis.

  12. Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?

    Science.gov (United States)

    La Marca, Valeria; Maresca, Bernardetta; Spagnuolo, Maria Stefania; Cigliano, Luisa; Dal Piaz, Fabrizio; Di Iorio, Giuseppe; Abrescia, Paolo

    2016-04-01

    24-Hydroxycholesterol (24OH-C) is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects (54% vs 68% of total 24OH-C, p=0.0005; n=8). Similarly, the level of 24OH-C esters in plasma was lower in patients than in controls (62% vs 77% of total 24OH-C; p=0.0076). The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls (p=0.0085). As differences in the concentration of the LCAT stimulator Apolipoprotein E were not found, we hypothesized that the reduced 24OH-C esterification in CSF of patients might depend on oxidative stress. We actually found that oxidative stress reduced LCAT activity in vitro, and 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture. Enhanced LCAT secretion from astrocytes might represent an adaptive response to the increase of non-esterified 24OH-C percentage, aimed to avoid the accumulation of this neurotoxic compound. The low degree of 24OH-C esterification in CSF or plasma might reflect reduced activity of LCAT during neurodegeneration. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  13. Sensing Human Activity: GPS Tracking

    Science.gov (United States)

    van der Spek, Stefan; van Schaick, Jeroen; de Bois, Peter; de Haan, Remco

    2009-01-01

    The enhancement of GPS technology enables the use of GPS devices not only as navigation and orientation tools, but also as instruments used to capture travelled routes: as sensors that measure activity on a city scale or the regional scale. TU Delft developed a process and database architecture for collecting data on pedestrian movement in three European city centres, Norwich, Rouen and Koblenz, and in another experiment for collecting activity data of 13 families in Almere (The Netherlands) for one week. The question posed in this paper is: what is the value of GPS as ‘sensor technology’ measuring activities of people? The conclusion is that GPS offers a widely useable instrument to collect invaluable spatial-temporal data on different scales and in different settings adding new layers of knowledge to urban studies, but the use of GPS-technology and deployment of GPS-devices still offers significant challenges for future research. PMID:22574061

  14. Sensing Human Activity: GPS Tracking

    Directory of Open Access Journals (Sweden)

    Remco de Haan

    2009-04-01

    Full Text Available The enhancement of GPS technology enables the use of GPS devices not only as navigation and orientation tools, but also as instruments used to capture travelled routes: as sensors that measure activity on a city scale or the regional scale. TU Delft developed a process and database architecture for collecting data on pedestrian movement in three European city centres, Norwich, Rouen and Koblenz, and in another experiment for collecting activity data of 13 families in Almere (The Netherlands for one week. The question posed in this paper is: what is the value of GPS as ‘sensor technology’ measuring activities of people? The conclusion is that GPS offers a widely useable instrument to collect invaluable spatial-temporal data on different scales and in different settings adding new layers of knowledge to urban studies, but the use of GPS-technology and deployment of GPS-devices still offers significant challenges for future research.

  15. Sensing human activity : GPS tracking

    NARCIS (Netherlands)

    van der Spek, Stefan; van Schaick, Jeroen; de Bois, P.G.; de Haan, Remco

    2009-01-01

    The enhancement of GPS technology enables the use of GPS devices not only as navigation and orientation tools, but also as instruments used to capture travelled routes: as sensors that measure activity on a city scale or the regional scale. TU Delft developed a process and database architecture for

  16. Affinity purification of recombinant human plasminogen activator ...

    African Journals Online (AJOL)

    Affinity purification of recombinant human plasminogen activator from ... Screening antibody was performed using rhPA milk in an ELISA-elution assay. ... useful for purifying other tPA mutants or other novel recombinant milkderived proteins.

  17. The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

    Science.gov (United States)

    Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

    2018-03-21

    It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

  18. A human activity approach to User Interfaces

    DEFF Research Database (Denmark)

    Bødker, Susanne

    1989-01-01

    the work situations in which computer-based artifacts are used: The framework deals with the role of the user interface in purposeful human work. Human activity theory is used in this analysis. The purpose of this article is to make the reader curious and hopefully open his or her eyes to a somewhat...

  19. Mice Deficient in lysophosphatidic acid acyltransferase delta (Lpaatδ)/acylglycerophosphate acyltransferase 4 (Agpat4) Have Impaired Learning and Memory.

    Science.gov (United States)

    Bradley, Ryan M; Mardian, Emily B; Bloemberg, Darin; Aristizabal Henao, Juan J; Mitchell, Andrew S; Marvyn, Phillip M; Moes, Katherine A; Stark, Ken D; Quadrilatero, Joe; Duncan, Robin E

    2017-11-15

    We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here, we report that Lpaat δ -/- mice display impaired spatial learning and memory compared to wild-type littermates in the Morris water maze and our investigation of potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged. Relative abundance of the important brain fatty acid docosahexaenoic acid was also unchanged in phosphatidylserine, phosphatidylglycerol, and cardiolipin, in agreement with prior data on PC, PE and PI. In phosphatidic acid, it was increased. Specific decreases in ethanolamine-containing phospholipids were detected in mitochondrial lipids, but the function of brain mitochondria in Lpaat δ -/- mice was unchanged. Importantly, we found that Lpaat δ -/- mice have a significantly and drastically lower brain content of the N -methyl-d-asparate (NMDA) receptor subunits NR1, NR2A, and NR2B, as well as the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1, compared to wild-type mice. However, general dysregulation of PI-mediated signaling is not likely responsible, since phospho-AKT and phospho-mTOR pathway regulation was unaffected. Our findings indicate that Lpaat δ deficiency causes deficits in learning and memory associated with reduced NMDA and AMPA receptors. Copyright © 2017 American Society for Microbiology.

  20. Human body contour data based activity recognition.

    Science.gov (United States)

    Myagmarbayar, Nergui; Yuki, Yoshida; Imamoglu, Nevrez; Gonzalez, Jose; Otake, Mihoko; Yu, Wenwei

    2013-01-01

    This research work is aimed to develop autonomous bio-monitoring mobile robots, which are capable of tracking and measuring patients' motions, recognizing the patients' behavior based on observation data, and providing calling for medical personnel in emergency situations in home environment. The robots to be developed will bring about cost-effective, safe and easier at-home rehabilitation to most motor-function impaired patients (MIPs). In our previous research, a full framework was established towards this research goal. In this research, we aimed at improving the human activity recognition by using contour data of the tracked human subject extracted from the depth images as the signal source, instead of the lower limb joint angle data used in the previous research, which are more likely to be affected by the motion of the robot and human subjects. Several geometric parameters, such as, the ratio of height to weight of the tracked human subject, and distance (pixels) between centroid points of upper and lower parts of human body, were calculated from the contour data, and used as the features for the activity recognition. A Hidden Markov Model (HMM) is employed to classify different human activities from the features. Experimental results showed that the human activity recognition could be achieved with a high correct rate.

  1. Expression of tung tree diacylglycerol acyltransferase 1 in E. coli

    Directory of Open Access Journals (Sweden)

    Klasson K Thomas

    2011-07-01

    Full Text Available Abstract Background Diacylglycerol acyltransferases (DGATs catalyze the final and rate-limiting step of triacylglycerol (TAG biosynthesis in eukaryotic organisms. Database search has identified at least 59 DGAT1 sequences from 48 organisms, but the expression of any DGAT1 as a full-length protein in E. coli had not been reported because DGAT1s are integral membrane proteins and difficult to express and purify. The objective of this study was to establish a procedure for expressing full-length DGAT1 in E. coli. Results An expression plasmid containing the open reading frame for tung tree (Vernicia fordii DGAT1 fused to maltose binding protein and poly-histidine affinity tags was constructed and expressed in E. coli BL21(DE3. Immunoblotting showed that the recombinant DGAT1 (rDGAT1 was expressed, but mostly targeted to the membranes and insoluble fractions. Extensive degradation also occurred. Nonetheless, the fusion protein was partially purified from the soluble fraction by Ni-NTA and amylose resin affinity chromatography. Multiple proteins co-purified with DGAT1 fusion protein. These fractions appeared yellow in color and contained fatty acids. The rDGAT1 was solubilized from the insoluble fraction by seven detergents and urea, with SDS and Triton X-100 being the most effective detergents. The solubilized rDGAT1 was partially purified by Ni-NTA affinity chromatography. PreScission protease digestion confirmed the identity of rDGAT1 and showed extensive precipitation following Ni-NTA affinity purification. Conclusions This study reports the first procedure for expressing full-length DGAT1 from any species using a bacterial expression system. The results suggest that recombinant DGAT1 is degraded extensively from the carboxyl terminus and associated with other proteins, lipids, and membranes.

  2. Human activities affecting trace gases and climate

    International Nuclear Information System (INIS)

    Braatz, B.; Ebert, C.

    1990-01-01

    The Earth's climate has been in a constant state of change throughout geologic time due to natural perturbations in the global geobiosphere. However, various human activities have the potential to cause future global warming over a relatively short amount of time. These activities, which affect the Earth's climate by altering the concentrations of trace gases in the atmosphere, include energy consumption, particularly fossil-fuel consumption; industrial processes (production and use of chlorofluorocarbons, halons, and chlorocarbons, landfilling of wastes, and cement manufacture); changes in land use patterns, particularly deforestation and biomass burning; and agricultural practices (waste burning, fertilizer usage, rice production, and animal husbandry). Population growth is an important underlying factor affecting the level of growth in each activity. This paper describes how the human activities listed above contribute to atmospheric change, the current pattern of each activity, and how levels of each activity have changed since the early part of this century

  3. Phylogenetic analysis of glycerol 3-phosphate acyltransferases in opisthokonts reveals unexpected ancestral complexity and novel modern biosynthetic components.

    Directory of Open Access Journals (Sweden)

    Heather C Smart

    Full Text Available Glycerolipid synthesis represents a central metabolic process of all forms of life. In the last decade multiple genes coding for enzymes responsible for the first step of the pathway, catalyzed by glycerol 3-phosphate acyltransferase (GPAT, have been described, and characterized primarily in model organisms like Saccharomyces cerevisiae and mice. Notoriously, the fungal enzymes share low sequence identity with their known animal counterparts, and the nature of their homology is unclear. Furthermore, two mitochondrial GPAT isoforms have been described in animal cells, while no such enzymes have been identified in Fungi. In order to determine if the yeast and mammalian GPATs are representative of the set of enzymes present in their respective groups, and to test the hypothesis that metazoan orthologues are indeed absent from the fungal clade, a comparative genomic and phylogenetic analysis was performed including organisms spanning the breadth of the Opisthokonta supergroup. Surprisingly, our study unveiled the presence of 'fungal' orthologs in the basal taxa of the holozoa and 'animal' orthologues in the basal holomycetes. This includes a novel clade of fungal homologues, with putative peroxisomal targeting signals, of the mitochondrial/peroxisomal acyltransferases in Metazoa, thus potentially representing an undescribed metabolic capacity in the Fungi. The overall distribution of GPAT homologues is suggestive of high relative complexity in the ancestors of the opisthokont clade, followed by loss and sculpting of the complement in the descendent lineages. Divergence from a general versatile metabolic model, present in ancestrally deduced GPAT complements, points to distinctive contributions of each GPAT isoform to lipid metabolism and homeostasis in contemporary organisms like humans and their fungal pathogens.

  4. Inhibition of ghrelin O-acyltransferase attenuates food deprivation-induced increases in ingestive behavior.

    Science.gov (United States)

    Teubner, Brett J W; Garretson, John T; Hwang, Yousang; Cole, Philip A; Bartness, Timothy J

    2013-04-01

    Ghrelin is an orexigenic hormone produced by the stomach in direct proportion to the time since the last meal and has therefore been called a 'hunger signal'. The octanoylation of ghrelin is critical for its orexigenic functions and is dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. The GOAT inhibitor, GO-CoA-Tat, decreases the circulating concentrations of octanoylated ghrelin and attenuates weight gain on a high fat diet in mice. Unlike rats and mice, Siberian hamsters and humans do not increase food intake after food deprivation, but increase food hoarding after food deprivation. In Siberian hamsters, exogenous ghrelin increases ingestive behaviors similarly to 48-56 h food deprivation. Therefore, we tested the necessity of increased ghrelin in food-deprived Siberian hamsters to stimulate ingestive behaviors. To do so we used our simulated natural housing system that allows hamsters to forage for and hoard food. Animals were given an injection of GO-CoA-Tat (i.p., 11 μmol/kg) every 6h because that is the duration of its effective inhibition of octanoylated ghrelin concentrations during a 48 h food deprivation. We found that GO-CoA-Tat attenuated food foraging (0-1h), food intake (0-1 and 2-4h), and food hoarding (0-1h and 2 and 3 days) post-refeeding compared with saline treated animals. This suggests that increased octanoylated ghrelin concentrations play a role in the food deprivation-induced increases in ingestive behavior. Therefore, ghrelin is a critical aspect of the multi-faceted mechanisms that stimulate ingestive behaviors, and might be a critical point for a successful clinical intervention scheme in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  6. Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors.

    Science.gov (United States)

    Cernak, Tim; Gesmundo, Nathan J; Dykstra, Kevin; Yu, Yang; Wu, Zhicai; Shi, Zhi-Cai; Vachal, Petr; Sperbeck, Donald; He, Shuwen; Murphy, Beth Ann; Sonatore, Lisa; Williams, Steven; Madeira, Maria; Verras, Andreas; Reiter, Maud; Lee, Claire Heechoon; Cuff, James; Sherer, Edward C; Kuethe, Jeffrey; Goble, Stephen; Perrotto, Nicholas; Pinto, Shirly; Shen, Dong-Ming; Nargund, Ravi; Balkovec, James; DeVita, Robert J; Dreher, Spencer D

    2017-05-11

    Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate the application of miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on the frontlines of a lead optimization effort to develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed on ∼1 mg scale using glass microvials providing a miniaturized high-throughput experimentation capability that was used to study a challenging S N Ar reaction. The availability of robust synthetic chemistry conditions discovered in these miniaturized investigations enabled the development of structure-activity relationships that ultimately led to the discovery of soluble, selective, and potent inhibitors of DGAT1.

  7. Smartphone-based human activity recognition

    OpenAIRE

    Reyes Ortiz, Jorge Luis

    2014-01-01

    Cotutela Universitat Politècnica de Catalunya i Università degli Studi di Genova Human Activity Recognition (HAR) is a multidisciplinary research field that aims to gather data regarding people's behavior and their interaction with the environment in order to deliver valuable context-aware information. It has nowadays contributed to develop human-centered areas of study such as Ambient Intelligence and Ambient Assisted Living, which concentrate on the improvement of people's Quality of Lif...

  8. Induction of 1-acylglycerophosphocholine acyltransferase genes by fibrates in the liver of rats.

    Science.gov (United States)

    Yamazaki, Tohru; Wakabayashi, Michiko; Ikeda, Erika; Tanaka, Shizuyo; Sakamoto, Takeshi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

    2012-01-01

    The effect of fibrates (clofibric acid, bezafibrate and fenofibrate) on the gene expression and activity of 1-acylglycerophosphocholine acyltransferase (LPCAT) was investigated. The administration of 0.1% (w/w) clofibric acid, bezafibrate or fenofibrate in diet for 14 d to rats induced LPCAT activity in hepatic microsomes in the following order: fenofibrate>bezafibrate>clofibric acid. The LPCAT induced by fenofibrate preferred to arachidonoyl-CoA and linoleoyl-CoA to a greater extent than did LPCAT in control microsomes. The treatment with the fibrates resulted in upregulation of the relative expression of mRNAs encoding LPCAT3 and LPCAT4 in the following order: fenofibrate>bezafibrate>clofibric acid. The administration of fibrates did not change the expression of genes encoding either LPCAT1 or LPCAT2. The treatment with fibrates elevated relative levels of both mRNAs encoding Δ6 desaturase (Fads2) and Δ5 desaturase (Fads1) in the order of fenofibrate>bezafibrate>clofibric acid, and the extent of the increase in the level of Δ6 desaturase mRNA was greater than that of Δ5 desaturase. Fatty acid profile in hepatic phosphatidylcholine (PC) was significantly changed by the treatments with fibrates. These results suggest (i) that fibrates induce LPCAT activity in hepatic microsomes by elevating the expression of genes encoding LPCAT3 and LPCAT4, (ii) that the changes in fatty acid profile of hepatic PC are, in part, due to the elevated expression of two isoforms, LPCAT3 and LPCAT4, and (iii) that the ability of fibrates to induce these changes are in the order of fenofibrate>bezafibrate>clofibric acid.

  9. Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function.

    Science.gov (United States)

    Lopez, Adam M; Jones, Ryan Dale; Repa, Joyce J; Turley, Stephen D

    2018-06-07

    Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase 1 (SOAT1) or sterol O-acyltransferase 2 (SOAT2) in various cell types, and lecithin cholesterol acyltransferase (LCAT) in plasma. Esterified cholesterol (EC) and triacylglycerol (TAG) contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase (LAL) within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C2 (NPC2) and Niemann-Pick C1 (NPC1), unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol. Mutations in either NPC1 or NPC2 lead to continuing entrapment of UC in all organs, resulting in multisystem disease which includes hepatic dysfunction and in some cases liver failure. These studies investigated primarily whether elimination of SOAT2 in NPC1-deficient mice impacted hepatic UC sequestration, inflammation, and transaminase activities. Measurements were made in 7 wk-old mice fed a low-cholesterol chow diet or one enriched with cholesterol starting 2 wk before study. In the chow-fed mice, NPC1:SOAT2 double knockouts, compared to their littermates lacking only NPC1, had 20% less liver mass, 28% lower hepatic UC concentrations, and plasma ALT and AST activities that were decreased by 48% and 36%, respectively. mRNA expression levels for several markers of inflammation were all significantly lower in the NPC1 mutants lacking SOAT2. The existence of a new class of potent and selective SOAT2 inhibitors provides an opportunity for exploring if suppression of this enzyme could potentially become an adjunctive therapy for liver disease in NPC1 deficiency.

  10. Expression of tung seed diacylglycerol acyltransferases (DGAT) in E. coli and yeast

    Science.gov (United States)

    Diacylglycerol acyltransferases (DGATs) catalyze the last step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Plants and animals deficient in DGATs accumulate less TAG, resist obesity, and/or lack milk secretion. Over-expression of the DGATs increases TAG content in seeds and other t...

  11. Reprogramming Acyl Carrier Protein Interactions of an Acyl-CoA Promiscuous trans-Acyltransferase

    DEFF Research Database (Denmark)

    Ye, Zhixia; Musiol-Kroll, Ewa Maria; Weber, Tilmann

    2014-01-01

    Protein interactions between acyl carrier proteins (ACPs) and trans-acting acyltransferase domains (trans-ATs) are critical for regioselective extender unit installation by many polyketide synthases, yet little is known regarding the specificity of these interactions, particularly for trans-ATs w...

  12. Supplementation with linoleic acid-rich soybean oil stimulates macrophage foam cell formation via increased oxidative stress and diacylglycerol acyltransferase1-mediated triglyceride biosynthesis.

    Science.gov (United States)

    Rom, Oren; Jeries, Helana; Hayek, Tony; Aviram, Michael

    2017-01-02

    During the last decades there has been a staggering rise in human consumption of soybean oil (SO) and its major polyunsaturated fatty acid linoleic acid (LA). The role of SO or LA in cardiovascular diseases is highly controversial, and their impact on macrophage foam cell formation, the hallmark of early atherogenesis, is unclear. To investigate the effects of high SO or LA intake on macrophage lipid metabolism and the related mechanisms of action, C57BL/6 mice were orally supplemented with increasing levels of SO-based emulsion or equivalent levels of purified LA for 1 month, followed by analyses of lipid accumulation and peroxidation in aortas, serum and in peritoneal macrophages (MPM) of the mice. Lipid peroxidation and triglyceride mass in aortas from SO or LA supplemented mice were dose-dependently and significantly increased. In MPM from SO or LA supplemented mice, lipid peroxides were significantly increased and a marked accumulation of cellular triglycerides was found in accordance with enhanced triglyceride biosynthesis rate and overexpression of diacylglycerol acyltransferase1 (DGAT1), the key enzyme in triglyceride biosynthesis. In cultured J774A.1 macrophages treated with SO or LA, triglyceride accumulated via increased oxidative stress and a p38 mitogen-activated protein kinase (MAPK)-mediated overexpression of DGAT1. Accordingly, anti-oxidants (pomegranate polyphenols), inhibition of p38 MAPK (by SB202190) or DGAT1 (by oleanolic acid), all significantly attenuated SO or LA-induced macrophage triglyceride accumulation. These findings reveal novel mechanisms by which supplementation with SO or LA stimulate macrophage foam cell formation, suggesting a pro-atherogenic role for overconsumption of SO or LA. © 2016 BioFactors, 43(1):100-116, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  13. The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis

    Science.gov (United States)

    Huang, Long Shuang; Mathew, Biji; Zhao, Yutong; Noth, Imre; Reddy, Sekhar P.; Harijith, Anantha; Usatyuk, Peter V.; Berdyshev, Evgeny V.; Kaminski, Naftali; Zhou, Tong; Zhang, Wei; Zhang, Yanmin; Rehman, Jalees; Kotha, Sainath R.; Gurney, Travis O.; Parinandi, Narasimham L.; Lussier, Yves A.; Garcia, Joe G. N.

    2014-01-01

    Rationale: Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis. Objectives: To define a role for LYCAT in human and murine models of pulmonary fibrosis. Methods: We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge. Measurements and Main Results: LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. LYCAT mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, hLYCAT overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. In vitro studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection. Conclusions: This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis. PMID

  14. Scaling behavior of online human activity

    Science.gov (United States)

    Zhao, Zhi-Dan; Cai, Shi-Min; Huang, Junming; Fu, Yan; Zhou, Tao

    2012-11-01

    The rapid development of the Internet technology enables humans to explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e., traces), we can get insights about the dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, books, and movies rating, are comprehensively investigated by using the detrended fluctuation analysis technique and the multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three types of media show similar scaling properties with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based on their activities (i.e., rating per unit time), we find that the scaling exponents of the interevent time series in the three groups are different. Hence, these results suggest that a stronger long-range correlations exist in these collective behaviors. Furthermore, their information complexities vary in the three groups. To explain the differences of the collective behaviors restricted to the three groups, we study the dynamic behavior of human activity at the individual level, and find that the dynamic behaviors of a few users have extremely small scaling exponents associated with long-range anticorrelations. By comparing the interevent time distributions of four representative users, we can find that the bimodal distributions may bring forth the extraordinary scaling behaviors. These results of the analysis of the online human activity in the e-commerce may not only provide insight into its dynamic behaviors but may also be applied to acquire potential economic interest.

  15. Food & Fitness. Directory. Human Nutrition Activities.

    Science.gov (United States)

    Department of Agriculture, Washington, DC.

    Activities of the following regulatory and food service agencies of the Department of Agriculture are described: (1) Agricultural Research Service; (2) Cooperative State Research Service; (3) Economic Research Service; (4) Human Nutrition Information Service; (5) Office of Grants and Program Systems; (6) Office of International Cooperation and…

  16. Understanding Usability Work as a Human Activity

    DEFF Research Database (Denmark)

    Nørgaard, Mie

    Three core themes are explored in eight papers: Usability work as a human activity, usability practice and methods, and persuasiveness of evaluation results and feedback. We explore how usability work is much more than methods and work procedures, and argue that maturing our understanding...

  17. BACTERICIDAL ACTIVITY OF HUMAN SERA AGAINST ...

    African Journals Online (AJOL)

    hi-tech

    East African Medical Journal Vol. 77 No. 12 December 2000. BACTERICIDAL ACTIVITY OF HUMAN SERA AGAINST SALMONELLA TYPHI AND SALMONELLA PARATYPHI A, B, C. E.O. Igumbor, BSc, MSc, PhD, Department of Medical Microbiology, School of Medicine, University of Zimbabwe P.O. Box Al78, Avondale, ...

  18. Recruiting a new substrate for triacylglycerol synthesis in plants: the monoacylglycerol acyltransferase pathway.

    Directory of Open Access Journals (Sweden)

    James R Petrie

    Full Text Available BACKGROUND: Monoacylglycerol acyltransferases (MGATs are predominantly associated with lipid absorption and resynthesis in the animal intestine where they catalyse the first step in the monoacylglycerol (MAG pathway by acylating MAG to form diacylglycerol (DAG. Typical plant triacylglycerol (TAG biosynthesis routes such as the Kennedy pathway do not include an MGAT step. Rather, DAG and TAG are synthesised de novo from glycerol-3-phosphate (G-3-P by a series of three subsequent acylation reactions although a complex interplay with membrane lipids exists. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that heterologous expression of a mouse MGAT acyltransferase in Nicotiana benthamiana significantly increases TAG accumulation in vegetative tissues despite the low levels of endogenous MAG substrate available. In addition, DAG produced by this acyltransferase can serve as a substrate for both native and coexpressed diacylglycerol acyltransferases (DGAT. Finally, we show that the Arabidopsis thaliana GPAT4 acyltransferase can produce MAG in Saccharomyces cerevisiae using oleoyl-CoA as the acyl-donor. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the concept of a new method of increasing oil content in vegetative tissues by using MAG as a substrate for TAG biosynthesis. Based on in vitro yeast assays and expression results in N. benthamiana, we propose that co-expression of a MAG synthesising enzyme such as A. thaliana GPAT4 and a MGAT or bifunctional M/DGAT can result in DAG and TAG synthesis from G-3-P via a route that is independent and complementary to the endogenous Kennedy pathway and other TAG synthesis routes.

  19. Discovery of a novel acyl-CoA: cholesterol acyltransferase inhibitor: the synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety.

    Science.gov (United States)

    Ogino, Masaki; Nakada, Yoshihisa; Negoro, Nobuyuki; Itokawa, Shigekazu; Nishimura, Satoshi; Sanada, Tsukasa; Satomi, Tomoko; Kita, Shunbun; Kubo, Kazuki; Marui, Shogo

    2011-01-01

    As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.

  20. Real-time Human Activity Recognition

    Science.gov (United States)

    Albukhary, N.; Mustafah, Y. M.

    2017-11-01

    The traditional Closed-circuit Television (CCTV) system requires human to monitor the CCTV for 24/7 which is inefficient and costly. Therefore, there’s a need for a system which can recognize human activity effectively in real-time. This paper concentrates on recognizing simple activity such as walking, running, sitting, standing and landing by using image processing techniques. Firstly, object detection is done by using background subtraction to detect moving object. Then, object tracking and object classification are constructed so that different person can be differentiated by using feature detection. Geometrical attributes of tracked object, which are centroid and aspect ratio of identified tracked are manipulated so that simple activity can be detected.

  1. Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

    Science.gov (United States)

    Murtuza, Mohammad I; Isokawa, Masako

    2018-01-01

    Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild-type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR1a may be a prerequisite for the production of GOAT. Application of fluorescein isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting that extracellularly applied non-octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain. © 2017 International Society for Neurochemistry.

  2. Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases.

    Science.gov (United States)

    Eichmann, Thomas O; Kumari, Manju; Haas, Joel T; Farese, Robert V; Zimmermann, Robert; Lass, Achim; Zechner, Rudolf

    2012-11-30

    Adipose triglyceride lipase (ATGL) is rate-limiting for the initial step of triacylglycerol (TAG) hydrolysis, generating diacylglycerol (DAG) and fatty acids. DAG exists in three stereochemical isoforms. Here we show that ATGL exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone. The selectivity of ATGL broadens to the sn-1 position upon stimulation of the enzyme by its co-activator CGI-58. sn-1,3 DAG is the preferred substrate for the consecutive hydrolysis by hormone-sensitive lipase. Interestingly, diacylglycerol-O-acyltransferase 2, present at the endoplasmic reticulum and on lipid droplets, preferentially esterifies sn-1,3 DAG. This suggests that ATGL and diacylglycerol-O-acyltransferase 2 act coordinately in the hydrolysis/re-esterification cycle of TAGs on lipid droplets. Because ATGL preferentially generates sn-1,3 and sn-2,3, it suggests that TAG-derived DAG cannot directly enter phospholipid synthesis or activate protein kinase C without prior isomerization.

  3. Monitoring Human Activity through Portable Devices

    Directory of Open Access Journals (Sweden)

    G. Sebestyen

    2012-06-01

    Full Text Available Monitoring human activity may be useful for medical supervision and for prophylactic purposes. Mobile devices like intelligent phones or watches have multiple sensors and wireless communication capabilities which can be used for this purpose. This paper presents some integrated solutions for determining and continuous monitoring of a person’s state. Aspects taken into consideration are: activity detection and recognition based on acceleration sensors, wireless communication protocols for data acquisition, web monitoring, alerts generation and statistical processing of multiple sensorial data. As practical implementations two case studies are presented, one using an intelligent phone and another using a mixed signal processor integrated in a watch.

  4. Effect of losartan on human platelet activation.

    Science.gov (United States)

    Guerra-Cuesta, J I; Montón, M; Rodríguez-Feo, J A; Jiménez, A M; González-Fernández, F; Rico, L A; García, R; Gómez, J; Farré, J; Casado, S; López-Farré, A

    1999-03-01

    Previous studies have demonstrated that losartan can block the thromboxane A2 receptor on the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. Platelets were obtained from 15 healthy men, aged 26-40 years. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by the thromboxane A2 analog U46619 (5 x 10(-6) mol/l) or ADP (10(-5) mol/l). U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-dependent manner. Only a high dose of EXP 3174 (5 x 10(-5) mol/l), the in vivo active metabolite of losartan, was able to attenuate U46619-induced platelet activation. Captopril, an angiotensin I converting inhibitor, failed to modify U46619-induced platelet aggregation. Furthermore, the binding of [3H]-U46619 to platelets was competitively inhibited by losartan, whereas only a high dose of EXP 3174 reduced the binding of [3H]-U46619. Captopril failed to modify the binding of [3H]-U46619 to platelets. Losartan also reduced the platelet activation induced by ADP (10(-5) mol/l), a platelet agonist partially dependent on thromboxane A2. In addition, when thromboxane A2 generation was blocked by aspirin, ADP-induced platelet aggregation was inhibited to a similar degree to the inhibition induced by losartan. Exogenous angiotensin II did not elicit any modification of either U46619- or ADP-stimulated platelet aggregation. Losartan decreased platelet aggregation by a thromboxane A2-dependent mechanism. EXP 3174 was less potent than losartan in reducing thromboxane A2-dependent platelet activation. Captopril and exogenous angiotensin II had no effect on human platelet activation. These results suggest that losartan reduced thromboxane A2-dependent platelet activation independently of its effect on angiotensin II.

  5. Familial lecithin-cholesterol acyltransferase (LCAT) deficiency; a differential of proteinuria

    OpenAIRE

    Althaf, Mohammed Mahdi; Almana, Hadeel; Abdelfadiel, Ahmed; Amer, Sadiq Mohammed; Al-Hussain, Turki Omar

    2015-01-01

    Background: Lecithin cholesterol acyltransferase (LCAT) is an important enzyme in cholesterol metabolism that is involved in the esterification of cholesterol. A lack of this enzyme results in deranged metabolic pathways that are not completely understood, resulting in abnormal deposition of lipids in several organs. Clinically, it manifests with proteinuria, dyslipidemia and corneal opacity with progressive chronic kidney disease resulting in end-stage renal disease. Case Presentation: We he...

  6. Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle

    OpenAIRE

    Sears, Avery E.; Palczewski, Krzysztof

    2016-01-01

    Lecithin:retinol acyltransferase (LRAT) catalyzes the acyl transfer from the sn-1 position of phosphatidylcholine (PC) to all-trans-retinol, creating fatty acid retinyl esters (palmitoyl, stearoyl, and some unsaturated derivatives). In the eye, these retinyl esters are substrates for the 65 kDa retinoid isomerase (RPE65). LRAT is well characterized biochemically, and recent structural data from closely related family members of the NlpC/P60 superfamily and a chimeric protein have established ...

  7. Molecular characterisation of a recombinant bovine glycine N-acyltransferase / Christoffel Petrus Stephanus Badenhorst

    OpenAIRE

    Badenhorst, Christoffel Petrus Stephanus

    2010-01-01

    Conjugation of glycine to organic acids is an important detoxification mechanism. Metabolites of aspirin and industrial solvents, benzoic acid found in plant material and many endogenous metabolites are detoxified by conjugation to glycine. The enzyme responsible for glycine conjugation, glycine N-acyltransferase (GL YAT), is investigated in this study. The enzyme is also important for the management of organic acidemias which are inherited metabolic diseases. However, not all ...

  8. Acute activation, desensitization and smoldering activation of human acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Barbara G Campling

    Full Text Available The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β22β2 and (α4β22α4. The (α4β22β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β22α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

  9. Physical Human Activity Recognition Using Wearable Sensors

    Directory of Open Access Journals (Sweden)

    Ferhat Attal

    2015-12-01

    Full Text Available This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle. Three main steps describe the activity recognition process: sensors’ placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN, Support Vector Machines (SVM, Gaussian Mixture Models (GMM, and Random Forest (RF as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM and Hidden Markov Model (HMM, are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

  10. Physical Human Activity Recognition Using Wearable Sensors.

    Science.gov (United States)

    Attal, Ferhat; Mohammed, Samer; Dedabrishvili, Mariam; Chamroukhi, Faicel; Oukhellou, Latifa; Amirat, Yacine

    2015-12-11

    This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle). Three main steps describe the activity recognition process: sensors' placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN), Support Vector Machines (SVM), Gaussian Mixture Models (GMM), and Random Forest (RF) as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM) and Hidden Markov Model (HMM), are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

  11. The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex.

    Science.gov (United States)

    Gay, Darren C; Wagner, Drew T; Meinke, Jessica L; Zogzas, Charles E; Gay, Glen R; Keatinge-Clay, Adrian T

    2016-03-01

    Polyketides such as the clinically-valuable antibacterial agent mupirocin are constructed by architecturally-sophisticated assembly lines known as trans-acyltransferase polyketide synthases. Organelle-sized megacomplexes composed of several copies of trans-acyltransferase polyketide synthase assembly lines have been observed by others through transmission electron microscopy to be located at the Bacillus subtilis plasma membrane, where the synthesis and export of the antibacterial polyketide bacillaene takes place. In this work we analyze ten crystal structures of trans-acyltransferase polyketide synthases ketosynthase domains, seven of which are reported here for the first time, to characterize a motif capable of zippering assembly lines into a megacomplex. While each of the three-helix LINKS (Laterally-INteracting Ketosynthase Sequence) motifs is observed to similarly dock with a spatially-reversed copy of itself through hydrophobic and ionic interactions, the amino acid sequences of this motif are not conserved. Such a code is appropriate for mediating homotypic contacts between assembly lines to ensure the ordered self-assembly of a noncovalent, yet tightly-knit, enzymatic network. LINKS-mediated lateral interactions would also have the effect of bolstering the vertical association of the polypeptides that comprise a polyketide synthase assembly line. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Functional group and stereochemical requirements for substrate binding by ghrelin O-acyltransferase revealed by unnatural amino acid incorporation.

    Science.gov (United States)

    Cleverdon, Elizabeth R; Davis, Tasha R; Hougland, James L

    2018-04-21

    Ghrelin is a small peptide hormone that undergoes a unique posttranslational modification, serine octanoylation, to play its physiological roles in processes including hunger signaling and glucose metabolism. Ghrelin O-acyltransferase (GOAT) catalyzes this posttranslational modification, which is essential for ghrelin to bind and activate its cognate GHS-R1a receptor. Inhibition of GOAT offers a potential avenue for modulating ghrelin signaling for therapeutic effect. Defining the molecular characteristics of ghrelin that lead to binding and recognition by GOAT will facilitate the development and optimization of GOAT inhibitors. We show that small peptide mimics of ghrelin substituted with 2,3-diaminopropanoic acid in place of the serine at the site of octanoylation act as submicromolar inhibitors of GOAT. Using these chemically modified analogs of desacyl ghrelin, we define key functional groups within the N-terminal sequence of ghrelin essential for binding to GOAT and determine GOAT's tolerance to backbone methylations and altered amino acid stereochemistry within ghrelin. Our study provides a structure-activity analysis of ghrelin binding to GOAT that expands upon activity-based investigations of ghrelin recognition and establishes a new class of potent substrate-mimetic GOAT inhibitors for further investigation and therapeutic interventions targeting ghrelin signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Does solar activity affect human happiness?

    Science.gov (United States)

    Kristoufek, Ladislav

    2018-03-01

    We investigate the direct influence of solar activity (represented by sunspot numbers) on human happiness (represented by the Twitter-based Happiness Index). We construct four models controlling for various statistical and dynamic effects of the analyzed series. The final model gives promising results. First, there is a statistically significant negative influence of solar activity on happiness which holds even after controlling for the other factors. Second, the final model, which is still rather simple, explains around 75% of variance of the Happiness Index. Third, our control variables contribute significantly as well: happiness is higher in no sunspots days, happiness is strongly persistent, there are strong intra-week cycles and happiness peaks during holidays. Our results strongly contribute to the topical literature and they provide evidence of unique utility of the online data.

  14. Activation of human herpesvirus replication by apoptosis.

    Science.gov (United States)

    Prasad, Alka; Remick, Jill; Zeichner, Steven L

    2013-10-01

    A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

  15. Statistics and risk philosophy in human activities

    International Nuclear Information System (INIS)

    Failla, L.

    1983-01-01

    Two leading interpretations of the use of statistics exist, the first one considering statistics as a physical law regulating the phenomena studied, and the other considering statistics as a method allowing to achieve exhaustive knowledge of the phenomena. The Author chooses the second theory, applies this concept of statistics to the risk involved in human activities and discusses the different kinds of risk in this field. The Author distinguishes between the risk that can be eliminated or at least reduced, and the risk inherent in the activity itself, that can never be completely eliminated -unless the activity is suppressed-; yet, also this kind of risk can be kept under control. Furthermore, she distinguishes between risks that can or cannot be foreseen. The Author supports the theory according to which the risk foreseen must be prevented through up-to-date techniques: this should be done coherently with the aim of the activity but independently of the economic cost. The theory considering risk probability as a physical law is mainly based on events happened in the past: it uses the occurrence probability as a law. This theory accepts the statistical risk and estimates its costs, including the ''human cost''. The Author examines the different statistical possibilities to study this specific phenomenon: so, the possibility to avoid the risks may arise along with -last but not least- the opportunity to eliminate or reduce the damage connected. On the contrary, statistics used as a physical law implies the acceptable of a given amount of risk compared with the cost of improving the technical conditions required to eliminate damages. In the end, a practical example of this theory is described

  16. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James

    2011-08-01

    Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

  17. The spatial structure of transnational human activity.

    Science.gov (United States)

    Deutschmann, Emanuel

    2016-09-01

    Starting from conflictive predictions of hitherto disconnected debates in the natural and social sciences, this article examines the spatial structure of transnational human activity (THA) worldwide (a) across eight types of mobility and communication and (b) in its development over time. It is shown that the spatial structure of THA is similar to that of animal displacements and local-scale human motion in that it can be approximated by Lévy flights with heavy tails that obey power laws. Scaling exponent and power-law fit differ by type of THA, being highest in refuge-seeking and tourism and lowest in student exchange. Variance in the availability of resources and opportunities for satisfying associated needs appears to explain these differences. Over time (1960-2010), the Lévy-flight pattern remains intact and remarkably stable, contradicting the popular notion that socio-technological trends lead to a "death of distance." Humans have not become more "global" over time, they rather became more mobile in general, i.e. they move and communicate more at all distances. Hence, it would be more adequate to speak of "mobilization" than of "globalization." Longitudinal change occurs only in some types of THA and predominantly at short distances, indicating regional rather than global shifts. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

    Full Text Available Telomerase activity has been measured in a wide variety of cancerous and non-cancerous tissue types, and the vast majority of clinical studies have shown a direct correlation between it and the presence of cancerous cells. Telomerase plays a key role in cellular immortality and tumorigenesis. Telomerase is activated in 80–90% of human carcinomas, but not in normal somatic cells, therefore, its detection holds promise as a diagnostic marker for cancer. Measurable levels of telomerase have been detected in malignant cells from various samples: tissue from gestational trophoblastic neoplasms; squamous carcinoma cells from oral rinses; lung carcinoma cells from bronchial washings; colorectal carcinoma cells from colonic luminal washings; bladder carcinoma cells from urine or bladder washings; and breast carcinoma or thyroid cancer cells from fine needle aspirations. Such clinical tests for telomerase can be useful as non-invasive and cost-effective methods for early detection and monitoring of cancer. In addition, telomerase activity has been shown to correlate with poor clinical outcome in late-stage diseases such as non-small cell lung cancer, colorectal cancer, and soft tissue sarcomas. In such cases, testing for telomerase activity can be used to identify patients with a poor prognosis and to select those who might benefit from adjuvant treatment. Our review of the latest medical advances in this field reveals that telomerase holds great promise as a biomarker for early cancer detection and monitoring, and has considerable potential as the basis for developing new anticancer therapies.

  19. Identification and Characterization of Sterol Acyltransferases Responsible for Steryl Ester Biosynthesis in Tomato

    Directory of Open Access Journals (Sweden)

    Juan A. Lara

    2018-05-01

    Full Text Available Steryl esters (SEs serve as a storage pool of sterols that helps to maintain proper levels of free sterols (FSs in cell membranes throughout plant growth and development, and participates in the recycling of FSs and fatty acids released from cell membranes in aging tissues. SEs are synthesized by sterol acyltransferases, a family of enzymes that catalyze the transfer of fatty acil groups to the hydroxyl group at C-3 position of the sterol backbone. Sterol acyltransferases are categorized into acyl-CoA:sterol acyltransferases (ASAT and phospholipid:sterol acyltransferases (PSAT depending on whether the fatty acyl donor substrate is a long-chain acyl-CoA or a phospolipid. Until now, only Arabidopsis ASAT and PSAT enzymes (AtASAT1 and AtPSAT1 have been cloned and characterized in plants. Here we report the identification, cloning, and functional characterization of the tomato (Solanum lycopersicum cv. Micro-Tom orthologs. SlPSAT1 and SlASAT1 were able to restore SE to wild type levels in the Arabidopsis psat1-2 and asat1-1 knock-out mutants, respectively. Expression of SlPSAT1 in the psat1-2 background also prevented the toxicity caused by an external supply of mevalonate and the early senescence phenotype observed in detached leaves of this mutant, whereas expression of SlASAT1 in the asat1-1 mutant revealed a clear substrate preference of the tomato enzyme for the sterol precursors cycloartenol and 24-methylene cycloartanol. Subcellular localization studies using fluorescently tagged SlPSAT1 and SlASAT1 proteins revealed that SlPSAT1 localize in cytoplasmic lipid droplets (LDs while, in contrast to the endoplasmic reticulum (ER localization of AtASAT1, SlASAT1 resides in the plasma membrane (PM. The possibility that PM-localized SlASAT1 may act catalytically in trans on their sterol substrates, which are presumably embedded in the ER membrane, is discussed. The widespread expression of SlPSAT1 and SlASAT1 genes in different tomato organs together

  20. Glycerol-3-phosphate acyltransferase 2 expression modulates cell roughness and membrane permeability: An atomic force microscopy study.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Cattaneo

    Full Text Available In mammalian cells, de novo glycerolipid synthesis begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferases (GPAT. GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions, and overexpressed in several types of cancers and cancer-derived human cell lines where its expression contributes to the tumor phenotype. Using gene silencing and atomic force microscopy, we studied the correlation between GPAT2 expression and cell surface topography, roughness and membrane permeability in MDA-MB-231 cells. In addition, we analyzed the glycerolipid composition by gas-liquid chromatography. GPAT2 expression altered the arachidonic acid content in glycerolipids, and the lack of GPAT2 seems to be partially compensated by the overexpression of another arachidonic-acid-metabolizing enzyme, AGPAT11. GPAT2 expressing cells exhibited a rougher topography and less membrane damage than GPAT2 silenced cells. Pore-like structures were present only in GPAT2 subexpressing cells, correlating with higher membrane damage evidenced by lactate dehydrogenase release. These GPAT2-induced changes are consistent with its proposed function as a tumor-promoting gene, and might be used as a phenotypic differentiation marker. AFM provides the basis for the identification and quantification of those changes, and demonstrates the utility of this technique in the study of cancer cell biology.

  1. Sympathetic activation during early pregnancy in humans

    Science.gov (United States)

    Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2012-01-01

    Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

  2. Timing of nurses activities: human resources management

    Directory of Open Access Journals (Sweden)

    Hamid Hosein Poor

    2016-11-01

    Full Text Available Costs of human resources include a high percentage of hospital’s costs; therefore, determination of number of real and optimal employees needed for organizations is very important. In the meantime, the optimal organization of nurses, as the biggest human resource in health care organizations, is of great importance. The present study aimed to assess the distribution of nurses’ activities in shifts and the results of productivity in human resources management in Imam Khomeini hospital in Shirvan. The present cross-sectional study was conducted in 2016. All nurses, working in three shifts of morning, afternoon, and evening in emergency unit and general units of Imam Khomeini hospital, Shirvan, were enrolled into the study through census methods. The instrument, used in this study, was the checklist of timing activities and patients’ satisfaction from nurses. The statistical software SPSS was used for analysis. Mean age of employees in these two units/wards was 31 years and mean duration of work experience was 5.24 years, The difference was significant between the two wards. necessity of the work, especially in emergency unit, are issues that need more assessment and need to be adjusted. Given the high volume of non-care matters of nursing staff, including writing services, including completing paper records and work with HIS (Hospital Information System, which has been emphasized in several studies, new definition of service and use of artificial intelligence with high efficacy is proposed. The status of the available equipment, availability, and efficiency of digital equipment and hoteling state of wards and hospitals also play an important factor in the distribution of time of nursing care activities. Employment of nurses to perform non-nursing duties, because of the shortage of other classes or lack of their permanent presence and based on Although there were differences in standard time of direct and indirect care in emergency unit and

  3. Human activity and rest in situ.

    Science.gov (United States)

    Roenneberg, Till; Keller, Lena K; Fischer, Dorothee; Matera, Joana L; Vetter, Céline; Winnebeck, Eva C

    2015-01-01

    Our lives are structured by the daily alternation of activity and rest, of wake and sleep. Despite significant advances in circadian and sleep research, we still lack answers to many of the most fundamental questions about this conspicuous behavioral pattern. We strongly believe that investigating this pattern in entrained conditions, real-life and daily contexts-in situ-will help the field to elucidate some of these central questions. Here, we present two common approaches for in situ investigation of human activity and rest: the Munich ChronoType Questionnaire (MCTQ) and actimetry. In the first half of this chapter, we provide detailed instructions on how to use and interpret the MCTQ. In addition, we give an overview of the main insights gained with this instrument over the past 10 years, including some new findings on the interaction of light and age on sleep timing. In the second half of this chapter, we introduce the reader to the method of actimetry and share our experience in basic analysis techniques, including visualization, smoothing, and cosine model fitting of in situ recorded data. Additionally, we describe our new approach to automatically detect sleep from activity recordings. Our vision is that the broad use of such easy techniques in real-life settings combined with automated analyses will lead to the creation of large databases. The resulting power of big numbers will promote our understanding of such fundamental biological phenomena as sleep. © 2015 Elsevier Inc. All rights reserved.

  4. Long-term constraints on human activity

    Energy Technology Data Exchange (ETDEWEB)

    Lovins, A. B.

    1976-04-01

    Biophysical and other ''outer limits'' of food, land, water, climatic change, stratospheric chemistry, energy, hazardous substances, non-fuel minerals, human stress, and social and ecological stability raise fundamental questions about present trends in management methods and in global organization. The diverse outer limits reflect complex, poorly perceived, and often unsuspected, interconnections between numerous biological and geophysical processes, many of which are obscure or still unknown. Our lack of predictive power, let alone of quantitative understanding, implies a need to treat essential life-support systems with great caution and forbearance, lest we erode safety margins whose importance we do not yet appreciate. Even those outer limits which now seem remote are relevant to present policy, as their timely avoidance may require us to discard otherwise attractive short-term policies in favor of others that offer less immediate advantage but that retain options which may be needed later. Such alternative policies may have to rely more on social than on technical innovation in order to address underlying disequilibria rather than merely palliating their symptoms. Moreover, some outer limits are sufficiently imminent, or require such long lead-times to avoid, that fundamental changes in policy, in institutions, and in the degree of global interdependence, seem necessary if we are to live to enjoy some of the later and more interesting limits to human activity.

  5. The role of lecithin cholesterol acyltransferase and organic substances from coal in the etiology of Balkan endemic nephropathy: A new hypothesis

    Science.gov (United States)

    Pavlovic, N.M.; Orem, W.H.; Tatu, C.A.; Lerch, H.E.; Bunnell, J.E.; Feder, G.L.; Kostic, E.N.; Ordodi, V.L.

    2008-01-01

    Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p = 0.02) and (p = 0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population. ?? 2007 Elsevier Ltd. All rights reserved.

  6. Discovery of a potent and orally available acyl-CoA: cholesterol acyltransferase inhibitor as an anti-atherosclerotic agent: (4-phenylcoumarin)acetanilide derivatives.

    Science.gov (United States)

    Ogino, Masaki; Fukui, Seiji; Nakada, Yoshihisa; Tokunoh, Ryosuke; Itokawa, Shigekazu; Kakoi, Yuichi; Nishimura, Satoshi; Sanada, Tsukasa; Fuse, Hiromitsu; Kubo, Kazuki; Wada, Takeo; Marui, Shogo

    2011-01-01

    Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).

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

    OpenAIRE

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

    2011-01-01

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

  8. ASSESSMENT OF HUMAN RESOURCES FOR REGIONAL INNOVATION ACTIVITY

    Directory of Open Access Journals (Sweden)

    R. R. Lukyanova

    2010-03-01

    Full Text Available The paper deals with the issues of human resource development regarding an innovation activity. Concepts of labor and human resources have been surveyed. An integral index for assessment of human resources for regional innovation activity has been developed and assessment of the Russian regions has been made on the basis of it. Development tendencies of modern human resources for innovation activity in Russia have been revealed.

  9. Plant Acyl-CoA:Lysophosphatidylcholine Acyltransferases (LPCATs) Have Different Specificities in Their Forward and Reverse Reactions*

    Science.gov (United States)

    Lager, Ida; Yilmaz, Jenny Lindberg; Zhou, Xue-Rong; Jasieniecka, Katarzyna; Kazachkov, Michael; Wang, Peng; Zou, Jitao; Weselake, Randall; Smith, Mark A.; Bayon, Shen; Dyer, John M.; Shockey, Jay M.; Heinz, Ernst; Green, Allan; Banas, Antoni; Stymne, Sten

    2013-01-01

    Acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT) enzymes have central roles in acyl editing of phosphatidylcholine (PC). Plant LPCAT genes were expressed in yeast and characterized biochemically in microsomal preparations of the cells. Specificities for different acyl-CoAs were similar for seven LPCATs from five different species, including species accumulating hydroxylated acyl groups in their seed oil, with a preference for C18-unsaturated acyl-CoA and low activity with palmitoyl-CoA and ricinoleoyl (12-hydroxyoctadec-9-enoyl)-CoA. We showed that Arabidopsis LPCAT1 and LPCAT2 enzymes catalyzed the acylation and de-acylation of both sn positions of PC, with a preference for the sn-2 position. When acyl specificities of the Arabidopsis LPCATs were measured in the reverse reaction, sn-2-bound oleoyl, linoleoyl, and linolenoyl groups from PC were transferred to acyl-CoA to a similar extent. However, a ricinoleoyl group at the sn-2-position of PC was removed 4–6-fold faster than an oleoyl group in the reverse reaction, despite poor utilization in the forward reaction. The data presented, taken together with earlier published reports on in vivo lipid metabolism, support the hypothesis that plant LPCAT enzymes play an important role in regulating the acyl-CoA composition in plant cells by transferring polyunsaturated and hydroxy fatty acids produced on PC directly to the acyl-CoA pool for further metabolism or catabolism. PMID:24189065

  10. Synthesis and characterisation of 5-acyl-6,7-dihydrothieno[3,2-c]pyridine inhibitors of Hedgehog acyltransferase

    Directory of Open Access Journals (Sweden)

    Thomas Lanyon-Hogg

    2016-06-01

    Full Text Available In this data article we describe synthetic and characterisation data for four members of the 5-acyl-6,7-dihydrothieno[3,2-c]pyridine (termed “RU-SKI” class of inhibitors of Hedgehog acyltransferase, including associated NMR spectra for final compounds. RU-SKI compounds were selected for synthesis based on their published high potencies against the enzyme target. RU-SKI 41 (9a, RU-SKI 43 (9b, RU-SKI 101 (9c, and RU-SKI 201 (9d were profiled for activity in the related article “Click chemistry armed enzyme linked immunosorbent assay to measure palmitoylation by Hedgehog acyltransferase” (Lanyon-Hogg et al., 2015 [1]. 1H NMR spectral data indicate different amide conformational ratios between the RU-SKI inhibitors, as has been observed in other 5-acyl-6,7-dihydrothieno[3,2-c]pyridines. The synthetic and characterisation data supplied in the current article provide validated access to the class of RU-SKI inhibitors.

  11. The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells.

    Science.gov (United States)

    La Marca, Valeria; Spagnuolo, Maria Stefania; Cigliano, Luisa; Marasco, Daniela; Abrescia, Paolo

    2014-07-01

    Cholesterol is mostly removed from the CNS by its conversion to cerebrosterol (24(S)-hydroxycholesterol, 24(S)OH-C), which is transported to the circulation for bile formation in liver. A neurotoxic role of this oxysterol was previously demonstrated in cell culture. Here, we provide evidence that the enzyme lecithin-cholesterol acyltransferase, long known to esterify cholesterol, also produces monoesters of 24(S)OH-C. Proteoliposomes containing apolipoprotein A-I or apolipoprotein E were used to stimulate the enzyme activity and entrap the formed esters. Proteoliposomes with apolipoprotein A-I were found to be more active than those with apolipoprotein E in stimulating the production of oxysteryl esters. Cholesterol and 24(S)OH-C were found to compete for enzyme activity. High levels of haptoglobin, as those circulating during the acute inflammatory phase, inhibited 24(S)OH-C esterification. When highly neurotoxic 24(S)OH-C was treated with enzyme and proteoliposomes before incubation with differentiated SH-SY5Y cells, the neuron survival improved. The esters of 24(S)OH-C, embedded into proteoliposomes by the enzyme and isolated from unesterified 24(S)OH-C by gel filtration chromatography, did not enter the neurons in culture. These results suggest that the enzyme, in the presence of the apolipoproteins, converts 24(S)OH-C into esters restricted to the extracellular environment, thus preventing or limiting oxysterol-induced neurotoxic injuries to neurons in culture. 24-hydroxycholesterol (24(S)OH-C) is neurotoxic. The enzyme lecithin-cholesterol acyltransferase (LCAT) synthesizes monoesters of 24(S)OH-C in reaction mixtures with proteoliposomes containing phospholipids and apolipoprotein A-I or apolipoprotein E. The esters, also produced by incubation of cerebrospinal fluid only with tritiated 24(S)OH-C, are embedded into lipoproteins that do not enter neurons in culture. The enzyme activity limits the toxicity of 24-hydroxycholesterol in neuron culture. © 2014

  12. Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

    Science.gov (United States)

    2013-01-01

    Background Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. Methods We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. Results We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. Conclusions This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific

  13. Activation of human stearoyl-coenzyme A desaturase 1 contributes to the lipogenic effect of PXR in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    Full Text Available The pregnane X receptor (PXR was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1, long chain free fatty acid elongase (FAE, and lecithin-cholesterol acyltransferase (LCAT, while the expression of acyl:cholesterol acetyltransferase(ACAT1 was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR, the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene.

  14. Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome.

    Science.gov (United States)

    Vaziri, Nosratola D; Kim, Choong H; Phan, Dennis; Kim, Sara; Liang, Kaihui

    2004-07-01

    Nephrotic syndrome is associated with hypercholesterolemia, hypertriglyceridemia, and marked elevations of plasma low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypertriglyceridemia in nephrotic syndrome is accompanied by increased hepatic fatty acid synthesis, elevated triglyceride secretion, as well as lipoprotein lipase, VLDL-receptor, and hepatic triglyceride lipase deficiencies, which lead to impaired clearance of triglyceride-rich lipoproteins. Acyl CoA: diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl CoA to 1, 2-diacylglycerol to form triglyceride. Two distinct DGATs (DGAT-1 and DGAT2) have recently been identified in the liver and other tissues. The present study tested the hypothesis that the reported increase in hepatic triglyceride secretion in nephrotic syndrome may be caused by up-regulation of DGAT. Male Sprague-Dawley rats were rendered nephrotic by two sequential injections of puromycin aminonucleoside (130 mg/kg on day 1 and 60 mg/kg on day 14) and studied on day 30. Placebo-treated rats served as controls. Hepatic DGAT-1 and DGAT-2 mRNA abundance and enzymatic activity were measured. The nephrotic group exhibited heavy proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and marked elevation of VLDL concentration. Hepatic DGAT-1 mRNA, DGAT-1, and total DGAT activity were significantly increased, whereas DGAT-2 mRNA abundance and activity were unchanged in the nephrotic rats compared to the control animals. The functional significance of elevation of DGAT activity was illustrated by the reduction in microsomal free fatty acid concentration in the liver of nephrotic animals. Nephrotic syndrome results in up-regulation of hepatic DGAT-1 expression and activity, which can potentially contribute to the associated hypertriglyceridemia by enhancing triglyceride synthesis. Thus, it appears that both depressed catabolism and increased synthetic capacity contribute to

  15. Some kinetic properties of plasma lecithin-cholesterol acyltransferase in hyper-alphalipoproteinemia in man

    International Nuclear Information System (INIS)

    Nikiforova, A.A.; Alksnis, E.G.; Ivanova, E.M.

    1985-01-01

    The aim of this investigation was to study some kinetic properties of lecithin-cholesterol acyltransferase (LCAT) in the blood plasma of patients with hyper-alpha-lipoproteinemia, enabling the presence of LCAT isozymes in the blood to be detected. The velocity of the LCAT reaction was judged by determining labeled CHE formed from 14 C-nonesterified CH and lecithin of HDL on incubation of the latter with the enzyme. Dependence of the velocity of the LCAT reaction on concentration of substrate (nonesterified HDL cholesterol) in four subjects with hyper-alpha-lipoproteinemia is shown

  16. Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

    Science.gov (United States)

    Futatsugi, Kentaro; Kung, Daniel W; Orr, Suvi T M; Cabral, Shawn; Hepworth, David; Aspnes, Gary; Bader, Scott; Bian, Jianwei; Boehm, Markus; Carpino, Philip A; Coffey, Steven B; Dowling, Matthew S; Herr, Michael; Jiao, Wenhua; Lavergne, Sophie Y; Li, Qifang; Clark, Ronald W; Erion, Derek M; Kou, Kou; Lee, Kyuha; Pabst, Brandon A; Perez, Sylvie M; Purkal, Julie; Jorgensen, Csilla C; Goosen, Theunis C; Gosset, James R; Niosi, Mark; Pettersen, John C; Pfefferkorn, Jeffrey A; Ahn, Kay; Goodwin, Bryan

    2015-09-24

    The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp(3)-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.

  17. The climatic change induced by human activities

    International Nuclear Information System (INIS)

    Balairon Ruiz, L.

    2004-01-01

    The climate of the Earth is a changing climate. Along their history many natural climate changes have existed in all time scales. At the present time we use the term climate changes have existed in all time scales. At the present time we use the term climate change in a restricted way, understanding that we have referring to a singular change that has their origin in the modification of the natural composition of the atmosphere. The increase of greenhouse gases from the second half the XVIII century, is due to the human activities of fossil fuels burning to obtain energy and to industrial and agricultural activities needing for the development of a world which population has been duplicated between 1960 and 2000, until overcoming the 6,000 million inhabitants. In particular, the concentrations of carbon dioxide-CO 2 have increased in a 34%. The more recent emission scenarios proposed by the IPCC (SRES, 2000) are based on hypothesis about the population evolution, the energy consumption and the word patterns of development, which are grouped in four families dominated as A1, A2, B1 and B2. The answer for these scenarios from a range of climate models results in an increase of the world average surface atmospheric temperature between 1,4 degree centigrade and 5,8 degree centigrade and a corresponding sea level rise understood between 9 cm and 88 cm. The changes in the precipitation patterns show us that could be above to the current one in high and media latitudes and below in subtropical latitudes, with exceptions highly depending of the model used. (Author)

  18. Novel lysophospholipid acyltransferase PLAT1 of Aurantiochytrium limacinum F26-b responsible for generation of palmitate-docosahexaenoate-phosphatidylcholine and phosphatidylethanolamine.

    Directory of Open Access Journals (Sweden)

    Eriko Abe

    Full Text Available N-3 polyunsaturated fatty acids (PUFA, such as docosahexaenoic acid (DHA, 22:6n-3, have been reported to play roles in preventing cardiovascular diseases. The major source of DHA is fish oils but a recent increase in the global demand of DHA and decrease in fish stocks require a substitute. Thraustochytrids, unicellular marine protists belonging to the Chromista kingdom, can synthesize large amounts of DHA, and, thus, are expected to be an alternative to fish oils. DHA is found in the acyl chain(s of phospholipids as well as triacylglycerols in thraustochytrids; however, how thraustochytrids incorporate DHA into phospholipids remains unknown. We report here a novel lysophospholipid acyltransferase (PLAT1, which is responsible for the generation of DHA-containing phosphatidylcholine and phosphatidylethanolamine in thraustochytrids. The PLAT1 gene, which was isolated from the genomic DNA of Aurantiochytrium limacinum F26-b, was expressed in Saccharomyces cerevisiae, and the FLAG-tagged recombinant enzyme was characterized after purification with anti-FLAG affinity gel. PLAT1 shows wide specificity for donor substrates as well as acceptor substrates in vitro, i.e, the enzyme can adopt lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylserine and lysophosphatidylinositol as acceptor substrates, and 15:0/16:0-CoA and DHA-CoA as donor substrates. In contrast to the in vitro experiment, only lysophosphatidylcholine acyltransferase and lysophosphatidylethanolamine acyltransferase activities were decreased in plat1-knockout mutants, resulting in a decrease of 16:0-DHA-phosphatidylcholine (PC [PC(38:6] and 16:0-DHA-phosphatidylethanolamine (PE [PE(38:6], which are two major DHA-containing phospholipids in A. limacinum F26-b. However, the amounts of other phospholipid species including DHA-DHA-PC [PC(44:12] and DHA-DHA-PE [PE(44:12] were almost the same in plat-knockout mutants and the wild-type. These results indicate that PLAT1 is the

  19. Decision Support System Development for Human Extravehicular Activity

    Data.gov (United States)

    National Aeronautics and Space Administration — The extension of human presence into deep space will depend on how successfully human planetary extravehicular activities (EVAs) are conducted without real-time...

  20. Genome-Wide Identification of BAHD Acyltransferases and In vivo Characterization of HQT-like Enzymes Involved in Caffeoylquinic Acid Synthesis in Globe Artichoke

    Science.gov (United States)

    Moglia, Andrea; Acquadro, Alberto; Eljounaidi, Kaouthar; Milani, Anna M.; Cagliero, Cecilia; Rubiolo, Patrizia; Genre, Andrea; Cankar, Katarina; Beekwilder, Jules; Comino, Cinzia

    2016-01-01

    Globe artichoke (Cynara cardunculus L. var. scolymus) is a rich source of compounds promoting human health (phytonutrients), among them caffeoylquinic acids (CQAs), mainly represented by chlorogenic acid (CGA), and dicaffeoylquinic acids (diCQAs). The enzymes involved in their biosynthesis belong to the large family of BAHD acyltransferases. Following a survey of the globe artichoke genome, we identified 69 BAHD proteins carrying the catalytic site (HXXXD). Their phylogenetic analysis together with another 43 proteins, from 21 species, representative of the BAHD family, highlighted their grouping in seven major clades. Nine globe artichoke acyltransferases clustered in a sub-group of Clade V, with 3 belonging to hydroxycinnamoyl-CoA:quinate hydroxycinnamoyl transferase (HQT) and 2 to hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT) like proteins. We focused our attention on the former, HQT1, HQT2, and HQT3, as they are known to play a key role in CGA biosynthesis. The expression of genes coding for the three HQTs and correlation of expression with the CQA content is reported for different globe artichoke tissues. For the first time in the globe artichoke, we developed and applied the virus-induced gene silencing approach with the goal of assessing in vivo the effect of HQT1 silencing, which resulted in a marked reduction of both CGA and diCQAs. On the other hand, when the role of the three HQTs was assessed in leaves of Nicotiana benthamiana through their transient overexpression, significant increases in mono- and diCQAs content were observed. Using transient GFP fusion proteins expressed in N. benthamiana leaves we also established the sub-cellular localization of these three enzymes. PMID:27721818

  1. Analysis of Gait Pattern to Recognize the Human Activities

    Directory of Open Access Journals (Sweden)

    Jay Prakash Gupta

    2014-09-01

    Full Text Available Human activity recognition based on the computer vision is the process of labelling image sequences with action labels. Accurate systems for this problem are applied in areas such as visual surveillance, human computer interaction and video retrieval. The challenges are due to variations in motion, recording settings and gait differences. Here we propose an approach to recognize the human activities through gait. Activity recognition through Gait is the process of identifying an activity by the manner in which they walk. The identification of human activities in a video, such as a person is walking, running, jumping, jogging etc are important activities in video surveillance. We contribute the use of Model based approach for activity recognition with the help of movement of legs only. Experimental results suggest that our method are able to recognize the human activities with a good accuracy rate and robust to shadows present in the videos.

  2. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  3. Reshaping Human Antibodies: Grafting an Antilysozyme Activity

    Science.gov (United States)

    Verhoeyen, Martine; Milstein, Cesar; Winter, Greg

    1988-03-01

    The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the ``humanizing'' of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.

  4. A Review on Video-Based Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Shian-Ru Ke

    2013-06-01

    Full Text Available This review article surveys extensively the current progresses made toward video-based human activity recognition. Three aspects for human activity recognition are addressed including core technology, human activity recognition systems, and applications from low-level to high-level representation. In the core technology, three critical processing stages are thoroughly discussed mainly: human object segmentation, feature extraction and representation, activity detection and classification algorithms. In the human activity recognition systems, three main types are mentioned, including single person activity recognition, multiple people interaction and crowd behavior, and abnormal activity recognition. Finally the domains of applications are discussed in detail, specifically, on surveillance environments, entertainment environments and healthcare systems. Our survey, which aims to provide a comprehensive state-of-the-art review of the field, also addresses several challenges associated with these systems and applications. Moreover, in this survey, various applications are discussed in great detail, specifically, a survey on the applications in healthcare monitoring systems.

  5. Effects of human activities on global climate

    Energy Technology Data Exchange (ETDEWEB)

    Kellogg, W W

    1977-01-01

    At present it is difficult to make any predictions for the natural course of climate in the next several decades. However by using climate models, predictions of the cause of climate changes as a result of anthropogenic influences can be made, other external factors remaining the same. Experiments with a number of different models have converged on approximately the same conclusions: the largest single effect of human activities on climate is due to an increase in atmospheric carbon dioxide concentration through fossil fuel combustion, i.e., air and thermal pollution, which contributes to a warming of the lower atmosphere; the best estimate of the warming of the mean surface temperature of the earth is about 1C by 2000 AD and 3C by 2050 AD with 3 to 5 times that increase in polar regions, and an uncertainty of roughly a factor of two. These conclusions assume a continued quasi exponential rate of release of carbon dioxide to the atmosphere. Absorption of the added carbon dioxide is expected to take between 1000 and 1500 years. If all economically recoverable fossil fuel is burned in the next few centuries, the atmospheric concentration of carbon dioxide would increase by 5 to 8 times. An example of a natural warming on a similar scale to that expected in the middle of the next century occurred 4000 to 8000 years ago. Generally there was more rainfall especially over the present sub-tropical deserts, but some regions in middle and high latitudes were drier than now. The extent of Arctic and Antarctic sea ice would be influenced. The total volume of the major ice sheets would change, but a change in sea level cannot yet be predicted with any confidence.

  6. Human Activity Recognition Using Heterogeneous Sensors

    NARCIS (Netherlands)

    Shoaib, M.

    Physical activities play an important role in our physical and mental well-being. The lack of such activities can negatively affect our well-being. Though people know the importance of physical activities, still they need regular motivational feedback to remain active in their daily life. In order

  7. Identification of a pair of phospholipid:diacylglycerol acyltransferases from developing flax (Linum usitatissimum L.) seed catalyzing the selective production of trilinolenin.

    Science.gov (United States)

    Pan, Xue; Siloto, Rodrigo M P; Wickramarathna, Aruna D; Mietkiewska, Elzbieta; Weselake, Randall J

    2013-08-16

    The oil from flax (Linum usitatissimum L.) has high amounts of α-linolenic acid (ALA; 18:3(cis)(Δ9,12,15)) and is one of the richest sources of omega-3 polyunsaturated fatty acids (ω-3-PUFAs). To produce ∼57% ALA in triacylglycerol (TAG), it is likely that flax contains enzymes that can efficiently transfer ALA to TAG. To test this hypothesis, we conducted a systematic characterization of TAG-synthesizing enzymes from flax. We identified several genes encoding acyl-CoA:diacylglycerol acyltransferases (DGATs) and phospholipid:diacylglycerol acyltransferases (PDATs) from the flax genome database. Due to recent genome duplication, duplicated gene pairs have been identified for all genes except DGAT2-2. Analysis of gene expression indicated that two DGAT1, two DGAT2, and four PDAT genes were preferentially expressed in flax embryos. Yeast functional analysis showed that DGAT1, DGAT2, and two PDAT enzymes restored TAG synthesis when produced recombinantly in yeast H1246 strain. The activity of particular PDAT enzymes (LuPDAT1 and LuPDAT2) was stimulated by the presence of ALA. Further seed-specific expression of flax genes in Arabidopsis thaliana indicated that DGAT1, PDAT1, and PDAT2 had significant effects on seed oil phenotype. Overall, this study indicated the existence of unique PDAT enzymes from flax that are able to preferentially catalyze the synthesis of TAG containing ALA acyl moieties. The identified LuPDATs may have practical applications for increasing the accumulation of ALA and other polyunsaturated fatty acids in oilseeds for food and industrial applications.

  8. Identification of a Pair of Phospholipid:Diacylglycerol Acyltransferases from Developing Flax (Linum usitatissimum L.) Seed Catalyzing the Selective Production of Trilinolenin*

    Science.gov (United States)

    Pan, Xue; Siloto, Rodrigo M. P.; Wickramarathna, Aruna D.; Mietkiewska, Elzbieta; Weselake, Randall J.

    2013-01-01

    The oil from flax (Linum usitatissimum L.) has high amounts of α-linolenic acid (ALA; 18:3cisΔ9,12,15) and is one of the richest sources of omega-3 polyunsaturated fatty acids (ω-3-PUFAs). To produce ∼57% ALA in triacylglycerol (TAG), it is likely that flax contains enzymes that can efficiently transfer ALA to TAG. To test this hypothesis, we conducted a systematic characterization of TAG-synthesizing enzymes from flax. We identified several genes encoding acyl-CoA:diacylglycerol acyltransferases (DGATs) and phospholipid:diacylglycerol acyltransferases (PDATs) from the flax genome database. Due to recent genome duplication, duplicated gene pairs have been identified for all genes except DGAT2-2. Analysis of gene expression indicated that two DGAT1, two DGAT2, and four PDAT genes were preferentially expressed in flax embryos. Yeast functional analysis showed that DGAT1, DGAT2, and two PDAT enzymes restored TAG synthesis when produced recombinantly in yeast H1246 strain. The activity of particular PDAT enzymes (LuPDAT1 and LuPDAT2) was stimulated by the presence of ALA. Further seed-specific expression of flax genes in Arabidopsis thaliana indicated that DGAT1, PDAT1, and PDAT2 had significant effects on seed oil phenotype. Overall, this study indicated the existence of unique PDAT enzymes from flax that are able to preferentially catalyze the synthesis of TAG containing ALA acyl moieties. The identified LuPDATs may have practical applications for increasing the accumulation of ALA and other polyunsaturated fatty acids in oilseeds for food and industrial applications. PMID:23824186

  9. Molecular Characterization of the Elaeis guineensis Medium-Chain Fatty Acid Diacylglycerol Acyltransferase DGAT1-1 by Heterologous Expression in Yarrowia lipolytica.

    Directory of Open Access Journals (Sweden)

    Laure Aymé

    Full Text Available Diacylglycerol acyltransferases (DGAT are involved in the acylation of sn-1,2-diacylglycerol. Palm kernel oil, extracted from Elaeis guineensis (oil palm seeds, has a high content of medium-chain fatty acids mainly lauric acid (C12:0. A putative E. guineensis diacylglycerol acyltransferase gene (EgDGAT1-1 is expressed at the onset of lauric acid accumulation in the seed endosperm suggesting that it is a determinant of medium-chain triacylglycerol storage. To test this hypothesis, we thoroughly characterized EgDGAT1-1 activity through functional complementation of a Yarrowia lipolytica mutant strain devoid of neutral lipids. EgDGAT1-1 expression is sufficient to restore triacylglycerol accumulation in neosynthesized lipid droplets. A comparative functional study with Arabidopsis thaliana DGAT1 highlighted contrasting substrate specificities when the recombinant yeast was cultured in lauric acid supplemented medium. The EgDGAT1-1 expressing strain preferentially accumulated medium-chain triacylglycerols whereas AtDGAT1 expression induced long-chain triacylglycerol storage in Y. lipolytica. EgDGAT1-1 localized to the endoplasmic reticulum where TAG biosynthesis takes place. Reestablishing neutral lipid accumulation in the Y. lipolytica mutant strain did not induce major reorganization of the yeast microsomal proteome. Overall, our findings demonstrate that EgDGAT1-1 is an endoplasmic reticulum DGAT with preference for medium-chain fatty acid substrates, in line with its physiological role in palm kernel. The characterized EgDGAT1-1 could be used to promote medium-chain triacylglycerol accumulation in microbial-produced oil for industrial chemicals and cosmetics.

  10. In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia.

    Science.gov (United States)

    King, Andrew J; Segreti, Jason A; Larson, Kelly J; Souers, Andrew J; Kym, Philip R; Reilly, Regina M; Collins, Christine A; Voorbach, Martin J; Zhao, Gang; Mittelstadt, Scott W; Cox, Bryan F

    2010-07-10

    Postprandial serum triglyceride concentrations have recently been identified as a major, independent risk factor for future cardiovascular events. As a result, postprandial hyperlipidemia has emerged as a potential therapeutic target. The purpose of this study was two-fold. Firstly, to describe and characterize a standardized model of postprandial hyperlipidemia in multiple rodent species; and secondly, apply these rodent models to the evaluation of a novel class of pharmacologic agent; acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitors. Serum triglycerides were measured before and for 4h after oral administration of a standardized volume of corn oil, to fasted C57BL/6, ob/ob, apoE(-/-) and CD-1 mice; Sprague-Dawley and JCR/LA-cp rats; and normolipidemic and hyperlipidemic hamsters. Intragastric administration of corn oil increased serum triglycerides in all animals evaluated, however the magnitude and time-course of the postprandial triglyceride excursion varied. The potent and selective DGAT-1 inhibitor A-922500 (0.03, 0.3 and 3 mg/kg, p.o.), dose-dependently attenuated the maximal postprandial rise in serum triglyceride concentrations in all species tested. At the highest dose of DGAT-1 inhibitor, the postprandial triglyceride response was abolished. This study provides a comprehensive characterization of the time-course of postprandial hyperlipidemia in rodents. In addition, the ability of DGAT-1 inhibitors to attenuate postprandial hyperlipidemia in multiple rodent models, including those that feature insulin resistance, is documented. Exaggerated postprandial hyperlipidemia is inherent to insulin-resistant states in humans and contributes to the substantially elevated cardiovascular risk observed in these patients. Therefore, by attenuating postprandial hyperlipidemia, DGAT-1 inhibition may represent a novel therapeutic approach to reduce cardiovascular risk. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Human activities threatening the biodiversity of the Uzungwa Scarp ...

    African Journals Online (AJOL)

    Studies of human activities in the Uzungwa Scarp Forest Reserve, Udzungwa Mountains, were conducted in March-April and September 1997, in the western and southern parts of the forest. Different human activities, such as timber and pole cutting and withies harvesting, as well as the collection of non-timber forest ...

  12. Human Activity Recognition in AAL Environments Using Random Projections

    Directory of Open Access Journals (Sweden)

    Robertas Damaševičius

    2016-01-01

    Full Text Available Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject’s body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL, for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD data are presented.

  13. Human Activity Recognition in AAL Environments Using Random Projections.

    Science.gov (United States)

    Damaševičius, Robertas; Vasiljevas, Mindaugas; Šalkevičius, Justas; Woźniak, Marcin

    2016-01-01

    Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject's body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL), for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD) data are presented.

  14. Brain activation during human male ejaculation

    NARCIS (Netherlands)

    Holstege, Ger; Georgiadis, Janniko R.; Paans, Anne M.J.; Meiners, Linda C.; Graaf, Ferdinand H.C.E. van der; Reinders, A.A.T.Simone

    2003-01-01

    Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers.

  15. Pharmacological Inhibition of Monoacylglycerol O-Acyltransferase 2 Improves Hyperlipidemia, Obesity, and Diabetes by Change in Intestinal Fat Utilization.

    Directory of Open Access Journals (Sweden)

    Kazumi Take

    Full Text Available Monoacylglycerol O-acyltransferase 2 (MGAT2 catalyzes the synthesis of diacylglycerol (DG, a triacylglycerol precursor and potential peripheral target for novel anti-obesity therapeutics. High-throughput screening identified lead compounds with MGAT2 inhibitory activity. Through structural modification, a potent, selective, and orally bioavailable MGAT2 inhibitor, compound A (compA, was discovered. CompA dose-dependently inhibited postprandial increases in plasma triglyceride (TG levels. Metabolic flux analysis revealed that compA inhibited triglyceride/diacylglycerol resynthesis in the small intestine and increased free fatty acid and acyl-carnitine with shorter acyl chains than originally labelled fatty acid. CompA decreased high-fat diet (HFD intake in C57BL/6J mice. MGAT2-null mice showed a similar phenotype as compA-treated mice and compA did not suppress a food intake in MGAT2 KO mice, indicating that the anorectic effects were dependent on MGAT2 inhibition. Chronic administration of compA significantly prevented body weight gain and fat accumulation in mice fed HFD. MGAT2 inhibition by CompA under severe diabetes ameliorated hyperglycemia and fatty liver in HFD-streptozotocin (STZ-treated mice. Homeostatic model assessments (HOMA-IR revealed that compA treatment significantly improved insulin sensitivity. The proximal half of the small intestine displayed weight gain following compA treatment. A similar phenomenon has been observed in Roux-en-Y gastric bypass-treated animals and some studies have reported that this intestinal remodeling is essential to the anti-diabetic effects of bariatric surgery. These results clearly demonstrated that MGAT2 inhibition improved dyslipidemia, obesity, and diabetes, suggesting that compA is an effective therapeutic for obesity-related metabolic disorders.

  16. Pharmacological Inhibition of Monoacylglycerol O-Acyltransferase 2 Improves Hyperlipidemia, Obesity, and Diabetes by Change in Intestinal Fat Utilization

    Science.gov (United States)

    Take, Kazumi; Mochida, Taisuke; Maki, Toshiyuki; Satomi, Yoshinori; Hirayama, Megumi; Nakakariya, Masanori; Amano, Nobuyuki; Adachi, Ryutaro; Sato, Kenjiro; Kitazaki, Tomoyuki; Takekawa, Shiro

    2016-01-01

    Monoacylglycerol O-acyltransferase 2 (MGAT2) catalyzes the synthesis of diacylglycerol (DG), a triacylglycerol precursor and potential peripheral target for novel anti-obesity therapeutics. High-throughput screening identified lead compounds with MGAT2 inhibitory activity. Through structural modification, a potent, selective, and orally bioavailable MGAT2 inhibitor, compound A (compA), was discovered. CompA dose-dependently inhibited postprandial increases in plasma triglyceride (TG) levels. Metabolic flux analysis revealed that compA inhibited triglyceride/diacylglycerol resynthesis in the small intestine and increased free fatty acid and acyl-carnitine with shorter acyl chains than originally labelled fatty acid. CompA decreased high-fat diet (HFD) intake in C57BL/6J mice. MGAT2-null mice showed a similar phenotype as compA-treated mice and compA did not suppress a food intake in MGAT2 KO mice, indicating that the anorectic effects were dependent on MGAT2 inhibition. Chronic administration of compA significantly prevented body weight gain and fat accumulation in mice fed HFD. MGAT2 inhibition by CompA under severe diabetes ameliorated hyperglycemia and fatty liver in HFD-streptozotocin (STZ)-treated mice. Homeostatic model assessments (HOMA-IR) revealed that compA treatment significantly improved insulin sensitivity. The proximal half of the small intestine displayed weight gain following compA treatment. A similar phenomenon has been observed in Roux-en-Y gastric bypass-treated animals and some studies have reported that this intestinal remodeling is essential to the anti-diabetic effects of bariatric surgery. These results clearly demonstrated that MGAT2 inhibition improved dyslipidemia, obesity, and diabetes, suggesting that compA is an effective therapeutic for obesity-related metabolic disorders. PMID:26938273

  17. Window Size Impact in Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Oresti Banos

    2014-04-01

    Full Text Available Signal segmentation is a crucial stage in the activity recognition process; however, this has been rarely and vaguely characterized so far. Windowing approaches are normally used for segmentation, but no clear consensus exists on which window size should be preferably employed. In fact, most designs normally rely on figures used in previous works, but with no strict studies that support them. Intuitively, decreasing the window size allows for a faster activity detection, as well as reduced resources and energy needs. On the contrary, large data windows are normally considered for the recognition of complex activities. In this work, we present an extensive study to fairly characterize the windowing procedure, to determine its impact within the activity recognition process and to help clarify some of the habitual assumptions made during the recognition system design. To that end, some of the most widely used activity recognition procedures are evaluated for a wide range of window sizes and activities. From the evaluation, the interval 1–2 s proves to provide the best trade-off between recognition speed and accuracy. The study, specifically intended for on-body activity recognition systems, further provides designers with a set of guidelines devised to facilitate the system definition and configuration according to the particular application requirements and target activities.

  18. Activation of human immunodeficiency virus by radiation

    International Nuclear Information System (INIS)

    Beer, J.Z.; Zmudzka, B.Z.

    1991-01-01

    It was recently demonstrated that ultraviolet radiation (UVR) can induce the HIV promoter as well as activate the complete virus in cultured cells (Valerie et al., 1988). This and subsequent observations, reviewed in this article, suggest a possibility that radiation exposure may accelerate development of AIDS in HIV-infected individuals. They also indicate that studies on HIV activation by stressors, including radiation, may advance our understanding of some phenomena that follow HIV infection. (author)

  19. Robust, synergistic regulation of human gene expression using TALE activators.

    Science.gov (United States)

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

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

    International Nuclear Information System (INIS)

    Dobiasova, M.; Schuetzova, M.

    1986-01-01

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

  1. ActivityNet: A Large-Scale Video Benchmark for Human Activity Understanding

    KAUST Repository

    Heilbron, Fabian Caba

    2015-06-02

    In spite of many dataset efforts for human action recognition, current computer vision algorithms are still severely limited in terms of the variability and complexity of the actions that they can recognize. This is in part due to the simplicity of current benchmarks, which mostly focus on simple actions and movements occurring on manually trimmed videos. In this paper we introduce ActivityNet, a new largescale video benchmark for human activity understanding. Our benchmark aims at covering a wide range of complex human activities that are of interest to people in their daily living. In its current version, ActivityNet provides samples from 203 activity classes with an average of 137 untrimmed videos per class and 1.41 activity instances per video, for a total of 849 video hours. We illustrate three scenarios in which ActivityNet can be used to compare algorithms for human activity understanding: untrimmed video classification, trimmed activity classification and activity detection.

  2. ActivityNet: A Large-Scale Video Benchmark for Human Activity Understanding

    KAUST Repository

    Heilbron, Fabian Caba; Castillo, Victor; Ghanem, Bernard; Niebles, Juan Carlos

    2015-01-01

    In spite of many dataset efforts for human action recognition, current computer vision algorithms are still severely limited in terms of the variability and complexity of the actions that they can recognize. This is in part due to the simplicity of current benchmarks, which mostly focus on simple actions and movements occurring on manually trimmed videos. In this paper we introduce ActivityNet, a new largescale video benchmark for human activity understanding. Our benchmark aims at covering a wide range of complex human activities that are of interest to people in their daily living. In its current version, ActivityNet provides samples from 203 activity classes with an average of 137 untrimmed videos per class and 1.41 activity instances per video, for a total of 849 video hours. We illustrate three scenarios in which ActivityNet can be used to compare algorithms for human activity understanding: untrimmed video classification, trimmed activity classification and activity detection.

  3. Dietary methanol regulates human gene activity.

    Directory of Open Access Journals (Sweden)

    Anastasia V Shindyapina

    Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

  4. Human activity spaces and plague risks in three contrasting ...

    African Journals Online (AJOL)

    Since 1980 plague has been a human threat in the Western Usambara Mountains in Tanzania. However, the spatial-temporal pattern of plague occurrence remains poorly understood. The main objective of this study was to gain understanding of human activity patterns in relation to spatial distribution of fleas in Lushoto ...

  5. Cytotoxic activities of Coriolus versicolor (Yunzhi) extracts on human ...

    African Journals Online (AJOL)

    SERVER

    2007-08-06

    Aug 6, 2007 ... four human liver cancer (7703, HepG2, 7721, PLC) and four human breast cancer (Bcap37, ZR75-30,. MCF-7, T-47D) cell lines ... Key words: Coriolus versicolor, fruit body, polysaccharide, anti-tumor. INTRODUCTION. Coriolus ... somewhat in structure, composition, and physiological activity. The present ...

  6. Human activity and the spread of Phytophthora ramorum

    Science.gov (United States)

    Hall J. Cushman; Michelle Cooper; Ross K. Meentemeyer; Shelly Benson

    2008-01-01

    Increasing numbers of studies are finding that humans can facilitate the spread of exotic plant species in protected wildlands. Hiking trails commonly serve as conduits for invaders and the number of exotic plant species occurring in protected areas is often correlated positively with visitation rates. Despite such evidence linking human activity to the spread of...

  7. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    of the human trapezius muscle can be independently activated by voluntary command, indicating neuromuscular compartmentalization of the trapezius muscle. The independent activation of the upper and lower subdivisions of the trapezius is in accordance with the selective innervation by the fine cranial and main...... branch of the accessory nerve to the upper and lower subdivisions. These findings provide new insight into motor control characteristics, learning possibilities, and function of the clinically relevant human trapezius muscle....

  8. Supporting Human Activities - Exploring Activity-Centered Computing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Bardram, Jakob

    2002-01-01

    In this paper we explore an activity-centered computing paradigm that is aimed at supporting work processes that are radically different from the ones known from office work. Our main inspiration is healthcare work that is characterized by an extreme degree of mobility, many interruptions, ad-hoc...

  9. Instrumental Neutron Activation Analysis for Human Hair

    International Nuclear Information System (INIS)

    Ratanatongchai, W.; Dharmvanij, W; Chongkum, S.

    1998-01-01

    Hair samples from students aged between 7 to 22 years old were analysed by neutron activation analysis at nuclear research reactor TRR-1.M1. From qualitative analysis of short-lived isotopes, A1, V, Ca, I, Cl, Mn, and Na were found. The quantity of those elements can be classified into three groups. The first group is A1, Ca, Na and Cl with variance less than 10%. The second group is V and I with variance between 10% to 50% and the third group, Mn, two samples have concentration about 12 times higher than the others

  10. Natural radiation exposure modified by human activities

    International Nuclear Information System (INIS)

    Fujimoto, Kenzo

    1995-01-01

    We are now living in the radiation environment modified by our technology. It is usually called 'Technologically Enhanced Natural Radiation' and have been discussed in the UNSCEAR Reports as an important source of exposure. The terrestrial radionuclide concentrations as well as the intensity of cosmic rays are considered to have been constant after our ancestors came down from trees and started walking on their two feet. However, we have been changing our environment to be more comfortable for our life and consequently ambient radiation levels are nomore what used to be. In this paper exposures due to natural radiation modified by our following activities are discussed: housing, balneology, cave excursion, mountain climbing, skiing, swimming, smoking and usage of mineral water, well water, coal, natural gas, phosphate rocks and minerals. In the ICRP Publication No. 39, it is clearly mentioned that even natural radiation should be controlled as far as it is controllable. We have to pay more attention to our activities not to enhance the exposure due to unnecessary, avoidable radiation. (author)

  11. Antivirulence activity of the human gut metabolome.

    Science.gov (United States)

    Antunes, L Caetano M; McDonald, Julie A K; Schroeter, Kathleen; Carlucci, Christian; Ferreira, Rosana B R; Wang, Melody; Yurist-Doutsch, Sophie; Hira, Gill; Jacobson, Kevan; Davies, Julian; Allen-Vercoe, Emma; Finlay, B Brett

    2014-07-29

    The mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor of Salmonella virulence, obliterating expression of the Salmonella pathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential. Importance: Microbes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication. Copyright © 2014 Antunes et al.

  12. Human Activity and Pollution in Antarctica

    Science.gov (United States)

    Graf, H.-F.; Shirsat, S. V.; Podzun, R.

    2009-04-01

    A regional climate chemistry model is used to determine the level of pollution of the Antarctic continent due to anthropogenic and natural emission of sulphur species. Based on an emission inventory for the year 2004/2005 including emissions from energy use and ground traffic at and between Antarctic research stations, flight activity, tourist and scientific ship operations, and emissions from the Mt. Erebus volcano, atmospheric concentration and deposition rates of sulphur species and black carbon were simulated at 0.5 degree resolution for the whole Antarctic continent. The biggest anthropogenic source of pollution is ship operations. These concentrate near the Antarctic Peninsula and close to the big scientific stations at Queen Maud Land and in the Ross sea area. The prevailing winds guarantee that most of the anthropogenic emissions from sources near the coast will be blown to lower latitudes and do not affect the continent. While atmospheric concentrations over vast areas remain extremely low, in some places locally concentrations and deposition rates are reached that may be detectable by in-situ measurements and give rise to concern. Especially at the Peninsula atmospheric concentrations and surface deposition of sulphur and soot are dominated by ship emissions. The largest part of shipping activity in this region is from tourist ships, a strongly increasing business. The by far biggest source of sulphur species in Antarctica is the Mt. Erebus volcano. It is also the only source that remains equally strong in polar winter. However, due to its high altitude and the long life time of SO2, especially in winter resulting in long range transport and dilution, Erebus emissions contribute relatively little to deposition of sulphur in the most anthropogenic polluted areas while they dominate the sulphur deposition in central Antarctica.

  13. Anti-complement activities of human breast-milk.

    Science.gov (United States)

    Ogundele, M O

    1999-08-01

    It has long been observed that the human milk possesses significant anti-inflammatory properties, while simultaneously protecting the infant against many intestinal and respiratory pathogens. There is, however, a paucity of information on the degree and extent of this anti-inflammatory activity. In the present study, the inhibitory effects of different fractions of human milk on serum complement activity were analysed. Colostrum and milk samples from healthy voluntary lactating donors at different postpartum ages were obtained and pooled normal human serum was used as source of complement in a modified CH50 assay. Inherent complement activity in human milk was also investigated by measuring the deposition of an activated C3 fragment on a serum-sensitive bacteria, and by haemolytic assays. Most whole- and defatted-milk samples consistently showed a dose-dependent inhibition of the serum complement activity. This inhibition was greater in mature milk compared to transitional milk samples. It was enhanced by inactivation of milk complement, and diminished by centrifugation of milk samples, which partly removed fat and larger protein components including casein micelles. Inherent complement activity in human milk was also demonstrated by haemolysis of sensitised sheep erythrocytes and deposition of C3 fragments on solid-phase bacteria. These activities were highest in the colostrum and gradually decreased as lactation proceeded. Several natural components abundant in the fluid phase of the human breast-milk have been shown to be inhibitors of complement activation in vitro. Their physiological significance probably reside in their ability to prevent inflammatory-induced tissue damage of the delicate immature gastrointestinal tract of the new-born as well as the mammary gland itself, which may arise from ongoing complement activation.

  14. Antiproliferative activity of recombinant human interferon-λ2 ...

    African Journals Online (AJOL)

    Antiproliferative activity of recombinant human interferon-λ2 expressed in stably ... The representing 26 kDa protein band of IFN-λ2 was detected by SDS-PAGE and ... The antiproliferative activity of hIFN-λ2 was determined by MTT assay.

  15. A Hierarchical Representation for Human Activity Recognition with Noisy Labels

    NARCIS (Netherlands)

    Hu, N.; Englebienne, G.; Lou, Z.; Kröse, B.

    2015-01-01

    Human activity recognition is an essential task for robots to effectively and efficiently interact with the end users. Many machine learning approaches for activity recognition systems have been proposed recently. Most of these methods are built upon a strong assumption that the labels in the

  16. Human activity understanding for robot-assisted living

    NARCIS (Netherlands)

    Hu, N.

    2016-01-01

    This thesis investigated the problem of understanding human activities, at different levels of granularity and taking into account both the variability in activities and annotator disagreement. To be able to capture the large variations within each of the action classes, we propose a model that uses

  17. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  18. Fire, Climate, and Human Activity: A Combustive Combination

    Science.gov (United States)

    Kehrwald, N. M.; Battistel, D.; Argiriadis, E.; Barbante, C.; Barber, L. B.; Fortner, S. K.; Jasmann, J.; Kirchgeorg, T.; Zennaro, P.

    2017-12-01

    Ice and lake core records demonstrate that fires caused by human activity can dominate regional biomass burning records in the Common Era. These major increases in fires are often associated with extensive land use change such as an expansion in agriculture. Regions with few humans, relatively stable human populations and/or unvarying land use often have fire histories that are dominated by climate parameters such as temperature and precipitation. Here, we examine biomass burning recorded in ice cores from northern Greenland (NEEM, (77°27'N; 51°3.6'W), Alaska (Juneau Icefield, 58° 35' N; 134° 29'W) and East Antarctica (EPICA DOME C; 75°06'S; 123°21'E), along with New Zealand lake cores to investigate interactions between climate, fire and human activity. Biomarkers such as levoglucosan, and its isomers mannosan and galactosan, can only be produced by cellulose combustion and therefore are specific indicators of past fire activity archived in ice and lake cores. These fire histories add another factor to climate proxies from the same core, and provide a comparison to regional fire syntheses from charcoal records and climate models. For example, fire data from the JSBACH-Spitfire model for the past 2000 years demonstrates that a climate-only scenario would not increase biomass burning in high northern latitudes for the past 2000 years, while NEEM ice core and regional pollen records demonstrate both increased fire activity and land use change that may be ascribed to human activity. Additional biomarkers such as fecal sterols in lake sediments can determine when people were in an area, and can help establish if an increased human presence in an area corresponds with intensified fire activity. This combination of specific biomarkers, other proxy data, and model output can help determine the relative impact of humans versus climate factors on regional fire activity.

  19. Activation of peroxisome proliferator-activated receptor-α enhances fatty acid oxidation in human adipocytes

    International Nuclear Information System (INIS)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki; Kawada, Teruo

    2011-01-01

    Highlights: → PPARα activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. → PPARα activation also increased insulin-dependent glucose uptake in human adipocytes. → PPARα activation did not affect lipid accumulation in human adipocytes. → PPARα activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-α (PPARα) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPARα in adipocytes have been unclarified. We examined the functions of PPARα using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPARα by GW7647, a potent PPARα agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPARγ, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPARα activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPARγ is activated. On the other hand, PPARα activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPARα-dependent manner. Moreover, PPARα activation increased the production of CO 2 and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPARα stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPARα agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected effects of PPARα activation are very valuable for managing diabetic conditions accompanied by obesity, because

  20. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    Science.gov (United States)

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

  1. Comprehensive in Vitro Analysis of Acyltransferase Domain Exchanges in Modular Polyketide Synthases and Its Application for Short-Chain Ketone Production

    Energy Technology Data Exchange (ETDEWEB)

    Yuzawa, Satoshi [Univ. of California, Berkeley, CA (United States); Deng, Kai [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Sandia National Lab. (SNL-CA), Livermore, CA (United States); Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Baidoo, Edward E. K. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Northen, Trent R. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Adams, Paul D. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Katz, Leonard [Univ. of California, Berkeley, CA (United States); Synthetic Biology Research Center, Emeryville, CA (United States); Keasling, Jay D. [Univ. of California, Berkeley, CA (United States); Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Synthetic Biology Research Center, Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-08-22

    Type I modular polyketide synthases (PKSs) are polymerases that utilize acyl-CoAs as substrates. Each polyketide elongation reaction is catalyzed by a set of protein domains called a module. Each module usually contains an acyltransferase (AT) domain, which determines the specific acyl-CoA incorporated into each condensation reaction. Although a successful exchange of individual AT domains can lead to the biosynthesis of a large variety of novel compounds, hybrid PKS modules often show significantly decreased activities. Using monomodular PKSs as models, we have systematically analyzed in this paper the segments of AT domains and associated linkers in AT exchanges in vitro and have identified the boundaries within a module that can be used to exchange AT domains while maintaining protein stability and enzyme activity. Importantly, the optimized domain boundary is highly conserved, which facilitates AT domain replacements in most type I PKS modules. To further demonstrate the utility of the optimized AT domain boundary, we have constructed hybrid PKSs to produce industrially important short-chain ketones. Our in vitro and in vivo analysis demonstrated production of predicted ketones without significant loss of activities of the hybrid enzymes. Finally, these results greatly enhance the mechanistic understanding of PKS modules and prove the benefit of using engineered PKSs as a synthetic biology tool for chemical production.

  2. Human Activity Recognition from Body Sensor Data using Deep Learning.

    Science.gov (United States)

    Hassan, Mohammad Mehedi; Huda, Shamsul; Uddin, Md Zia; Almogren, Ahmad; Alrubaian, Majed

    2018-04-16

    In recent years, human activity recognition from body sensor data or wearable sensor data has become a considerable research attention from academia and health industry. This research can be useful for various e-health applications such as monitoring elderly and physical impaired people at Smart home to improve their rehabilitation processes. However, it is not easy to accurately and automatically recognize physical human activity through wearable sensors due to the complexity and variety of body activities. In this paper, we address the human activity recognition problem as a classification problem using wearable body sensor data. In particular, we propose to utilize a Deep Belief Network (DBN) model for successful human activity recognition. First, we extract the important initial features from the raw body sensor data. Then, a kernel principal component analysis (KPCA) and linear discriminant analysis (LDA) are performed to further process the features and make them more robust to be useful for fast activity recognition. Finally, the DBN is trained by these features. Various experiments were performed on a real-world wearable sensor dataset to verify the effectiveness of the deep learning algorithm. The results show that the proposed DBN outperformed other algorithms and achieves satisfactory activity recognition performance.

  3. Reassessing the Potential Activities of Plant CGI-58 Protein.

    Directory of Open Access Journals (Sweden)

    Abdallah Khatib

    Full Text Available Comparative Gene Identification-58 (CGI-58 is a widespread protein found in animals and plants. This protein has been shown to participate in lipolysis in mice and humans by activating Adipose triglyceride lipase (ATGL, the initial enzyme responsible for the triacylglycerol (TAG catabolism cascade. Human mutation of CGI-58 is the cause of Chanarin-Dorfman syndrome, an orphan disease characterized by a systemic accumulation of TAG which engenders tissue disorders. The CGI-58 protein has also been shown to participate in neutral lipid metabolism in plants and, in this case, a mutation again provokes TAG accumulation. Although its roles as an ATGL coactivator and in lipid metabolism are quite clear, the catalytic activity of CGI-58 is still in question. The acyltransferase activities of CGI-58 have been speculated about, reported or even dismissed and experimental evidence that CGI-58 expressed in E. coli possesses an unambiguous catalytic activity is still lacking. To address this problem, we developed a new set of plasmids and site-directed mutants to elucidate the in vivo effects of CGI-58 expression on lipid metabolism in E. coli. By analyzing the lipid composition in selected E. coli strains expressing CGI-58 proteins, and by reinvestigating enzymatic tests with adequate controls, we show here that recombinant plant CGI-58 has none of the proposed activities previously described. Recombinant plant and mouse CGI-58 both lack acyltransferase activity towards either lysophosphatidylglycerol or lysophosphatidic acid to form phosphatidylglycerol or phosphatidic acid and recombinant plant CGI-58 does not catalyze TAG or phospholipid hydrolysis. However, expression of recombinant plant CGI-58, but not mouse CGI-58, led to a decrease in phosphatidylglycerol in all strains of E. coli tested, and a mutation of the putative catalytic residues restored a wild-type phenotype. The potential activities of plant CGI-58 are subsequently discussed.

  4. Reassessing the Potential Activities of Plant CGI-58 Protein

    Science.gov (United States)

    Khatib, Abdallah; Arhab, Yani; Bentebibel, Assia; Abousalham, Abdelkarim; Noiriel, Alexandre

    2016-01-01

    Comparative Gene Identification-58 (CGI-58) is a widespread protein found in animals and plants. This protein has been shown to participate in lipolysis in mice and humans by activating Adipose triglyceride lipase (ATGL), the initial enzyme responsible for the triacylglycerol (TAG) catabolism cascade. Human mutation of CGI-58 is the cause of Chanarin-Dorfman syndrome, an orphan disease characterized by a systemic accumulation of TAG which engenders tissue disorders. The CGI-58 protein has also been shown to participate in neutral lipid metabolism in plants and, in this case, a mutation again provokes TAG accumulation. Although its roles as an ATGL coactivator and in lipid metabolism are quite clear, the catalytic activity of CGI-58 is still in question. The acyltransferase activities of CGI-58 have been speculated about, reported or even dismissed and experimental evidence that CGI-58 expressed in E. coli possesses an unambiguous catalytic activity is still lacking. To address this problem, we developed a new set of plasmids and site-directed mutants to elucidate the in vivo effects of CGI-58 expression on lipid metabolism in E. coli. By analyzing the lipid composition in selected E. coli strains expressing CGI-58 proteins, and by reinvestigating enzymatic tests with adequate controls, we show here that recombinant plant CGI-58 has none of the proposed activities previously described. Recombinant plant and mouse CGI-58 both lack acyltransferase activity towards either lysophosphatidylglycerol or lysophosphatidic acid to form phosphatidylglycerol or phosphatidic acid and recombinant plant CGI-58 does not catalyze TAG or phospholipid hydrolysis. However, expression of recombinant plant CGI-58, but not mouse CGI-58, led to a decrease in phosphatidylglycerol in all strains of E. coli tested, and a mutation of the putative catalytic residues restored a wild-type phenotype. The potential activities of plant CGI-58 are subsequently discussed. PMID:26745266

  5. A Multiscale Survival Process for Modeling Human Activity Patterns.

    Science.gov (United States)

    Zhang, Tianyang; Cui, Peng; Song, Chaoming; Zhu, Wenwu; Yang, Shiqiang

    2016-01-01

    Human activity plays a central role in understanding large-scale social dynamics. It is well documented that individual activity pattern follows bursty dynamics characterized by heavy-tailed interevent time distributions. Here we study a large-scale online chatting dataset consisting of 5,549,570 users, finding that individual activity pattern varies with timescales whereas existing models only approximate empirical observations within a limited timescale. We propose a novel approach that models the intensity rate of an individual triggering an activity. We demonstrate that the model precisely captures corresponding human dynamics across multiple timescales over five orders of magnitudes. Our model also allows extracting the population heterogeneity of activity patterns, characterized by a set of individual-specific ingredients. Integrating our approach with social interactions leads to a wide range of implications.

  6. Modeling and Visualization of Human Activities for Multicamera Networks

    Directory of Open Access Journals (Sweden)

    Aswin C. Sankaranarayanan

    2009-01-01

    Full Text Available Multicamera networks are becoming complex involving larger sensing areas in order to capture activities and behavior that evolve over long spatial and temporal windows. This necessitates novel methods to process the information sensed by the network and visualize it for an end user. In this paper, we describe a system for modeling and on-demand visualization of activities of groups of humans. Using the prior knowledge of the 3D structure of the scene as well as camera calibration, the system localizes humans as they navigate the scene. Activities of interest are detected by matching models of these activities learnt a priori against the multiview observations. The trajectories and the activity index for each individual summarize the dynamic content of the scene. These are used to render the scene with virtual 3D human models that mimic the observed activities of real humans. In particular, the rendering framework is designed to handle large displays with a cluster of GPUs as well as reduce the cognitive dissonance by rendering realistic weather effects and illumination. We envision use of this system for immersive visualization as well as summarization of videos that capture group behavior.

  7. Detection of cardiac activity changes from human speech

    Science.gov (United States)

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

    2015-05-01

    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  8. 3D Data Acquisition Platform for Human Activity Understanding

    Science.gov (United States)

    2016-03-02

    SECURITY CLASSIFICATION OF: In this project, we incorporated motion capture devices, 3D vision sensors, and EMG sensors to cross validate...multimodality data acquisition, and address fundamental research problems of representation and invariant description of 3D data, human motion modeling and...applications of human activity analysis, and computational optimization of large-scale 3D data. The support for the acquisition of such research

  9. Mapping Cumulative Impacts of Human Activities on Marine Ecosystems

    OpenAIRE

    , Seaplan

    2018-01-01

    Given the diversity of human uses and natural resources that converge in coastal waters, the potential independent and cumulative impacts of those uses on marine ecosystems are important to consider during ocean planning. This study was designed to support the development and implementation of the 2009 Massachusetts Ocean Management Plan. Its goal was to estimate and visualize the cumulative impacts of human activities on coastal and marine ecosystems in the state and federal waters off of Ma...

  10. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China (China); Chonan, Ritsu [Koei Kogyo Co., Ltd., Tokyo, 101-0063 Japan (Japan); Yamahara, Johji [Pharmafood Institute, Kyoto, 602-8136 Japan (Japan); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 China (China); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, NSW 2000 Australia (Australia)

    2014-10-15

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  11. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    International Nuclear Information System (INIS)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-01-01

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  12. Impact of the human activities on the climate

    International Nuclear Information System (INIS)

    Deque, M.

    2007-01-01

    In the framework of the A2 scenario of the GIEC, the possible impacts on the french climate, of the human activities are examined. It seems that the human activities imposed and will be able to impose a faster change of the climate than the natural changes. For the hundred coming years the main characteristics could be: an increase of the temperature, an increase of the rains in winter and a decrease in summer, a decrease of the water in soils expected in freezing areas and an increase of the drought periods. (A.L.B.)

  13. Chloride transport in human fibroblasts is activated by hypotonic shock

    Energy Technology Data Exchange (ETDEWEB)

    Rugolo, M.; Mastocola, T.; Flamigni, A.; Lenaz, G. (Universita' di Bologna (Italy))

    1989-05-15

    Incubation of human skin fibroblasts in hypotonic media induced the activation of {sup 36}Cl- efflux which was roughly proportional to the decrease in the osmolality of the media. The efflux of {sup 36}Cl- was insensitive to DIDS plus furosemide and inhibited by addition of a Cl- channel blocker such as 5-nitro-2-(3-phenyl propylamino) benzoic acid (NPPB). We propose that a conductive pathway for Cl- transport, almost silent in isotonic conditions, is activated by exposing human fibroblasts to hypotonic shock, this conclusion being supported by evidence that also {sup 36}Cl- influx was enhanced by hypotonic medium.

  14. Human Reliability Assessment and Human Performance Evaluation: Research and Analysis Activities at the U.S. NRC

    International Nuclear Information System (INIS)

    Ramey-Smith, A.M.

    1998-01-01

    The author indicates the themes of the six programs identified by the US NRC mission on human performance and human reliability activities. They aim at developing the technical basis to support human performance, at developing and updating a model of human performance and human reliability, at fostering national and international dialogue and cooperation efforts on human performance evaluation, at conducting operating events analysis and database development, and at providing support to human performance and human reliability inspection

  15. Acute sterol o-acyltransferase 2 (SOAT2 knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

    Directory of Open Access Journals (Sweden)

    Stephanie M Marshall

    Full Text Available The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE. We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2 increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD, the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

  16. Therapeutic strategies for metabolic diseases: Small-molecule diacylglycerol acyltransferase (DGAT) inhibitors.

    Science.gov (United States)

    Naik, Ravi; Obiang-Obounou, Brice W; Kim, Minkyoung; Choi, Yongseok; Lee, Hyun Sun; Lee, Kyeong

    2014-11-01

    Metabolic diseases such as atherogenic dyslipidemia, hepatic steatosis, obesity, and type II diabetes are emerging as major global health problems. Acyl-CoA:diacylglycerol acyltransferase (DGAT) is responsible for catalyzing the final reaction in the glycerol phosphate pathway of triglycerol synthesis. It has two isoforms, DGAT-1 and DGAT-2, which are widely expressed and present in white adipose tissue. DGAT-1 is most highly expressed in the small intestine, whereas DGAT-2 is primarily expressed in the liver. Therefore, the selective inhibition of DGAT-1 has become an attractive target with growing potential for the treatment of obesity and type II diabetes. Furthermore, DGAT-2 has been suggested as a new target for the treatment of DGAT-2-related liver diseases including hepatic steatosis, hepatic injury, and fibrosis. In view the discovery of drugs that target DGAT, herein we attempt to provide insight into the scope and further reasons for optimization of DGAT inhibitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Glycerol-3-phosphate Acyltransferase 1 Promotes Tumor Cell Migration and Poor Survival in Ovarian Carcinoma.

    Science.gov (United States)

    Marchan, Rosemarie; Büttner, Bettina; Lambert, Jörg; Edlund, Karolina; Glaeser, Iris; Blaszkewicz, Meinolf; Leonhardt, Gregor; Marienhoff, Lisa; Kaszta, Darius; Anft, Moritz; Watzl, Carsten; Madjar, Katrin; Grinberg, Marianna; Rempel, Eugen; Hergenröder, Roland; Selinski, Silvia; Rahnenführer, Jörg; Lesjak, Michaela S; Stewart, Joanna D; Cadenas, Cristina; Hengstler, Jan G

    2017-09-01

    Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth. Cancer Res; 77(17); 4589-601. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Identification and Characterization of Diacylglycerol Acyltransferase from Oleaginous Fungus Mucor circinelloides.

    Science.gov (United States)

    Zhang, Luning; Zhang, Huaiyuan; Song, Yuanda

    2018-01-24

    Acyl-CoA:diacylglycerol acyltransferase (DGAT) is a pivotal regulator of triacylglycerol (TAG) synthesis. The oleaginous fungus Mucor circinelloides has four putative DGATs: McDGAT1A, McDGAT1B, McDGAT2A, and McDGAT2B, classified into the DGAT1 and DGAT2 subfamilies, respectively. To identify and characterize DGATs in M. circinelloides, these four genes were expressed in Saccharomyces cerevisiae H1246 (TAG-deficient quadruple mutant), individually. TAG biosynthesis was restored only by the expression of McDGAT2B, and TAG content was significantly higher in the mutants with McDGAT2B expression than in a S. cerevisiae mutant with endogenous DGA1 expression. McDGAT2B prefers saturated fatty acids to monounsaturated fatty acids and has an obvious preference for C18:3 (ω-6) according to the results of substrate preference experiments. Furthermore, only the mRNA expression pattern of McDGAT2B correlated with TAG biosynthesis during a fermentation process. Our experiments strongly indicate that McDGAT2B is crucial for TAG accumulation, suggesting that it may be an essential target for metabolic engineering aimed at increasing lipid content of M. circinelloides.

  19. Magnetogastrographic detection of gastric electrical response activity in humans

    International Nuclear Information System (INIS)

    Irimia, Andrei; Richards, William O; Bradshaw, L Alan

    2006-01-01

    The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre- and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre- and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders

  20. RNA-Guided Activation of Pluripotency Genes in Human Fibroblasts

    DEFF Research Database (Denmark)

    Xiong, Kai; Zhou, Yan; Blichfeld, Kristian Aabo

    2017-01-01

    -associated protein 9 (dCas9)-VP64 (CRISPRa) alone, or a combination of dCas9-VP64 and MS2-P65-HSF1 [synergistic activation mediator (SAM) system] mediated activation of five pluripotency genes: KLF4 (K), LIN28 (L), MYC (M), OCT4 (O), and SOX2 (S) in human cells (HEK293T, HeLa, HepG2, and primary fibroblasts...... could be obtained from these SAM fibroblasts. In conclusion, our study showed that CRISPR/Cas9-based ATFs are potent to activate and maintain transcription of endogenous human pluripotent genes. However, future improvements of the system are still required to improve activation efficiency and cellular...

  1. The significance of human factors in nuclear activities

    International Nuclear Information System (INIS)

    Weil, L.; Berg, H.P.

    1999-01-01

    Human factors is an aspect increasingly investigated in the last few years in efforts and programmes for enhancing the operational safety of nuclear systems. Methodology has been elaborated for analysis and evaluation of human reliability, or development of instruments supporting the decisions to be taken by the operators at the man-control room interface of nuclear installations, as well as initial approaches to introduce organisational factors which may influence the man-machine function allocation, and thus are an element of the safety culture concept. The significance of human factors in nuclear activities, as well as activities at the national and international level for optimisation of the man-machine interface and the man-organisation interface are discussed. (orig./CB) [de

  2. Towards discrete wavelet transform-based human activity recognition

    Science.gov (United States)

    Khare, Manish; Jeon, Moongu

    2017-06-01

    Providing accurate recognition of human activities is a challenging problem for visual surveillance applications. In this paper, we present a simple and efficient algorithm for human activity recognition based on a wavelet transform. We adopt discrete wavelet transform (DWT) coefficients as a feature of human objects to obtain advantages of its multiresolution approach. The proposed method is tested on multiple levels of DWT. Experiments are carried out on different standard action datasets including KTH and i3D Post. The proposed method is compared with other state-of-the-art methods in terms of different quantitative performance measures. The proposed method is found to have better recognition accuracy in comparison to the state-of-the-art methods.

  3. Impact Of Human Activities On Ecosystem In Rivers State, Nigeria ...

    African Journals Online (AJOL)

    This study was to assess the percent sample population size of people involved in selected human economic activities and the impact on ecosystem in Rivers State. The data for this study was obtained from a sample size of 1000 respondents who were purposively selected from the study area. Purposive sample was used ...

  4. Relating Eye Activity Measures to Human Controller Remnant Characteristics

    NARCIS (Netherlands)

    Popovici, A; Zaal, P.M.T.; Pool, D.M.; Mulder, M.; Sawaragi, T

    2016-01-01

    This study attempts to partially explain the characteristics of the human perceptual remnant, following Levison’s representation of the remnant as an equivalent observation noise. Eye activity parameters are recorded using an eye tracker in two compensatory tracking tasks in which the visual

  5. Human Activity Recognition Using Hierarchically-Mined Feature Constellations

    NARCIS (Netherlands)

    Oikonomopoulos, A.; Pantic, Maja

    In this paper we address the problem of human activity modelling and recognition by means of a hierarchical representation of mined dense spatiotemporal features. At each level of the hierarchy, the proposed method selects feature constellations that are increasingly discriminative and

  6. Focus-of-attention for human activity recognition from UAVs

    NARCIS (Netherlands)

    Burghouts, G.J.; Eekeren, A.W.M. van; Dijk, J.

    2014-01-01

    This paper presents a system to extract metadata about human activities from full-motion video recorded from a UAV. The pipeline consists of these components: tracking, motion features, representation of the tracks in terms of their motion features, and classification of each track as one of the

  7. Tactile interactions activate mirror system regions in the human brain.

    Science.gov (United States)

    McKyton, Ayelet

    2011-12-07

    Communicating with others is essential for the development of a society. Although types of communications, such as language and visual gestures, were thoroughly investigated in the past, little research has been done to investigate interactions through touch. To study this we used functional magnetic resonance imaging. Twelve participants were scanned with their eyes covered while stroking four kinds of items, representing different somatosensory stimuli: a human hand, a realistic rubber hand, an object, and a simple texture. Although the human and the rubber hands had the same overall shape, in three regions there was significantly more blood oxygen level dependent activation when touching the real hand: the anterior medial prefrontal cortex, the ventral premotor cortex, and the posterior superior temporal cortex. The last two regions are part of the mirror network and are known to be activated through visual interactions such as gestures. Interestingly, in this study, these areas were activated through a somatosensory interaction. A control experiment was performed to eliminate confounds of temperature, texture, and imagery, suggesting that the activation in these areas was correlated with the touch of a human hand. These results reveal the neuronal network working behind human tactile interactions, and highlight the participation of the mirror system in such functions.

  8. Activation of the lectin complement pathway on human renal ...

    African Journals Online (AJOL)

    This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro. Flow cytometry analysis, immunofluorescence staining and Western blot were used to detect the cell surface ...

  9. Linguistic Human Rights Discourse in Deaf Community Activism

    Science.gov (United States)

    Murray, Joseph J.

    2015-01-01

    The past three decades of activism for linguistic human rights (Skutnabb-Kangas 2000) have witnessed examples of language planning by various national and supranational actors in national and international spaces, with an exchange of ideas and strategies employed by national, regional, and worldwide organizations. In many countries a key goal of…

  10. Activation of human T lymphocytes by Leishmania lipophosphoglycan

    DEFF Research Database (Denmark)

    Kemp, M; Theander, T G; Handman, E

    1991-01-01

    This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon......, the results suggest that human T lymphocytes can respond to glycolipid antigens....

  11. Activation of the insular cortex during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Williamson, James; Nobrega, A C; McColl, R

    1997-01-01

    role as a site for regulation of autonomic activity. 2. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3. Increases in regional cerebral blood flow...... during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling...... alone. 5. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical...

  12. Enhanced root growth in phosphate-starved Arabidopsis by stimulating de novo phospholipid biosynthesis through the overexpression of LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE 2 (LPAT2).

    Science.gov (United States)

    Angkawijaya, Artik Elisa; Nguyen, Van Cam; Nakamura, Yuki

    2017-09-01

    Upon phosphate starvation, plants retard shoot growth but promote root development presumably to enhance phosphate assimilation from the ground. Membrane lipid remodelling is a metabolic adaptation that replaces membrane phospholipids by non-phosphorous galactolipids, thereby allowing plants to obtain scarce phosphate yet maintain the membrane structure. However, stoichiometry of this phospholipid-to-galactolipid conversion may not account for the massive demand of membrane lipids that enables active growth of roots under phosphate starvation, thereby suggesting the involvement of de novo phospholipid biosynthesis, which is not represented in the current model. We overexpressed an endoplasmic reticulum-localized lysophosphatidic acid acyltransferase, LPAT2, a key enzyme that catalyses the last step of de novo phospholipid biosynthesis. Two independent LPAT2 overexpression lines showed no visible phenotype under normal conditions but showed increased root length under phosphate starvation, with no effect on phosphate starvation response including marker gene expression, root hair development and anthocyanin accumulation. Accompanying membrane glycerolipid profiling of LPAT2-overexpressing plants revealed an increased content of major phospholipid classes and distinct responses to phosphate starvation between shoot and root. The findings propose a revised model of membrane lipid remodelling, in which de novo phospholipid biosynthesis mediated by LPAT2 contributes significantly to root development under phosphate starvation. © 2017 John Wiley & Sons Ltd.

  13. Murine Diacylglycerol Acyltransferase-2 (DGAT2) Can Catalyze Triacylglycerol Synthesis and Promote Lipid Droplet Formation Independent of Its Localization to the Endoplasmic Reticulum*

    Science.gov (United States)

    McFie, Pamela J.; Banman, Shanna L.; Kary, Steven; Stone, Scot J.

    2011-01-01

    Triacylglycerol (TG) is the major form of stored energy in eukaryotic organisms and is synthesized by two distinct acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes, DGAT1 and DGAT2. Both DGAT enzymes reside in the endoplasmic reticulum (ER), but DGAT2 also co-localizes with mitochondria and lipid droplets. In this report, we demonstrate that murine DGAT2 is part of a multimeric complex consisting of several DGAT2 subunits. We also identified the region of DGAT2 responsible for its localization to the ER. A DGAT2 mutant lacking both its transmembrane domains, although still associated with membranes, was absent from the ER and instead localized to mitochondria. Unexpectedly, this mutant was still active and capable of interacting with lipid droplets to promote TG storage. Additional experiments indicated that the ER targeting signal was present in the first transmembrane domain (TMD1) of DGAT2. When fused to a fluorescent reporter, TMD1, but not TMD2, was sufficient to target mCherry to the ER. Finally, the interaction of DGAT2 with lipid droplets was dependent on the C terminus of DGAT2. DGAT2 mutants, in which regions of the C terminus were either truncated or specific regions were deleted, failed to co-localize with lipid droplets when cells were oleate loaded to stimulate TG synthesis. Our findings demonstrate that DGAT2 is capable of catalyzing TG synthesis and promote its storage in cytosolic lipid droplets independent of its localization in the ER. PMID:21680734

  14. Human Error Probability Assessment During Maintenance Activities of Marine Systems

    Directory of Open Access Journals (Sweden)

    Rabiul Islam

    2018-03-01

    Full Text Available Background: Maintenance operations on-board ships are highly demanding. Maintenance operations are intensive activities requiring high man–machine interactions in challenging and evolving conditions. The evolving conditions are weather conditions, workplace temperature, ship motion, noise and vibration, and workload and stress. For example, extreme weather condition affects seafarers' performance, increasing the chances of error, and, consequently, can cause injuries or fatalities to personnel. An effective human error probability model is required to better manage maintenance on-board ships. The developed model would assist in developing and maintaining effective risk management protocols. Thus, the objective of this study is to develop a human error probability model considering various internal and external factors affecting seafarers' performance. Methods: The human error probability model is developed using probability theory applied to Bayesian network. The model is tested using the data received through the developed questionnaire survey of >200 experienced seafarers with >5 years of experience. The model developed in this study is used to find out the reliability of human performance on particular maintenance activities. Results: The developed methodology is tested on the maintenance of marine engine's cooling water pump for engine department and anchor windlass for deck department. In the considered case studies, human error probabilities are estimated in various scenarios and the results are compared between the scenarios and the different seafarer categories. The results of the case studies for both departments are also compared. Conclusion: The developed model is effective in assessing human error probabilities. These probabilities would get dynamically updated as and when new information is available on changes in either internal (i.e., training, experience, and fatigue or external (i.e., environmental and operational conditions

  15. ACYLTRANSFERASE ACTIVITIES OF THE HIGH-MOLECULAR-MASS ESSENTIAL PENICILLIN-BINDING PROTEINS

    NARCIS (Netherlands)

    ADAM, M; DAMBLON, C; JAMIN, M; ZORZI, W; DUSART, [No Value; GALLENI, M; ELKHARROUBI, A; PIRAS, G; SPRATT, BG; KECK, W; COYETTE, J; GHUYSEN, JM; NGUYENDISTECHE, M; FRERE, JM

    1991-01-01

    The high-molecular-mass penicillin-binding proteins (HMM-PBPs), present in the cytoplasmic membranes of all eubacteria, are involved in important physiological events such as cell elongation, septation or shape determination. Up to now it has, however, been very difficult or impossible to study the

  16. TECHNOLOGY AND INNOVATION IN HUMAN ACTIVITY OF THE INFORMATION AGE: HUMAN AND ICT

    Directory of Open Access Journals (Sweden)

    Oleksandr Yu. Burov

    2016-01-01

    Full Text Available In the article a brief overview of projects initiated by the U.S. National Science Foundation that related to new knowledge on integration and mutual development of social systems is proposed. The projects have a potential for transformation of science and researches, improvement of life quality and economy prosperity, as well as they should ensure outrunning development of information and communication technologies for all spheres of human activity: anthropocentric computerization, integration of information and informatics, robust intelligence, cyber-human systems, as well as two cross-technical areas - human and/or robots interaction, security and information protection.

  17. Prediction of Human Activity by Discovering Temporal Sequence Patterns.

    Science.gov (United States)

    Li, Kang; Fu, Yun

    2014-08-01

    Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units.

  18. Telomere elongation in immortal human cells without detectable telomerase activity.

    Science.gov (United States)

    Bryan, T M; Englezou, A; Gupta, J; Bacchetti, S; Reddel, R R

    1995-09-01

    Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessary for immortalization. All normal human fibroblasts tested were negative for telomerase activity. Thirteen out of 13 DNA tumor virus-transformed cell cultures were also negative in the pre-crisis (i.e. non-immortalized) stage. Of 35 immortalized cell lines, 20 had telomerase activity as expected, but 15 had no detectable telomerase. The 15 telomerase-negative immortalized cell lines all had very long and heterogeneous telomeres of up to 50 kb. Hybrids between telomerase-negative and telomerase-positive cells senesced. Two senescent hybrids demonstrated telomerase activity, indicating that activation of telomerase is not sufficient for immortalization. Some hybrid clones subsequently recommenced proliferation and became immortalized either with or without telomerase activity. Those without telomerase activity also had very long and heterogeneous telomeres. Taken together, these data suggest that the presence of lengthened or stabilized telomeres is necessary for immortalization, and that this may be achieved either by the reactivation of telomerase or by a novel and as yet unidentified mechanism.

  19. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  20. Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities.

    Science.gov (United States)

    Piwetz, Sarah; Lundquist, David; Würsig, Bernd

    2015-01-01

    Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts. © 2015 Elsevier Ltd All rights reserved.

  1. Human activity and climate variability project: annual report 2001

    International Nuclear Information System (INIS)

    Harle, K.J.; Heijnis, H.; Henderson-Sellers, A.; Sharmeen, S.; Zahorowski, W.

    2002-01-01

    Knowledge of the state of the Australian environment, including natural climate variability, prior to colonial settlement is vital if we are to define and understand the impact of over two hundred years of post-industrial human activity on our landscape. ANSTO, in conjunction with university partners, is leading a major research effort to provide natural archives of human activity and climate variability over the last 500 years in Australia, utilising a variety of techniques, including lead-210 and radiocarbon dating and analyses of proxy indicators (such as microfossils) as well as direct evidence (such as trace elements) of human activity and climate variability. The other major project objectives were to contribute to the understanding of the impact of human induced and natural aerosols in the East Asian region on climate through analysis and sourcing of fine particles and characterisation of air samples using radon concentrations and to contribute to the improvement of land surface parameterisation schemes and investigate the potential to use stable isotopes to improve global climate models and thus improve our understanding of future climate

  2. How consumer physical activity monitors could transform human physiology research

    Science.gov (United States)

    Hall Brown, Tyish S.; Collier, Scott R.; Sandberg, Kathryn

    2017-01-01

    A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O2, and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing. PMID:28052867

  3. How consumer physical activity monitors could transform human physiology research.

    Science.gov (United States)

    Wright, Stephen P; Hall Brown, Tyish S; Collier, Scott R; Sandberg, Kathryn

    2017-03-01

    A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O 2 , and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing. Copyright © 2017 the American Physiological Society.

  4. Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

    Directory of Open Access Journals (Sweden)

    Kandhasamy Sowndhararajan

    2016-11-01

    Full Text Available The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG. The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz, theta (4–8 Hz, alpha (8–13 Hz, beta (13–30 Hz and gamma (30–50 Hz, and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the

  5. Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

    Science.gov (United States)

    Sowndhararajan, Kandhasamy; Kim, Songmun

    2016-01-01

    The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG). The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–50 Hz), and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the

  6. Toshiba's activity concerning technology succession and human resource development

    International Nuclear Information System (INIS)

    Ogura, Kenji; Hoshide, Akehiko

    2008-01-01

    Recently, from the viewpoint of the reduction of carbon-dioxide emission that cause global warming and the energy security, the importance of nuclear power generation is recognized again as an effective approach for solving the problems, and many nuclear power plants are planed to be constructed worldwide. On the other hand, the experienced engineers will face the time of the retirement in the near future and technology succession and human resource development has become important problems. In this paper, Toshiba's Nuclear Energy Systems and Services Division's activity concerning technology succession and human resource development will be introduced. (author)

  7. Transposable element activity, genome regulation and human health.

    Science.gov (United States)

    Wang, Lu; Jordan, I King

    2018-03-02

    A convergence of novel genome analysis technologies is enabling population genomic studies of human transposable elements (TEs). Population surveys of human genome sequences have uncovered thousands of individual TE insertions that segregate as common genetic variants, i.e. TE polymorphisms. These recent TE insertions provide an important source of naturally occurring human genetic variation. Investigators are beginning to leverage population genomic data sets to execute genome-scale association studies for assessing the phenotypic impact of human TE polymorphisms. For example, the expression quantitative trait loci (eQTL) analytical paradigm has recently been used to uncover hundreds of associations between human TE insertion variants and gene expression levels. These include population-specific gene regulatory effects as well as coordinated changes to gene regulatory networks. In addition, analyses of linkage disequilibrium patterns with previously characterized genome-wide association study (GWAS) trait variants have uncovered TE insertion polymorphisms that are likely causal variants for a variety of common complex diseases. Gene regulatory mechanisms that underlie specific disease phenotypes have been proposed for a number of these trait associated TE polymorphisms. These new population genomic approaches hold great promise for understanding how ongoing TE activity contributes to functionally relevant genetic variation within and between human populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Activation of human factor V by factor Xa and thrombin

    International Nuclear Information System (INIS)

    Monkovic, D.D.; Tracy, P.B.

    1990-01-01

    The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate-polycarylamide gel electrophoresis followed by either autoradiography of 125 I-labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin-activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of M r 220,000 and 105,000. Although thrombin cleaved the M r 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the M r 220,000 peptide. The factor Xa dependent functional assessment of 125 I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the M r 220,000 peptide. The data indicate that factor Xa is as efficient an enzyme toward factor V as thrombin

  9. Inflammatory aetiology of human myometrial activation tested using directed graphs.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available THERE ARE THREE MAIN HYPOTHESES FOR THE ACTIVATION OF THE HUMAN UTERUS AT LABOUR: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from the literature to develop causal pathway models for the activation of human myometrium. The data provided quantitative RT-PCR results on key genes from samples taken before and during labour. Principal component analysis showed that pre-labour samples form a homogenous group compared to those during labour. We therefore modelled the alternative causal pathways in non-labouring samples using directed graphs and statistically compared the likelihood of the different models using structural equations and D-separation approaches. Using the computer program LISREL, inflammatory activation as a primary event was highly consistent with the data (p = 0.925, progesterone withdrawal, as a primary event, is plausible (p = 0.499, yet comparatively unlikely, oxytocin receptor mediated initiation is less compatible with the data (p = 0.091. DGraph, a software program that creates directed graphs, produced similar results (p= 0.684, p= 0.280, and p = 0.04, respectively. This outcome supports an inflammatory aetiology for human labour. Our results demonstrate the value of directed graphs in determining the likelihood of causal relationships in biology in situations where experiments are not possible.

  10. The anti-papillomavirus activity of human and bovine lactoferricin.

    Science.gov (United States)

    Mistry, Nitesh; Drobni, Peter; Näslund, Jonas; Sunkari, Vivekananda Gupta; Jenssen, Håvard; Evander, Magnus

    2007-09-01

    Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is necessary for the development of cervical cancer. We have previously found that lactoferrin has antiviral activity against HPV-16 and others have demonstrated that lactoferricin, an N-terminal fragment of lactoferrin, has inhibitory activities against several viruses. Two cell lines and two virus types, HPV-5 and HPV-16, were used to study if lactoferrin and lactoferricin could inhibit HPV pseudovirus (PsV) infection. We demonstrated that bovine lactoferrin (bLf) and human lactoferrin (hLf) were both potent inhibitors of HPV-5 and -16 PsV infections. Among the four lactoferricin derivatives we analyzed, a 15 amino acid peptide from bovine lactoferricin (bLfcin) 17-31 was the most potent inhibitor of both HPV-5 and HPV-16 PsV infection. Among the other derivatives, the human lactoferricin (hLfcin) 1-49 showed some antiviral activity against HPV PsV infection while bLfcin 17-42 inhibited only HPV-5 PsV infection in one of the cell lines. When we studied initial attachment of HPV-16, only bLfcin 17-42 and hLfcin 1-49 had an antiviral effect. This is the first time that lactoferricin was demonstrated to have an inhibitory effect on HPV infection and the antiviral activity differed depending on size, charge and structures of the lactoferricin.

  11. Human Activity Recognition by Combining a Small Number of Classifiers.

    Science.gov (United States)

    Nazabal, Alfredo; Garcia-Moreno, Pablo; Artes-Rodriguez, Antonio; Ghahramani, Zoubin

    2016-09-01

    We consider the problem of daily human activity recognition (HAR) using multiple wireless inertial sensors, and specifically, HAR systems with a very low number of sensors, each one providing an estimation of the performed activities. We propose new Bayesian models to combine the output of the sensors. The models are based on a soft outputs combination of individual classifiers to deal with the small number of sensors. We also incorporate the dynamic nature of human activities as a first-order homogeneous Markov chain. We develop both inductive and transductive inference methods for each model to be employed in supervised and semisupervised situations, respectively. Using different real HAR databases, we compare our classifiers combination models against a single classifier that employs all the signals from the sensors. Our models exhibit consistently a reduction of the error rate and an increase of robustness against sensor failures. Our models also outperform other classifiers combination models that do not consider soft outputs and an Markovian structure of the human activities.

  12. Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

    International Nuclear Information System (INIS)

    Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

    1990-01-01

    Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

  13. Metabolic activity and collagen turnover in human tendon in response to physical activity

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, H; Miller, B F

    2005-01-01

    Connective tissue of the human tendon plays an important role in force transmission. The extracellular matrix turnover of tendon is influenced by physical activity. Blood flow, oxygen demand, and the level of collagen synthesis and matrix metalloproteinases increase with mechanical loading. Gene...... of overuse tendon injuries occurring during sport, work or leisure-related activities....

  14. Exploring Human Activity Patterns Using Taxicab Static Points

    Directory of Open Access Journals (Sweden)

    Bin Jiang

    2012-06-01

    Full Text Available This paper explores the patterns of human activities within a geographical space by adopting the taxicab static points which refer to the locations with zero speed along the tracking trajectory. We report the findings from both aggregated and individual aspects. Results from the aggregated level indicate the following: (1 Human activities exhibit an obvious regularity in time, for example, there is a burst of activity during weekend nights and a lull during the week. (2 They show a remarkable spatial drifting pattern, which strengthens our understanding of the activities in any given place. (3 Activities are heterogeneous in space irrespective of their drifting with time. These aggregated results not only help in city planning, but also facilitate traffic control and management. On the other hand, investigations on an individual level suggest that (4 activities witnessed by one taxicab will have different temporal regularity to another, and (5 each regularity implies a high level of prediction with low entropy by applying the Lempel-Ziv algorithm.

  15. A Salmonella typhimurium-translocated Glycerophospholipid:Cholesterol Acyltransferase Promotes Virulence by Binding to the RhoA Protein Switch Regions

    Energy Technology Data Exchange (ETDEWEB)

    LaRock, Doris L.; Brzovic, Peter S.; Levin, Itay; Blanc, Marie-Pierre; Miller, Samuel I.

    2012-08-24

    Salmonella enterica serovar typhimurium translocates a glycerophospholipid: cholesterol acyltransferase (SseJ) into the host cytosol after its entry into mammalian cells. SseJ is recruited to the cytoplasmic face of the host cell phagosome membrane where it is activated upon binding the small GTPase, RhoA. SseJ is regulated similarly to cognate eukaryotic effectors, as only the GTP-bound form of RhoA family members stimulates enzymatic activity. Using NMR and biochemistry, this work demonstrates that SseJ competes effectively with Rhotekin, ROCK, and PKN1 in binding to a similar RhoA surface. The RhoA surface that binds SseJ includes the regulatory switch regions that control activation of mammalian effectors. These data were used to create RhoA mutants with altered SseJ binding and activation. This structure-function analysis supports a model in which SseJ activation occurs predominantly through binding to residues within switch region II. We further defined the nature of the interaction between SseJ and RhoA by constructing SseJ mutants in the RhoA binding surface. These data indicate that SseJ binding to RhoA is required for recruitment of SseJ to the endosomal network and for full Salmonella virulence for inbred susceptible mice, indicating that regulation of SseJ by small GTPases is an important virulence strategy of this bacterial pathogen. The dependence of a bacterial effector on regulation by a mammalian GTPase defines further how intimately host pathogen interactions have coevolved through similar and divergent evolutionary strategies.

  16. HMM Adaptation for Improving a Human Activity Recognition System

    Directory of Open Access Journals (Sweden)

    Rubén San-Segundo

    2016-09-01

    Full Text Available When developing a fully automatic system for evaluating motor activities performed by a person, it is necessary to segment and recognize the different activities in order to focus the analysis. This process must be carried out by a Human Activity Recognition (HAR system. This paper proposes a user adaptation technique for improving a HAR system based on Hidden Markov Models (HMMs. This system segments and recognizes six different physical activities (walking, walking upstairs, walking downstairs, sitting, standing and lying down using inertial signals from a smartphone. The system is composed of a feature extractor for obtaining the most relevant characteristics from the inertial signals, a module for training the six HMMs (one per activity, and the last module for segmenting new activity sequences using these models. The user adaptation technique consists of a Maximum A Posteriori (MAP approach that adapts the activity HMMs to the user, using some activity examples from this specific user. The main results on a public dataset have reported a significant relative error rate reduction of more than 30%. In conclusion, adapting a HAR system to the user who is performing the physical activities provides significant improvement in the system’s performance.

  17. Bacterial expression of human kynurenine 3-monooxygenase: solubility, activity, purification.

    Science.gov (United States)

    Wilson, K; Mole, D J; Binnie, M; Homer, N Z M; Zheng, X; Yard, B A; Iredale, J P; Auer, M; Webster, S P

    2014-03-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington's disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Bacterial expression of human kynurenine 3-monooxygenase: Solubility, activity, purification☆

    Science.gov (United States)

    Wilson, K.; Mole, D.J.; Binnie, M.; Homer, N.Z.M.; Zheng, X.; Yard, B.A.; Iredale, J.P.; Auer, M.; Webster, S.P.

    2014-01-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington’s disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. PMID:24316190

  19. Human hair identification by instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Cho, S.Y.; Jang, S.G.; Chung, Y.S.

    1998-01-01

    Nondestructive neutron activation technique was used to analyze 17 elements (Al, As, Au, Ba, Br, Cl, Cu, Hg, I, K, Mg, Mn, Na, Sb, Sr, V and Zn) in 75 human hair samples in 5 different locations, respectively, from 15 glassware workers. The analytical results were treated further statistically to find the elemental distribution among different human hairs and to identify the individual's hair. The identifying probability of one's hair by the comparison of elemental concentrations is found to be 10 4 -10 6 times higher from the same person's than from any other person's. The standard deviation of the elemental concentrations of samples taken from 5 different locations of one person is about 5 time smaller than the standard deviation for individual's hair. These data support the possibility of using NAA of hair for human hair identification. (author)

  20. Assessment of Nicotine Exposure From Active Human Cigarette Smoking Time

    Directory of Open Access Journals (Sweden)

    Cahours Xavier

    2017-09-01

    Full Text Available The burning of a cigarette is a series of consecutive sequences of both passive and active burnings when a smoking cycle is applied to the cigarette. A previous study, using a smoking machine, showed that cigarette nicotine yields are dependent linearly on the difference between the time of smouldering (passive burning and the time of smoking (active burning. It is predicted that the smoker’s nicotine yield increases when the intensity of smoking increases, i.e., when the time to smoke a cigarette (smoking time decreases. Note that observations made on machines might not be comparable to human behaviours. The aim of this study was to determine whether nicotine mouth-level exposure could be predicted through measurement of human smoking time. A smoking behaviour study was conducted to compare human smoking nicotine yields obtained from both filter tip analysis and the cigarette burning time model. Results showed that smokers’ exposure to the smoke depends essentially on the speed at which the cigarette is smoked. An increase in human smoking intensity, resulting in a decrease in smoking time, generates an increase in smoke exposure, whatever the puff number, puff duration, puff volume and filter ventilation (open or blocked. The association of a machine smoking yield with a corresponding smoking time, and the time taken by a consumer to smoke the cigarette would provide information on the exposure to smoke constituents in a simple and effective manner.

  1. Legal regime of human activities in outer space law

    Science.gov (United States)

    Golda, Carlo

    1994-01-01

    Current developments in space activities increasingly involve the presence of humans on board spacecraft and, in the near future, on the Moon, on Mars, on board Space Stations, etc. With respect to these challenges, the political and legal issues connected to the status of astronauts are largely unclear and require a new doctrinal attention. In the same way, many legal and political questions remain open in the structure of future space crews: the need for international standards in the definition and training of astronauts, etc.; but, first of all, an international uniform legal definition of astronauts. Moreover, the legal structure for human life and operations in outer space can be a new and relevant paradigm for the definition of similar rules in all the situations and environments in which humans are involved in extreme frontiers. The present article starts from an overview on the existing legal and political definitions of 'astronauts', moving to the search of a more useful definition. This is followed by an analysis of the concrete problems created by human space activities, and the legal and political responses to them (the need for a code of conduct; the structure of the crew and the existing rules in the US and ex-USSR; the new legal theories on the argument; the definition and structure of a code of conduct; the next legal problems in fields such as privacy law, communications law, business law, criminal law, etc.).

  2. Definitive characterization of human thymine glycol N-glycosylase activity

    International Nuclear Information System (INIS)

    Higgins, S.A.; Frenkel, K.; Cummings, A.; Teebor, G.W.

    1987-01-01

    An N-glycosylase activity that released cis-[ 3 H]-5,6-dihydroxy-5,6-dihydrothymine (thymine glycol, TG) from chemically oxidized poly(dA-[ 3 H]dT) was unambiguously characterized both in extracts of HeLa cells and in purified Escherichia coli endonuclease III. This was accomplished by use of a microderivatization procedure that quantitatively converted cis-TG to 5-hydroxy-5-methylhydantoin (HMH). The reaction products were analyzed by high-pressure liquid chromatography before and after derivation by using cis-[ 14 C]TG and [ 14 C]HMH, which had been independently synthesized, as reference compounds. This technique facilitated construction of a v/[E]/sub t/ plot for the enzyme activity in HeLa cells, permitting estimation of its specific activity. The results obtained prove the existence of both human and bacterial N-glycosylase activities that effect removal of TG from DNA

  3. Human temporal cortical single neuron activity during working memory maintenance.

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-06-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  4. Human Temporal Cortical Single Neuron Activity During Working Memory Maintenance

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-01-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  5. Radioimmunological activity of 22K variant of human growth hormone

    International Nuclear Information System (INIS)

    Camillo, M.A.P.; Ribela, M.T.C.P.; Rogero, J.R.

    1986-01-01

    From a preparation of human growth hormone its integral variant (hGH-22K) was isolated by isoelectric focusing, having a pI of 5,20 and relative mobility (Rm) of 0,621 in the polyacrylamide gel electrophoresis. Several experiments for the characterization of the isolated variant were carried out. The immunological properties was tested by radioimmunoassay (RIE), in which the activity of the isolated variant and the activity of the total preparation were compared. The dose response-curves obtained by RIE were found to be considered parallels (p [pt

  6. Metabolites of alectinib in human: their identification and pharmacological activity

    Directory of Open Access Journals (Sweden)

    Mika Sato-Nakai

    2017-07-01

    Full Text Available Two metabolites (M4 and M1b in plasma and four metabolites (M4, M6, M1a and M1b in faeces were detected through the human ADME study following a single oral administration of [14C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib. In plasma, M4 was a major metabolite and M1b was a minor metabolite. The contribution to in vivo pharmacological activity of these circulating metabolites was assessed from their in vitro pharmacological activity and plasma protein binding. M4 had a similar cancer cell growth inhibitory activity and plasma protein binding to that of alectinib, suggesting its contribution to the antitumor activity of alectinib, whereas the pharmacological activity of M1b was insignificant.

  7. Early development of synchrony in cortical activations in the human.

    Science.gov (United States)

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Human medial frontal cortex activity predicts learning from errors.

    Science.gov (United States)

    Hester, Robert; Barre, Natalie; Murphy, Kevin; Silk, Tim J; Mattingley, Jason B

    2008-08-01

    Learning from errors is a critical feature of human cognition. It underlies our ability to adapt to changing environmental demands and to tune behavior for optimal performance. The posterior medial frontal cortex (pMFC) has been implicated in the evaluation of errors to control behavior, although it has not previously been shown that activity in this region predicts learning from errors. Using functional magnetic resonance imaging, we examined activity in the pMFC during an associative learning task in which participants had to recall the spatial locations of 2-digit targets and were provided with immediate feedback regarding accuracy. Activity within the pMFC was significantly greater for errors that were subsequently corrected than for errors that were repeated. Moreover, pMFC activity during recall errors predicted future responses (correct vs. incorrect), despite a sizeable interval (on average 70 s) between an error and the next presentation of the same recall probe. Activity within the hippocampus also predicted future performance and correlated with error-feedback-related pMFC activity. A relationship between performance expectations and pMFC activity, in the absence of differing reinforcement value for errors, is consistent with the idea that error-related pMFC activity reflects the extent to which an outcome is "worse than expected."

  9. Influence of vestibular activation on respiration in humans

    Science.gov (United States)

    Monahan, Kevin D.; Sharpe, Melissa K.; Drury, Daniel; Ertl, Andrew C.; Ray, Chester A.

    2002-01-01

    The purpose of this study was to determine the effects of the semicircular canals and otolith organs on respiration in humans. On the basis of animal studies, we hypothesized that vestibular activation would elicit a vestibulorespiratory reflex. To test this hypothesis, respiratory measures, arterial blood pressure, and heart rate were measured during engagement of semicircular canals and/or otolith organs. Dynamic upright pitch and roll (15 cycles/min), which activate the otolith organs and semicircular canals, increased respiratory rate (Delta2 +/- 1 and Delta3 +/- 1 breaths/min, respectively; P < 0.05). Dynamic yaw and lateral pitch (15 cycles/min), which activate the semicircular canals, increased respiration similarly (Delta3 +/- 1 and Delta2 +/- 1, respectively; P < 0.05). Dynamic chair rotation (15 cycles/min), which mimics dynamic yaw but eliminates neck muscle afferent, increased respiration (Delta3 +/- 1; P < 0.05) comparable to dynamic yaw (15 cycles/min). Increases in respiratory rate were graded as greater responses occurred during upright (Delta5 +/- 2 breaths/min) and lateral pitch (Delta4 +/- 1) and roll (Delta5 +/- 1) performed at 30 cycles/min. Increases in breathing frequency resulted in increases in minute ventilation during most interventions. Static head-down rotation, which activates otolith organs, did not alter respiratory rate (Delta1 +/- 1 breaths/min). Collectively, these data indicate that semicircular canals, but not otolith organs or neck muscle afferents, mediate increased ventilation in humans and support the concept that vestibular activation alters respiration in humans.

  10. Anticancer activities of bovine and human lactoferricin-derived peptides.

    Science.gov (United States)

    Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

    2017-02-01

    Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

  11. Human Activity Recognition as Time-Series Analysis

    Directory of Open Access Journals (Sweden)

    Hyesuk Kim

    2015-01-01

    Full Text Available We propose a system that can recognize daily human activities with a Kinect-style depth camera. Our system utilizes a set of view-invariant features and the hidden state conditional random field (HCRF model to recognize human activities from the 3D body pose stream provided by MS Kinect API or OpenNI. Many high-level daily activities can be regarded as having a hierarchical structure where multiple subactivities are performed sequentially or iteratively. In order to model effectively these high-level daily activities, we utilized a multiclass HCRF model, which is a kind of probabilistic graphical models. In addition, in order to get view-invariant, but more informative features, we extract joint angles from the subject’s skeleton model and then perform the feature transformation to obtain three different types of features regarding motion, structure, and hand positions. Through various experiments using two different datasets, KAD-30 and CAD-60, the high performance of our system is verified.

  12. Robust Indoor Human Activity Recognition Using Wireless Signals.

    Science.gov (United States)

    Wang, Yi; Jiang, Xinli; Cao, Rongyu; Wang, Xiyang

    2015-07-15

    Wireless signals-based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI) of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP) and access points (AP). First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions' CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO) signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM) based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

  13. Robust Indoor Human Activity Recognition Using Wireless Signals

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2015-07-01

    Full Text Available Wireless signals–based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP and access points (AP. First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions’ CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

  14. Cortical GABAergic excitation contributes to epileptic activities around human glioma

    Science.gov (United States)

    Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

    2015-01-01

    Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

  15. An acyltransferase gene that putatively functions in anthocyanin modification was horizontally transferred from Fabaceae into the genus Cuscuta

    Directory of Open Access Journals (Sweden)

    Ting Sun

    2016-06-01

    Full Text Available Horizontal gene transfer (HGT refers to the flow of genetic materials to non-offspring, and occasionally HGT in plants can improve the adaptation of organisms in new niches due to expanded metabolic capability. Anthocyanins are an important group of water-soluble red, purple, or blue secondary metabolites, whose diversity results from modification after the main skeleton biosynthesis. Cuscuta is a stem holoparasitic genus, whose members form direct connection with hosts to withdraw water, nutrients, and macromolecules. Such intimate association is thought to increase the frequency of HGT. By transcriptome screening for foreign genes in Cuscuta australis, we discovered that one gene encoding a putative anthocyanin acyltransferase gene of the BAHD family, which is likely to be involved in anthocyanin modification, was acquired by C. australis from Fabaceae through HGT. The anthocyanin acyltransferase-like (AT-like gene was confirmed to be present in the genome assembly of C. australis and the transcriptomes of Cuscuta pentagona. The higher transcriptional level in old stems is consistent with its putative function in secondary metabolism by stabilizing anthocyanin at neutral pH and thus HGT of this AT-like gene may have improved biotic and abiotic resistance of Cuscuta.

  16. Listening to humans walking together activates the social brain circuitry.

    Science.gov (United States)

    Saarela, Miiamaaria V; Hari, Riitta

    2008-01-01

    Human footsteps carry a vast amount of social information, which is often unconsciously noted. Using functional magnetic resonance imaging, we analyzed brain networks activated by footstep sounds of one or two persons walking. Listening to two persons walking together activated brain areas previously associated with affective states and social interaction, such as the subcallosal gyrus bilaterally, the right temporal pole, and the right amygdala. These areas seem to be involved in the analysis of persons' identity and complex social stimuli on the basis of auditory cues. Single footsteps activated only the biological motion area in the posterior STS region. Thus, hearing two persons walking together involved a more widespread brain network than did hearing footsteps from a single person.

  17. Aloe vera extract activity on human corneal cells.

    Science.gov (United States)

    Woźniak, Anna; Paduch, Roman

    2012-02-01

    Ocular diseases are currently an important problem in modern societies. Patients suffer from various ophthalmologic ailments namely, conjunctivitis, dry eye, dacryocystitis or degenerative diseases. Therefore, there is a need to introduce new treatment methods, including medicinal plants usage. Aloe vera [Aloe barbadensis Miller (Liliaceae)] possesses wound-healing properties and shows immunomodulatory, anti-inflammatory or antioxidant activities. NR uptake, MTT, DPPH• reduction, Griess reaction, ELISA and rhodamine-phalloidin staining were used to test toxicity, antiproliferative activity, reactive oxygen species (ROS) reduction, nitric oxide (NO) and cytokine level, and distribution of F-actin in cells, respectively. The present study analyzes the effect of Aloe vera extracts obtained with different solvents on in vitro culture of human 10.014 pRSV-T corneal cells. We found no toxicity of ethanol, ethyl acetate and heptane extracts of Aloe vera on human corneal cells. No ROS reducing activity by heptane extract and trace action by ethanol (only at high concentration 125 µg/ml) extract of Aloe vera was observed. Only ethyl acetate extract expressed distinct free radical scavenging effect. Plant extracts decreased NO production by human corneal cells as compared to untreated controls. The cytokine (IL-1β, IL-6, TNF-α and IL-10) production decreased after the addition of Aloe vera extracts to the culture media. Aloe vera contains multiple pharmacologically active substances which are capable of modulating cellular phenotypes and functions. Aloe vera ethanol and ethyl acetate extracts may be used in eye drops to treat inflammations and other ailments of external parts of the eye such as the cornea.

  18. Isothiocyanates: An Overview of Their Antimicrobial Activity against Human Infections

    Directory of Open Access Journals (Sweden)

    Letizia Romeo

    2018-03-01

    Full Text Available The use of plant-derived products as antimicrobial agents has been investigated in depth. Isothiocyanates (ITCs are bioactive products resulting from enzymatic hydrolysis of glucosinolates (GLs, the most abundant secondary metabolites in the botanical order Brassicales. Although the antimicrobial activity of ITCs against foodborne and plant pathogens has been well documented, little is known about their antimicrobial properties against human pathogens. This review collects studies that focus on this topic. Particular focus will be put on ITCs’ antimicrobial properties and their mechanism of action against human pathogens for which the current therapeutic solutions are deficient and therefore of prime importance for public health. Our purpose was the evaluation of the potential use of ITCs to replace or support the common antibiotics. Even though ITCs appear to be effective against the most important human pathogens, including bacteria with resistant phenotypes, the majority of the studies did not show comparable results and thus it is very difficult to compare the antimicrobial activity of the different ITCs. For this reason, a standard method should be used and further studies are needed.

  19. Human activity and damaging landslides and floods on Madeira Island

    Science.gov (United States)

    Baioni, D.

    2011-11-01

    Over the last few decades, the island of Madeira has become an important offshore tourism and business center, with rapid economic and demographic development that has caused changes to the landscape due to human activity. In Madeira's recent history, there has been an increase over time in the frequency of occurrence of damaging landslide and flood events. As a result, the costs of restoration work due to damage caused by landslide and flood events have become a larger and larger component of Madeira's annual budget. Landslides and floods in Madeira deserve particular attention because they represent the most serious hazard to human life, to property, and to the natural environment and its important heritage value. The work reported on in this paper involved the analysis of historical data regarding damaging landslide and flood events on Madeira (in particular from 1941 to 1991) together with data on geological characteristics, topographic features, and climate, and from field observations. This analysis showed that the main factor triggering the occurrence of damaging landslide and flood events is rainfall, but that the increase in the number of damaging events recorded on Madeira Island, especially in recent times, seems to be related mostly to human activity, specifically to economic development and population growth, rather than to natural factors.

  20. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  1. Human activity and damaging landslides and floods on Madeira Island

    Directory of Open Access Journals (Sweden)

    D. Baioni

    2011-11-01

    Full Text Available Over the last few decades, the island of Madeira has become an important offshore tourism and business center, with rapid economic and demographic development that has caused changes to the landscape due to human activity. In Madeira's recent history, there has been an increase over time in the frequency of occurrence of damaging landslide and flood events. As a result, the costs of restoration work due to damage caused by landslide and flood events have become a larger and larger component of Madeira's annual budget. Landslides and floods in Madeira deserve particular attention because they represent the most serious hazard to human life, to property, and to the natural environment and its important heritage value.

    The work reported on in this paper involved the analysis of historical data regarding damaging landslide and flood events on Madeira (in particular from 1941 to 1991 together with data on geological characteristics, topographic features, and climate, and from field observations. This analysis showed that the main factor triggering the occurrence of damaging landslide and flood events is rainfall, but that the increase in the number of damaging events recorded on Madeira Island, especially in recent times, seems to be related mostly to human activity, specifically to economic development and population growth, rather than to natural factors.

  2. Using human brain activity to guide machine learning.

    Science.gov (United States)

    Fong, Ruth C; Scheirer, Walter J; Cox, David D

    2018-03-29

    Machine learning is a field of computer science that builds algorithms that learn. In many cases, machine learning algorithms are used to recreate a human ability like adding a caption to a photo, driving a car, or playing a game. While the human brain has long served as a source of inspiration for machine learning, little effort has been made to directly use data collected from working brains as a guide for machine learning algorithms. Here we demonstrate a new paradigm of "neurally-weighted" machine learning, which takes fMRI measurements of human brain activity from subjects viewing images, and infuses these data into the training process of an object recognition learning algorithm to make it more consistent with the human brain. After training, these neurally-weighted classifiers are able to classify images without requiring any additional neural data. We show that our neural-weighting approach can lead to large performance gains when used with traditional machine vision features, as well as to significant improvements with already high-performing convolutional neural network features. The effectiveness of this approach points to a path forward for a new class of hybrid machine learning algorithms which take both inspiration and direct constraints from neuronal data.

  3. Source strengths for indoor human activities that resuspend particulate matter.

    Science.gov (United States)

    Ferro, Andrea R; Kopperud, Royal J; Hildemann, Lynn M

    2004-03-15

    A mathematical model was applied to continuous indoor and outdoor particulate matter (PM) measurements to estimate source strengths for a variety of prescribed human activities that resuspend house dust in the home. Activities included folding blankets, folding clothes, dry dusting, making a bed, dancing on a rug, dancing on a wood floor, vacuuming, and walking around and sitting on upholstered furniture. Although most of the resuspended particle mass from these activities was larger than 5 microm in diameter, the resuspension of PM2.5 and PM5 was substantial, with source strengths ranging from 0.03 to 0.5 mg min(-1) for PM2.5 and from 0.1 to 1.4 mg min(-1) for PM5. Source strengths for PM > 5 microm could not be quantified due to instrument limitations. The source strengths were found to be a function of the number of persons performing the activity, the vigor of the activity, the type of activity, and the type of flooring.

  4. SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-acylglycerol-3-phosphate O-acyltransferases of budding yeast

    DEFF Research Database (Denmark)

    Benghezal, Mohammed; Roubaty, Carole; Veepuri, Vijayanath

    2007-01-01

    Phosphatidic acid is the intermediate, from which all glycerophospholipids are synthesized. In yeast, it is generated from lysophosphatidic acid, which is acylated by Slc1p, an sn-2-specific, acyl-coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal...

  5. Effects of the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism on fatty acid, protein, and mineral composition of dairy cattle milk

    NARCIS (Netherlands)

    Bovenhuis, H.; Visker, M.H.P.W.; Poulsen, N.A.; Sehested, J.; Valenberg, van H.J.F.; Arendonk, van J.A.M.; Larsen, L.B.; Buitenhuis, A.J.

    2016-01-01

    Several studies have described associations between the diacylglycerol o-acyltransferase 1 (DGAT1) K232A polymorphism and routinely collected milk production traits but not much is known about effects of the DGAT1 polymorphism on detailed milk composition. The aim of this study was to estimate

  6. Human factors in remote control engineering development activities

    International Nuclear Information System (INIS)

    Clarke, M.M.; Hamel, W.R.; Draper, J.V.

    1983-01-01

    Human factors engineering, which is an integral part of the advanced remote control development activities at the Oak Ridge National Laboratory, is described. First, work at the Remote Systems Development Facility (RSDF) has shown that operators can perform a wide variety of tasks, some of which were not specifically designed for remote systems, with a dextrous electronic force-reflecting servomanipulator and good television remote viewing capabilities. Second, the data collected during mock-up remote maintenance experiments at the RSDF have been analyzed to provide guidelines for the design of human interfaces with an integrated advanced remote maintenance system currently under development. Guidelines have been provided for task allocation between operators, remote viewing systems, and operator controls. 6 references, 5 figures, 2 tables

  7. Immunosuppressive activity of human cord-blood lipoproteins

    International Nuclear Information System (INIS)

    Forte, T.M.; Davis, P.A.; Curtiss, L.K.

    1985-01-01

    It is now known that the role of plasma lipoproteins is multifunctional. More recently it has been shown that lipoproteins may regulate immune responses as well. Low-density lipoproteins carrying apolipoprotein B (apoB) are known to suppress phytohemagglutinin (PHA) activated lymphocytes by inhibiting DNA synthesis. More recently, an immunoregulatory role has been described for another apolipoprotein, apoE, which is found in low quantities in normal plasma. In these studies with human umbilical-cord blood the authors were intrigued by two factors: the low level of LDL and hence apoB, and the elevated quantity of apoE. This study examines the hypothesis that apoE may regulate lymphocyte function in the human fetus

  8. Lecithin-cholesterol acyltransferase (LCAT) catalyzes transacylation of intact cholesteryl esters. Evidence for the partial reversal of the forward LCAT reaction

    International Nuclear Information System (INIS)

    Sorci-Thomas, M.; Babiak, J.; Rudel, L.L.

    1990-01-01

    Lecithin-cholesterol acyltransferase (LCAT) catalyzes the intravascular synthesis of lipoprotein cholesteryl esters by converting cholesterol and lecithin to cholesteryl ester and lysolecithin. LCAT is unique in that it catalyzes sequential reactions within a single polypeptide sequence. In this report we find that LCAT mediates a partial reverse reaction, the transacylation of lipoprotein cholesteryl oleate, in whole plasma and in a purified, reconstituted system. As a result of the reverse transacylation reaction, a linear accumulation of [3H]cholesterol occurred during incubations of plasma containing high density lipoprotein labeled with [3H]cholesteryl oleate. When high density lipoprotein labeled with cholesteryl [14C]oleate was also included in the incubation the labeled fatty acyl moiety remained in the cholesteryl [14C]oleate pool showing that the formation of labeled cholesterol did not result from hydrolysis of the doubly labeled cholesteryl esters. The rate of release of [3H]cholesterol was only about 10% of the forward rate of esterification of cholesterol using partially purified human LCAT and was approximately 7% in whole monkey plasma. Therefore, net production of cholesterol via the reverse LCAT reaction would not occur. [3H]Cholesterol production from [3H]cholesteryl oleate was almost completely inhibited by a final concentration of 1.4 mM 5,5'-dithiobis(nitrobenzoic acid) during incubation with either purified LCAT or whole plasma. Addition of excess lysolecithin to the incubation system did not result in the formation of [14C]oleate-labeled lecithin, showing that the reverse reaction found here for LCAT was limited to the last step of the reaction. To explain these results we hypothesize that LCAT forms a [14C]oleate enzyme thioester intermediate after its attack on the cholesteryl oleate molecule

  9. Disturbances of electrodynamic activity affect abortion in human

    International Nuclear Information System (INIS)

    Jandová, A; Cifra, M; Pokorný, J; Nedbalová, M; Dohnalová, A; Kobilková, J; Cocek, A

    2011-01-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich; he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  10. Disturbances of electrodynamic activity affect abortion in human

    Science.gov (United States)

    Jandová, A.; Nedbalová, M.; Kobilková, J.; Čoček, A.; Dohnalová, A.; Cifra, M.; Pokorný, J.

    2011-12-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  11. Super Normal Vector for Human Activity Recognition with Depth Cameras.

    Science.gov (United States)

    Yang, Xiaodong; Tian, YingLi

    2017-05-01

    The advent of cost-effectiveness and easy-operation depth cameras has facilitated a variety of visual recognition tasks including human activity recognition. This paper presents a novel framework for recognizing human activities from video sequences captured by depth cameras. We extend the surface normal to polynormal by assembling local neighboring hypersurface normals from a depth sequence to jointly characterize local motion and shape information. We then propose a general scheme of super normal vector (SNV) to aggregate the low-level polynormals into a discriminative representation, which can be viewed as a simplified version of the Fisher kernel representation. In order to globally capture the spatial layout and temporal order, an adaptive spatio-temporal pyramid is introduced to subdivide a depth video into a set of space-time cells. In the extensive experiments, the proposed approach achieves superior performance to the state-of-the-art methods on the four public benchmark datasets, i.e., MSRAction3D, MSRDailyActivity3D, MSRGesture3D, and MSRActionPairs3D.

  12. Workshop on Human Activity at Scale in Earth System Models

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Melissa R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Aziz, H. M. Abdul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Coletti, Mark A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kennedy, Joseph H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nair, Sujithkumar S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Omitaomu, Olufemi A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-01-26

    Changing human activity within a geographical location may have significant influence on the global climate, but that activity must be parameterized in such a way as to allow these high-resolution sub-grid processes to affect global climate within that modeling framework. Additionally, we must have tools that provide decision support and inform local and regional policies regarding mitigation of and adaptation to climate change. The development of next-generation earth system models, that can produce actionable results with minimum uncertainties, depends on understanding global climate change and human activity interactions at policy implementation scales. Unfortunately, at best we currently have only limited schemes for relating high-resolution sectoral emissions to real-time weather, ultimately to become part of larger regions and well-mixed atmosphere. Moreover, even our understanding of meteorological processes at these scales is imperfect. This workshop addresses these shortcomings by providing a forum for discussion of what we know about these processes, what we can model, where we have gaps in these areas and how we can rise to the challenge to fill these gaps.

  13. Evaluation of Hemagglutination Activity of Chitosan Nanoparticles Using Human Erythrocytes

    Directory of Open Access Journals (Sweden)

    Jefferson Muniz de Lima

    2015-01-01

    Full Text Available Chitosan is a polysaccharide composed of randomly distributed chains of β-(1-4 D-glucosamine and N-acetyl-D-glucosamine. This compound is obtained by partial or total deacetylation of chitin in acidic solution. The chitosan-based hemostatic agents have been gaining much attention in the management of bleeding. The aim of this study was to evaluate in vitro hemagglutination activity of chitosan nanoparticles using human erythrocytes. The preparation of nanoparticles was achieved by ionotropic gelification technique followed by neutralization with NaOH 1 mol/L−1. The hemagglutination activity was performed on a solution of 2% erythrocytes (pH 7.4 on PBS collected from five healthy volunteers. The hemolysis determination was made by spectrophotometric analysis. Chitosan nanoparticle solutions without NaOH addition changed the reddish colour of the wells into brown, suggesting an oxidative reaction of hemoglobin and possible cell lysis. All neutralized solutions of chitosan nanoparticles presented positive haemagglutination, without any change in reaction color. Chitosan nanoparticles presented hemolytic activity ranging from 186.20 to 223.12%, while neutralized solutions ranged from 2.56 to 72.54%, comparing to distilled water. Results highlight the need for development of new routes of synthesis of chitosan nanoparticles within human physiologic pH.

  14. Human activities and climate and environment changes: an inevitable relation

    International Nuclear Information System (INIS)

    Sanchez, Aretha

    2009-01-01

    The human interference in the environment and the consequent climate change is today a consensus. The climate change can be local, regional and global. The global climate change is mainly caused by the greenhouse gases, and consequently the climate change intervenes in the environment. The interference cycle emerges in several forms and results in several consequences. However, the Global Warming has certainly the most import global impact. The main cause of the increase in the temperature (Greenhouse Effect) is the intensive use of the fossil fuels. Thus, to minimize the climatic changes actions are necessary to reduce, to substitute and to use with more efficient the fossil fuels. Looking at the past, the old agriculturists may have released greenhouse gases since thousand years ago, thus, modifying slowly but in significant form the earth climate much before the Industrial Age. If this theory is confirmed, its consequences would be decisive for the man history in the planet. For example, in parts of the North America and Europe the current temperatures could be even four Celsius degrees smaller. This change in temperature is enough to hinder agricultural used of these regions and consequently to diminish the human development. The main focus of this work is to perform a retrospective in some of civilizations who collapse due to environmental problems and make a historical description of the human activities (agriculture and livestock) since the primordium of the man up to the Industrial Age, aiming at the man interference on the natural dynamics of the global climate and the environment. This work will show through data comparisons and inferences that the gases emissions from these activities had a significant magnitude comparatively by the emissions after the Industrial Age. It is also demonstrated that the climate and environment interference was inevitable because the human evolution was caused by these activities. Another important point of this work is to

  15. Probiotic Activity of Saccharomyces cerevisiae var. boulardii Against Human Pathogens

    Directory of Open Access Journals (Sweden)

    Katarzyna Rajkowska

    2012-01-01

    Full Text Available Infectious diarrhoea is associated with a modification of the intestinal microflora and colonization of pathogenic bacteria. Tests were performed for seven probiotic yeast strains of Saccharomyces cerevisiae var. boulardii, designated for the prevention and treatment of diarrhoea. To check their possible effectiveness against diarrhoea of different etiologies, the activity against a variety of human pathogenic or opportunistic bacteria was investigated in vitro. In mixed cultures with S. cerevisiae var. boulardii, a statistically significant reduction was observed in the number of cells of Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus, by even 55.9 % in the case of L. monocytogenes compared with bacterial monocultures. The influence of yeasts was mostly associated with the shortening of the bacterial lag phase duration, more rapid achievement of the maximum growth rates, and a decrease by 4.4–57.1 % (L. monocytogenes, P. aeruginosa, or an increase by 1.4–70.6 % (Escherichia coli, Enterococcus faecalis, Salmonella Typhimurium in the exponential growth rates. Another issue included in the research was the ability of S. cerevisiae var. boulardii to bind pathogenic bacteria to its cell surface. Yeasts have shown binding capacity of E. coli, S. Typhimurium and additionally of S. aureus, Campylobacter jejuni and E. faecalis. However, no adhesion of L. monocytogenes and P. aeruginosa to the yeast cell wall was noted. The probiotic activity of S. cerevisiae var. boulardii against human pathogens is related to a decrease in the number of viable and active cells of bacteria and the binding capacity of yeasts. These processes may limit bacterial invasiveness and prevent bacterial adherence and translocation in the human intestines.

  16. A Novel Energy-Efficient Approach for Human Activity Recognition.

    Science.gov (United States)

    Zheng, Lingxiang; Wu, Dihong; Ruan, Xiaoyang; Weng, Shaolin; Peng, Ao; Tang, Biyu; Lu, Hai; Shi, Haibin; Zheng, Huiru

    2017-09-08

    In this paper, we propose a novel energy-efficient approach for mobile activity recognition system (ARS) to detect human activities. The proposed energy-efficient ARS, using low sampling rates, can achieve high recognition accuracy and low energy consumption. A novel classifier that integrates hierarchical support vector machine and context-based classification (HSVMCC) is presented to achieve a high accuracy of activity recognition when the sampling rate is less than the activity frequency, i.e., the Nyquist sampling theorem is not satisfied. We tested the proposed energy-efficient approach with the data collected from 20 volunteers (14 males and six females) and the average recognition accuracy of around 96.0% was achieved. Results show that using a low sampling rate of 1Hz can save 17.3% and 59.6% of energy compared with the sampling rates of 5 Hz and 50 Hz. The proposed low sampling rate approach can greatly reduce the power consumption while maintaining high activity recognition accuracy. The composition of power consumption in online ARS is also investigated in this paper.

  17. Nattokinase-promoted tissue plasminogen activator release from human cells.

    Science.gov (United States)

    Yatagai, Chieko; Maruyama, Masugi; Kawahara, Tomoko; Sumi, Hiroyuki

    2008-01-01

    When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration. Copyright 2009 S. Karger AG, Basel.

  18. Activity of upper limb muscles during human walking.

    Science.gov (United States)

    Kuhtz-Buschbeck, Johann P; Jing, Bo

    2012-04-01

    The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Towards a sensor for detecting human presence and activity

    OpenAIRE

    Benezeth , Yannick; Laurent , Hélène; Emile , Bruno; Rosenberger , Christophe

    2011-01-01

    International audience; In this paper, we propose a vision-based system for human detection and tracking in indoor environment allowing to collect higher level information on people activity. The developed presence sensor based on video analysis, using a static camera is ¯rst of all presented. Composed of three main steps, the ¯rst one consists in change detection using a background model updated at di®erent levels to manage the most common variations of the environment. A moving objects trac...

  20. Groundwater impacts of foreseeable human activities on a HLW repository

    International Nuclear Information System (INIS)

    Coleman, N.M.

    1993-01-01

    The Nuclear Regulatory Commission (NRC) staff has begun a program of Systematic Regulatory Analysis (SRA) to help ensure that all important technical issues related to the disposal of civilian, high-level nuclear wastes will be identified prior to the receipt of a license application. Large-scale groundwater withdrawals near a repository could have significant impacts on the groundwater flow system. Future large-scale withdrawals of groundwater could occur to support irrigation to growing population centers, such as Las Vegas. Various scenarios of groundwater withdrawals, along with other scenarios of future human activity, will need to be tested before evaluation of the Yucca Mountain site is complete

  1. Bio-activity of aminosulfonyl ureas in the light of nucleic acid bases and DNA base pair interaction.

    Science.gov (United States)

    Mondal Roy, Sutapa

    2018-08-01

    The quantum chemical descriptors based on density functional theory (DFT) are applied to predict the biological activity (log IC 50 ) of one class of acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors, viz. aminosulfonyl ureas. ACAT are very effective agents for reduction of triglyceride and cholesterol levels in human body. Successful two parameter quantitative structure-activity relationship (QSAR) models are developed with a combination of relevant global and local DFT based descriptors for prediction of biological activity of aminosulfonyl ureas. The global descriptors, electron affinity of the ACAT inhibitors (EA) and/or charge transfer (ΔN) between inhibitors and model biosystems (NA bases and DNA base pairs) along with the local group atomic charge on sulfonyl moiety (∑Q Sul ) of the inhibitors reveals more than 90% efficacy of the selected descriptors for predicting the experimental log (IC 50 ) values. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Hepatic cholesterol ester hydrolase in human liver disease.

    Science.gov (United States)

    Simon, J B; Poon, R W

    1978-09-01

    Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

  3. Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

    Directory of Open Access Journals (Sweden)

    Magdalena Markowicz-Piasecka

    2017-01-01

    Full Text Available The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM may predispose to Alzheimer’s disease (AD. The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition and BuChE (IC50 = 28 nmol/mL, mixed type inhibition, while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL. Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.

  4. Some human activities to decrease public radiation dose

    International Nuclear Information System (INIS)

    Pan Ziqiang; Guo Minqiang

    1994-01-01

    The necessity of studying the variations in radiation levels from the balance viewpoint is discussed. Some human activities may increase, while others may decrease, radiation dose to population. In 1988, China's investigation showed that travel by air caused a raise of population collective dose by 3.6 x 10 1 man·Sv, while travel by ship, train and vehicle lead to a drop of 5.36 x 10 2 man·Sv, and that dwellings of coal cinder brick decreased collective dose by 3.5 x 10 3 man·Sv, while buildings of reinforced concrete structure increased collective dose by 3.7 x 10 3 man·Sv. It is inadequate to only study those activities which may increase radiation levels

  5. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  6. Modelling large scale human activity in San Francisco

    Science.gov (United States)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

  7. Combining users' activity survey and simulators to evaluate human activity recognition systems.

    Science.gov (United States)

    Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

    2015-04-08

    Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

  8. Combining Users’ Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

    Directory of Open Access Journals (Sweden)

    Gorka Azkune

    2015-04-01

    Full Text Available Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

  9. Combining Users' Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

    Science.gov (United States)

    Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

    2015-01-01

    Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant. PMID:25856329

  10. Structure of human milk bile salt activated lipase

    International Nuclear Information System (INIS)

    Baba, T.; Downs, D.; Jackson, K.W.; Tang, J.; Wang, Chi-Sun

    1991-01-01

    The structure and some functional sites of human milk bile salt activated lipase (BAL) were studied by cDNA cloning and chemical analysis of the enzyme. Eighteen cDNA clones of human BAL were identified from lactating human breast cDNA libraries in λgt11 and λgt10 with antibody and synthetic oligonucleotides as probes. The sequence of four clones was sufficient to construct a 3018-bp BAL cDNA structure. This sequence codes for an open reading frame of 742 amino acid residues. There is a putative signal sequence of 20 residues which is followed by the amino-terminal sequence of BAL, and the mature BAL contains 722 amino acid residues. The cDNA sequence also contains a 678-base 5'-untranslated sequence, a 97-base 3'-untranslated region, and a 14-base poly(A) tail. The sequence of a 1.8-kbp insert of clone G10-4A differs from that of the other cDNA in that it contains a deletion of 198 bases (1966-2163) corresponding to 66 amino acid residues. By use of BAL cDAN as probe, it was found that the major molecular species of BAL mRNA in human mammary gland HBL-100 cells had a size of 2.9 kb and two minor species had sizes of 3.8 and 5.1 kb by Northern blot analyses. These chemical studies established that the active site of human milk BAL is located at serine-194, the N-glycosylation site is present at asparagine-187, the O-glycosylation region is in the 16 repeating units near the C-terminus, and the heparin binding domain is in the N-terminal region. The authors have also determined the location of disulfide bridges as Cys64-Cys80 and Cys246-Cys257. The cyanogen bromide cleavage and the partial sequencing of CNBr peptides also confirmed the location of methionines in the polypeptide chain as well as the deduced cDNA sequence of BAL

  11. Human PrimPol activity is enhanced by RPA.

    Science.gov (United States)

    Martínez-Jiménez, María I; Lahera, Antonio; Blanco, Luis

    2017-04-10

    Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.

  12. Deep Recurrent Neural Networks for Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Abdulmajid Murad

    2017-11-01

    Full Text Available Adopting deep learning methods for human activity recognition has been effective in extracting discriminative features from raw input sequences acquired from body-worn sensors. Although human movements are encoded in a sequence of successive samples in time, typical machine learning methods perform recognition tasks without exploiting the temporal correlations between input data samples. Convolutional neural networks (CNNs address this issue by using convolutions across a one-dimensional temporal sequence to capture dependencies among input data. However, the size of convolutional kernels restricts the captured range of dependencies between data samples. As a result, typical models are unadaptable to a wide range of activity-recognition configurations and require fixed-length input windows. In this paper, we propose the use of deep recurrent neural networks (DRNNs for building recognition models that are capable of capturing long-range dependencies in variable-length input sequences. We present unidirectional, bidirectional, and cascaded architectures based on long short-term memory (LSTM DRNNs and evaluate their effectiveness on miscellaneous benchmark datasets. Experimental results show that our proposed models outperform methods employing conventional machine learning, such as support vector machine (SVM and k-nearest neighbors (KNN. Additionally, the proposed models yield better performance than other deep learning techniques, such as deep believe networks (DBNs and CNNs.

  13. Dynamic Stimuli And Active Processing In Human Visual Perception

    Science.gov (United States)

    Haber, Ralph N.

    1990-03-01

    Theories of visual perception traditionally have considered a static retinal image to be the starting point for processing; and has considered processing both to be passive and a literal translation of that frozen, two dimensional, pictorial image. This paper considers five problem areas in the analysis of human visually guided locomotion, in which the traditional approach is contrasted to newer ones that utilize dynamic definitions of stimulation, and an active perceiver: (1) differentiation between object motion and self motion, and among the various kinds of self motion (e.g., eyes only, head only, whole body, and their combinations); (2) the sources and contents of visual information that guide movement; (3) the acquisition and performance of perceptual motor skills; (4) the nature of spatial representations, percepts, and the perceived layout of space; and (5) and why the retinal image is a poor starting point for perceptual processing. These newer approaches argue that stimuli must be considered as dynamic: humans process the systematic changes in patterned light when objects move and when they themselves move. Furthermore, the processing of visual stimuli must be active and interactive, so that perceivers can construct panoramic and stable percepts from an interaction of stimulus information and expectancies of what is contained in the visual environment. These developments all suggest a very different approach to the computational analyses of object location and identification, and of the visual guidance of locomotion.

  14. Human Endogenous Retrovirus W Activity in Cartilage of Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Signy Bendiksen

    2014-01-01

    Full Text Available The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV-WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven.

  15. Deep Recurrent Neural Networks for Human Activity Recognition.

    Science.gov (United States)

    Murad, Abdulmajid; Pyun, Jae-Young

    2017-11-06

    Adopting deep learning methods for human activity recognition has been effective in extracting discriminative features from raw input sequences acquired from body-worn sensors. Although human movements are encoded in a sequence of successive samples in time, typical machine learning methods perform recognition tasks without exploiting the temporal correlations between input data samples. Convolutional neural networks (CNNs) address this issue by using convolutions across a one-dimensional temporal sequence to capture dependencies among input data. However, the size of convolutional kernels restricts the captured range of dependencies between data samples. As a result, typical models are unadaptable to a wide range of activity-recognition configurations and require fixed-length input windows. In this paper, we propose the use of deep recurrent neural networks (DRNNs) for building recognition models that are capable of capturing long-range dependencies in variable-length input sequences. We present unidirectional, bidirectional, and cascaded architectures based on long short-term memory (LSTM) DRNNs and evaluate their effectiveness on miscellaneous benchmark datasets. Experimental results show that our proposed models outperform methods employing conventional machine learning, such as support vector machine (SVM) and k-nearest neighbors (KNN). Additionally, the proposed models yield better performance than other deep learning techniques, such as deep believe networks (DBNs) and CNNs.

  16. Human Activity Recognition Supported on Indoor Localization: A Systematic Review.

    Science.gov (United States)

    Cerón, Jesús; López, Diego M

    2018-01-01

    The number of older adults is growing worldwide. This has a social and economic impact in all countries because of the increased number of older adults affected by chronic diseases, health emergencies, and disabilities, representing at the end high cost for the health system. To face this problem, the Ambient Assisted Living (AAL) domain has emerged. Its main objective is to extend the time that older adults can live independently in their homes. AAL is supported by different fields and technologies, being Human Activity Recognition (HAR), control of vital signs and location tracking the three of most interest during the last years. To perform a systematic review about Human Activity Recognition (HAR) approaches supported on Indoor Localization (IL) and vice versa, describing the methods they have used, the accuracy they have obtained and whether they have been directed towards the AAL domain or not. A systematic review of six databases was carried out (ACM, IEEE Xplore, PubMed, Science Direct and Springer). 27 papers were found. They were categorised into three groups according their approach: paper focus on 1. HAR, 2. IL, 3. HAR and IL. A detailed analysis of the following factors was performed: type of methods and technologies used for HAR, IL and data fusion, as well as the precision obtained for them. This systematic review shows that the relationship between HAR and IL has been very little studied, therefore providing insights of its potential mutual support to provide AAL solutions.

  17. Global Proteome Analysis Identifies Active Immunoproteasome Subunits in Human Platelets*

    Science.gov (United States)

    Klockenbusch, Cordula; Walsh, Geraldine M.; Brown, Lyda M.; Hoffman, Michael D.; Ignatchenko, Vladimir; Kislinger, Thomas; Kast, Juergen

    2014-01-01

    The discovery of new functions for platelets, particularly in inflammation and immunity, has expanded the role of these anucleate cell fragments beyond their primary hemostatic function. Here, four in-depth human platelet proteomic data sets were generated to explore potential new functions for platelets based on their protein content and this led to the identification of 2559 high confidence proteins. During a more detailed analysis, consistently high expression of the proteasome was discovered, and the composition and function of this complex, whose role in platelets has not been thoroughly investigated, was examined. Data set mining resulted in identification of nearly all members of the 26S proteasome in one or more data sets, except the β5 subunit. However, β5i, a component of the immunoproteasome, was identified. Biochemical analyses confirmed the presence of all catalytically active subunits of the standard 20S proteasome and immunoproteasome in human platelets, including β5, which was predominantly found in its precursor form. It was demonstrated that these components were assembled into the proteasome complex and that standard proteasome as well as immunoproteasome subunits were constitutively active in platelets. These findings suggest potential new roles for platelets in the immune system. For example, the immunoproteasome may be involved in major histocompatibility complex I (MHC I) peptide generation, as the MHC I machinery was also identified in our data sets. PMID:25146974

  18. Global proteome analysis identifies active immunoproteasome subunits in human platelets.

    Science.gov (United States)

    Klockenbusch, Cordula; Walsh, Geraldine M; Brown, Lyda M; Hoffman, Michael D; Ignatchenko, Vladimir; Kislinger, Thomas; Kast, Juergen

    2014-12-01

    The discovery of new functions for platelets, particularly in inflammation and immunity, has expanded the role of these anucleate cell fragments beyond their primary hemostatic function. Here, four in-depth human platelet proteomic data sets were generated to explore potential new functions for platelets based on their protein content and this led to the identification of 2559 high confidence proteins. During a more detailed analysis, consistently high expression of the proteasome was discovered, and the composition and function of this complex, whose role in platelets has not been thoroughly investigated, was examined. Data set mining resulted in identification of nearly all members of the 26S proteasome in one or more data sets, except the β5 subunit. However, β5i, a component of the immunoproteasome, was identified. Biochemical analyses confirmed the presence of all catalytically active subunits of the standard 20S proteasome and immunoproteasome in human platelets, including β5, which was predominantly found in its precursor form. It was demonstrated that these components were assembled into the proteasome complex and that standard proteasome as well as immunoproteasome subunits were constitutively active in platelets. These findings suggest potential new roles for platelets in the immune system. For example, the immunoproteasome may be involved in major histocompatibility complex I (MHC I) peptide generation, as the MHC I machinery was also identified in our data sets. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Modelling of the Human Knee Joint Supported by Active Orthosis

    Science.gov (United States)

    Musalimov, V.; Monahov, Y.; Tamre, M.; Rõbak, D.; Sivitski, A.; Aryassov, G.; Penkov, I.

    2018-02-01

    The article discusses motion of a healthy knee joint in the sagittal plane and motion of an injured knee joint supported by an active orthosis. A kinematic scheme of a mechanism for the simulation of a knee joint motion is developed and motion of healthy and injured knee joints are modelled in Matlab. Angles between links, which simulate the femur and tibia are controlled by Simulink block of Model predictive control (MPC). The results of simulation have been compared with several samples of real motion of the human knee joint obtained from motion capture systems. On the basis of these analyses and also of the analysis of the forces in human lower limbs created at motion, an active smart orthosis is developed. The orthosis design was optimized to achieve an energy saving system with sufficient anatomy, necessary reliability, easy exploitation and low cost. With the orthosis it is possible to unload the knee joint, and also partially or fully compensate muscle forces required for the bending of the lower limb.

  20. Modelling of the Human Knee Joint Supported by Active Orthosis

    Directory of Open Access Journals (Sweden)

    Musalimov V.

    2018-02-01

    Full Text Available The article discusses motion of a healthy knee joint in the sagittal plane and motion of an injured knee joint supported by an active orthosis. A kinematic scheme of a mechanism for the simulation of a knee joint motion is developed and motion of healthy and injured knee joints are modelled in Matlab. Angles between links, which simulate the femur and tibia are controlled by Simulink block of Model predictive control (MPC. The results of simulation have been compared with several samples of real motion of the human knee joint obtained from motion capture systems. On the basis of these analyses and also of the analysis of the forces in human lower limbs created at motion, an active smart orthosis is developed. The orthosis design was optimized to achieve an energy saving system with sufficient anatomy, necessary reliability, easy exploitation and low cost. With the orthosis it is possible to unload the knee joint, and also partially or fully compensate muscle forces required for the bending of the lower limb.

  1. Tracking urban human activity from mobile phone calling patterns.

    Science.gov (United States)

    Monsivais, Daniel; Ghosh, Asim; Bhattacharya, Kunal; Dunbar, Robin I M; Kaski, Kimmo

    2017-11-01

    Timings of human activities are marked by circadian clocks which in turn are entrained to different environmental signals. In an urban environment the presence of artificial lighting and various social cues tend to disrupt the natural entrainment with the sunlight. However, it is not completely understood to what extent this is the case. Here we exploit the large-scale data analysis techniques to study the mobile phone calling activity of people in large cities to infer the dynamics of urban daily rhythms. From the calling patterns of about 1,000,000 users spread over different cities but lying inside the same time-zone, we show that the onset and termination of the calling activity synchronizes with the east-west progression of the sun. We also find that the onset and termination of the calling activity of users follows a yearly dynamics, varying across seasons, and that its timings are entrained to solar midnight. Furthermore, we show that the average mid-sleep time of people living in urban areas depends on the age and gender of each cohort as a result of biological and social factors.

  2. Tracking urban human activity from mobile phone calling patterns.

    Directory of Open Access Journals (Sweden)

    Daniel Monsivais

    2017-11-01

    Full Text Available Timings of human activities are marked by circadian clocks which in turn are entrained to different environmental signals. In an urban environment the presence of artificial lighting and various social cues tend to disrupt the natural entrainment with the sunlight. However, it is not completely understood to what extent this is the case. Here we exploit the large-scale data analysis techniques to study the mobile phone calling activity of people in large cities to infer the dynamics of urban daily rhythms. From the calling patterns of about 1,000,000 users spread over different cities but lying inside the same time-zone, we show that the onset and termination of the calling activity synchronizes with the east-west progression of the sun. We also find that the onset and termination of the calling activity of users follows a yearly dynamics, varying across seasons, and that its timings are entrained to solar midnight. Furthermore, we show that the average mid-sleep time of people living in urban areas depends on the age and gender of each cohort as a result of biological and social factors.

  3. Blood-group-Ii-active gangliosides of human erythrocyte membranes

    International Nuclear Information System (INIS)

    Feizi, T.; Childs, R.A.; Hakomori, S.-I.; Powell, M.E.

    1978-01-01

    More than ten new types of gangliosides, in addition to haematoside and sialosylparagloboside, were isolated from human erythrocyte membranes. These were separated by successive chromatographies on DAEA-Sephadex, on porous silica-gel columns and on thin-layer silica gel as acetylated compounds. Highly potent blood-group-Ii and moderate blood-group-H activities were demonstrated in some of the ganglioside fractions. The gangliosides incorporated into chlolesterol/phosphatidylcholine liposomes stoicheiometrically inhibited binding of anti-(blood-group-I and i) antibodies to a radioiodinated blood-group-Ii-active glycoprotein. The fraction with the highest blood-group-I activity, I(g) fraction, behaved like sialosyl-deca- to dodeca-glycosylceramides on t.l.c. Certain blood-group-I and most of the i-determinants were in partially or completely cryptic form and could be unmasked by sialidase treatment. Thus the I and i antigens, which are known to occur on internal structures of blood-group-ABH-active glycoproteins in secretions, also occur in the interior of the carbohydrate chains of erythrocyte gangliosides. (author)

  4. Bifenthrin activates homotypic aggregation in human T-cell lines.

    Science.gov (United States)

    Hoffman, Nataly; Tran, Van; Daniyan, Anthony; Ojugbele, Olutosin; Pryor, Stephen C; Bonventre, Josephine A; Flynn, Katherine; Weeks, Benjamin S

    2006-03-01

    Here, we addressed the concern that, despite the lack of overt toxicity, exposure to low levels of the common household pyrethroid pesticide, bifenthrin, could cause harm to the immune system. To do this, we measure the effect of bifenthrin on phytohemagglutinin (PHA) activation of homotypic aggregation in human T-cell lines. The human CD4+ H9, and Jurkat cell lines and the human promonocyte U937 cell line, were exposed to varying concentrations of bifenthrin. Cell viability was determined using the AlmarBlue Toxicity Assay. Concentrations of bifenthrin which did not reduce cell viability were determined and these concentrations were tested for the effect of bifenthrin on PHA-mediated homotypic aggregation. Blocking antibodies to ICAM and LFA-1 were used to disrupt aggregation and a nonspecific IgG was used as a control. Bifenthrin was found to be nontoxic at concentrations ranging from 10(-4) to 10(-13) M. Bifenthrin did not inhibit PHA induced cell aggregation in all cell lines tested. However, at 10(-4) M, bifenthrin to form aggregates stimulated homotypic aggregation in the H9 and Jurkat T-cell lines. The bifenthrin-induced aggregate formation, like that seen with PHA, was blocked by treating the cells with antibodies to either LFA-1 or ICAM. The results here show that bifenthrin activates T-cell function by stimulating ICAM/LFA-1 mediated homotypic aggregation. This data suggests that exposure to bifenthrin, even at "acceptable" limits, can increase the risk for and frequency of inflammatory responses and diseases such as asthma.

  5. Production of biologically active recombinant human factor H in Physcomitrella.

    Science.gov (United States)

    Büttner-Mainik, Annette; Parsons, Juliana; Jérôme, Hanna; Hartmann, Andrea; Lamer, Stephanie; Schaaf, Andreas; Schlosser, Andreas; Zipfel, Peter F; Reski, Ralf; Decker, Eva L

    2011-04-01

    The human complement regulatory serum protein factor H (FH) is a promising future biopharmaceutical. Defects in the gene encoding FH are associated with human diseases like severe kidney and retinal disorders in the form of atypical haemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis II (MPGN II) or age-related macular degeneration (AMD). There is a current need to apply intact full-length FH for the therapy of patients with congenital or acquired defects of this protein. Application of purified or recombinant FH (rFH) to these patients is an important and promising approach for the treatment of these diseases. However, neither protein purified from plasma of healthy individuals nor recombinant protein is currently available on the market. Here, we report the first stable expression of the full-length human FH cDNA and the subsequent production of this glycoprotein in a plant system. The moss Physcomitrella patens perfectly suits the requirements for the production of complex biopharmaceuticals as this eukaryotic system not only offers an outstanding genetical accessibility, but moreover, proteins can be produced safely in scalable photobioreactors without the need for animal-derived medium compounds. Transgenic moss lines were created, which express the human FH cDNA and target the recombinant protein to the culture supernatant via a moss-derived secretion signal. Correct processing of the signal peptide and integrity of the moss-produced rFH were verified via peptide mapping by mass spectrometry. Ultimately, we show that the rFH displays complement regulatory activity comparable to FH purified from plasma. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  6. Alterations in calcium metabolism during human monocyte activation

    International Nuclear Information System (INIS)

    Scully, S.P.

    1984-01-01

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

  7. Uncovering intrinsic modular organization of spontaneous brain activity in humans.

    Directory of Open Access Journals (Sweden)

    Yong He

    Full Text Available The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz, spontaneous fluctuations of the blood oxygen level dependent (BOLD signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in

  8. Transgenic chickens expressing human urokinase-type plasminogen activator.

    Science.gov (United States)

    Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

    2013-09-01

    Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

  9. Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells.

    Science.gov (United States)

    Gerashchenko, O L; Zhuravel, E V; Skachkova, O V; Khranovska, N N; Filonenko, V V; Pogrebnoy, P V; Soldatkina, M A

    2013-06-01

    The aim of the study was in vitro analysis of biological activity of recombinant human beta-defensin-4 (rec-hBD-4). hBD-4 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E. coli BL21(DE3) cells. To purify soluble fusion GST-hBD-4 protein, affinity chromatography was applied. Rec-hBD-4 was cleaved from the fusion protein with thrombin, and purified by reverse phase chromatography on Sep-Pack C18. Effects of rec-hBD-4 on proliferation, viability, cell cycle distribution, substrate-independent growth, and mobility of cultured human cancer cells of A431, A549, and TPC-1 lines were analyzed by direct cell counting technique, MTT assay, flow cytofluorometry, colony forming assay in semi-soft medium, and wound healing assay. Rec-hBD-4 was expressed in bacterial cells as GST-hBD-4 fusion protein, and purified by routine 3-step procedure (affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography). Analysis of in vitro activity of rec-hBD-4 toward three human cancer cell lines has demonstrated that the defensin is capable to affect cell behaviour in concentration-dependent manner. In 1-100 nM concentrations rec-hBD-4 significantly stimulates cancer cell proliferation and viability, and promotes cell cycle progression through G2/M checkpoint, greatly enhances colony-forming activity and mobility of the cells. Treatment of the cells with 500 nM of rec-hBD-4 resulted in opposite effects: significant suppression of cell proliferation and viability, blockage of cell cycle in G1/S checkpoint, significant inhibition of cell migration and colony forming activity. Recombinant human beta-defensin-4 is biologically active peptide capable to cause oppositely directed effects toward biologic features of cancer cells in vitro dependent on its concentration.

  10. Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity.

    Science.gov (United States)

    Kuchiike, Daisuke; Uto, Yoshihiro; Mukai, Hirotaka; Ishiyama, Noriko; Abe, Chiaki; Tanaka, Daichi; Kawai, Tomohito; Kubo, Kentaro; Mette, Martin; Inui, Toshio; Endo, Yoshio; Hori, Hitoshi

    2013-07-01

    The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.

  11. The influence of human activity in the Arctic on climate and climate impacts

    Energy Technology Data Exchange (ETDEWEB)

    Huntington, H.P. [23834 The Clearing Dr., Eagle River, AK 99577 (United States); Boyle, M. [Institute for Resources, Environment and Sustainability, University of British Columbia, 2202 Main Mall, Vancouver, BC, V6S 1K4 (Canada); Flowers, G.E. [Department of Earth Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6 (Canada); Weatherly, J.W. [Snow and Ice Division, Cold Regions Research and Engineering Laboratory, 72 Lyme Road, Hanover, NH 03755 (United States); Hamilton, L.C. [Department of Sociology, University of New Hampshire, 20 College Road, Durham, NH 03824 (United States); Hinzman, L. [Water and Environment Research Center, University of Alaska Fairbanks, P.O. Box 755860, Fairbanks, AK 99775 (United States); Gerlach, C. [Department of Anthropology, University of Alaska Fairbanks, P.O. Box 757720, Fairbanks, AK 99775 (United States); Zulueta, R. [Department of Biology, Global Change Research Group, San Diego State University, 5500 Campanile Drive, PS-240, San Diego, CA 92182 (United States); Nicolson, C. [Department of Natural Resources Conservation, University of Massachusetts, 160 Holdsworth Way, Amherst, MA , 01003 (United States); Overpeck, J. [Institute for the Study of Planet Earth, University of Arizona, 715 North Park Avenue, 2nd Floor, Tucson, AZ, 85721 (United States)

    2007-05-15

    Human activities in the Arctic are often mentioned as recipients of climate-change impacts. In this paper we consider the more complicated but more likely possibility that human activities themselves can interact with climate or environmental change in ways that either mitigate or exacerbate the human impacts. Although human activities in the Arctic are generally assumed to be modest, our analysis suggests that those activities may have larger influences on the arctic system than previously thought. Moreover, human influences could increase substantially in the near future. First, we illustrate how past human activities in the Arctic have combined with climatic variations to alter biophysical systems upon which fisheries and livestock depend. Second, we describe how current and future human activities could precipitate or affect the timing of major transitions in the arctic system. Past and future analyses both point to ways in which human activities in the Arctic can substantially influence the trajectory of arctic system change.

  12. Environmental layout complexity affects neural activity during navigation in humans.

    Science.gov (United States)

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Exosomes: novel effectors of human platelet lysate activity

    Directory of Open Access Journals (Sweden)

    E Torreggiani

    2014-09-01

    Full Text Available Despite the popularity of platelet-rich plasma (PRP and platelet lysate (PL in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF, vascular endothelial growth factor (VEGF, platelet-derived growth factor (PDGF-BB and transforming growth factor beta 1 (TGF-β1 as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

  14. Kinase activation through dimerization by human SH2-B.

    Science.gov (United States)

    Nishi, Masahiro; Werner, Eric D; Oh, Byung-Chul; Frantz, J Daniel; Dhe-Paganon, Sirano; Hansen, Lone; Lee, Jongsoon; Shoelson, Steven E

    2005-04-01

    The isoforms of SH2-B, APS, and Lnk form a family of signaling proteins that have been described as activators, mediators, or inhibitors of cytokine and growth factor signaling. We now show that the three alternatively spliced isoforms of human SH2-B readily homodimerize in yeast two-hybrid and cellular transfections assays, and this is mediated specifically by a unique domain in its amino terminus. Consistent with previous reports, we further show that the SH2 domains of SH2-B and APS bind JAK2 at Tyr813. These findings suggested a model in which two molecules of SH2-B or APS homodimerize with their SH2 domains bound to two JAK2 molecules, creating heterotetrameric JAK2-(SH2-B)2-JAK2 or JAK2-(APS)2-JAK2 complexes. We further show that APS and SH2-B isoforms heterodimerize. At lower levels of SH2-B or APS expression, dimerization approximates two JAK2 molecules to induce transactivation. At higher relative concentrations of SH2-B or APS, kinase activation is blocked. SH2-B or APS homodimerization and SH2-B/APS heterodimerization thus provide direct mechanisms for activating and inhibiting JAK2 and other kinases from the inside of the cell and for potentiating or attenuating cytokine and growth factor receptor signaling when ligands are present.

  15. Elastolytic activity of human blood monocytes characterized by a new monoclonal antibody against human leucocyte elastase. Relationship to rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jensen, H S; Christensen, L D

    1990-01-01

    The leucocyte elastase of human blood monocytes was investigated by applying a new monoclonal antibody which did not block the enzyme activity against elastin. In a fixed population of mononuclear cells (MNC) and using fluorescence activated cell sorting (FACS), the human leucocyte elastase (HLE...

  16. Isolation and expression analysis of glycerol-3-phosphate acyltransferase genes from peanuts (Arachis hypogaea L.

    Directory of Open Access Journals (Sweden)

    Chi, X.

    2015-09-01

    Full Text Available sn-Glycerol-3-phosphate acyltransferase (GPAT catalyzes the committed step in the production of glycerolipids. The functions of GPAT genes have been intensively studied in Arabidopsis, but not in peanuts (Arachis hypogaea L.. In this study, six AhGPAT genes were isolated from peanuts. Quantitative real-time RT-PCR analysis indicated that the AhGPAT9 transcript was more abundant in the stems, flowers, and seeds, whereas the transcript abundances of five other genes were higher in the leaves or flowers than in the other tissues examined. During seed development, the transcript levels of AhGPAT9 gradually increased, whereas the transcript levels of the other five genes decreased. In addition, the levels of AhGPAT2 transcript were distinctly enhanced after exposure to all four kinds of stress treatments except for ABA-treated leaves. The transcripts of AhGPAT1, AhGPAT6, AhGPAT8 and AhATS1 increased substantially in roots exposed to salt, drought, and ABA stress. The expressions of AhGPAT6, AhGPAT8, AhGPAT9 and AhATS1 were slightly higher in leaves under certain stress conditions than under normal conditions. The present study provides significant information for modifying oil deposition and improving the abiotic stress resistance of peanuts through molecular breeding.La aciltransferasa sn-glicerol-3-fosfato (ATGP cataliza el comprometido paso de la producción de glicerolípidos. Las funciones de los genes AhATGP se han estudiado intensivamente en Arabidopsis, pero no en cacahuete (Arachis hypogaea L.. En este estudio, seis genes AhATGP se aislaron a partir de cacahuetes. El análisis a tiempo real RT-PCR cuantitativa indicó que la transcripción AhATGP9 fue más abundante en tallos, flores y semillas, mientras que la abundancia de la transcripción de los otros cinco genes fueron mayores en hojas o flores que en los otros tejidos examinados. Durante el desarrollo de la semilla, los niveles de transcripción de AhATGP9 aumentaron gradualmente

  17. Neutron activation analysis of organohalogens in Chinese human hair

    International Nuclear Information System (INIS)

    Zhang, H.; Chai, Z.F.; Chinese Academy of Sciences, Beijing; Sun, H.B.; Xu, H.F.

    2007-01-01

    To effectively extract organohalogens from human hair, two factors, the extracting time and hair length on the extraction efficiency of organohalogens were studied by neutron activation analysis (NAA) and gas chromatograph-electron capture detector (GC-ECD), respectively. Furthermore, the concentrations of extractable organohalogens (EOX) and extractable persistent organohalogens (EPOX) in hair samples from angioma and control babies were also measured by the established method. The results indicated that the optimal Soxhlet-extraction time for EOX and EPOX in hair was from 8 to 11 hours, and the extraction efficiencies for organochlorine pesticides in hair were in the order of powder >2 mm>5 mm. Also, the mean levels of EOCl and EPOCl in hair of the angioma babies were significantly higher than those in the control babies (P EOCl EPOCl <0.05), which implied the possible relationship between the environmental pollution and angioma. (author)

  18. Impacts of human activity on reindeer and caribou: The matter

    Directory of Open Access Journals (Sweden)

    Ingunn Vistnes

    2007-04-01

    Full Text Available The impacts of human activity and infrastructure development on reindeer and caribou (Rangifer tarandus have been studied for decades and have resulted in numerous debates among scientists, developers and indigenous people affected. Herein, we discuss the development within this field of research in the context of choice of spatial and temporal scale and concurrent trends in wildlife disturbance studies. Before the 1980s, the vast majority of Rangifer disturbance studies were behavioural studies of individual animals exposed directly to potential disturbance sources. Most of these local studies reported few and short-term impacts on Rangifer. Around the mid 1980s focus shifted to regional scale landscape ecology studies, reporting that reindeer and caribou reduced the use of areas within 5 km from infrastructure and human activity by 50-95%, depending on type of disturbance, landscape, season, sensitivity of herds, and sex and age distribution of animals. In most cases where avoidance was documented a smaller fraction of the animals, typically bulls, were still observed closer to infrastructure or human activity. Local-scale behavioural studies of individual animals may provide complementary information, but will alone seriously underestimate potential regional impacts. Of 85 studies reviewed, 83% of the regional studies concluded that the impacts of human activity were significant, while only 13% of the local studies did the same. Traditional ecological knowledge may further increase our understanding of disturbance effects.Effekter av menneskelig aktivitet på rein og caribou: Betydningen av valg av skalaAbstract in Norwegian / Sammendrag: Effektene av menneskelig aktivitet og utbygging på rein og caribou (Rangifer tarandus har vært studert i flere tiår og har resultert i utallige debatter mellom forskere, utbyggere og berørt urbefolkning. I denne artikkelen diskuterer vi utviklingen innenfor dette forskningsfeltet i forhold til valg av

  19. Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

    Science.gov (United States)

    Song, Hyun-Ouk; Ryu, Jae-Sook

    2013-08-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

  20. Role of synchronized oscillatory brain activity for human pain perception.

    Science.gov (United States)

    Hauck, Michael; Lorenz, Jürgen; Engel, Andreas K

    2008-01-01

    The understanding of cortical pain processing in humans has significantly improved since the development of modern neuroimaging techniques. Non-invasive electrophysiological approaches such as electro- and magnetoencephalography have proven to be helpful tools for the real-time investigation of neuronal signals and synchronous communication between cortical areas. In particular, time-frequency decomposition of signals recorded with these techniques seems to be a promising approach because different pain-related oscillatory changes can be observed within different frequency bands, which are likely to be linked to specific sensory and motor functions. In this review we discuss the latest evidence on pain-induced time-frequency signals and propose that changes in oscillatory activity reflect an essential communication mechanism in the brain that is modulated during pain processing. The importance of synchronization processes for normal and pathological pain processing, such as chronic pain states, is discussed.

  1. Safety activities and human resource development at NCA

    International Nuclear Information System (INIS)

    Kumanomido, Hironori; Sakurada, Koichi; Yanagisawa, Shigeru; Masuyama, Tadaharu

    2015-01-01

    Toshiba Nuclear Critical Assembly (NCA) has been safely operated since the first criticality in December 1963. The topics covered in this Yayoi Meeting Report are: (1) the outline of NCA, (2) the safety control situation mainly after the Great East Japan Earthquake in 2011, (3) educational training incorporates the lessons learned in this earthquake, and (4) human resource development during 2008-2015. Regarding safety control, facility maintenance has been conducted systematically according to the maintenance plan from the viewpoint of preventive maintenance. Regarding educational training, two disaster handling training based on the safety regulation and one nuclear emergency drill based on the emergency drill plan for licensee of nuclear energy activity based on the Act of Special Measures Concerning Nuclear Emergency Preparedness every year. Regarding human resource development, development training was given to 358 people including students. This year, training that does not require NCA operation was conducted including gamma-ray spectrum measurement of NCA fuel rod and neutron deceleration property measurement using 252 Cf neutron source. (S.K.)

  2. NASA Aerosciences Activities to Support Human Space Flight

    Science.gov (United States)

    LeBeau, Gerald J.

    2011-01-01

    The Lyndon B. Johnson Space Center (JSC) has been a critical element of the United State's human space flight program for over 50 years. It is the home to NASA s Mission Control Center, the astronaut corps, and many major programs and projects including the Space Shuttle Program, International Space Station Program, and the Orion Project. As part of JSC's Engineering Directorate, the Applied Aeroscience and Computational Fluid Dynamics Branch is charted to provide aerosciences support to all human spacecraft designs and missions for all phases of flight, including ascent, exo-atmospheric, and entry. The presentation will review past and current aeroscience applications and how NASA works to apply a balanced philosophy that leverages ground testing, computational modeling and simulation, and flight testing, to develop and validate related products. The speaker will address associated aspects of aerodynamics, aerothermodynamics, rarefied gas dynamics, and decelerator systems, involving both spacecraft vehicle design and analysis, and operational mission support. From these examples some of NASA leading aerosciences challenges will be identified. These challenges will be used to provide foundational motivation for the development of specific advanced modeling and simulation capabilities, and will also be used to highlight how development activities are increasing becoming more aligned with flight projects. NASA s efforts to apply principles of innovation and inclusion towards improving its ability to support the myriad of vehicle design and operational challenges will also be briefly reviewed.

  3. Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells

    International Nuclear Information System (INIS)

    Sanli, Toran; Rashid, Ayesha; Liu Caiqiong

    2010-01-01

    Purpose: Adenosine monophosphate (AMP)-activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for radiosensitization of human cancer cells. Methods and Materials: Lung, prostate, and breast cancer cells were treated with IR (2-8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin. Then, cells were subjected to either lysis and immunoblotting, immunofluorescence microscopy, clonogenic survival assays, or cell cycle analysis. Results: IR induced a robust phosphorylation and activation of AMPK in all tumor cells, independent of LKB1. IR activated AMPK first in the nucleus, and this extended later into cytoplasm. The ATM inhibitor KU-55933 blocked IR activation of AMPK. AMPK inhibition with Compound C or anti-AMPK α subunit small interfering RNA (siRNA) blocked IR induction of the cell cycle regulators p53 and p21 waf/cip as well as the IR-induced G2/M arrest. Compound C caused resistance to IR, increasing the surviving fraction after 2 Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after 2 Gy further. Conclusions: We provide evidence that IR activates AMPK in human cancer cells in an LKB1-independent manner, leading to induction of p21 waf/cip and regulation of the cell cycle and survival. AMPK appears to (1) participate in an ATM-AMPK-p21 waf/cip pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.

  4. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    Directory of Open Access Journals (Sweden)

    Maraziotis Theodore

    2007-10-01

    Full Text Available Abstract Background Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC and p75NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Methods Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75NTR and phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were used. The labeling index (LI, defined as the percentage of positive (labeled cells out of the total number of tumor cells counted, was determined. Results Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75NTR receptor expression was found in a small percentage of tumor cells (~1% in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK and c-Jun (pc-Jun were

  5. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    International Nuclear Information System (INIS)

    Assimakopoulou, Martha; Kondyli, Maria; Gatzounis, George; Maraziotis, Theodore; Varakis, John

    2007-01-01

    Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75 NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75 NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75 NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75 NTR , and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75 NTR and phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined. Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75 NTR receptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor

  6. Mycobacterium leprae alters classical activation of human monocytes in vitro.

    Science.gov (United States)

    Fallows, Dorothy; Peixoto, Blas; Kaplan, Gilla; Manca, Claudia

    2016-01-01

    Macrophages play a central role in the pathogenesis of leprosy, caused by Mycobacterium leprae. The polarized clinical presentations in leprosy are associated with differential immune activation. In tuberculoid leprosy, macrophages show a classical activation phenotype (M1), while macrophages in lepromatous disease display characteristics of alternative activation (M2). Bacille Calmette-Guérin (BCG) vaccination, which protects against leprosy, can promote sustained changes in monocyte response to unrelated pathogens and may preferentially direct monocytes towards an M1 protective phenotype. We previously reported that M. leprae can dampen the response of naïve human monocytes to a strong inducer of pro-inflammatory cytokines, such as BCG. Here, we investigated the ability of the pathogen to alter the direction of macrophage polarization and the impact of BCG vaccination on the monocyte response to M. leprae. We show that in vitro exposure of monocytes from healthy donors to M. leprae interferes with subsequent M1 polarization, indicated by lower levels of M1-associated cytokine/chemokines released and reduced expression of M1 cell surface markers. Exposure to M. leprae phenolic glycolipid (PGL) 1, instead of whole bacteria, demonstrated a similar effect on M1 cytokine/chemokine release. In addition, we found that monocytes from 10-week old BCG-vaccinated infants released higher levels of the pro-inflammatory cytokines TNF-α and IL-1β in response to M. leprae compared to those from unvaccinated infants. Exposure to M. leprae has an inhibitory effect on M1 macrophage polarization, likely mediated through PGL-1. By directing monocyte/macrophages preferentially towards M1 activation, BCG vaccination may render the cells more refractory to the inhibitory effects of subsequent M. leprae infection.

  7. Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells

    Science.gov (United States)

    Porter, Michael; Karp, Matthew; Killedar, Smruti; Bauer, Stephen M.; Guo, Jia; Williams, D'Ann; Breysse, Patrick; Georas, Steve N.; Williams, Marc A.

    2007-01-01

    Epidemiologic studies have associated exposure to airborne particulate matter (PM) with exacerbations of asthma. It is unknown how different sources of PM affect innate immunity. We sought to determine how car- and diesel exhaust–derived PM affects dendritic cell (DC) activation. DC development was modeled using CD34+ hematopoietic progenitors. Airborne PM was collected from exhaust plenums of Fort McHenry Tunnel providing car-enriched particles (CEP) and diesel-enriched particles (DEP). DC were stimulated for 48 hours with CEP, DEP, CD40-ligand, or lipopolysaccharide. DC activation was assessed by flow cytometry, enzyme-linked immunosorbent assay, and standard culture techniques. DEP increased uptake of fluorescein isothiocyanate–dextran (a model antigen) by DC. Diesel particles enhanced cell-surface expression of co-stimulatory molecules (e.g., CD40 [P < 0.01] and MHC class II [P < 0.01]). By contrast, CEP poorly affected antigen uptake and expression of cell surface molecules, and did not greatly affect cytokine secretion by DC. However, DEP increased production of TNF, IL-6, and IFN-γ (P < 0.01), IL-12 (P < 0.05), and vascular endothelial growth factor (P < 0.001). In co-stimulation assays of PM-exposed DC and alloreactive CD4+ T cells, both CEP and DEP directed a Th2-like pattern of cytokine production (e.g., enhanced IL-13 and IL-18 and suppressed IFN-γ production). CD4+ T cells were not functionally activated on exposure to either DEP or CEP. Car- and diesel-enriched particles exert a differential effect on DC activation. Our data support the hypothesis that DEP (and to a lesser extent CEP) regulate important functional aspects of human DC, supporting an adjuvant role for this material. PMID:17630318

  8. Human Secretory IgM Antibodies Activate Human Complement and Offer Protection at Mucosal Surface.

    Science.gov (United States)

    Michaelsen, T E; Emilsen, S; Sandin, R H; Granerud, B K; Bratlie, D; Ihle, O; Sandlie, I

    2017-01-01

    IgM molecules circulate in serum as large polymers, mainly pentamers, which can be transported by the poly-Ig receptor (pIgR) across epithelial cells to mucosal surfaces and released as secretory IgM (SIgM). The mucosal SIgM molecules have non-covalently attached secretory component (SC), which is the extracellular part of pIgR which is cleaved from the epithelial cell membrane. Serum IgM antibodies do not contain SC and have previously been shown to make a conformational change from 'a star' to a 'staple' conformation upon reaction with antigens on a cell surface, enabling them to activate complement. However, it is not clear whether SIgM similarly can induce complement activation. To clarify this issue, we constructed recombinant chimeric (mouse/human) IgM antibodies against hapten 5-iodo-4-hydroxy-3-nitro-phenacetyl (NIP) and in addition studied polyclonal IgM formed after immunization with a meningococcal group B vaccine. The monoclonal and polyclonal IgM molecules were purified by affinity chromatography on a column containing human SC in order to isolate joining-chain (J-chain) containing IgM, followed by addition of excess amounts of soluble SC to create SIgM (IgM J+ SC+). These SIgM preparations were tested for complement activation ability and shown to be nearly as active as the parental IgM J+ molecules. Thus, SIgM may offer protection against pathogens at mucosal surface by complement-mediated cell lysis or by phagocytosis mediated by complement receptors present on effector cells on mucosa. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  9. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    Directory of Open Access Journals (Sweden)

    Dario Moreira-Arce

    Full Text Available Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in

  10. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    Science.gov (United States)

    Moreira-Arce, Dario; Vergara, Pablo M; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants

  11. Muscle cooling delays activation of the muscle metaboreflex in humans.

    Science.gov (United States)

    Ray, C A; Hume, K M; Gracey, K H; Mahoney, E T

    1997-11-01

    Elevation of muscle temperature has been shown to increase muscle sympathetic nerve activity (MSNA) during isometric exercise in humans. The purpose of the present study was to evaluate the effect of muscle cooling on MSNA responses during exercise. Eight subjects performed ischemic isometric handgrip at 30% of maximal voluntary contraction to fatigue followed by 2 min of postexercise muscle ischemia (PEMI), with and without local cooling of the forearm. Local cooling of the forearm decreased forearm muscle temperature from 31.8 +/- 0.4 to 23.1 +/- 0.8 degrees C (P = 0.001). Time to fatigue was not different during the control and cold trials (156 +/- 11 and 154 +/- 5 s, respectively). Arterial pressures and heart rate were not significantly affected by muscle cooling during exercise, although heart rate tended to be higher during the second minute of exercise (P = 0.053) during muscle cooling. Exercise-induced increases in MSNA were delayed during handgrip with local cooling compared with control. However, MSNA responses at fatigue and PEMI were not different between the two conditions. These findings suggest that muscle cooling delayed the activation of the muscle metaboreflex during ischemic isometric exercise but did not prevent its full expression during fatiguing contraction. These results support the concept that muscle temperature can play a role in the regulation of MSNA during exercise.

  12. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

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

    Science.gov (United States)

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

    2015-08-28

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

  14. Azoreductase activity of anaerobic bacteria isolated from human intestinal microflora.

    Science.gov (United States)

    Rafii, F; Franklin, W; Cerniglia, C E

    1990-01-01

    A plate assay was developed for the detection of anaerobic bacteria that produce azoreductases. With this plate assay, 10 strains of anaerobic bacteria capable of reducing azo dyes were isolated from human feces and identified as Eubacterium hadrum (2 strains), Eubacterium spp. (2 species), Clostridium clostridiiforme, a Butyrivibrio sp., a Bacteroides sp., Clostridium paraputrificum, Clostridium nexile, and a Clostridium sp. The average rate of reduction of Direct Blue 15 dye (a dimethoxybenzidine-based dye) in these strains ranged from 16 to 135 nmol of dye per min per mg of protein. The enzymes were inactivated by oxygen. In seven isolates, a flavin compound (riboflavin, flavin adenine dinucleotide, or flavin mononucleotide) was required for azoreductase activity. In the other three isolates and in Clostridium perfringens, no added flavin was required for activity. Nondenaturing polyacrylamide gel electrophoresis showed that each bacterium expressed only one azoreductase isozyme. At least three types of azoreductase enzyme were produced by the different isolates. All of the azoreductases were produced constitutively and released extracellularly. Images PMID:2202258

  15. Azoreductase activity of anaerobic bacteria isolated from human intestinal microflora.

    Science.gov (United States)

    Rafii, F; Franklin, W; Cerniglia, C E

    1990-07-01

    A plate assay was developed for the detection of anaerobic bacteria that produce azoreductases. With this plate assay, 10 strains of anaerobic bacteria capable of reducing azo dyes were isolated from human feces and identified as Eubacterium hadrum (2 strains), Eubacterium spp. (2 species), Clostridium clostridiiforme, a Butyrivibrio sp., a Bacteroides sp., Clostridium paraputrificum, Clostridium nexile, and a Clostridium sp. The average rate of reduction of Direct Blue 15 dye (a dimethoxybenzidine-based dye) in these strains ranged from 16 to 135 nmol of dye per min per mg of protein. The enzymes were inactivated by oxygen. In seven isolates, a flavin compound (riboflavin, flavin adenine dinucleotide, or flavin mononucleotide) was required for azoreductase activity. In the other three isolates and in Clostridium perfringens, no added flavin was required for activity. Nondenaturing polyacrylamide gel electrophoresis showed that each bacterium expressed only one azoreductase isozyme. At least three types of azoreductase enzyme were produced by the different isolates. All of the azoreductases were produced constitutively and released extracellularly.

  16. Activation of ERK mitogen-activated protein kinase in human cells by the mycotoxin patulin

    International Nuclear Information System (INIS)

    Wu, T.-S.; Yu, F.-Y.; Su, C.-C.; Kan, J.-C.; Chung, C.-P.; Liu, B.-H.

    2005-01-01

    Patulin (PAT), a mycotoxin produced by certain species of Penicillium and Aspergillus, is often detectable in moldy fruits and their derivative products. PAT led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 μM PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 h incubation with 0.05 μM of PAT. Treatment of human PBMCs for 30 min with 30 μM PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 μM PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression

  17. Can human activities alter the drowning fate of barrier islands?

    Science.gov (United States)

    Lorenzo-Trueba, J.; Ashton, A. D.; Jin, D.; Hoagland, P.; Kite-Powell, H.

    2012-12-01

    Low-lying coastal barriers face an uncertain future over the coming century and beyond as sea levels rise, with many projections suggesting end-of-century rates of sea-level rise as high or higher than 1 cm/yr. Geologically, such rates of sea-level rise have been experienced several thousand years ago and we can use our understanding of geological processes and sedimentary evidence to help unravel the dynamics of natural barriers experiencing sea-level rise. Along many modern coastal barriers, however, anthropic change, such as beach nourishment, dune construction, and emplacement of hard structures, plays a dominant role in coastline dynamics. A fundamental question to be addressed is whether human activities intended to preserve infrastructure and beach recreation may make wholesale collapse, or 'drowning,' of barrier systems more likely. Here we present a numerical modeling tool that couples natural processes and the human responses to these changes (and the subsequent of human responses on natural processes). Recent theoretical model development suggests that barriers are intrinsically morphodynamic features, responding to sea-level rise in complex ways through the interactions of marine processes and barrier overwash. Undeveloped coastal barriers would therefore respond to an accelerated sea-level rise in complex, less predictable manners than suggested by existing long-term models. We have developed a model that examines non-equilibrium cross-shore evolution of barrier systems at decadal to centennial temporal scales, focusing on the interactions between processes of shoreface evolution and overwash deposition. Model responses demonstrate two means of barrier collapse during sea-level rise: 'height drowning', which occurs when overwash fluxes are insufficient to maintain the landward migration rate required to keep in pace with sea-level rise, and 'width drowning', which occurs when the shoreface response is insufficient to maintain the barrier geometry

  18. Exergy performance of human body under physical activities

    International Nuclear Information System (INIS)

    Mady, Carlos Eduardo Keutenedjian; Albuquerque, Cyro; Fernandes, Tiago Lazzaretti; Hernandez, Arnaldo José; Saldiva, Paulo Hilário Nascimento; Yanagihara, Jurandir Itizo; Oliveira, Silvio de

    2013-01-01

    The aim of this work is to apply performance indicators for individuals under physical activity based on the concepts of exergy destroyed and exergy efficiency. The cardiopulmonary exercise test is one of the most used tests to assess the functional capacity of individuals with varying degrees of physical training. To perform the exergy analysis during the test, it is necessary to calculate heat and mass flow rates, associated with radiation, convection, vaporization and respiration, determined from the measurements and some relations found in the literature. The energy balance allowed the determination of the internal temperature over time and the exergy variation of the body along the experiment. Eventually, it was possible to calculate the destroyed exergy and the exergy efficiency from the exergy analysis. The exergy rates and flow rates are dependent of the exercise level and the body metabolism. The results show that the relation between the destroyed exergy and the metabolism is almost constant during the test, furthermore its value has a great dependence of the subject age. From the exergy analysis it was possible to divide the subjects according to their training level, for the same destroyed exergy, subjects with higher lactate threshold can perform more work. - Highlights: • Exergy analysis was applied to the human body under physical activities. • Concept of maximum available work from ATP hydrolysis was compared with exergy analysis results. • For the same destroyed exergy, subjects with higher lactate threshold can perform more work. • Runners during physical activities tend to a state of minimum destroyed exergy and maximum exergy efficiency

  19. Polystyrene nanoparticles activate ion transport in human airway epithelial cells

    Directory of Open Access Journals (Sweden)

    McCarthy J

    2011-06-01

    Full Text Available J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify

  20. Human activity and landscape change at Adjiyska Vodenitsa, central Bulgaria

    Science.gov (United States)

    Chiverrell, R. C.; Archibald, Z.

    2009-04-01

    reflects processes during the late Holocene, with the low level hill slopes flanking the river littered with small agricultural communities. It is easy to envisage the landscape as one made susceptible to erosion by human activity feeding materials through the Momina Klissoura Gorge to the Belovo fan near the settlement at Adjiyska Vodenitsa. Sharp increases in non-arboreal pollen during the period 2880-1620 BP, associated with Greek and Roman times, in the Rila Mountains, have been attributed to seasonal animal husbandry in the higher mountains, with associated permanent settlement in the surrounding lowlands.

  1. Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Weijer, Sebastiaan; de Vos, Alex F.; Pater, Jennie M.; Meijers, Joost C.; Hack, C. Erik; Levi, Marcel; van der Poll, Tom

    2004-01-01

    Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To

  2. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  3. Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.

    Science.gov (United States)

    Drake, Matthew G; Bivins-Smith, Elizabeth R; Proskocil, Becky J; Nie, Zhenying; Scott, Gregory D; Lee, James J; Lee, Nancy A; Fryer, Allison D; Jacoby, David B

    2016-09-01

    Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60-70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase-deficient transgenic mice, did not reduce eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.

  4. Inactivation of human DGAT2 by oxidative stress on cysteine residues

    Science.gov (United States)

    Choi, Kwangman; Kwon, Eun Bin; Kang, Mingu; Kim, Dong-eun; Jeong, Hyejeong; Kim, Janghwan; Kim, Jong Heon; Kim, Mun Ock; Han, Sang-Bae

    2017-01-01

    Diacylglycerol acyltransferases (DGATs) have a crucial role in the biosynthesis of triacylglycerol (TG), the major storage form of metabolic energy in eukaryotic organisms. Even though DGAT2, one of two distinct DGATs, has a vital role in TG biosynthesis, little is known about the regulation of DGAT2 activity. In this study, we examined the role of cysteine and its oxidation in the enzymatic activity of human DGAT2 in vitro. Human DGAT2 activity was considerably inhibited not only by thiol-modifying reagents (NEM and IA) but also by ROS-related chemicals (H2O2 and β-lapachone), while human DGAT1 and GPAT1 were little affected. Particularly, ROS-related chemicals concomitantly induced intermolecular disulfide crosslinking of human DGAT2. Both the oxidative inactivation and disulfide crosslinking were almost completely reversed by the treatment with DTT, a disulfide-reducing agent. These results clearly demonstrated the significant role of ROS-induced intermolecular crosslinking in the inactivation of human DGAT2 and also suggested DGAT2 as a redox-sensitive regulator in TG biosynthesis. PMID:28700690

  5. Quantifying the impact of human activity on temperatures in Germany

    Science.gov (United States)

    Benz, Susanne A.; Bayer, Peter; Blum, Philipp

    2017-04-01

    Human activity directly influences ambient air, surface and groundwater temperatures. Alterations of surface cover and land use influence the ambient thermal regime causing spatial temperature anomalies, most commonly heat islands. These local temperature anomalies are primarily described within the bounds of large and densely populated urban settlements, where they form so-called urban heat islands (UHI). This study explores the anthropogenic impact not only for selected cities, but for the thermal regime on a countrywide scale, by analyzing mean annual temperature datasets in Germany in three different compartments: measured surface air temperature (SAT), measured groundwater temperature (GWT), and satellite-derived land surface temperature (LST). As a universal parameter to quantify anthropogenic heat anomalies, the anthropogenic heat intensity (AHI) is introduced. It is closely related to the urban heat island intensity, but determined for each pixel (for satellite-derived LST) or measurement point (for SAT and GWT) of a large, even global, dataset individually, regardless of land use and location. Hence, it provides the unique opportunity to a) compare the anthropogenic impact on temperatures in air, surface and subsurface, b) to find main instances of anthropogenic temperature anomalies within the study area, in this case Germany, and c) to study the impact of smaller settlements or industrial sites on temperatures. For all three analyzed temperature datasets, anthropogenic heat intensity grows with increasing nighttime lights and declines with increasing vegetation, whereas population density has only minor effects. While surface anthropogenic heat intensity cannot be linked to specific land cover types in the studied resolution (1 km × 1 km) and classification system, both air and groundwater show increased heat intensities for artificial surfaces. Overall, groundwater temperature appears most vulnerable to human activity; unlike land surface temperature

  6. A Novel Wearable Sensor-Based Human Activity Recognition Approach Using Artificial Hydrocarbon Networks.

    Science.gov (United States)

    Ponce, Hiram; Martínez-Villaseñor, María de Lourdes; Miralles-Pechuán, Luis

    2016-07-05

    Human activity recognition has gained more interest in several research communities given that understanding user activities and behavior helps to deliver proactive and personalized services. There are many examples of health systems improved by human activity recognition. Nevertheless, the human activity recognition classification process is not an easy task. Different types of noise in wearable sensors data frequently hamper the human activity recognition classification process. In order to develop a successful activity recognition system, it is necessary to use stable and robust machine learning techniques capable of dealing with noisy data. In this paper, we presented the artificial hydrocarbon networks (AHN) technique to the human activity recognition community. Our artificial hydrocarbon networks novel approach is suitable for physical activity recognition, noise tolerance of corrupted data sensors and robust in terms of different issues on data sensors. We proved that the AHN classifier is very competitive for physical activity recognition and is very robust in comparison with other well-known machine learning methods.

  7. Modeling of human factor Va inactivation by activated protein C

    Directory of Open Access Journals (Sweden)

    Bravo Maria

    2012-05-01

    Full Text Available Abstract Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (FXa and its cofactor FVa plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC, an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative

  8. Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system.

    Science.gov (United States)

    Cheng, Liang; Zhang, Zheng; Li, Guangming; Li, Feng; Wang, Li; Zhang, Liguo; Zurawski, Sandra M; Zurawski, Gerard; Levy, Yves; Su, Lishan

    2017-10-27

    TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro. For example, CpG-A was most efficient to induce IFN-α production in vitro. In contrast, CpG-B, R848 and Poly I:C stimulated much more IFN-α than CpG-A in vivo. Importantly, the human innate immune response to specific TLR-Ls in humanized mice was different from that reported in C57BL/6 mice, but similar to that reported in nonhuman primates. Furthermore, we found that different TLR-Ls distinctively activated and mobilized human plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs) and monocytes in different organs. Finally, we showed that, as adjuvants, CpG-B, R848 and Poly I:C can all enhance antigen specific CD4 + T cell response, while only R848 and Poly I:C induced CD8 + cytotoxic T cells response to a CD40-targeting HIV vaccine in humanized mice, correlated with their ability to activate human mDCs but not pDCs. We conclude that humanized mice serve as a highly relevant model to evaluate and rank the human immunologic effects of novel adjuvants in vivo prior to testing in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by Apolipoprotein N-Acyltransferase BCG_2070c.

    OpenAIRE

    Brülle Juliane K; Tschumi Andreas; Sander Peter

    2013-01-01

    BACKGROUND: Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In ...

  10. Atherogenic Impact of Lecithin-Cholesterol Acyltransferase and Its Relation to Cholesterol Esterification Rate in HDL (FERHDL) and AIP [log(TG/HDL-C)] Biomarkers: The Butterfly Effect?

    Czech Academy of Sciences Publication Activity Database

    Dobiášová, Milada

    2017-01-01

    Roč. 66, č. 2 (2017), s. 193-203 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : lecithin-cholesterol acyltransferase (LCAT) * atherosclerosis * FERHDL (fractional esterification rate in HDL) * AIP (atherogenic index of plasma, log(TG/HDL-C) * biomarkers of cardiometabolic risk * lipoprotein particle size Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 1.461, year: 2016

  11. Protein composition of catalytically active human telomerase from immortal cells

    DEFF Research Database (Denmark)

    Cohen, Scott B; Graham, Mark E; Lovrecz, George O

    2007-01-01

    Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for approximately 90% of human cancers. We have purified human telomerase approximately 10(8)-fold, with the final elution dependent on th...

  12. Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

    Science.gov (United States)

    Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S

    2013-12-01

    Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

  13. Human Research Program Human Health Countermeasures Element Extravehicular Activity (EVA) Risk Standing Review Panel (SRP)

    Science.gov (United States)

    Norfleet, William; Harris, Bernard

    2009-01-01

    The Extravehicular Activity (EVA) Risk Standing Review Panel (SRP) was favorably impressed by the operational risk management approach taken by the Human Research Program (HRP) Integrated Research Plan (IRP) to address the stated life sciences issues. The life sciences community at the Johnson Space Center (JSC) seems to be focused on operational risk management. This approach is more likely to provide risk managers with the information they need at the time they need it. Concerning the information provided to the SRP by the EVA Physiology, Systems, and Performance Project (EPSP), it is obvious that a great deal of productive activity is under way. Evaluation of this information was hampered by the fact that it often was not organized in a fashion that reflects the "Gaps and Tasks" approach of the overall Human Health Countermeasures (HHC) effort, and that a substantial proportion of the briefing concerned subjects that, while interesting, are not part of the HHC Element (e.g., the pressurized rover presentation). Additionally, no information was provided on several of the tasks or how they related to work underway or already accomplished. This situation left the SRP having to guess at the efforts and relationship to other elements, and made it hard to easily map the EVA Project efforts currently underway, and the data collected thus far, to the gaps and tasks in the IRP. It seems that integration of the EPSP project into the HHC Element could be improved. Along these lines, we were concerned that our SRP was split off from the other participating SRPs at an early stage in the overall agenda for the meeting. In reality, the concerns of EPSP and other projects share much common ground. For example, the commonality of the concerns of the EVA and exercise physiology groups is obvious, both in terms of what reduced exercise capacity can do to EVA capability, and how the exercise performed during an EVA could contribute to an overall exercise countermeasure prescription.

  14. Human population and activities in Forsmark. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced.The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations.The data in this description is essential for future evaluations of the impact on the environment and its human population (Environmental Impact Assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments.The actual area for the study is in this report called 'the Forsmark area', an area of 19.5 km{sup 2} near Forsmark nuclear power plant. The land use in the Forsmark area differs notably from the land use in Uppsala laen (laen = county). Only 0.04% of the total area is developed (built-up) compared to 4.9% in Uppsala laen and only 4% is agricultural land compared to 25% in the county. Furthermore, there are far more forest, wetlands and water areas in the Forsmark area. The forest area represents as much as 72.5% of the total area.The Forsmark area is uninhabited, and its surroundings are very sparsely populated. In 2002, the population density in Forsmark was 1.8 inhabitants per square kilometre, which was 24 times lower than in Uppsala laen. The population density in the

  15. Human population and activities in Forsmark. Site description

    International Nuclear Information System (INIS)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced.The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations.The data in this description is essential for future evaluations of the impact on the environment and its human population (Environmental Impact Assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments.The actual area for the study is in this report called 'the Forsmark area', an area of 19.5 km 2 near Forsmark nuclear power plant. The land use in the Forsmark area differs notably from the land use in Uppsala laen (laen = county). Only 0.04% of the total area is developed (built-up) compared to 4.9% in Uppsala laen and only 4% is agricultural land compared to 25% in the county. Furthermore, there are far more forest, wetlands and water areas in the Forsmark area. The forest area represents as much as 72.5% of the total area.The Forsmark area is uninhabited, and its surroundings are very sparsely populated. In 2002, the population density in Forsmark was 1.8 inhabitants per square kilometre, which was 24 times lower than in Uppsala laen. The population density in the parish has been

  16. Seasonal variations in health-related human physical activity.

    Science.gov (United States)

    Reilly, Thomas; Peiser, Benny

    2006-01-01

    There are profound fluctuations in climate that occur within the annual cycle of seasonal changes. The severity of these changes depends on latitude of location and prevailing topography. Living creatures have evolved means of coping with seasonal extremes. Endogenous circannual cycles, at least in humans, appear to have been masked by mechanisms employed to cope with environmental changes. Physical activity levels tend to be lower in winter than in summer, mediating effects on health-related fitness. In athletes, seasonal changes are dictated by requirements of the annual programme of competitive engagements rather than an inherent circannual rhythm. Injury rates are influenced by seasonal environmental factors, notably in field sports. Season of birth has been related to susceptibility to selected morbidities, including mental ill-health. In age-restricted sports, there is a date-of-birth bias favouring those individuals born early in the competitive year. Trainers and selectors should acknowledge this trend if they are to avoid omitting gifted individuals, born later in the year, from talent development programmes.

  17. Rhythmic Working Memory Activation in the Human Hippocampus

    Directory of Open Access Journals (Sweden)

    Marcin Leszczyński

    2015-11-01

    Full Text Available Working memory (WM maintenance is assumed to rely on a single sustained process throughout the entire maintenance period. This assumption, although fundamental, has never been tested. We used intracranial electroencephalography (EEG recordings from the human hippocampus in two independent experiments to investigate the neural dynamics underlying WM maintenance. We observed periodic fluctuations between two different oscillatory regimes: Periods of “memory activation” were reflected by load-dependent alpha power reductions and lower levels of cross-frequency coupling (CFC. They occurred interleaved with periods characterized by load-independent high levels of alpha power and CFC. During memory activation periods, a relevant CFC parameter (load-dependent changes of the peak modulated frequency correlated with individual WM capacity. Fluctuations between these two periods predicted successful performance and were locked to the phase of endogenous delta oscillations. These results show that hippocampal maintenance is a dynamic rather than constant process and depends critically on a hierarchy of oscillations.

  18. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  19. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  20. Neutron activation analysis of arsenic and antimony in human hair

    International Nuclear Information System (INIS)

    Kanda, Yukio; Isono, Hideo; Kozuka, Hiroshi.

    1975-01-01

    A radiochemical neutron activation method for the determination of trace amounts of arsenic and antimony in human hair samples is studied. The sample of hair (100 mg) irradiated for 5 hours with a neutron flux of 2.1x10 12 n/cm 2 s was decomposed with a sulfuric-nitric acid mixture after addition of each 5 mg of arsenic and antimony as carrier. Arsine and stibine were evolved from the solution of decomposed hair by reduction with 3 g of granular zinc and were absorbed in 0.1N iodine solution for half an hour. Metal arsenic was separated from iodine solution by precipitation with sodium hypophosphite, followed by precipitation of antimony as sulfide with thioacetamide. These precipitates were dissolved and their gamma-ray spectra were measured with a well type 3''x3'' NaI(TI) detector equipped with a 200 channel pulse-height analyzer. After the measurement of gamma-ray spectra, the chemical yields were determined by colorimetric methods. The relative standard deviations were 7% and 4% for 0.01 μg As and 0.024 μg Sb, respectively. The sensitivity of this method was estimated to be 1x10 -3 μg for arsenic and 2x10 -3 μg for antimony. (auth.)

  1. Activities of nuclear human resource development in nuclear industry

    International Nuclear Information System (INIS)

    Tsujikura, Yonezo

    2010-01-01

    Since 2007, the JAIF (Japan Atomic Industrial Forum) had established the nuclear energy human resource development council to make analysis of the issue on nuclear human resource development. The author mainly contributed to develop its road map as a chairman of working group. Questionnaire survey to relevant parties on issues of nuclear human resource development had been conducted and the council identified the six relevant issues and ten recommendations. Both aspects for career design and skill-up program are necessary to develop nuclear human resource at each developing step and four respective central coordinating hubs should be linked to each sector participating in human resource development. (T. Tanaka)

  2. Reindeer and caribou (Rangifer tarandus response towards human activities

    Directory of Open Access Journals (Sweden)

    Eigil Reimers

    2009-01-01

    Full Text Available We address the question of how human activities and infrastructure influence reindeer/caribou’s (Rangifer tarandus behaviour and habitat use and review studies based on current methodologies. Anthropogenic activities have a direct affect on Rangifer behaviour through the senses hearing, sight and smell, and all of these are important tools for behavioural risk assessment. Short term indirect responses, such as habituation, sensitisation, avoidance, and displacement, develop through neutral, positive or negative associations towards stimulus in terms of Rangifer’s ability to experience, learn, and remember. Long term behavioural responses develop through interaction with predators and, for reindeer, also domestication. A survey of the literature dealing with behavioural studies reveals that although Rangifer in most cases retreat from anthropogenic activities, comfort distances (i.e. distances beyond which animal behaviour or activity are not influenced are relatively short. In most cases, energetic implications appear moderate and small compared to other natural, biotic influences such as disturbance (and death caused by insect and/or predator harassment. Unless obstructing access, physical constructions of various kinds apparently have limited effects on Rangifer behaviour or habitat use. On the other hand, constructions that do obstruct or limit access and recreational or other motorized and non-motorized activities appear to have stronger impacts on avoidance and redistribution of Rangifer. Behavioural effects that might decrease survival and reproduction include retreat from favourable habitat near disturbance sources and reduction of time spent feeding with resulting energy depletion over time. Rangifer habitat use, habitat avoidance, and feeding preferences are governed by a complexity of natural interacting factors. Domestication, habituation and sensitisation are essential in shaping Rangifer’s adaptability, and should be included

  3. Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT)

    Science.gov (United States)

    Kaylor, Joanna J.; Cook, Jeremy D.; Makshanoff, Jacob; Bischoff, Nicholas; Yong, Jennifer; Travis, Gabriel H.

    2014-01-01

    Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action. PMID:24799687

  4. Human activity and climate variability project - annual report 2002

    International Nuclear Information System (INIS)

    Chambers, S.; Harle, K.J.; Sharmeen, S.; Zahorowski, W.; Cohen, D.; Heijnis, H.; Henderson-Sellers, A

    2002-01-01

    Work is well underway on identifying the spatial and temporal extent, direction and range of trace element transport across Tasmania through analysis of lake sediments; A follow up investigation of sedimentation and pollution in the Nattai River catchment following the devastating 2001 bushfires in the region has been completed; The project has been extended to include investigations of evidence of human impacts in the highly sensitive and ecologically important Great Lakes of coastal NSW. This has involved the expansion of our collaboration to include Geoscience Australia; Contributions have been made to the IGBP HITE project. Further contributions will be made as the evidence gathered is drawn together and interpreted; Over the coming year, focus will be placed on completion of the investigation of the extent of aerial transport of trace elements across Tasmania over the last 200 years as well as evidence for human activity and impacts on the Great Lakes region of NSW. Further investigation of potential climate signals from sites in northern Australia will also be made. The first 12 months of data for all ACE-Asia radon and fine particle sites is now available with preliminary analyses performed; The seasonal variability of background radon concentration at each of the radon monitoring sites has been characterised for the available data; Major components related to industrial pollution and soil sources in China have been identified and quantified; Regional and seasonal variations and trends in aerosol constituents have been measured and compared across more than 2.8Mk 2 of sampling area; The Hok Tsui and Kosan detectors were visited for general maintenance and recalibration; A grant application to the APN has been submitted in support of regional inventory analyses based on radon time series; Progress on the processing and interpretation of radon data was presented at the Cape Grim Science Meeting (6-7 February 2002) and the 7th Biennial SPERA Conference on

  5. Human activity and climate variability project - annual report 2002

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, S; Harle, K J; Sharmeen, S; Zahorowski, W; Cohen, D; Heijnis, H; Henderson-Sellers, A [Australian Nuclear Science and Technology Organisation, Menai, NSW (Australia)

    2002-07-01

    Work is well underway on identifying the spatial and temporal extent, direction and range of trace element transport across Tasmania through analysis of lake sediments; A follow up investigation of sedimentation and pollution in the Nattai River catchment following the devastating 2001 bushfires in the region has been completed; The project has been extended to include investigations of evidence of human impacts in the highly sensitive and ecologically important Great Lakes of coastal NSW. This has involved the expansion of our collaboration to include Geoscience Australia; Contributions have been made to the IGBP HITE project. Further contributions will be made as the evidence gathered is drawn together and interpreted; Over the coming year, focus will be placed on completion of the investigation of the extent of aerial transport of trace elements across Tasmania over the last 200 years as well as evidence for human activity and impacts on the Great Lakes region of NSW. Further investigation of potential climate signals from sites in northern Australia will also be made. The first 12 months of data for all ACE-Asia radon and fine particle sites is now available with preliminary analyses performed; The seasonal variability of background radon concentration at each of the radon monitoring sites has been characterised for the available data; Major components related to industrial pollution and soil sources in China have been identified and quantified; Regional and seasonal variations and trends in aerosol constituents have been measured and compared across more than 2.8Mk{sup 2} of sampling area; The Hok Tsui and Kosan detectors were visited for general maintenance and recalibration; A grant application to the APN has been submitted in support of regional inventory analyses based on radon time series; Progress on the processing and interpretation of radon data was presented at the Cape Grim Science Meeting (6-7 February 2002) and the 7th Biennial SPERA Conference on

  6. Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

    International Nuclear Information System (INIS)

    Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

    2004-01-01

    The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

  7. Advanced Video Activity Analytics (AVAA): Human Performance Model Report

    Science.gov (United States)

    2017-12-01

    effectively. The goal of the modeling effort is to provide an understanding of the current state of the system with respect to the impact on human ...representation of the human ‒ machine system. Third, task network modeling is relatively easy to use and understand . Lastly, it is more cost effective and can...and communication issues. Proceedings of the Human Factors and Ergonomics Society Annual Meeting. 2006;48(2):2396–2400. Reid GB, Colle HA

  8. Investigation of cytogenetic activity of radioprotectors in human lymphocyte culture

    International Nuclear Information System (INIS)

    Egiazaryan, S.V.; Arutyunyan, R.M.

    1977-01-01

    Studied are the effects of the F-11 and F-37 indene preparations on chromosome aberrations induced in lymphocyte culture of peripheral human blood by thioTEP. Investigation into the action of the substance in euqimolar concentrations has not shown their protective effect. Indene preparations did not change the spectrum of chromosome aberrations induced by thioTEP as well as did not increase the level of chromosome aberrations in lumphocyte culture of human peripheral human blood

  9. Exploring Techniques for Vision Based Human Activity Recognition: Methods, Systems, and Evaluation

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2013-01-01

    Full Text Available With the wide applications of vision based intelligent systems, image and video analysis technologies have attracted the attention of researchers in the computer vision field. In image and video analysis, human activity recognition is an important research direction. By interpreting and understanding human activity, we can recognize and predict the occurrence of crimes and help the police or other agencies react immediately. In the past, a large number of papers have been published on human activity recognition in video and image sequences. In this paper, we provide a comprehensive survey of the recent development of the techniques, including methods, systems, and quantitative evaluation towards the performance of human activity recognition.

  10. The Consolidated Human Activity Database — Master Version (CHAD-Master) Technical Memorandum

    Science.gov (United States)

    This technical memorandum contains information about the Consolidated Human Activity Database -- Master version, including CHAD contents, inventory of variables: Questionnaire files and Event files, CHAD codes, and references.

  11. Global N Cycle: Fluxes and N2O Mixing Ratios Originating from Human Activity

    Data.gov (United States)

    National Aeronautics and Space Administration — Nitrogen is a major nutrient in terrestrial ecosystems and an important catalyst in tropospheric photochemistry. Over the last century human activities have...

  12. Global N Cycle: Fluxes and N2O Mixing Ratios Originating from Human Activity

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: Nitrogen is a major nutrient in terrestrial ecosystems and an important catalyst in tropospheric photochemistry. Over the last century human activities...

  13. Gastrointestinal-active oligosaccharides from human milk and functional foods

    NARCIS (Netherlands)

    Albrecht, S.A.

    2011-01-01

    Keywords: human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), konjac glucomannan (KGM), breast milk, baby feces, gastrointestinal metabolization, blood-group specific conjugates, CE-LIF-MSn

    Oligosaccharides, as present in human milk or supplemented to food, are

  14. Variability of human hepatic UDP-glucuronosyltransferase activity

    NARCIS (Netherlands)

    Little, JM; Lester, R; Kuipers, F; Vonk, R; Mackenzie, PI; Drake, RR; Frame, L; Radominska-Pandya, A

    1999-01-01

    The availability of a unique series of liver samples from human subjects, both control patients (9) and those with liver disease (6; biliary atresia (2), retransplant, chronic tyrosinemia type I, tyrosinemia, Wilson's disease) allowed us to characterize human hepatic UDP-glucuronosyltransferases

  15. Consolidated Human Activity Database (CHAD) for use in human exposure and health studies and predictive models

    Science.gov (United States)

    EPA scientists have compiled detailed data on human behavior from 22 separate exposure and time-use studies into CHAD. The database includes more than 54,000 individual study days of detailed human behavior.

  16. Human population and activities at Simpevarp. Site description

    International Nuclear Information System (INIS)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km 2 near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km 2 , three times lower than in Kalmar laen. The demography statistics show

  17. Human population and activities at Simpevarp. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km{sup 2} near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km{sup 2}, three times lower than in Kalmar laen. The

  18. Enabling Collaborative Human-Machine (H-M) Decision Making in Time-critical Activities

    Data.gov (United States)

    National Aeronautics and Space Administration — Self-adjusting autonomous systems (SAS) are spreading from well-defined control activities, such as manufacturing, to complex activities with multi-faceted human...

  19. Activity of antiretroviral drugs in human infections by opportunistic agents

    Directory of Open Access Journals (Sweden)

    Izabel Galhardo Demarchi

    2012-03-01

    Full Text Available Highly active antiretroviral therapy (HAART is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV, human herpes virus 8 (HHV-8, Epstein-Barr virus, hepatitis B virus (HBV, parvovirus B19 and cytomegalovirus (CMV. HAART has also led to a significant reduction in the incidence, and the modification of characteristics, of bacteremia by etiological agents such as Staphylococcus aureus, coagulase negative staphylococcus, non-typhoid species of Salmonella, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. HAART can modify the natural history of cryptosporidiosis and microsporidiosis, and restore mucosal immunity, leading to the eradication of Cryptosporidium parvum. A similar restoration of immune response occurs in infections by Toxoplasma gondii. The decline in the incidence of visceral leishmaniasis/HIV co-infection can be observed after the introduction of protease inhibitor therapy. Current findings are highly relevant for clinical medicine and may serve to reduce the number of prescribed drugs thereby improving the quality of life of patients with opportunistic diseases.A terapia HAART (terapia antirretroviral altamente ativa é usada em pacientes infectados pelo vírus da imunodeficiência humana (HIV e demonstrou diminuição significativa de infecções oportunistas, tais como as causadas por vírus, fungos, protozoários e bactérias. O uso da HAART está associado com a reconstituição imunológica e diminuição na prevalência de candidíase oral. A terapia antirretroviral beneficia pacientes co-infectados pelo HIV, v

  20. Radar cross section of human cardiopulmonary activity for recumbent subject.

    Science.gov (United States)

    Kiriazi, John E; Boric-Lubecke, Olga; Lubecke, Victor M

    2009-01-01

    The radar cross section (RCS) corresponding to human cardio-respiratory motion is measured for a subject in two different recumbent positions. Lying face-up (supine), the subject showed an RCS of 0.326 m(2). But when lying face-down (prone), the RCS increased to 2.9 m(2). This is the first reported RCS measurement corresponding to human cardio-respiratory motion. The results obtained in this experiment suggest modeling the upper part of the human body as a half-cylinder where the front body corresponds to the cylindrical surface and the back corresponds to the rectangular one.

  1. In silico characterization of 1,2-diacylglycerol cholinephosphotransferase and lysophospha-tidylcholine acyltransferase genes in Glycine max L. Merrill.

    Science.gov (United States)

    Sousa, C S; Barros, B A; Barh, D; Ghosh, P; Azevedo, V; Barros, E G; Moreira, M A

    2016-08-26

    The enzymes 1,2-diacylglycerol cholinephosphotrans-ferase (CPT) and lysophosphatidylcholine acyltransferase (LPCAT) are important in lipid metabolism in soybean seeds. Thus, understand-ing the genes that encode these enzymes may enable their modification and aid the improvement of soybean oil quality. In soybean, the genes encoding these enzymes have not been completely described; there-fore, this study aimed to identify, characterize, and analyze the in silico expression of these genes in soybean. We identified two gene models encoding CPT and two gene models encoding LPCAT, one of which presented an alternative transcript. The sequences were positioned on the physical map of soybean and the promoter regions were analyzed. Cis-elements responsible for seed-specific expression and responses to biotic and abiotic stresses were identified. Virtual expression analysis of the gene models for CPT and LPCAT indicated that these genes are expressed under different stress conditions, in somatic embryos during differentiation, in immature seeds, root tissues, and calli. Putative ami-no acid sequences revealed the presence of transmembrane domains, and analysis of the cellular localization of these enzymes revealed they are located in the endoplasmic reticulum.

  2. The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation.

    Science.gov (United States)

    Favennec, Marie; Hennart, Benjamin; Caiazzo, Robert; Leloire, Audrey; Yengo, Loïc; Verbanck, Marie; Arredouani, Abdelilah; Marre, Michel; Pigeyre, Marie; Bessede, Alban; Guillemin, Gilles J; Chinetti, Giulia; Staels, Bart; Pattou, François; Balkau, Beverley; Allorge, Delphine; Froguel, Philippe; Poulain-Godefroy, Odile

    2015-10-01

    This study characterized the kynurenine pathway (KP) in human obesity by evaluating circulating levels of kynurenines and the expression of KP enzymes in adipose tissue. Tryptophan and KP metabolite levels were measured in serum of individuals from the D.E.S.I.R. cohort (case-cohort study: 212 diabetic, 836 randomly sampled) and in women with obesity, diabetic or normoglycemic, from the ABOS cohort (n = 100). KP enzyme gene expressions were analyzed in omental and subcutaneous adipose tissue of women from the ABOS cohort, in human primary adipocytes and in monocyte-derived macrophages. In the D.E.S.I.R. cohort, kynurenine levels were positively associated with body mass index (BMI) (P = 4.68 × 10(-19) ) and with a higher HOMA2-IR insulin resistance index (P = 6.23 × 10(-4) ). The levels of kynurenine, kynurenic acid, and quinolinic acid were associated with higher BMI (P KMO], and kynurenine aminotransferase III [CCBL2]) was increased in the omental adipose tissue of women with obesity compared to lean (P KMO that is not expressed in these cells. The expressions of IDO1, KYNU, KMO, and CCBL2 were higher in proinflammatory than in anti-inflammatory macrophages (P KMO activation. © 2015 The Obesity Society.

  3. Through the Interface - a human activity approach to user interfaces

    DEFF Research Database (Denmark)

    Bødker, Susanne

    In providing a theoretical framework for understanding human- computer interaction as well as design of user interfaces, this book combines elements of anthropology, psychology, cognitive science, software engineering, and computer science. The framework examines the everyday work practices of us...

  4. Global Night-Time Lights for Observing Human Activity

    Science.gov (United States)

    Hipskind, Stephen R.; Elvidge, Chris; Gurney, K.; Imhoff, Mark; Bounoua, Lahouari; Sheffner, Edwin; Nemani, Ramakrishna R.; Pettit, Donald R.; Fischer, Marc

    2011-01-01

    We present a concept for a small satellite mission to make systematic, global observations of night-time lights with spatial resolution suitable for discerning the extent, type and density of human settlements. The observations will also allow better understanding of fine scale fossil fuel CO2 emission distribution. The NASA Earth Science Decadal Survey recommends more focus on direct observations of human influence on the Earth system. The most dramatic and compelling observations of human presence on the Earth are the night light observations taken by the Defence Meteorological System Program (DMSP) Operational Linescan System (OLS). Beyond delineating the footprint of human presence, night light data, when assembled and evaluated with complementary data sets, can determine the fine scale spatial distribution of global fossil fuel CO2 emissions. Understanding fossil fuel carbon emissions is critical to understanding the entire carbon cycle, and especially the carbon exchange between terrestrial and oceanic systems.

  5. Erosion of the Mekong delta: the role of human activities

    Science.gov (United States)

    Anthony, E.; Dussouillez, P.; Goichot, M.; Brunier, G.; Dolique, F.; Nguyen, V.; Loisel, H.; Mangin, A.; Vantrepotte, V.

    2013-12-01

    River deltas are threatened by dams, dykes, flow channelling, and aggregate extraction. These activities outweigh climate change and sea-level rise in causing delta vulnerability1, and will aggravate the impacts to be expected from these effects2. We show here from analysis of: (1) delta channel morphology and sediment budgets, and (2) satellite imagery, that the Mekong delta, considered as the world's third largest, and hitherto strongly prograding, is now in a phase of large-scale erosion. We discuss the mechanistic links involved in erosion and the way these are related to human activities. High-resolution (2.5 m) SPOT 5 images for the years 2003, 2007, 2011/12 covering 405 km of the delta shoreline show an overall retreat rate of over 8 m a year. 75% of the analysed shoreline, i.e., the muddy western sector, is now retreating at rates exceeding 50 m a year in places. The sandy river-mouth sector maintains a semblance of stability, but with strong variations. We attribute erosion to a cascade of morphosedimentary changes linked to sediment mining from the deltaic channels and upstream dam interception. We estimated from Meris satellite imagery an annual 5% decrease in surface suspended concentrations exiting at the mouths of the Mekong over the period 2003-2011 that may reflect increased trapping of mud behind dams in China. We also infer modification of river-mouth and coastal mud storage patterns resulting from a loss of ca. 200 million m3 of delta channel sediments between 1998 and 2008 from aggregate extraction. Dykes have been shown to result in increased channel flow velocities during the high-discharge monsoon season, favouring further channel deepening3. Stronger river-mouth outflow velocities during this season may be leading to export of a greater proportion of mud far offshore of the coastal longshore transport corridor that ensured mud supply to, and past progradation of, the muddy western coast. In contrast, greater seawater penetration in the

  6. CD1 and mycobacterial lipids activate human T cells.

    Science.gov (United States)

    Van Rhijn, Ildiko; Moody, D Branch

    2015-03-01

    For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T-cell receptors (TCRs) recognize CD1-lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T-cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal-associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline-encoded mycolyl-reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T-cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Protein S binding to human endothelial cells is required for expression of cofactor activity for activated protein C

    NARCIS (Netherlands)

    Hackeng, T. M.; Hessing, M.; van 't Veer, C.; Meijer-Huizinga, F.; Meijers, J. C.; de Groot, P. G.; van Mourik, J. A.; Bouma, B. N.

    1993-01-01

    An important feedback mechanism in blood coagulation is supplied by the protein C/protein S anticoagulant pathway. In this study we demonstrate that the binding of human protein S to cultured human umbilical vein endothelial cells (HUVECs) is required for the expression of cofactor activity of

  8. The physical activity levels among people living with human ...

    African Journals Online (AJOL)

    J.M. Frantz

    2014-02-13

    Feb 13, 2014 ... activities because they are often not motivated to exercise (Buch- holz & Purath ..... Physical Activity and Hypertension among University .... Endurance and Resistance Exercise on HIV Metabolic Abnormalities: A Pilot. Study.

  9. Antiproliferative activity of recombinant human interferon-λ2 ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... antiviral activity, antiproliferative activity and in vivo antitumor activity .... bovine serum albumin (BSA) and 0.05% (v/v) Tween 20 in PBS at room temperature for 1 h .... identified and developed into an important insect embryo.

  10. Corticospinal contribution to arm muscle activity during human walking

    DEFF Research Database (Denmark)

    Barthélemy, Dorothy; Nielsen, Jens Bo

    2010-01-01

    inhibitory interneurones, the suppression is in all likelihood caused by removal of a corticospinal contribution to the ongoing EMG activity. The data thus suggest that the motor cortex makes an active contribution, through the corticospinal tract, to the ongoing EMG activity in arm muscles during walking....

  11. Predicting human activities in sequences of actions in RGB-D videos

    Science.gov (United States)

    Jardim, David; Nunes, Luís.; Dias, Miguel

    2017-03-01

    In our daily activities we perform prediction or anticipation when interacting with other humans or with objects. Prediction of human activity made by computers has several potential applications: surveillance systems, human computer interfaces, sports video analysis, human-robot-collaboration, games and health-care. We propose a system capable of recognizing and predicting human actions using supervised classifiers trained with automatically labeled data evaluated in our human activity RGB-D dataset (recorded with a Kinect sensor) and using only the position of the main skeleton joints to extract features. Using conditional random fields (CRFs) to model the sequential nature of actions in a sequence has been used before, but where other approaches try to predict an outcome or anticipate ahead in time (seconds), we try to predict what will be the next action of a subject. Our results show an activity prediction accuracy of 89.9% using an automatically labeled dataset.

  12. Setting the scene: Human activities, environmental impacts and governance arrangements in Antarctica

    NARCIS (Netherlands)

    Tin, T.; Lamers, M.A.J.; Liggett, D.; Maher, P.T.; Hughes, K.A.

    2014-01-01

    The scope and intensity of human activity in the Antarctic region has changed considerably over the past 100 years, resulting in significant modifications to the Antarctic environment and its ecosystems, and to the institutional arrangements governing human activities. Since the nineteenth century,

  13. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

    NARCIS (Netherlands)

    Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.

    2015-01-01

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely

  14. Report: EPA Prepared to Implement Strategic Human Capital Management Activities But Challenges Remain

    Science.gov (United States)

    Report #2004-P-00024, September 20, 2004. EPA’s headquarters and regional offices are prepared to implement strategic human capital management activities, but an alignment of office-level activities to the Agency’s Strategy for Human Capital is lacking.

  15. Sitting is the new smoking : online complex human activity recognition with smartphones and wearables

    NARCIS (Netherlands)

    Shoaib, Muhammad

    2017-01-01

    Human activity recognition plays an important role in fitness tracking, health monitoring, context-aware feedback and self-management of smartphones and wearable devices. These devices are equipped with different sensors which can be used to recognize various human activities. A significant amount of

  16. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    NARCIS (Netherlands)

    Self, Matthew W.; Peters, Judith C.; Possel, Jessy K.; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

    2016-01-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive

  17. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    NARCIS (Netherlands)

    Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive

  18. A survey on using domain and contextual knowledge for human activity recognition in video streams

    NARCIS (Netherlands)

    Onofri, L.; Soda, P.; Pechenizkiy, M.; Iannello, G.

    2016-01-01

    Human activity recognition has gained an increasing relevance in computer vision and it can be tackled with either non-hierarchical or hierarchical approaches. The former, also known as single-layered approaches, are those that represent and recognize human activities directly from the extracted

  19. A Pattern Mining Approach to Sensor-based Human Activity Recognition

    DEFF Research Database (Denmark)

    Gu, Tao; Wang, Liang; Wu, Zhanqing

    2011-01-01

    Recognizing human activities from sensor readings has recently attracted much research interest in pervasive computing due to its potential in many applications such as assistive living and healthcare. This task is particularly challenging because human activities are often performed in not only...

  20. [The importance of physical activity and fitness for human health].

    Science.gov (United States)

    Brandes, M

    2012-01-01

    The decline of physical activity is considered to play an important role in the deterioration of health predictors, such as overweight, and the associated increase of cardiovascular and all-cause mortality. Therefore, most interventional strategies aim for increasing physical activity. Instead of physical activity, some studies use physical fitness as a key variable. Though physical fitness is influenced by genetic factors, physical fitness has to be developed by physical activity. As recent reports demonstrate the prospective associations between physical fitness and health and mortality, these associations are not reported for physical activity. Due to the fact that physical fitness-in contrast to physical activity-is evaluated with standardized laboratory measurements, it appears advisable to assess physical fitness for prospective health perspectives. Although physical fitness is determined by genetics, physical activity is the primary modifiable determinant for increasing physical fitness and should be aimed for to improve physical fitness in interventional strategies.

  1. Purified human somatomedin A and rat multiplication stimulating activity

    Energy Technology Data Exchange (ETDEWEB)

    Rechler, M M; Fryklund, L; Nissley, S P; Hall, K; Podskalny, J M; Skottner, A; Moses, A C [National Institutes of Health, Bethesda, Md. (USA); Kabi AB, Stockholm [Sweden; National Inst. of Arthritis, Metabolism and Digestive Diseases, Bethesda, Md. (USA). Diabetes Branch)

    1978-01-01

    Specific receptors for MSA and/or somatomedin A could be demonstrated in intact cells or membranes from chick embryo fibroblasts, human fibroblasts, human placenta, rat liver, and the BRL 3A2 cell line, a subclone of the line that produces MSA. Unlabeled MSA and somatomedin A inhibited the binding of /sup 125/I-labeled MSA and /sup 125/I-labeled somatomedin A to each of these receptors with comparable potency. In chick embryo fibroblasts, human fibroblasts, and human placental membranes, the binding of both radioactive ligands also was inhibited by insulin, consistent with the interpretation that /sup 125/I-labeled MSA and /sup 125/I-labeled somatomedin A were binding to the same receptor. By contrast, in the BRL 3A2 cell line, insulin inhibited the binding of /sup 125/I-labeled somatomedin A, but not the binding of /sup 125/I-labeled MSA, suggesting that the two labeled peptides were binding to different receptors in this cell line. Moreover, /sup 125/I-labeled MSA, but not /sup 125/I-labeled somatomedin A, bound specifically to rat liver plasma membranes. These results indicate that human somatomedin A and rat MSA are closely related, but not identical, peptides.

  2. The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

    OpenAIRE

    Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.

    2013-01-01

    The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find...

  3. Guinea pig complement potently measures vibriocidal activity of human antibodies in response to cholera vaccines.

    Science.gov (United States)

    Kim, Kyoung Whun; Jeong, Soyoung; Ahn, Ki Bum; Yang, Jae Seung; Yun, Cheol-Heui; Han, Seung Hyun

    2017-12-01

    The vibriocidal assay using guinea pig complement is widely used for the evaluation of immune responses to cholera vaccines in human clinical trials. However, it is unclear why guinea pig complement has been used over human complement in the measurement of vibriocidal activity of human sera and there have not been comparison studies for the use of guinea pig complement over those from other species. Therefore, we comparatively investigated the effects of complements derived from human, guinea pig, rabbit, and sheep on vibriocidal activity. Complements from guinea pig, rabbit, and human showed concentration-dependent vibriocidal activity in the presence of quality control serum antibodies. Of these complements, guinea pig complement was the most sensitive and effective over a wide concentration range. When the vibriocidal activity of complements was measured in the absence of serum antibodies, human, sheep, and guinea pig complements showed vibriocidal activity up to 40-fold, 20-fold, and 1-fold dilution, respectively. For human pre- and post-vaccination sera, the most potent vibriocidal activity was observed when guinea pig complement was used. In addition, the highest fold-increases between pre- and post- vaccinated sera were obtained with guinea pig complement. Furthermore, human complement contained a higher amount of V. cholerae- and its lipopolysaccharide-specific antibodies than guinea pig complement. Collectively, these results suggest that guinea pig complements are suitable for vibriocidal assays due to their high sensitivity and effectiveness to human sera.

  4. FCJ-195 Privacy, Responsibility, and Human Rights Activism

    Directory of Open Access Journals (Sweden)

    Becky Kazansky

    2015-06-01

    Full Text Available In this article, we argue that many difficulties associated with the protection of digital privacy are rooted in the framing of privacy as a predominantly individual responsibility. We examine how models of privacy protection, such as Notice and Choice, contribute to the ‘responsibilisation’ of human rights activists who rely on the use of technologies for their work. We also consider how a group of human rights activists countered technology-mediated threats that this ‘responsibilisation’ causes by developing a collective approach to address their digital privacy and security needs. We conclude this article by discussing how technological tools used to maintain or counter the loss of privacy can be improved in order to support the privacy and digital security of human rights activists.

  5. Endogenous pyrogen activity in human plasma after exercise.

    Science.gov (United States)

    Cannon, J G; Kluger, M J

    1983-05-06

    Plasma obtained from human subjects after exercise and injected intraperitoneally into rats elevated rat rectal temperature and depressed plasma iron and zinc concentrations. The pyrogenic component was heat-denaturable and had an apparent molecular weight of 14,000 daltons. Human mononuclear leukocytes obtained after exercise and incubated in vitro released a factor into the medium that also elevated body temperature in rats and reduced trace metal concentrations. These results suggest that endogenous pyrogen, a protein mediator of fever and trace metal metabolism during infection, is released during exercise.

  6. Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

    Science.gov (United States)

    Watanabe, Takahiro; Kawamura, Tatsuyoshi; Jacob, Sharon E; Aquilino, Elisabeth A; Orenstein, Jan M; Black, Jodi B; Blauvelt, Andrew

    2002-10-01

    Pityriasis rosea is a common skin disease that has been suspected to have a viral etiology. We performed nested polymerase chain reaction to detect human herpesvirus-7, human herpesvirus-6, and cytomegalovirus DNA in lesional skin, nonlesional skin, peripheral blood mononuclear cells, serum, and saliva samples isolated from 14 pityriasis rosea patients. Viral mRNA expression and virion visualization within lesional skin were studied by in situ hybridization and transmission electron microscopy, respectively. By nested polymerase chain reaction, human herpesvirus-7 DNA was present in lesional skin (93%), nonlesional skin (86%), saliva (100%), peripheral blood mononuclear cells (83%), and serum (100%) samples, whereas human herpesvirus-6 DNA was detected in lesional skin (86%), nonlesional skin (79%), saliva (80%), peripheral blood mononuclear cells (83%), and serum (88%) samples. By contrast, cytomegalovirus DNA was not detected in these tissues. Control samples from 12 healthy volunteers and 10 psoriasis patients demonstrated rare positivity for either human herpesvirus-7 or human herpesvirus-6 DNA in skin or serum. By in situ hybridization, infiltrating mononuclear cells expressing human herpesvirus-7 and human herpesvirus-6 mRNA were identified in perivascular and periappendageal areas in 100% and 75% pityriasis rosea skin lesions, respectively, compared to herpesviral mRNA positivity in only 13% normal skin and psoriasis skin controls. Transmission electron microscopy failed to reveal herpesviral virions in pityriasis rosea lesional skin. Nested polymerase chain reaction and in situ hybridization enabled detection of human herpesvirus-7 and human herpesvirus-6 in skin and other tissues isolated from patients with pityriasis rosea. These results suggest that pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

  7. Activation of human immunodeficiency virus by ultraviolet radiation

    International Nuclear Information System (INIS)

    Zmudzka, B.Z.; Beer, J.Z.

    1990-01-01

    This article reviews the current status of knowledge about UV-induced HIV activation. A brief description of HIV structure and, in particular, its gene promoter is given. The effects of UVR exposure of cells on HIV activation and HIV promoter induction will be reviewed. Some events that follow production of DNA damage and lead, via activation of an oncogene, to HIV promoter induction will be discussed. Possible consequences of promoter induction and HIV activation for the cell and the virus are mentioned. The review concludes with a discussion of practical aspects and perspectives in this research area. (author)

  8. Influence of human activity patterns on epidemiology of plague in ...

    African Journals Online (AJOL)

    Human plague has been a recurring public health threat in some villages in the Western Usambara Mountains, Tanzania, in the period between 1980 and 2004. Despite intensive past biological and medical research, the reasons for the plague outbreaks in the same set of villages remain unknown. Plague research needs ...

  9. Human ADAM 12 (meltrin alpha) is an active metalloprotease

    DEFF Research Database (Denmark)

    Loechel, F; Gilpin, B J; Engvall, E

    1998-01-01

    The ADAMs (a disintegrin and metalloprotease) are a family of multidomain proteins with structural homology to snake venom metalloproteases. We recently described the cloning and sequencing of human ADAM 12 (meltrin alpha). In this report we provide evidence that the metalloprotease domain of ADAM...

  10. Biodiversity and human activities in the Udzungwa Mountain forests ...

    African Journals Online (AJOL)

    It was established that local communities around the forest highly depend on the natural forests for forest products. Most human uses were for traditional medicine, fuelwood and building materials. Quality hardwoods Khaya anthotheca, Afzelia quanzensis, Milicia excelsa and Ocotea usambarensis were noted. To reduce ...

  11. A novel framework for intelligent surveillance system based on abnormal human activity detection in academic environments.

    Science.gov (United States)

    Al-Nawashi, Malek; Al-Hazaimeh, Obaida M; Saraee, Mohamad

    2017-01-01

    Abnormal activity detection plays a crucial role in surveillance applications, and a surveillance system that can perform robustly in an academic environment has become an urgent need. In this paper, we propose a novel framework for an automatic real-time video-based surveillance system which can simultaneously perform the tracking, semantic scene learning, and abnormality detection in an academic environment. To develop our system, we have divided the work into three phases: preprocessing phase, abnormal human activity detection phase, and content-based image retrieval phase. For motion object detection, we used the temporal-differencing algorithm and then located the motions region using the Gaussian function. Furthermore, the shape model based on OMEGA equation was used as a filter for the detected objects (i.e., human and non-human). For object activities analysis, we evaluated and analyzed the human activities of the detected objects. We classified the human activities into two groups: normal activities and abnormal activities based on the support vector machine. The machine then provides an automatic warning in case of abnormal human activities. It also embeds a method to retrieve the detected object from the database for object recognition and identification using content-based image retrieval. Finally, a software-based simulation using MATLAB was performed and the results of the conducted experiments showed an excellent surveillance system that can simultaneously perform the tracking, semantic scene learning, and abnormality detection in an academic environment with no human intervention.

  12. Human Activity Differentially Redistributes Large Mammals in the Canadian Rockies National Parks

    Directory of Open Access Journals (Sweden)

    James Kimo. Rogala

    2011-09-01

    Full Text Available National parks are important for conservation of species such as wolves (Canis lupus and elk (Cervus canadensis. However, topography, vegetation conditions, and anthropogenic infrastructure within parks may limit available habitat. Human activity on trails and roads may lead to indirect habitat loss, further limiting available habitat. Predators and prey may respond differentially to human activity, potentially disrupting ecological processes. However, research on such impacts to wildlife is incomplete, especially at fine spatial and temporal scales. Our research investigated the relationship between wolf and elk distribution and human activity using fine-scale Global Positioning System (GPS wildlife telemetry locations and hourly human activity measures on trails and roads in Banff, Kootenay, and Yoho National Parks, Canada. We observed a complex interaction between the distance animals were located from trails and human activity level resulting in species adopting both mutual avoidance and differential response behaviors. In areas < 50 m from trails human activity led to a mutual avoidance response by both wolves and elk. In areas 50 - 400 m from trails low levels of human activity led to differential responses; wolves avoided these areas, whereas elk appeared to use these areas as a predation refugia. These differential impacts on elk and wolves may have important implications for trophic dynamics. As human activity increased above two people/hour, areas 50 - 400 m from trails were mutually avoided by both species, resulting in the indirect loss of important montane habitat. If park managers are concerned with human impacts on wolves and elk, or on these species' trophic interactions with other species, they can monitor locations near trails and roads and consider hourly changes of human activity levels in areas important to wildlife.

  13. Anticancer activities of bovine and human lactoferricin-derived peptides

    NARCIS (Netherlands)

    Arias, M.; Hilchie, A.L.; Haney, E.F.; Bolscher, J.G.M.; Hyndman, M.E.; Hancock, R.E.W.; Vogel, H.J.

    2017-01-01

    Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits

  14. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activities of new curcumin analogs as carbonic anhydrase II (CA-II) inhibitor. Methods: Carbonic anhydrase II (CA-II) inhibition was determined by each ligand capability to inhibit the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used to dissolve each ...

  15. Human Spaceflight: Activities for the Intermediate and Junior High Student.

    Science.gov (United States)

    Hartsfield, John W.; Hartsfield, Kendra J.

    Since its beginning, space science has created high interest and continues to prod the imagination of students. This activity packet, which has been designed to enhance the curriculum and challenge gifted students, contains background information on spaceflight as well as 24 interdisciplinary classroom activities, 3 crossword puzzles, and 3 word…

  16. Spatiotemporal Data Mining, Analysis, and Visualization of Human Activity Data

    Science.gov (United States)

    Li, Xun

    2012-01-01

    This dissertation addresses the research challenge of developing efficient new methods for discovering useful patterns and knowledge in large volumes of electronically collected spatiotemporal activity data. I propose to analyze three types of such spatiotemporal activity data in a methodological framework that integrates spatial analysis, data…

  17. Optimizing human activity patterns using global sensitivity analysis.

    Science.gov (United States)

    Fairchild, Geoffrey; Hickmann, Kyle S; Mniszewski, Susan M; Del Valle, Sara Y; Hyman, James M

    2014-12-01

    Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule's regularity for a population. We show how to tune an activity's regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.

  18. Human dignity and the future of the voluntary active euthanasia ...

    African Journals Online (AJOL)

    The issue of voluntary active euthanasia was thrust into the public policy arena by the Stransham-Ford lawsuit. The High Court legalised voluntary active euthanasia – however, ostensibly only in the specific case of Mr Stransham-Ford. The Supreme Court of Appeal overturned the High Court judgment on technical grounds, ...

  19. Activated T lymphocytes disappear from circulation during endotoxemia in humans

    DEFF Research Database (Denmark)

    Suarez Krabbe, Karen; Kemp, Helle Bruunsgaard; Qvist, Jesper

    2002-01-01

    of disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)). In conclusion, endotoxin-induced lymphopenia reflects the disappearance from the circulation of activated lymphocytes prone to undergo apoptosis....

  20. Similarity of hydrolyzing activity of human and rat small intestinal disaccharidases

    Directory of Open Access Journals (Sweden)

    Oku T

    2011-06-01

    Full Text Available Tsuneyuki Oku¹, Kenichi Tanabe¹, Shigeharu Ogawa², Naoki Sadamori¹, Sadako Nakamura¹¹Graduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; ²Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured disaccharidase activity in humans and rats using identical preparation and assay methods, and investigated the similarity in hydrolyzing activity. Small intestinal samples without malignancy were donated by five patients who had undergone bladder tumor surgery, and homogenates were prepared to measure disaccharidase activity. Adult rat homogenates were prepared using small intestine.Results: Maltase activity was the highest among the five disaccharidases, followed by sucrase and then palatinase in humans and rats. Trehalase activity was slightly lower than that of palatinase in humans and was similar to that of sucrase in rats. Lactase activity was the lowest in humans, but was similar to that of palatinase in rats. Thus, the hydrolyzing activity of five disaccharidases was generally similar in humans and rats. The relative activity of sucrose and palatinase versus maltase was generally similar between humans and rats. The ratio of rat to human hydrolyzing activity of maltase, sucrase, and palatinase was 1.9–3.1, but this was not a significant difference. Leaf extract from Morus alba strongly inhibited the activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and the degree of inhibition was similar in humans and rats. L-arabinose mildly inhibited sucrase activity, but hardly inhibited the activity of maltase, palatinase, trehalase and lactase in humans and rats. The digestibility of 1-kestose, galactosylsucrose, and panose by small intestinal enzymes was very similar between humans and

  1. Structural and Affinity Determinants in the Interaction between Alcohol Acyltransferase from F. x ananassa and Several Alcohol Substrates: A Computational Study.

    Directory of Open Access Journals (Sweden)

    Carlos Navarro-Retamal

    Full Text Available Aroma and flavor are important factors of fruit quality and consumer preference. The specific pattern of aroma is generated during ripening by the accumulation of volatiles compounds, which are mainly esters. Alcohol acyltransferase (AAT (EC 2.3.1.84 catalyzes the esterification reaction of aliphatic and aromatic alcohols and acyl-CoA into esters in fruits and flowers. In Fragaria x ananassa, there are different volatiles compounds that are obtained from different alcohol precursors, where octanol and hexanol are the most abundant during fruit ripening. At present, there is not structural evidence about the mechanism used by the AAT to synthesize esters. Experimental data attribute the kinetic role of this enzyme to 2 amino acidic residues in a highly conserved motif (HXXXD that is located in the middle of the protein. With the aim to understand the molecular and energetic aspects of volatiles compound production from F. x ananassa, we first studied the binding modes of a series of alcohols, and also different acyl-CoA substrates, in a molecular model of alcohol acyltransferase from Fragaria x ananassa (SAAT using molecular docking. Afterwards, the dynamical behavior of both substrates, docked within the SAAT binding site, was studied using routine molecular dynamics (MD simulations. In addition, in order to correlate the experimental and theoretical data obtained in our laboratories, binding free energy calculations were performed; which previous results suggested that octanol, followed by hexanol, presented the best affinity for SAAT. Finally, and concerning the SAAT molecular reaction mechanism, it is suggested from molecular dynamics simulations that the reaction mechanism may proceed through the formation of a ternary complex, in where the Histidine residue at the HXXXD motif deprotonates the alcohol substrates. Then, a nucleophilic attack occurs from alcohol charged oxygen atom to the carbon atom at carbonyl group of the acyl CoA. This

  2. Current status and issues of nuclear human resource development/General activities of Japan nuclear human resource development network

    International Nuclear Information System (INIS)

    Murakami, Hiroyuki; Hino, Sadami; Tsuru, Hisanori

    2013-01-01

    The Japan Nuclear Human Resource Development Network (JN-HRD Net) was established in November 2010 with the aim of developing a framework for mutual cooperation and information sharing among nuclear-related organizations. Although the tasks and goals of developing human resources in the nuclear field have been shifted since the accident at the Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Plant, the necessity of fostering capable personnel in this field stays unchanged and the importance of our network activities has further emphasized. The meeting of JN-HRD Net was held on the 5th of February 2013, where its activities by each field were reported and views and opinions were actively exchanged between more than 90 participants. This paper briefly describes current status and issues of JN-HRD Net and its general activities conducted by the JN-HRD Net secretariat. (J.P.N.)

  3. Managing the Activities Against Trafficking in Human Beings

    OpenAIRE

    Ion GANE

    2012-01-01

    Organized crime has a long history and has permanently adapted to the weaknesses of the legal system, procedures and operational capabilities of the national Law Enforcement Agencies. Economic discomfort appears to be the main reason for illegal migration movement throughout the world. Due to unemployment, many human beings become victims of trafficking- prostitution and slavery. Nevertheless, many of the willing migrants undertake the hazardous travel to their destination country with crimin...

  4. The physical activity levels among people living with human ...

    African Journals Online (AJOL)

    J.M. Frantz

    2014-02-13

    Feb 13, 2014 ... Furthermore, the presence of obesity, dietary imbalances and sedentary ... activities/exercises in people living with HIV/AIDS while being treated with ..... Smoking in Dyslipidaemia in HIV-Infected Patients with Lipodystrophy.

  5. Antibacterial activity of mangrove leaf extracts against human pathogens

    Digital Repository Service at National Institute of Oceanography (India)

    Sahoo, G.; Mulla, N.S.S.; Ansari, Z.A.; Mohandass, C.

    ., Salmonella typhi, Proteus vulgaris and Proteus mirabilis. As compared to aqueous, ethanol extract showed broad-spectrum activity. The multidrug-resistant (MDR) bacteria Salmonella typhi was inhibited by the ethanol extract of S. alba leaf whereas the other...

  6. Genetic Analysis of Daily Activity in Humans and Mice

    National Research Council Canada - National Science Library

    Takahashi, Joseph

    1999-01-01

    .... We have characterized variation in five circadian phenotypes: free-running circadian period, phase angle of entrainment, amplitude of the circadian rhythm, circadian activity level, and dissociation of rhythmicity...

  7. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT...

  8. Collaborative Human Engineering Work in Space Exploration Extravehicular Activities (EVA)

    Science.gov (United States)

    DeSantis, Lena; Whitmore, Mihriban

    2007-01-01

    A viewgraph presentation on extravehicular activities in space exploration in collaboration with other NASA centers, industries, and universities is shown. The topics include: 1) Concept of Operations for Future EVA activities; 2) Desert Research and Technology Studies (RATS); 3) Advanced EVA Walkback Test; 4) Walkback Subjective Results; 5) Integrated Suit Test 1; 6) Portable Life Support Subsystem (PLSS); 7) Flex PLSS Design Process; and 8) EVA Information System; 9)

  9. Brain Mapping of Ghrelin O-Acyltransferase in Goldfish (Carassius Auratus): Novel Roles for the Ghrelinergic System in Fish?

    Science.gov (United States)

    Blanco, Ayelén M; Sánchez-Bretaño, Aída; Delgado, María J; Valenciano, Ana I

    2016-06-01

    Ghrelin O-acyltransferase (GOAT) is the enzyme responsible for acylation of ghrelin, a gut-brain hormone with important roles in many physiological functions in vertebrates. Many aspects of GOAT remain to be elucidated, especially in fish, and particularly its anatomical distribution within the different brain areas has never been reported to date. The present study aimed to characterize the brain mapping of GOAT using RT-qPCR and immunohistochemistry in a teleost, the goldfish (Carassius auratus). Results show that goat transcripts are expressed in different brain areas of the goldfish, with the highest levels in the vagal lobe. Using immunohistochemistry, we also report the presence of GOAT immunoreactive cells in different encephalic areas, including the telencephalon, some hypothalamic nuclei, pineal gland, optic tectum and cerebellum, although they are especially abundant in the hindbrain. Particularly, an important signal is observed in the vagal lobe and some fiber tracts of the brainstem, such as the medial longitudinal fasciculus, Mauthneri fasciculus, secondary gustatory tract and spinothalamic tract. Most of the forebrain areas where GOAT is detected, particularly the hypothalamic nuclei, also express the ghs-r1a ghrelin receptor and other appetite-regulating hormones (e.g., orexin and NPY), supporting the role of ghrelin as a modulator of food intake and energy balance in fish. Present results are the first report on the presence of GOAT in the brain using imaging techniques. The high presence of GOAT in the hindbrain is a novelty, and point to possible new functions for the ghrelinergic system in fish. Anat Rec, 299:748-758, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Defining the extreme substrate specificity of Euonymus alatus diacylglycerol acetyltransferase, an unusual membrane-bound O-acyltransferase

    Science.gov (United States)

    Bansal, Sunil; Durrett, Timothy P.

    2016-01-01

    Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) synthesizes the unusually structured 3-acetyl-1,2-diacylglycerols (acetyl-TAG) found in the seeds of a few plant species. A member of the membrane-bound O-acyltransferase (MBOAT) family, EaDAcT transfers the acetyl group from acetyl-CoA to sn-1,2-diacylglycerol (DAG) to produce acetyl-TAG. In vitro assays demonstrated that the enzyme is also able to utilize butyryl-CoA and hexanoyl-CoA as acyl donors, though with much less efficiency compared with acetyl-CoA. Acyl-CoAs longer than eight carbons were not used by EaDAcT. This extreme substrate specificity of EaDAcT distinguishes it from all other MBOATs which typically catalyze the transfer of much longer acyl groups. In vitro selectivity experiments revealed that EaDAcT preferentially acetylated DAG molecules containing more double bonds over those with less. However, the enzyme was also able to acetylate saturated DAG containing medium chain fatty acids, albeit with less efficiency. Interestingly, EaDAcT could only acetylate the free hydroxyl group of sn-1,2-DAG but not the available hydroxyl groups in sn-1,3-DAG or in monoacylglycerols (MAG). Consistent with its similarity to the jojoba wax synthase, EaDAcT could acetylate fatty alcohols in vitro to produce alkyl acetates. Likewise, when coexpressed in yeast with a fatty acyl-CoA reductase capable of producing fatty alcohols, EaDAcT synthesized alkyl acetates although the efficiency of production was low. This improved understanding of EaDAcT specificity confirms that the enzyme preferentially utilizes acetyl-CoA to acetylate sn-1,2-DAGs and will be helpful in engineering the production of acetyl-TAG with improved functionality in transgenic plants. PMID:27688773

  11. Altered lipid composition and enhanced lipid production in green microalga by introduction of brassica diacylglycerol acyltransferase 2.

    Science.gov (United States)

    Ahmad, Irshad; Sharma, Anil K; Daniell, Henry; Kumar, Shashi

    2015-05-01

    Higher lipid biosynthesis and accumulation are important to achieve economic viability of biofuel production via microalgae. To enhance lipid content, Chlamydomonas reinhardtii was genetically engineered with a key enzyme diacylglycerol acyltransferase (BnDGAT2) from Brassica napus, responsible for neutral lipid biosynthesis. The transformed colonies harbouring aph7 gene, screened on hygromycin-supplemented medium, achieved transformation frequency of ~120 ± 10 colonies/1 × 10(6) cells. Transgene integration and expression were confirmed by PCR, Southern blots, staining lipid droplets, proteins and spectro-fluorometric analysis of Nile red-stained cells. The neutral lipid is a major class (over 80% of total lipids) and most significant requirement for biodiesel production; this was remarkably higher in the transformed alga than the untransformed control. The levels of saturated fatty acids in the transformed alga decreased to about 7% while unsaturated fatty acids increased proportionately when compared to wild type cells. Polyunsaturated fatty acids, especially α-linolenic acid, an essential omega-3 fatty acid, were enhanced up to 12% in the transformed line. Nile red staining confirmed formation of a large number of lipid globules in the transformed alga. Evaluation of long-term stability and vitality of the transgenic alga revealed that cryopreservation produced significantly higher quantity of lipid than those maintained continuously over 128 generations on solid medium. The overexpression of BnDGAT2 significantly altered the fatty acids profile in the transformed alga. Results of this study offer a valuable strategy of genetic manipulation for enhancing polyunsaturated fatty acids and neutral lipids for biofuel production in algae. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  12. Characterization of Trichome-Expressed BAHD Acyltransferases in Petunia axillaris Reveals Distinct Acylsugar Assembly Mechanisms within the Solanaceae1[OPEN

    Science.gov (United States)

    Uebler, Joseph B.; Liu, Xiaoxiao

    2017-01-01

    Acylsugars are synthesized in the glandular trichomes of the Solanaceae family and are implicated in protection against abiotic and biotic stress. Acylsugars are composed of either sucrose or glucose esterified with varying numbers of acyl chains of differing length. In tomato (Solanum lycopersicum), acylsugar assembly requires four acylsugar acyltransferases (ASATs) of the BAHD superfamily. Tomato ASATs catalyze the sequential esterification of acyl-coenzyme A thioesters to the R4, R3, R3ʹ, and R2 positions of sucrose, yielding a tetra-acylsucrose. Petunia spp. synthesize acylsugars that are structurally distinct from those of tomato. To explore the mechanisms underlying this chemical diversity, a Petunia axillaris transcriptome was mined for trichome preferentially expressed BAHDs. A combination of phylogenetic analyses, gene silencing, and biochemical analyses coupled with structural elucidation of metabolites revealed that acylsugar assembly is not conserved between tomato and petunia. In P. axillaris, tetra-acylsucrose assembly occurs through the action of four ASATs, which catalyze sequential addition of acyl groups to the R2, R4, R3, and R6 positions. Notably, in P. axillaris, PaxASAT1 and PaxASAT4 catalyze the acylation of the R2 and R6 positions of sucrose, respectively, and no clear orthologs exist in tomato. Similarly, petunia acylsugars lack an acyl group at the R3ʹ position, and congruently, an ortholog of SlASAT3, which catalyzes acylation at the R3ʹ position in tomato, is absent in P. axillaris. Furthermore, where putative orthologous relationships of ASATs are predicted between tomato and petunia, these are not supported by biochemical assays. Overall, these data demonstrate the considerable evolutionary plasticity of acylsugar biosynthesis. PMID:28701351

  13. Characterization of Trichome-Expressed BAHD Acyltransferases in Petunia axillaris Reveals Distinct Acylsugar Assembly Mechanisms within the Solanaceae.

    Science.gov (United States)

    Nadakuduti, Satya Swathi; Uebler, Joseph B; Liu, Xiaoxiao; Jones, A Daniel; Barry, Cornelius S

    2017-09-01

    Acylsugars are synthesized in the glandular trichomes of the Solanaceae family and are implicated in protection against abiotic and biotic stress. Acylsugars are composed of either sucrose or glucose esterified with varying numbers of acyl chains of differing length. In tomato ( Solanum lycopersicum ), acylsugar assembly requires four acylsugar acyltransferases (ASATs) of the BAHD superfamily. Tomato ASATs catalyze the sequential esterification of acyl-coenzyme A thioesters to the R4, R3, R3', and R2 positions of sucrose, yielding a tetra-acylsucrose. Petunia spp. synthesize acylsugars that are structurally distinct from those of tomato. To explore the mechanisms underlying this chemical diversity, a Petunia axillaris transcriptome was mined for trichome preferentially expressed BAHDs. A combination of phylogenetic analyses, gene silencing, and biochemical analyses coupled with structural elucidation of metabolites revealed that acylsugar assembly is not conserved between tomato and petunia. In P. axillaris , tetra-acylsucrose assembly occurs through the action of four ASATs, which catalyze sequential addition of acyl groups to the R2, R4, R3, and R6 positions. Notably, in P. axillaris , PaxASAT1 and PaxASAT4 catalyze the acylation of the R2 and R6 positions of sucrose, respectively, and no clear orthologs exist in tomato. Similarly, petunia acylsugars lack an acyl group at the R3' position, and congruently, an ortholog of SlASAT3, which catalyzes acylation at the R3' position in tomato, is absent in P. axillaris Furthermore, where putative orthologous relationships of ASATs are predicted between tomato and petunia, these are not supported by biochemical assays. Overall, these data demonstrate the considerable evolutionary plasticity of acylsugar biosynthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

  14. Determination of Sr90 activity in human bones

    International Nuclear Information System (INIS)

    Mendonca, Anamelia Habib

    1970-01-01

    Several studies have been published in the literature on the extent and levels of radioactive contamination of food chains caused by fallout from nuclear weapon tests. According to UNSCEAR, these studies cover a great number of:-areas of the developed world, though large, areas of Asia, Africa and South-America are left aside with only, unsatisfactory information about the levels, of radioactive contamination. In 1968, UNSCEAR recommended that a survey on the contamination of biological materials such as human - bone by fission products and particularly Sr 90 should be encouraged on those areas where only fragmentary information was available. UNSCEAR recommendations call upon the fact that many individuals on such areas of the world have been exposed to Sr 90 contamination from birth to their adult area. Therefore, that group have an Sr 90 skeletal burden very much different from people exposed only at adult age. Based on these considerations, UNSCEAR recommendations called for Sr 90 analysis on human bones from different age groups. In Brazil, studies on the of Sr 90 in human bone are practically non-existent, except for the year of 1959. Following UNSCEAR recommendations, we decided to perform such a survey on Sr 90 levels in human bones. Samples were collected from individuals that died in Rio de Janeiro from accidents. These samples were firstly classified according to social level in very poor and poor groups. Samples were then classified in three age groups ranging 0-18, 18-30 and 30-40 years of age. Results show that levels found in the Brazilian age groups are close to the ones observed in Chile (1969), Argentina and Australia (1966-1968) and slightly, higher than -those observed in Venezuela, Senegal and Jamaica (1969). If one compares the results obtained for the North and South hemispheres respectively, one sees that there was a more pronounced decrease in the levels of Sr 90 content of the of some regions of South America. Our results show no

  15. Contributions of climate change and human activities to runoff change in seven typical catchments across China.

    Science.gov (United States)

    Zhai, Ran; Tao, Fulu

    2017-12-15

    Climate change and human activities are two major factors affecting water resource change. It is important to understand the roles of the major factors in affecting runoff change in different basins for watershed management. Here, we investigated the trends in climate and runoff in seven typical catchments in seven basins across China from 1961 to 2014. Then we attributed the runoff change to climate change and human activities in each catchment and in three time periods (1980s, 1990s and 2000s), using the VIC model and long-term runoff observation data. During 1961-2014, temperature increased significantly, while the trends in precipitation were insignificant in most of the catchments and inconsistent among the catchments. The runoff in most of the catchments showed a decreasing trend except the Yingluoxia catchment in the northwestern China. The contributions of climate change and human activities to runoff change varied in different catchments and time periods. In the 1980s, climate change contributed more to runoff change than human activities, which was 84%, 59%, -66%, -50%, 59%, 94%, and -59% in the Nianzishan, Yingluoxia, Xiahui, Yangjiaping, Sanjiangkou, Xixian, and Changle catchment, respectively. After that, human activities had played a more essential role in runoff change. In the 1990s and 2000s, human activities contributed more to runoff change than in the 1980s. The contribution by human activities accounted for 84%, -68%, and 67% in the Yingluoxia, Xiahui, and Sanjiangkou catchment, respectively, in the 1990s; and -96%, -67%, -94%, and -142% in the Nianzishan, Yangjiaping, Xixian, and Changle catchment, respectively, in the 2000s. It is also noted that after 2000 human activities caused decrease in runoff in all catchments except the Yingluoxia. Our findings highlight that the effects of human activities, such as increase in water withdrawal, land use/cover change, operation of dams and reservoirs, should be well managed. Copyright © 2017 Elsevier

  16. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2009-11-20

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  17. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    International Nuclear Information System (INIS)

    Tachibana, Keisuke; Takeuchi, Kentaro; Inada, Hirohiko; Yamasaki, Daisuke; Ishimoto, Kenji; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Doi, Takefumi

    2009-01-01

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial β-oxidation. The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that plays an important role in the regulation of β-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPARα and found that PPARα induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPARα regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  18. Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Mervi Alanne-Kinnunen

    Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

  19. Human Activity-Understanding: A Multilayer Approach Combining Body Movements and Contextual Descriptors Analysis

    Directory of Open Access Journals (Sweden)

    Consuelo Granata

    2015-07-01

    Full Text Available A deep understanding of human activity is key to successful human-robot interaction (HRI. The translation of sensed human behavioural signals/cues and context descriptors into an encoded human activity remains a challenge because of the complex nature of human actions. In this paper, we propose a multilayer framework for the understanding of human activity to be implemented in a mobile robot. It consists of a perception layer which exploits a D-RGB-based skeleton tracking output used to simulate a physical model of virtual human dynamics in order to compensate for the inaccuracy and inconsistency of the raw data. A multi-support vector machine (MSVM model trained with features describing the human motor coordination through temporal segments in combination with environment descriptors (object affordance is used to recognize each sub-activity (classification layer. The interpretation of sequences of classified elementary actions is based on discrete hidden Markov models (DHMMs (interpretation layer. The framework assessment was performed on the Cornell Activity Dataset (CAD-120 [1]. The performances of our method are comparable with those presented in [2] and clearly show the relevance of this model-based approach.

  20. Micrurus snake venoms activate human complement system and generate anaphylatoxins

    Directory of Open Access Journals (Sweden)

    Tanaka Gabriela D

    2012-01-01

    Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

  1. COURAGE AND FEAR IN THE CONTEXT OF OPPOSITION OF HUMAN ACTIVITY AND INACTIVITY: EXISTENTIAL ASPECT

    Directory of Open Access Journals (Sweden)

    Dmytro Yu. Snitko

    2013-12-01

    Full Text Available The purpose of the article is to analyse fear and courage in the history of philosophy in the context of opposi-tion of human activity and inactivity that may lead to a profound understanding of the essence, causes and existen-tial aspects of human activity and inactivity. The implementation of the objective assumes the solution of the follow-ing tasks: analysis of philosophical interpretation of fear and courage; investigation of the relationship of fear and courage with active and passive forms of human being; revelation of existential dialectic of human activity and inac-tivity through the opposition of fear and courage. Methodology. The application of phenomenological approach and other methods of existential philosophy enabled to discover the importance of fear and courage for human existence. Significant contribution to the importance of the investigation of the fear-courage opposition in the context of hu-man activity and inactivity was made by M. Heidegger who pointed to the main modes of human being - «authen-tic» and «inauthentic» in the context of human activity and passivity. The application of hermeneutic method made possible the reconstruction of the reflection of fear-courage opposition in the history of philosophy. Scientific nov-elty. For the first time the analysis of the fear-courage opposition in the context of human activity and inactivity was carried out. Due to the analysis the fundamental existential character of the fear and courage opposition and its es-sential relationship with active and passive forms of human being were justified. Conclusions. In the course of this research it was found out that fear is closely connected with passive modes of human being. If classical philosophy placed emphasis on courage and associated fear with human mind and conscious decision, non-classical philosophy of the XIX century and existentialism focused on existential and ontological character of fear, its fundamental mean

  2. COURAGE AND FEAR IN THE CONTEXT OF OPPOSITION OF HUMAN ACTIVITY AND INACTIVITY: EXISTENTIAL ASPECT

    Directory of Open Access Journals (Sweden)

    Dmytro Yu. Snitko

    2013-12-01

    Full Text Available The purpose of the article is to analyse fear and courage in the history of philosophy in the context of opposition of human activity and inactivity that may lead to a profound understanding of the essence, causes and existential aspects of human activity and inactivity. The implementation of the objective assumes the solution of the following tasks: analysis of philosophical interpretation of  fear and courage; investigation of the relationship of fear and courage with active and passive forms of human being; revelation of existential dialectic of human activity and inactivity through the opposition of  fear and courage. Methodology. The application of phenomenological approach and other methods of existential philosophy enabled to discover the importance of fear and courage for human existence. Significant contribution to the importance of the investigation of the fear-courage opposition in the context of human activity and inactivity was made by M. Heidegger who pointed to the main modes of human being - «authentic» and «inauthentic» in the context of human activity and passivity. The application of hermeneutic method made possible the reconstruction of the reflection of fear-courage opposition in the history of philosophy. Scientific novelty. For the first time the analysis of the  fear-courage opposition in the context of human activity and inactivity was carried out. Due to the analysis the  fundamental existential character of the fear and courage opposition and its essential relationship with active and passive forms of human being were justified. Conclusions. In the course of this research it was found out that fear is closely connected with passive modes of human being.  If classical philosophy placed emphasis on courage and associated fear with  human mind and conscious decision,  non-classical philosophy of the XIX century and existentialism focused on existential and ontological character of fear, its fundamental meaning

  3. Immunomodulatory activity of interleukin-27 in human chronic periapical diseases.

    Science.gov (United States)

    Li, Juan; Wang, Rong; Huang, Shi-Guang

    2017-01-01

    This study aims to observe expression of IL-27 on different cells in periapical tissues of different types of human chronic periapical diseases. Periapical tissue specimens of 60 donors, including healthy control (n=20), periapical granuloma group (n=20) and radicular cysts group (n=20), were fixed in 10% buffered formalin, stained with hematoxylin and eosin for histopathology. Then specimens were stained with double- immuno-fluorescence assay for identification of IL-27-tryptase (mast cells, MCs), IL-27-CD14 (mononuclear phagocyte cells, MPs) and IL-27-CD31 (endothelial cells, ECs) double-positive cells in periapical tissues. The results indicated that compared with healthy control, the densities (cells/mm 2 ) of IL-27-tryptase, IL-27-CD14 and IL-27-CD31 double-positive cells were significantly increased in human chronic periapical diseases (periapical granuloma group and radicular cysts group) ( P cysts group was significantly higher than those in periapical granuloma group ( P periapical granuloma group had no significant difference with those in radicular cysts group ( P =0.170 and 0.138, respectively). IL-27-CD14 double positive cells density achieved to peak among three cell groups in radicular cysts groups. In conclusion, IL-27 expressed in MCs, MPs and ECs of human chronic periapical diseases with different degrees. IL-27-tryptase double-positive cells may participate in pathogenic mechanism of chronic periapical diseases, especially for formation of fibrous in periapical cysts. IL-27-CD14 and IL-27-CD31 double-positive cells may participate in immunologic response to resist periapical infection, and they may play an dual role in pathogenesis and localization of periapical diseases.

  4. The Role of Consciousness in Human Cognitive Activity

    Directory of Open Access Journals (Sweden)

    Victor M. Allakhverdov

    2009-01-01

    Full Text Available The problem of consciousness is examined in the article. It is argued that all the existing approaches to consciousness do not explain the role consciousness plays in human life. An attempt of revealing and describing the principles of the mind’s work is made. Experimental phenomena observed by the author and his followers, particularly, the tendency of previously non-realized ideas not to be realized subsequently, are reviewed. The discussion of these phenomena allows to formulate a novel view on the nature of consciousness.

  5. A Smart DNA Tweezer for Detection of Human Telomerase Activity.

    Science.gov (United States)

    Xu, Xiaowen; Wang, Lei; Li, Kan; Huang, Qihong; Jiang, Wei

    2018-03-06

    Reliable and accurate detection of telomerase activity is crucial to better understand its role in cancer cells and to further explore its function in cancer diagnosis and treatment. Here, we construct a smart DNA tweezer (DT) for detection of telomerase activity. The DT is assembled by three specially designed single-stranded oligonucleotides: a central strand dually labeled with donor/acceptor fluorophores and two arm strands containing overhangs complementary to telomerase reaction products (TRPs). It can get closed through hybridization with TRPs and get reopen through strand displacement reaction by TRPs' complementary sequences. First, under the action of telomerase, telomerase binding substrates (TS) are elongated to generate TRPs ended with telomeric repeats (TTAGGG) n . TRPs hybridize with the two arm overhangs cooperatively and strain DT to closed state, inducing an increased fluorescence resonance energy transfer (FRET) efficiency, which is utilized for telomerase activity detection. Second, upon introduction of a removal strand (RS) complementary to TRPs, the closed DT is relaxed to open state via the toehold-mediated strand displacement, inducing a decreased FRET efficiency, which is utilized for determination of TRP length distribution. The detection limit of telomerase activity is equivalent to 141 cells/μL for HeLa cells, and telomerase-active cellular extracts can be differentiated from telomerase-inactive cellular extracts. Furthermore, TRPs owning 1, 2, 3, 4, and ≥5 telomeric repeats are identified to account for 25.6%, 20.5%, 15.7%, 12.5%, and 25.7%, respectively. The proposed strategy will offer a new approach for reliable, accurate detection of telomerase activity and product length distribution for deeper studying its role and function in cancer.

  6. Antiviral activity of maca (Lepidium meyenii) against human influenza virus

    OpenAIRE

    Del Valle Mendoza, Juana; Pumarola, Tomas; Alzamora Gonzales, Libertad; Valle Mendoza, Luis Javier del

    2014-01-01

    Objective To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Methods Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic ...

  7. Invasin of Yersinia pseudotuberculosis activates human peripheral B cells.

    OpenAIRE

    Lundgren, E; Carballeira, N; Vazquez, R; Dubinina, E; Bränden, H; Persson, H; Wolf-Watz, H

    1996-01-01

    The Yersinia pseudotuberculosis cell surface-located protein invasin was found to promote binding between the pathogen and resting peripheral B cells via beta 1 integrin receptors (CD29). B cells responded by expressing several activation markers and by growing, In contrast, T cells did not react, although these cells express CD29. An isogenic invA mutant failed to activate B cells. The mutation could be complemented by providing the invA+ gene in trans. Purified invasin alone did not activat...

  8. Differential effects of human activity on Hawaiian spinner dolphins in their resting bays

    Directory of Open Access Journals (Sweden)

    Heather L. Heenehan

    2017-04-01

    Full Text Available Hawaiian spinner dolphins display predictable daily behavior, using shallow bays to rest during the daytime, bays that are also frequented by humans. All previous research on the potential response of Hawaiian spinner dolphins to human activity has been conducted visually, at the surface. In this study we take a different approach by using passive acoustic monitoring to analyze dolphin behavior and assess whether human activity affects the behavior of the animals. We used days (n=99 and hours (n=641 when dolphins were confirmed present in visual surveys between January 9, 2011 and August 15, 2012 and metrics generated from concomitant 30-second sound recordings (n=9615. Previous research found that the dolphins were predictably silent during rest and that acoustic activity matched general activity of the dolphins with higher acoustic activity before and after rest, and silence during rest. The daily pattern of dolphin whistle activity in Bay 2 and 4 (Kealakekua and Kauhako matched what would be expected from this earlier work. However, in Bay 1 and 3 (Makako and Honaunau there was no drop in dolphin whistle activity during rest. After assessing the relationship between time of day and dolphin acoustic activity, data on human presence were used to determine how variability in the dolphins’ acoustic activity might be explained by human activity (i.e. the number of vessels, kayaks and swimmer snorkelers present. Bay 2, the bay with the most human activity, showed no relationship between dolphin whistle activity and human presence (either vessels, kayaks, or swimmer/snorkelers. Although the relationships were weak, Bay 1 displayed a positive relationship between dolphin whistle activity and the number of vessels and swimmer/snorkelers present in the bay. Bay 4 also showed a positive relationship between dolphin whistle activity and the number of swimmer snorkelers. We also documented less sound being added to the soundscape with each additional

  9. Human dignity and the future of the voluntary active euthanasia debate in South Africa.

    Science.gov (United States)

    Jordaan, Donrich W

    2017-04-25

    The issue of voluntary active euthanasia was thrust into the public policy arena by the Stransham-Ford lawsuit. The High Court legalised voluntary active euthanasia - however, ostensibly only in the specific case of Mr Stransham-Ford. The Supreme Court of Appeal overturned the High Court judgment on technical grounds, not on the merits. This means that in future the courts can be approached again to consider the legalisation of voluntary active euthanasia. As such, Stransham-Ford presents a learning opportunity for both sides of the legalisation divide. In particular, conceptual errors pertaining to human dignity were made in Stransham-Ford, and can be avoided in future. In this article, I identify these errors and propose the following three corrective principles to inform future debate on the subject: (i) human dignity is violable; (ii) human suffering violates human dignity; and (iii) the 'natural' causes of suffering due to terminal illness do not exclude the application of human dignity.

  10. Biodiversity assessment of high rain forest under human activities: a ...

    African Journals Online (AJOL)

    Most of these species are under protection of International Union for Conservation of Natural Resources [Vulnerable, Endangered, Threatened species]. It is however concluded that all form of developmental operation activity at the Erinle forest have affected these conservation important species, and also transformed the ...

  11. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used ... intensive search for novel drugs is ongoing, through synthesis of new ..... License (http://creativecommons.org/licenses/by/. 4.0) and the ...