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Sample records for human arylamine n-acetyltransferase

  1. From arylamine N-acetyltransferase to folate-dependent acetyl CoA hydrolase: impact of folic acid on the activity of (HUMAN)NAT1 and its homologue (MOUSE)NAT2.

    Science.gov (United States)

    Laurieri, Nicola; Dairou, Julien; Egleton, James E; Stanley, Lesley A; Russell, Angela J; Dupret, Jean-Marie; Sim, Edith; Rodrigues-Lima, Fernando

    2014-01-01

    Acetyl Coenzyme A-dependent N-, O- and N,O-acetylation of aromatic amines and hydrazines by arylamine N-acetyltransferases is well characterised. Here, we describe experiments demonstrating that human arylamine N-acetyltransferase Type 1 and its murine homologue (Type 2) can also catalyse the direct hydrolysis of acetyl Coenzyme A in the presence of folate. This folate-dependent activity is exclusive to these two isoforms; no acetyl Coenzyme A hydrolysis was found when murine arylamine N-acetyltransferase Type 1 or recombinant bacterial arylamine N-acetyltransferases were incubated with folate. Proton nuclear magnetic resonance spectroscopy allowed chemical modifications occurring during the catalytic reaction to be analysed in real time, revealing that the disappearance of acetyl CH3 from acetyl Coenzyme A occurred concomitantly with the appearance of a CH3 peak corresponding to that of free acetate and suggesting that folate is not acetylated during the reaction. We propose that folate is a cofactor for this reaction and suggest it as an endogenous function of this widespread enzyme. Furthermore, in silico docking of folate within the active site of human arylamine N-acetyltransferase Type 1 suggests that folate may bind at the enzyme's active site, and facilitate acetyl Coenzyme A hydrolysis. The evidence presented in this paper adds to our growing understanding of the endogenous roles of human arylamine N-acetyltransferase Type 1 and its mouse homologue and expands the catalytic repertoire of these enzymes, demonstrating that they are by no means just xenobiotic metabolising enzymes but probably also play an important role in cellular metabolism. These data, together with the characterisation of a naphthoquinone inhibitor of folate-dependent acetyl Coenzyme A hydrolysis by human arylamine N-acetyltransferase Type 1/murine arylamine N-acetyltransferase Type 2, open up a range of future avenues of exploration, both for elucidating the developmental role of these

  2. Insights into the O-Acetylation Reaction of Hydroxylated Heterocyclic Amines by Human Arylamine N-Acetyltransferases: A Computational Study

    Energy Technology Data Exchange (ETDEWEB)

    Lau, E Y; Felton, J S; Lightstone, F C

    2006-06-06

    A computational study was performed to better understand the differences between human arylamine N-acetyltransferase (NAT) 1 and 2. Homology models were constructed from available crystal structures and comparisons of the active site residues 125, 127, and 129 for these two enzymes provide insight into observed substrate differences. The NAT2 model provided a basis for understanding how some of the common mutations may affect the structure of the protein. Molecular dynamics simulations of the human NAT models and the template structure (NAT from Mycobacterium smegmatis) were performed and showed the models to be stable and reasonable. Docking studies of hydroxylated heterocyclic amines in the models of NAT1 and NAT2 probed the differences exhibited by these two proteins with mutagenic agents. The hydroxylated heterocyclic amines were only able to fit into the NAT2 active site, and an alternative binding site by the P-loop was found using our models and will be discussed. Additionally, quantum mechanical calculations were performed to study the O-acetylation reaction of the hydroxylated heterocyclic amines N-OH MeIQx and N-OH PhIP. This study has given us insight into why there are substrate differences among isoenzymes and explains some of the polymorphic activity differences.

  3. Effects of human arylamine N-acetyltransferase I knockdown in triple-negative breast cancer cell lines.

    Science.gov (United States)

    Tiang, Jacky M; Butcher, Neville J; Minchin, Rodney F

    2015-04-01

    Expression of human arylamine N-acetyltransferase I (NAT1) has been associated with various cancer subtypes and inhibition of this enzyme with small molecule inhibitors or siRNA affects cell growth and survival. Here, we have investigated the role of NAT1 in the invasiveness of breast cancer cells both in vitro and in vivo. We knocked down NAT1 using a lentivirus-based shRNA approach and observed marked changes in cell morphology in the triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-436, and BT-549. Most notable was a reduction in the number and size of the filopodia protrusions on the surface of the cells. The loss of filopodia could be rescued by the reintroduction of NAT1 into the knockdown cells. NAT1 expression was localized to the lamellipodia and extended into the filopodia protrusions. In vitro invasion through Geltrex was significantly inhibited in both the MDA cell lines but not in the BT-549 cells. The expression of Snail increased when NAT1 was knocked down, while other genes associated with mesenchymal to epithelial transition (vimentin, cytokeratin-18, and Twist) did not show any changes. By contrast, both N-cadherin and β-catenin were significantly reduced. When MDA-MB-231 cells expressing shRNA were injected in vivo into BALB/c nu/nu nude mice, a significant reduction in the number of colonies that formed in the lungs was observed. Taken together, the results show that NAT1 can alter the invasion and metastatic properties of some triple-negative breast cancer cells but not all. The study suggests that NAT1 may be a novel therapeutic target in a subset of breast cancers.

  4. Evidence for arylamine N-acetyltransferase in Hymenolepis nana.

    Science.gov (United States)

    Chung, J G; Kuo, H M; Wu, L T; Lai, J M; Lee, J H; Hung, C F

    1997-02-01

    N-acetyltransferase activities with p-aminobenzoic acid and 2-aminofluorene were determined in Hymenolepis nana, a cestode found in the intestine of the Sprague-Dawley rats. The N-acetyltransferase activity was determined using an acetyl CoA recycling assay and high pressure liquid chromatography. The N-acetyltransferase activities from a number of Hymenolepis nana whole tissue homogenizations were found to be 2.83 +/- 0.31 nmole/min/mg for 2-aminofluorene and 2.07 +/- 0.24 nmole/min/mg for p-aminobenzoic acid. The apparent Km and Vmax were 1.06 +/- 0.38 mM and 8.92 +/- 1.46 nmol/min/mg for 2-aminofluorene, and 2.16 +/- 0.19 mM and 12.68 +/- 2.26 nmol/min/mg for p-aminobenzoic acid. The optimal pH value for the enzyme activity was pH 8.0 for both substrates tested. The optimal temperature for enzyme activity was 37 degrees C for both substrates. The N-acetyltransferase activity was inhibited by iodacetamide. At 0.25 mM iodacetamide the activity was reduced 50% and 1.0 mM iodacetamide inhibited activity more than 90%. Among a series of divalent cations and salts, Fe2+, Ca2+ and Zn2+ were demonstrated to be the most potent inhibi-tors. Among the protease inhibitors, only ethylenediaminetetraacetic acid significantly protected N-acetyltransferase. Iodoacetate, in contrast to other agents, markedly inhibited N-acetyltransferase activity. This is the first demonstration of acetyl CoA:arylamine N-acetyltransferase activity in a cestode and extends the number of phyla in which this activity has been found.

  5. Polymorphisms in the Human Cytochrome P450 and Arylamine N-Acetyltransferase: Susceptibility to Head and Neck Cancers

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    Rim Khlifi

    2013-01-01

    Full Text Available The occurrence of head and neck cancer (HNC is associated with smoking and alcohol drinking. Tobacco smoking exposes smokers to a series of carcinogenic chemicals. Cytochrome P450 enzymes (CYP450s, such as CYP1A1, CYP1B1, and CYP2D6, usually metabolize carcinogens to their inactive derivatives, but they occasionally convert the chemicals to more potent carcinogens. In addition, via CYP450 (CYP2E1 oxidase, alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Furthermore, two N-acetyltransferase isozymes (NATs, NAT1 and NAT2, are polymorphic and catalyze both N-acetylation and O-acetylation of aromatic and heterocyclic amine carcinogens. Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of HNC. It has been suggested that such polymorphisms may be linked to cancer susceptibility. In this paper, we select four cytochrome P450 enzymes (CYP1A1, CYP1BA1, CYP2D6, and CYP2E1, and two N-acetyltransferase isozymes (NAT1 and NAT2 in order to summarize and analyze findings from the literature related to HNC risk by focusing on (i the interaction between these genes and the environment, (ii the impact of genetic defect on protein activity and/or expression, and (iii the eventual involvement of race in such associations.

  6. Insights into the phylogeny or arylamine N-acetyltransferases in fungi.

    Science.gov (United States)

    Martins, Marta; Dairou, Julien; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Silar, Philippe

    2010-08-01

    Previous studies have shown that Eumycetes fungi can acylate arylamine thanks to arylamine N-acetyltransferases, xenobiotic-metabolizing enzymes also found in animals and bacteria. In this article, we present the results of mining 96 available fungal genome sequences for arylamine N-acetyltransferase genes and propose their phylogeny. The filamentous Pezizomycotina are shown to possess many putative N-acetyltransferases, whilst these are often lacking in other fungal groups. The evolution of the N-acetyltransferases is best explained by the presence of at least one gene in the opisthokont ancestor of the fungi and animal kingdoms, followed by recurrent gene losses and gene duplications. A possible horizontal gene transfer event may have occurred from bacteria to the basidiomycetous yeast Malassezia globosa.

  7. Kinetic characterisation of arylamine N-acetyltransferase from Pseudomonas aeruginosa

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    Sim Edith

    2007-03-01

    Full Text Available Abstract Background Arylamine N-acetyltransferases (NATs are important drug- and carcinogen-metabolising enzymes that catalyse the transfer of an acetyl group from a donor, such as acetyl coenzyme A, to an aromatic or heterocyclic amine, hydrazine, hydrazide or N-hydroxylamine acceptor substrate. NATs are found in eukaryotes and prokaryotes, and they may also have an endogenous function in addition to drug metabolism. For example, NAT from Mycobacterium tuberculosis has been proposed to have a role in cell wall lipid biosynthesis, and is therefore of interest as a potential drug target. To date there have been no studies investigating the kinetic mechanism of a bacterial NAT enzyme. Results We have determined that NAT from Pseudomonas aeruginosa, which has been described as a model for NAT from M. tuberculosis, follows a Ping Pong Bi Bi kinetic mechanism. We also describe substrate inhibition by 5-aminosalicylic acid, in which the substrate binds both to the free form of the enzyme and the acetyl coenzyme A-enzyme complex in non-productive reaction pathways. The true kinetic parameters for the NAT-catalysed acetylation of 5-aminosalicylic acid with acetyl coenzyme A as the co-factor have been established, validating earlier approximations. Conclusion This is the first reported study investigating the kinetic mechanism of a bacterial NAT enzyme. Additionally, the methods used herein can be applied to investigations of the interactions of NAT enzymes with new chemical entities which are NAT ligands. This is likely to be useful in the design of novel potential anti-tubercular agents.

  8. Acrolein, an α,β-unsaturated aldehyde, irreversibly inhibits the acetylation of aromatic amine xenobiotics by human arylamine N-acetyltransferase 1.

    Science.gov (United States)

    Bui, Linh C; Manaa, Amine; Xu, Ximing; Duval, Romain; Busi, Florent; Dupret, Jean-Marie; Rodrigues-Lima, Fernando; Dairou, Julien

    2013-07-01

    Acrolein is an electrophilic α,β-unsaturated aldehyde of industrial, pharmaceutic, and toxicologic importance to which we are exposed in environmental, occupational, and therapeutic situations. Acrolein is known to exert different biologic effects through reactions with cellular macromolecules such as DNA, certain proteins, or glutathione. In many situations (such as in tobacco smoke or other fumes), exposure to acrolein occurs concomitantly with other compounds such as aromatic amine chemicals. Interestingly, it has been shown that acrolein could impact the cellular metabolism of aromatic xenobiotics through an indirect mechanism based on the transcriptional induction of phase II xenobiotic-metabolizing enzymes. Here we report a novel mechanism by which acrolein acts on the metabolism of aromatic foreign chemicals. We provide molecular, kinetic, and cellular evidence that acrolein can react directly and irreversibly with arylamine N-acetyltransferases, a major family of xenobiotic-metabolizing enzymes involved in the metabolization of aromatic amine chemicals. Formation of an acrolein adduct with a catalytic cysteine residue in the active site is responsible for the impairment of aromatic amine acetylation by the enzyme. This biochemical process may represent an additional mechanism by which acrolein impacts the metabolism and fate of aromatic amine drugs and pollutants.

  9. From arylamine N-acetyltransferase to folate-dependent acetyl CoA hydrolase: impact of folic acid on the activity of (HUMANNAT1 and its homologue (MOUSENAT2.

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    Nicola Laurieri

    Full Text Available Acetyl Coenzyme A-dependent N-, O- and N,O-acetylation of aromatic amines and hydrazines by arylamine N-acetyltransferases is well characterised. Here, we describe experiments demonstrating that human arylamine N-acetyltransferase Type 1 and its murine homologue (Type 2 can also catalyse the direct hydrolysis of acetyl Coenzyme A in the presence of folate. This folate-dependent activity is exclusive to these two isoforms; no acetyl Coenzyme A hydrolysis was found when murine arylamine N-acetyltransferase Type 1 or recombinant bacterial arylamine N-acetyltransferases were incubated with folate. Proton nuclear magnetic resonance spectroscopy allowed chemical modifications occurring during the catalytic reaction to be analysed in real time, revealing that the disappearance of acetyl CH3 from acetyl Coenzyme A occurred concomitantly with the appearance of a CH3 peak corresponding to that of free acetate and suggesting that folate is not acetylated during the reaction. We propose that folate is a cofactor for this reaction and suggest it as an endogenous function of this widespread enzyme. Furthermore, in silico docking of folate within the active site of human arylamine N-acetyltransferase Type 1 suggests that folate may bind at the enzyme's active site, and facilitate acetyl Coenzyme A hydrolysis. The evidence presented in this paper adds to our growing understanding of the endogenous roles of human arylamine N-acetyltransferase Type 1 and its mouse homologue and expands the catalytic repertoire of these enzymes, demonstrating that they are by no means just xenobiotic metabolising enzymes but probably also play an important role in cellular metabolism. These data, together with the characterisation of a naphthoquinone inhibitor of folate-dependent acetyl Coenzyme A hydrolysis by human arylamine N-acetyltransferase Type 1/murine arylamine N-acetyltransferase Type 2, open up a range of future avenues of exploration, both for elucidating the

  10. Inflammatory cytokines suppress arylamine N-acetyltransferase 1 in cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the effect of inflammatory cytokines on arylamine N-acetyltransferase 1 (NAT1), which is a phase-Ⅱ enzyme involved in the biotransformation of aromatic and heterocyclic amines found in food, drugs and the environment.METHODS: Human cholangiocarcinoma KKU-100 cells were treated with a mixture of proinflammatory cytokines (interferon-y, interleukin-1β and tumor necrosis factor-α)for 48 h, and the effect on NAT1 activity was assessed by high performance liquid chromatography, while NAT1 expression was determined by reverse-transcription polymerase chain reaction. The oxidative stress on the cells was examined by the formation of nitric oxide,superoxide anion and glutathione (GSH) levels. The cells were also treated with S-nitroso-glutathione (GSNO), a nitric oxide donor, to see if the responses were similar to those obtained with the inflammatory cytokines.RESULTS: Cytokines suppressed NAT1 activity,reducing the Vmax without affecting the Km. Cytokines also had a significant impact on the induction of nitric oxide production and in reducing the redox ratios of glutathione (GSH) and GSH disulfide. Treatment with GSNO for 2-48 h reduced NAT1 activity without affecting the GSH ratio. Moreover, inflammatory cytokines and GSNO suppressed NAT1 mRNA expression.CONCLUSION: These findings indicate an association between inflammation and suppression of NAT1, which perhaps contributes to chemical-mediated toxicity and carcinogenesis.

  11. Polymorphisms of arylamine N-acetyltransferase2 and risk of lung and colorectal cancer

    OpenAIRE

    Amjad Mahasneh; Amal Jubaili; Ahmed El Bateiha; Mohammad Al-Ghazo; Ismail Matalka; Mousa Malkawi

    2012-01-01

    The arylamine N-acetyltransferase 2 (NAT2) enzymes detoxify a wide range of naturally occurring xenobiotics including carcinogens and drugs. Point mutations in the NAT2 gene result in the variant alleles M1 (NAT2 *5A), M2 (NAT2*6A), M3 (NAT2*7) and M4 (NAT2 *14A) from the wild-type WT (NAT2 *4) allele. The current study was aimed at screening genetic polymorphisms of NAT2 gene in 49 lung cancer patients, 54 colorectal cancer patients and 99 cancer-free controls, using PCR-RFLP. There were sig...

  12. Density Functional Theory Study on the Histidine-assisted Mechanism of Arylamine N-Acetyltransferase Acetylation

    Institute of Scientific and Technical Information of China (English)

    QIAO Qing-An; GAO Shan-Min; JIN Yue-Qing; CHEN Xin; SUN Xiao-Min; YANG Chuan-Lu

    2008-01-01

    Arylamine N-acetyltransferases (NATs, EC 2.3.1.5) catalyze the N-acetylation of primary arylamines, and play a key role in the biotransformation and metabolism of drugs, carcinogens, etc.In this paper, three possible reaction mechanisms are investigated and the results indicate that if the acetyl group directly transfers from the donor to the acceptor, the high activation energies will make it hard to obtain the target products.When using histidine to mediate the acetylation process, these energies will drop in the 15~45 kJ/mol range.If the histidine residue is protonated, the corresponding energies will be decreased by about 35~87 kJ/mol.The calculations predict an enzymatic acetylation mechanism that undergoes a thiolate-imidazolium pair, which agrees with the experimental results very well.

  13. Arylamine N-acetyltransferase 2 (NAT2 genetic diversity and traditional subsistence: a worldwide population survey.

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    Audrey Sabbagh

    Full Text Available Arylamine N-acetyltransferase 2 (NAT2 is involved in human physiological responses to a variety of xenobiotic compounds, including common therapeutic drugs and exogenous chemicals present in the diet and the environment. Many questions remain about the evolutionary mechanisms that have led to the high prevalence of slow acetylators in the human species. Evidence from recent surveys of NAT2 gene variation suggests that NAT2 slow-causing variants might have become targets of positive selection as a consequence of the shift in modes of subsistence and lifestyle in human populations in the last 10,000 years. We aimed to test more extensively the hypothesis that slow acetylation prevalence in humans is related to the subsistence strategy adopted by the past populations. To this end, published frequency data on the most relevant genetic variants of NAT2 were collected from 128 population samples (14,679 individuals representing different subsistence modes and dietary habits, allowing a thorough analysis at both a worldwide and continent scale. A significantly higher prevalence of the slow acetylation phenotype was observed in populations practicing farming (45.4% and herding (48.2% as compared to populations mostly relying on hunting and gathering (22.4% (P = 0.0007. This was closely mirrored by the frequency of the slow 590A variant that was found to occur at a three-fold higher frequency in food producers (25% as compared to hunter-gatherers (8%. These findings are consistent with the hypothesis that the Neolithic transition to subsistence economies based on agricultural and pastoral resources modified the selective regime affecting the NAT2 acetylation pathway. Furthermore, the vast amount of data collected enabled us to provide a comprehensive and up-to-date description of NAT2 worldwide genetic diversity, thus building up a useful resource of frequency data for further studies interested in epidemiological or anthropological research

  14. Some properties of acetyl-CoA:arylamine N-acetyltransferase (EC 2. 3. 1. 5) from rat pineal gland

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    Morton, D.J. (Department of Pharmacy, University of Zimbabwe, Harare, Zimbabwe)

    N-acetylation of serotonin to N-acetylserotonin in the pineal gland is catalysed by acetyl-CoA:arylamine N-acetyltransferase (SNAT). The present investigation was an attempt to design an assay technique which would permit sensitive evaluation of SNAT in order to evaluate some kinetic properties of the enzyme.

  15. Arylamine N-acetyltransferases--from drug metabolism and pharmacogenetics to identification of novel targets for pharmacological intervention.

    Science.gov (United States)

    Sim, Edith; Fakis, Giannoulis; Laurieri, Nicola; Boukouvala, Sotiria

    2012-01-01

    Arylamine N-acetyltransferases (NATs) are defined as xenobiotic metabolizing enzymes, adding an acetyl group from acetyl coenzyme A (CoA) to arylamines and arylhydrazines. NATs are found in organisms from bacteria and fungi to vertebrates. Several isoenzymes, often polymorphic, may be present in one organism. There are two functional polymorphic NATs in humans and polymorphisms in NAT2 underpinned pharmacogenetics as a discipline. NAT enzymes have had a role in important metabolic concepts: the identification of acetyl-CoA and endogenous metabolic roles in bacteria and in eukaryotic folate metabolism. In fungi, NAT is linked to formation of unique metabolites. A broad and exciting canvas of investigations has emerged over the past five years from fundamental studies on NAT enzymes. The role of human NAT1 in breast cancer where it is a biomarker and possible therapeutic target may also underlie NAT's early appearance during mammalian fetal development. Studies of NAT in Mycobacterium tuberculosis have identified potential therapeutic targets for tuberculosis whilst the role of NATs in fungi opens up potential toxicological intervention in agriculture. These developments are possible through the combination of genomics, enzymology and structural data. Strong binding of CoA to Bacillis anthracis NAT may point to divergent roles of NATs amongst organisms as does differential control of mammalian NAT gene expression. The powerful combination of phenotypic investigation following genetic manipulation of NAT genes from mice to mycobacteria has been coupled with generation of isoenzyme-specific inhibitors. This battery of molecular and systems biology approaches heralds a new era for NAT research in pharmacology and toxicology. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Polymorphisms of arylamine N-acetyltransferase2 and risk of lung and colorectal cancer.

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    Mahasneh, Amjad; Jubaili, Amal; El Bateiha, Ahmed; Al-Ghazo, Mohammad; Matalka, Ismail; Malkawi, Mousa

    2012-12-01

    The arylamine N-acetyltransferase 2 (NAT2) enzymes detoxify a wide range of naturally occurring xenobiotics including carcinogens and drugs. Point mutations in the NAT2 gene result in the variant alleles M1 (NAT2 *5A), M2 (NAT2*6A), M3 (NAT2*7) and M4 (NAT2 *14A) from the wild-type WT (NAT2 *4) allele. The current study was aimed at screening genetic polymorphisms of NAT2 gene in 49 lung cancer patients, 54 colorectal cancer patients and 99 cancer-free controls, using PCR-RFLP. There were significant differences in allele frequencies between lung cancer patients and controls in the WT, M2 and M3 alleles (p < 0.05). However, only M2 and M3 allele frequencies were different between colorectal cancer patients and controls (p < 0.05). There was a marginal significant difference in the distribution of rapid and slow acetylator genotypes between lung cancer patients and controls (p = 0.06 and p = 0.05, respectively), but not between colorectal cancer patients and controls (p = 1.0 and p = 0.95, respectively). Risk of lung cancer development was found to be lower in slow acetylators [odds ratio (OR): 0.51, 95% confidence interval (95% CI): 0.25, 1.02, p-value = 0.07]. No effect was observed in case of colorectal cancer. Our results showed that NAT2 genotypes and phenotypes might be involved in lung cancer but not colorectal cancer susceptibility in Jordan.

  17. Polymorphisms of arylamine N-acetyltransferase2 and risk of lung and colorectal cancer

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    Amjad Mahasneh

    2012-01-01

    Full Text Available The arylamine N-acetyltransferase 2 (NAT2 enzymes detoxify a wide range of naturally occurring xenobiotics including carcinogens and drugs. Point mutations in the NAT2 gene result in the variant alleles M1 (NAT2 *5A, M2 (NAT2*6A, M3 (NAT2*7 and M4 (NAT2 *14A from the wild-type WT (NAT2 *4 allele. The current study was aimed at screening genetic polymorphisms of NAT2 gene in 49 lung cancer patients, 54 colorectal cancer patients and 99 cancer-free controls, using PCR-RFLP. There were significant differences in allele frequencies between lung cancer patients and controls in the WT, M2 and M3 alleles (p < 0.05. However, only M2 and M3 allele frequencies were different between colorectal cancer patients and controls (p < 0.05. There was a marginal significant difference in the distribution of rapid and slow acetylator genotypes between lung cancer patients and controls (p = 0.06 and p = 0.05, respectively, but not between colorectal cancer patients and controls (p = 1.0 and p = 0.95, respectively. Risk of lung cancer development was found to be lower in slow acetylators [odds ratio (OR: 0.51, 95% confidence interval (95% CI: 0.25, 1.02, p-value = 0.07]. No effect was observed in case of colorectal cancer. Our results showed that NAT2 genotypes and phenotypes might be involved in lung cancer but not colorectal cancer susceptibility in Jordan.

  18. The Bacillus anthracis arylamine N-acetyltransferase ((BACAN)NAT1) that inactivates sulfamethoxazole, reveals unusual structural features compared with the other NAT isoenzymes

    DEFF Research Database (Denmark)

    Pluvinage, Benjamin; Li de la Sierra-Gallay, Inés; Kubiak, Xavier Jean Philippe

    2011-01-01

    Arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that biotransform arylamine drugs. The Bacillus anthracis (BACAN)NAT1 enzyme affords increased resistance to the antibiotic sulfamethoxazole through its acetylation. We report the structure of (BACAN)NAT1. Unexpectedly...... marked differences in the mode of binding and location of coenzymeA when compared to the other NATs. This suggests that the mechanisms of cofactor recognition by NATs is more diverse than expected and supports the cofactor-binding site as being a unique subsite to target in drug design against bacterial...

  19. Urinary acetylated metabolites and N-acetyltransferase-2 genotype in human subjects treated with a para-phenylenediamine-containing oxidative hair dye

    NARCIS (Netherlands)

    Nohynek, G.J.; Skare, J.A.; Meuling, W.J.A.; Hein, D.W.; Bie, A.T.H.J. de; Toutain, H.

    2004-01-01

    In the organism of mammals, important detoxification pathways of arylamines are catalysed by N-acetyltransferase 2 (NAT2). A recent case-control epidemiology study suggested that human NAT2 slow acetylators exposed to oxidative hair dyes may be at greater risk to develop bladder cancer. We therefore

  20. Urinary acetylated metabolites and N-acetyltransferase-2 genotype in human subjects treated with a para-phenylenediamine-containing oxidative hair dye

    NARCIS (Netherlands)

    Nohynek, G.J.; Skare, J.A.; Meuling, W.J.A.; Hein, D.W.; Bie, A.T.H.J. de; Toutain, H.

    2004-01-01

    In the organism of mammals, important detoxification pathways of arylamines are catalysed by N-acetyltransferase 2 (NAT2). A recent case-control epidemiology study suggested that human NAT2 slow acetylators exposed to oxidative hair dyes may be at greater risk to develop bladder cancer. We therefore

  1. Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in cryopreserved human hepatocytes.

    Science.gov (United States)

    Doll, Mark A; Hein, David W

    2017-07-01

    Genetic polymorphisms in human N-acetyltransferase 2 (NAT2) modify the metabolism of numerous drugs and carcinogens. These genetic polymorphisms modify both drug efficacy and toxicity and cancer risk associated with carcinogen exposure. Previous studies have suggested phenotypic heterogeneity among different NAT2 slow acetylator genotypes. NAT2 phenotype was investigated in vitro and in situ in samples of human hepatocytes obtained from various NAT2 slow and intermediate NAT2 acetylator genotypes. NAT2 gene dose response (NAT2*5B/*5B > NAT2*5B/*6A > NAT2*6A/*6A) was observed towards the N-acetylation of the NAT2-specific drug sulfamethazine by human hepatocytes both in vitro and in situ. N-acetylation of 4-aminobiphenyl, an arylamine carcinogen substrate for both N-acetyltransferase 1 and NAT2, showed the same trend both in vitro and in situ although the differences were not significant (p > 0.05). The N-acetylation of the N-acetyltransferase 1-specific substrate p-aminobenzoic acid did not follow this trend. In comparisons of NAT2 intermediate acetylator genotypes, differences in N-acetylation between NAT2*4/*5B and NAT2*4/*6B hepatocytes were not observed in vitro or in situ towards any of these substrates. These results further support phenotypic heterogeneity among NAT2 slow acetylator genotypes, consistent with differential risks of drug failure or toxicity and cancer associated with carcinogen exposure.

  2. The Bacillus anthracis arylamine N-acetyltransferase ((BACAN)NAT1) that inactivates sulfamethoxazole, reveals unusual structural features compared with the other NAT isoenzymes.

    Science.gov (United States)

    Pluvinage, Benjamin; Li de la Sierra-Gallay, Inés; Kubiak, Xavier; Xu, Ximing; Dairou, Julien; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2011-12-15

    Arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that biotransform arylamine drugs. The Bacillus anthracis (BACAN)NAT1 enzyme affords increased resistance to the antibiotic sulfamethoxazole through its acetylation. We report the structure of (BACAN)NAT1. Unexpectedly, endogenous coenzymeA was present in the active site. The structure suggests that, contrary to the other prokaryotic NATs, (BACAN)NAT1 possesses a 14-residue insertion equivalent to the "mammalian insertion", a structural feature considered unique to mammalian NATs. Moreover, (BACAN)NAT1 structure shows marked differences in the mode of binding and location of coenzymeA when compared to the other NATs. This suggests that the mechanisms of cofactor recognition by NATs is more diverse than expected and supports the cofactor-binding site as being a unique subsite to target in drug design against bacterial NATs.

  3. Identification of cancer chemopreventive isothiocyanates as direct inhibitors of the arylamine N-acetyltransferase-dependent acetylation and bioactivation of aromatic amine carcinogens

    Science.gov (United States)

    Duval, Romain; Xu, Ximing; Bui, Linh-Chi; Mathieu, Cécile; Petit, Emile; Cariou, Kevin; Dodd, Robert H.; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Aromatic amines (AAs) are chemicals of industrial, pharmacological and environmental relevance. Certain AAs, such as 4-aminobiphenyl (4-ABP), are human carcinogens that require enzymatic metabolic activation to reactive chemicals to form genotoxic DNA adducts. Arylamine N-acetyltransferases (NAT) are xenobiotic metabolizing enzymes (XME) that play a major role in this carcinogenic bioactivation process. Isothiocyanates (ITCs), including benzyl-ITC (BITC) and phenethyl-ITC (PEITC), are phytochemicals known to have chemopreventive activity against several aromatic carcinogens. In particular, ITCs have been shown to modify the bioactivation and subsequent mutagenicity of carcinogenic AA chemicals such as 4-ABP. However, the molecular and biochemical mechanisms by which these phytochemicals may modulate AA carcinogens bioactivation and AA-DNA damage remains poorly understood. This manuscript provides evidence indicating that ITCs can decrease the metabolic activation of carcinogenic AAs via the irreversible inhibition of NAT enzymes and subsequent alteration of the acetylation of AAs. We demonstrate that BITC and PEITC react with NAT1 and inhibit readily its acetyltransferase activity (ki = 200 M−1.s−1 and 66 M−1.s−1 for BITC and PEITC, respectively). Chemical labeling, docking approaches and substrate protection assays indicated that inhibition of the acetylation of AAs by NAT1 was due to the chemical modification of the enzyme active site cysteine. Moreover, analyses of AAs acetylation and DNA adducts in cells showed that BITC was able to modulate the endogenous acetylation and bioactivation of 4-ABP. In conclusion, we show that direct inhibition of NAT enzymes may be an important mechanism by which ITCs exert their chemopreventive activity towards AA chemicals. PMID:26840026

  4. Small molecule inhibition of arylamine N-acetyltransferase Type I inhibits proliferation and invasiveness of MDA-MB-231 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tiang, Jacky M. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Butcher, Neville J., E-mail: n.butcher@uq.edu.au [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Minchin, Rodney F. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia)

    2010-02-26

    Arylamine N-acetyltransferase 1 is a phase II metabolizing enzyme that has been associated with certain breast cancer subtypes. While it has been linked to breast cancer risk because of its role in the metabolic activation and detoxification of carcinogens, recent studies have suggested it may be important in cell growth and survival. To address the possible importance of NAT1 in breast cancer, we have used a novel small molecule inhibitor (Rhod-o-hp) of the enzyme to examine growth and invasion of the breast adenocarcinoma line MDA-MB-231. The inhibitor significantly reduced cell growth by increasing the percent of cells in G2/M phase of the cell cycle. Rhod-o-hp also reduced the ability of the MDA-MB-231 cells to grow in soft agar. Using an in vitro invasion assay, the inhibitor significantly reduced the invasiveness of the cells. To test whether this effect was due to inhibition of NAT1, the enzyme was knocked down using a lentivirus-based shRNA approach and invasion potential was significantly reduced. Taken together, the results of this study demonstrate that NAT1 activity may be important in breast cancer growth and metastasis. The study suggests that NAT1 is a novel target for breast cancer treatment.

  5. Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages.

    Directory of Open Access Journals (Sweden)

    Areej Abuhammad

    Full Text Available Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB. Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT. To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action

  6. 5-methyl-tetrahydrofolate and the S-adenosylmethionine cycle in C57BL/6J mouse tissues: gender differences and effects of arylamine N-acetyltransferase-1 deletion.

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    Katey L Witham

    Full Text Available Folate catabolism involves cleavage of the C(9-N(10 bond to form p-aminobenzoylgluamate (PABG and pterin. PABG is then acetylated by human arylamine N-acetyltransferase 1 (NAT1 before excretion in the urine. Mice null for the murine NAT1 homolog (Nat2 show several phenotypes consistent with altered folate homeostasis. However, the exact role of Nat2 in the folate pathway in vivo has not been reported. Here, we examined the effects of Nat2 deletion in male and female mice on the tissue levels of 5-methyl-tetrahydrofolate and the methionine-S-adenosylmethionine cycle. We found significant gender differences in hepatic and renal homocysteine, S-adenosylmethionine and methionine levels consistent with a more active methionine-S-adenosylmethionine cycle in female tissues. In addition, methionine levels were significantly higher in female liver and kidney. PABG was higher in female liver tissue but lower in kidney compared to male tissues. In addition, qPCR of mRNA extracted from liver tissue suggested a significantly lower level of Nat2 expression in female animals. Deletion of Nat2 affected liver 5- methyl-tetrahydrofolate in female mice but had little effect on other components of the methionine-S-adenosylmethionine cycle. No N-acetyl-PABG was observed in any tissues in Nat2 null mice, consistent with the role of Nat2 in PABG acetylation. Surprisingly, tissue PABG levels were similar between wild type and Nat2 null mice. These results show that Nat2 is not required to maintain tissue PABG homeostasis in vivo under normal conditions.

  7. Effects of single nucleotide polymorphisms on human N-acetyltransferase 2 structure and dynamics by molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    M Rajasekaran

    Full Text Available BACKGROUND: Arylamine N-acetyltransferase 2 (NAT2 is an important catalytic enzyme that metabolizes the carcinogenic arylamines, hydrazine drugs and chemicals. This enzyme is highly polymorphic in different human populations. Several polymorphisms of NAT2, including the single amino acid substitutions R64Q, I114T, D122N, L137F, Q145P, R197Q, and G286E, are classified as slow acetylators, whereas the wild-type NAT2 is classified as a fast acetylator. The slow acetylators are often associated with drug toxicity and efficacy as well as cancer susceptibility. The biological functions of these 7 mutations have previously been characterized, but the structural basis behind the reduced catalytic activity and reduced protein level is not clear. METHODOLOGY/PRINCIPAL FINDINGS: We performed multiple molecular dynamics simulations of these mutants as well as NAT2 to investigate the structural and dynamical effects throughout the protein structure, specifically the catalytic triad, cofactor binding site, and the substrate binding pocket. None of these mutations induced unfolding; instead, their effects were confined to the inter-domain, domain 3 and 17-residue insert region, where the flexibility was significantly reduced relative to the wild-type. Structural effects of these mutations propagate through space and cause a change in catalytic triad conformation, cofactor binding site, substrate binding pocket size/shape and electrostatic potential. CONCLUSIONS/SIGNIFICANCE: Our results showed that the dynamical properties of all the mutant structures, especially in inter-domain, domain 3 and 17-residue insert region were affected in the same manner. Similarly, the electrostatic potential of all the mutants were altered and also the functionally important regions such as catalytic triad, cofactor binding site, and substrate binding pocket adopted different orientation and/or conformation relative to the wild-type that may affect the functions of the mutants

  8. Effects of the butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on the arylamines N-acetyltransferase activity in rat white blood cells.

    Science.gov (United States)

    Lu, H F; Wu, H C; Chang, W C; Chung, J G

    1999-01-01

    Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) were used to determine any effects on the N-acetyltransferase (NAT) activity in rat whole blood and white blood cells as measured by high performance liquid chromatography assay for the amounts of N-acetyl-2-aminofluorene (AAF) and 2-aminofluorene (AF). Two assay systems were performed, one with cellular cytosols, the other with intact white blood cells. The NAT activity in the whole blood and white blood cell cytosols was suppressed by BHA and BHT in a dose-dependent manner, i.e. the higher the concentrations of BHA and BHT, the higher the inhibition of NAT activity. Time-course experiments showed that NAT activity measured from the intact white blood cells was inhibited by BHA and BHT up to 24 h. The results suggest that BHA and BHT suppressed AF acetylation in rat blood with intact white blood cells.

  9. Interaction of wild type, G68R and L125M isoforms of the arylamine-N-acetyltransferase from Mycobacterium tuberculosis with isoniazid: a computational study on a new possible mechanism of resistance.

    Science.gov (United States)

    Ramos, Ricardo Martins; Perez, Janaína Menezes; Baptista, Luis André; de Amorim, Hermes Luís Neubauer

    2012-09-01

    Isoniazid (INH) is a front-line drug used in the treatment of tuberculosis (TB), a disease that remains a major cause of death worldwide. Isoniazid is a prodrug, requiring activation in the mycobacterial cell by the catalase-peroxidase (CP) enzyme. Recent studies have suggested that acetylation of INH by the arylamine-N-acetyltransferase from Mycobacterium tuberculosis (TBNAT) may be a possible cause of inactivation of the drug thus resulting in resistant strains. In this study, computational techniques were applied to investigate the binding of isoniazid to three TBNAT isoforms: wild type, G68R and L125M. Since there is no experimental structure available, molecular dynamics (MD) simulations were initially used for the refinement of TBNAT homology models. Distinct conformations of the models were selected during the production stage of MD simulations for molecular docking experiments with the drug. Finally, each mode of binding was refined by new molecular MD simulations. Essential dynamics (ED) analysis and linear interaction energy calculations (LIE) were used to evaluate the impact of amino acid substitutions on the structural and binding properties of the enzymes. The results suggest that the wild type and the G68R TBNATs have a similar pattern of affinity to INH. On the other hand, the calculated enzyme-INH dissociation constant (KD) was estimated 33 times lower for L125M isoform in comparison with wild type enzyme. This last finding is consistent with the hypothesis that isolated mutations in the tbnat gene can produce M. tuberculosis strains resistant to isoniazid.

  10. Molecular Dynamics and Combined QM/MM Studies on the Deactivation of anti-Tubercular Drug Isoniazid by Arylamine N-Acetyltransferases

    Institute of Scientific and Technical Information of China (English)

    乔青安; 马翠华; 宋慧玲; 蔡红兰; 蔡政亭; 冯大诚

    2012-01-01

    Both a molecule dynamic study and a combined quantum mechanics and mole-cule mechanics(QM/MM) study on the acetylating deactivation mechanism of isoniazid were presented.This type of reaction was catalyzed by arylamine N-acetyltransferases(NATs) and the results strongly support a direct acetyl group transfer process rather than a stepwise one.The isoniazid was strictly restrained in proper relative position to accept the acetyl group by a Hydrogen-bond network formed by the residues at the active center.The residues,His110 and Cys70,would be functioned as 'general base' rather than 'general acid'.If all the residues(including H2O molecules) were removed from the system,the activation energy will be increased from 145.1 to 243.3 kJ/mol.The calculations met the experimental data with good agreement.

  11. The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): Structure, chromosomal localization, and tissue expression

    Energy Technology Data Exchange (ETDEWEB)

    Coon, S.L.; Bernard, M.; Roseboom, P.H. [National Institutes of Health, Bethesda, MD (United States)] [and others

    1996-05-15

    Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, HGMW-approved symbol AANAT;EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. We have found that the human AA-NAT gene spans {approx}2.5 kb, contains four exons, and is located at chromosome 17q25. The open reading frame encodes a 23.2-kDa protein that is {approx}80% identical to sheep and rat AA-NAT. The AA-NAT transcript ({approx}1 kb) is highly abundant in the pineal gland and is expressed at lower levels in the retina and in the Y79 retinoblastoma cell line. AA-NAT mRNA is also detectable at low levels in several brain regions and the pituitary gland, but not in several peripheral tissues examined. Brain and pituitary AA-NAT could modulate serotonin-dependent aspects of human behavior and pituitary function. 31 refs., 5 figs.

  12. Cell-free expression of human glucosamine 6-phosphate N-acetyltransferase (HsGNA1) for inhibitor screening.

    Science.gov (United States)

    Ma, Yi; Ghoshdastider, Umesh; Wang, Jufang; Ye, Wei; Dötsch, Volker; Filipek, Slawomir; Bernhard, Frank; Wang, Xiaoning

    2012-12-01

    Glucosamine 6-phosphate N-acetyltransferase (GNA1; EC 2.3.1.4) is required for the de novo synthesis of N-acetyl-d-glucosamine-6-phosphate (GlcNAc-6P), which is an essential precursor in Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) biosynthesis pathway. Therefore, GNA1 is indispensable for the viability of organisms. Here, a novel cell-free expression strategy was developed to efficiently produce large amounts of human GNA1(HsGNA1) and HsGNA1-sGFP for throughput inhibitor screening. The binding site of inhibitor glucose-6-phosphate (G6P) to hGNA was identified by simulated annealing. Subtle differences to the binding site of Aspergillius GNA1(AfGNA1) can be harnessed for inhibitor design. HsGNA1 may be also useful as an antimicrobial and chemotherapeutic target against cancer. Additionally HsGNA1 inhibitors/modulators can possibly be administered with other drugs in the next generation of personalized medicine.

  13. Catalytic properties and heat stabilities of novel recombinant human N-acetyltransferase 2 allozymes support existence of genetic heterogeneity within the slow acetylator phenotype.

    Science.gov (United States)

    Hein, David W; Doll, Mark A

    2017-08-01

    Human N-acetyltransferase 2 (NAT2) catalyzes the N-acetylation of numerous aromatic amine drugs such as sulfamethazine (SMZ) and hydrazine drugs such as isoniazid (INH). NAT2 also catalyzes the N-acetylation of aromatic amine carcinogens such as 2-aminofluorene and the O- and N,O-acetylation of aromatic amine and heterocyclic amine metabolites. Genetic polymorphism in NAT2 modifies drug efficacy and toxicity as well as cancer risk. Acetyltransferase catalytic activities and heat stability associated with six novel NAT2 haplotypes (NAT2*6C, NAT2*14C, NAT2*14D, NAT2*14E, NAT2*17, and NAT2*18) were compared with that of the reference NAT2*4 haplotype following recombinant expression in Escherichia coli. N-acetyltransferase activities towards SMZ and INH were significantly (p N-acetyltransferase activities catalyzed by NAT2 14C and NAT2 14D were significantly lower (p N-Acetylation catalyzed by recombinant human NAT2 17 was over several hundred-fold lower than by recombinant NAT2 4 precluding measurement of its kinetic or heat inactivation constants. Similar results were observed for the O-acetylation of N-hydroxy-2-aminofluorene and N-hydroxy-2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine and the intramolecular N,O-acetylation of N-hydroxy-N-acetyl-2-aminofluorene. The apparent V max of the novel recombinant NAT2 allozymes NAT2 6C, NAT2 14C, NAT2 14D, and NAT2 14E towards AF, 4-aminobiphenyl (ABP), and 3,2'-dimethyl-4-aminobiphenyl (DMABP) were each significantly (p  0.05) from recombinant NAT2 4. The apparent V max catalyzed by NAT2 14C and NAT2 14D were significantly lower (p < 0.05) than the apparent V max catalyzed by NAT2 6C and NAT2 14E towards AF, ABP, and DMABP. Heat inactivation rate constants for recombinant human NAT2 14C, 14D, 14E, and 18 were significantly (p < 0.05) higher than NAT2 4. These results provide further evidence of genetic heterogeneity within the NAT2 slow acetylator phenotype.

  14. Insight into cofactor recognition in arylamine N-acetyltransferase enzymes

    DEFF Research Database (Denmark)

    Xu, Ximing; Li de la Sierra-Gallay, Inés; Kubiak, Xavier Jean Philippe;

    2015-01-01

    for Bacillus anthracis NAT1 and Homo sapiens NAT2. Therefore, in contrast to previous data, this study shows that different orthologous NATs can bind their cofactors in a similar way, suggesting that the mode of binding CoA in this family of enzymes is less diverse than previously thought. Moreover...

  15. Human acetyl-CoA:glucosamine-6-phosphate N-acetyltransferase 1 has a relaxed donor specificity and transfers acyl groups up to four carbons in length.

    Science.gov (United States)

    Brockhausen, Inka; Nair, Dileep G; Chen, Min; Yang, Xiaojing; Allingham, John S; Szarek, Walter A; Anastassiades, Tassos

    2016-04-01

    Glucosamine-6-phosphate N-acetyltransferase1 (GNA1) catalyses the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to glucosamine-6-phosphate (GlcN6P) to form N-acetylglucosamine-6-phosphate (GlcNAc6P), which is an essential intermediate in UDP-GlcNAc biosynthesis. An analog of GlcNAc, N-butyrylglucosamine (GlcNBu) has shown healing properties for bone and articular cartilage in animal models of arthritis. The goal of this work was to examine whether GNA1 has the ability to transfer a butyryl group from butyryl-CoA to GlcN6P to form GlcNBu6P, which can then be converted to GlcNBu. We developed fluorescent and radioactive assays and examined the donor specificity of human GNA1. Acetyl, propionyl, n-butyryl, and isobutyryl groups were all transferred to GlcN6P, but isovaleryl-CoA and decanoyl-CoA did not serve as donor substrates. Site-specific mutants were produced to examine the role of amino acids potentially affecting the size and properties of the AcCoA binding pocket. All of the wild type and mutant enzymes showed activities of both acetyl and butyryl transfer and can therefore be used for the enzymatic synthesis of GlcNBu for biomedical applications.

  16. Occurrence, uses, and carcinogenicity of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2015-01-01

    Arylamines are chemically synthesized and contained in oxidants, epoxy polymers, explosives, fungicides, pesticides, colorants, polyurethanes, and used in rubber, pharmacology, cosmetics, and other chemical industries. Many arylamines are ubiquitously present in cigarette smoke, cooking fume hoods, foods, automobile exhaust, industrial sites, etc. Some arylamines can be generated through azo reduction by intestinal, skin, and environmental microorganisms from azo dyes that are widely used. Arylamines can also be generated by reduction of the nitro-group containing polyhydrated hydrocarbons including muntions. Some arylamines are released by burning nitrogen containing organic materials at high temperatures. Some medical drugs are also arylamines. Furthermore, many arylamines are essential constituents of normal metabolism or the result of abnormal metabolism or dietary sources. Some arylamines are mutagenic, carcinogenic or the cause of other kinds of maladies. Some arylamine are considered the major etiological agents of bladder tumors in humans and animals but may also induce other types of cancers in various organs. The organ, tissue, and species specificity of the arylamine-inducing carcinogenesis may be determined by their availability, distribution, and the presence of metabolic activation/detoxicification enzymes of each organ or tissue of different species. The ubiquitous arylamines, therefore, pose serious hazards to human health and environment. This article will address the occurrence, uses, carcinogenicity, and other arylamines-induced diseases.

  17. Carcinogenicity, allergenicity, and lupus-inducibility of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2016-01-01

    Arylamines are widely used in food, drugs, and cosmetics as well as other industries. These chemicals are present ubiquitously in cigarette smoke, smoke emitted from cooking fume hoods as well as are generated by diverse industries. Arylamines can be generated by cleavage of azo dyes by intestinal and skin microbiota. Some arylamines are used as drugs while others are constituents of human metabolism. Many of the arylamines are mutagenic and carcinogenic. They are generally recognized as the major cause of human bladder cancer, but arylamines can induce cancers of other organs in humans and animals. Some arylamines are allergenic, causing lupus like syndrome, or other maladies. In view of their unbiquitious nature and the diseases they cause, arylamines are probably the most important chemicals causing health problems.

  18. Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus

    DEFF Research Database (Denmark)

    Cocaign, Angélique; Kubiak, Xavier Jean Philippe; Xu, Ximing;

    2014-01-01

    -modifying enzyme from M. abscessus and provides bases to better understand the substrate/inhibitor-binding specificities among mycobacterial NATs and to identify/optimize specific inhibitors. These data should also contribute to the understanding of the mechanisms that are responsible for the pathogenicity...

  19. Metabolic activation of N-hydroxy arylamines, N-hydroxy heterocyclic amines and ring-hydroxymethyl polycyclic aromatic hydrocarbons by human sulfotransferases

    Energy Technology Data Exchange (ETDEWEB)

    Chou, H.C.

    1993-01-01

    Arylamines and polycyclic aromatic hydrocarbons (PAHs) are two major classes of chemical carcinogens. N-Hydroxylation of arylamines is regarded to be a necessary process for their mutagenicity and carcinogenicity, while alkyl-hydroxylation is the major metabolic pathway for alkyl-substituted PAHs. Evidence has been presented that sulfation of several N-hydroxy arylamines and hydroxymethyl PAHs is an important pathway leading to the formation of ultimate carcinogens in experiment animals. Sulfation of these chemicals forms putative sulfuric acid ester intermediates that can rearrange to electrophilic nitrenium or carbenium ions capable of forming covalent adducts with important cellular macromolecules. In order to study the metabolic activation by sulfotransferase(s) in various human tissue preparations an in vitro enzymatic assay was established. A metabolic phenotyping method was also developed for thermostable phenolsulfotransferase (TS-PST) in platelet homogenates (correlated with TS-PST activity in other tissues) based on a simple colorimetric assay using 2-naphthol as substrate. By using a PAPS-regenerating system to supply the activated sulfate and calf thymus DNA to trap the reactive metabolites, we found that N-hydroxy derivatives of the carcinogens, 4-aminobiphenyl (4-ABP), 4,4[prime]-methylene-bis(2-chloroaniline) (MOCA), 2-acetylaminofluorene (2-AAF), 2-aminofluorene (2-AF), 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), and 2-amino-6-methyldipyrido [1,2-1:3[prime],2[prime]-d]imidazole (Glu-P-1) were metabolically activated by human TS-PST. On the other hand, three methyl-hydroxylated derivatives (7-OH, 12-OH, and 7,12-diOH) of 7, 12-dimethylbenz[a]anthracene (DMBA) were metabolically activated by human steroid sulfotransferase. Human sulfotransferase(s)-mediated activation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was not observed.

  20. Reconstruction of N-acetyltransferase 2 haplotypes using PHASE.

    Science.gov (United States)

    Golka, Klaus; Blaszkewicz, Meinolf; Samimi, Mirabutaleb; Bolt, Hermann M; Selinski, Silvia

    2008-04-01

    The genotyping of N-acetyltransferase 2 (NAT2) by PCR/RFLP methods yields in a considerable percentage ambiguous results. To resolve this methodical problem a statistical approach was applied. PHASE v2.1.1, a statistical program for haplotype reconstruction was used to estimate haplotype pairs from NAT2 genotyping data, obtained by the analysis of seven single nucleotide polymorphisms relevant for Caucasians. In 1,011 out of 2,921 (35%) subjects the haplotype pairs were clearcut by the PCR/RFLP data only. For the majority of the data the applied method resulted in a multiplicity (2-4) of possible haplotype pairs. Haplotype reconstruction using PHASE v2.1.1 cleared this ambiguity in all cases but one, where an alternative haplotype pair was considered with a probability of 0.029. The estimation of the NAT2 haplotype is important because the assignment of the NAT2 alleles *12A, *12B, *12C or *13 to the rapid or slow NAT2 genotype has been discussed controversially. A clear assignment is indispensable in surveys of human bladder cancer caused by aromatic amine exposures. In conclusion, PHASE v2.1.1 software allowed an unambiguous haplotype reconstruction in 2,920 of 2,921 cases (>99.9%).

  1. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Cobbs Gary A

    2007-05-01

    Full Text Available Abstract Background N-acetyltransferase 1 (NAT1 and 2 (NAT2 are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD consist of Crohn's disease (CD and ulcerative colitis (UC, both are associated with increased colorectal cancer (CRC risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD. Methods A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes. Results No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs. Conclusion This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.

  2. Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT; a key enzyme for physiological and behavioral switch in arthropods

    Directory of Open Access Journals (Sweden)

    Susumu eHiragaki

    2015-04-01

    Full Text Available The evolution of N-acetyltransfeases (NATs seems complex. Vertebrate arylalkylamine N-acetyltransferase (aaNAT has been extensively studied since it Leads to the synthesis of melatonin, a multifunctional neurohormone prevalent in photoreceptor cells, and is known as as a chemical token of the night. Melatonin also serves as a scavenger for reactive oxygen species. This is also true with invertebrates. NAT therefore has distinct functional implications in circadian function, as timezymes (aaNAT, and also xenobiotic reactions (arylamine NAT or simply NAT. NATs belong to a broader enzyme group, the GCN5-related N-acetyltransferase superfamily. Due to low sequence homology and a seemingly fast rate of structural differentiation, the nomenclature for NATs can be confusing. The advent of bioinformatics, however, has helped to classify this group of enzymes; vertebrates have two distinct subgroups, the timezyme type and the xenobiotic type, which has a wider substrate range including imidazolamine, pharmacological drugs, environmental toxicants and even histone. Insect aaNAT (iaaNAT form their own clade in the phylogeny, distinct from vertebrate aaNATs. Arthropods are unique, since the phylum has exoskeleton in which quinones derived from N-acetylated monoamines function in coupling chitin and arthropodins. Monoamine oxidase (MAO activity is limited in insects, but NAT-mediated degradation prevails. However, unexpectedly iaaNAT occurs not only among arthropods but also among basal deuterostomia, and is therefore more apomorphic. Our analyses illustrate that iaaNATs has unique physiological roles but at the same time it plays a role in a timezyme function, at least in photoperiodism. Photoperiodism has been considered as a function of circadian system but the detailed molecular mechanism is not well understood. We propose a molecular hypothesis for photoperiodism in Antheraea pernyi based on the transcription regulation of NAT interlocked by the

  3. Structural Studies on a Glucosamine/Glucosaminide N-Acetyltransferase.

    Science.gov (United States)

    Dopkins, Brandon J; Tipton, Peter A; Thoden, James B; Holden, Hazel M

    2016-08-16

    Glucosamine/glucosaminide N-acetyltransferase or GlmA catalyzes the transfer of an acetyl group from acetyl CoA to the primary amino group of glucosamine. The enzyme from Clostridium acetobutylicum is thought to be involved in cell wall rescue. In addition to glucosamine, GlmA has been shown to function on di- and trisaccharides of glucosamine as well. Here we present a structural and kinetic analysis of the enzyme. For this investigation, eight structures were determined to resolutions of 2.0 Å or better. The overall three-dimensional fold of GlmA places it into the tandem GNAT superfamily. Each subunit of the dimer folds into two distinct domains which exhibit high three-dimensional structural similarity. Whereas both domains bind acetyl CoA, it is the C-terminal domain that is catalytically competent. On the basis of the various structures determined in this investigation, two amino acid residues were targeted for further study: Asp 287 and Tyr 297. Although their positions in the active site suggested that they may play key roles in catalysis by functioning as active site bases and acids, respectively, this was not borne out by characterization of the D287N and Y297F variants. The kinetic properties revealed that both residues were important for substrate binding but had no critical roles as acid/base catalysts. Kinetic analyses also indicated that GlmA follows an ordered mechanism with acetyl CoA binding first followed by glucosamine. The product N-acetylglucosamine is then released prior to CoA. The investigation described herein provides significantly new information on enzymes belonging to the tandem GNAT superfamily.

  4. N-acetylglucosamine sensing by a GCN5-related N-acetyltransferase induces transcription via chromatin histone acetylation in fungi

    Science.gov (United States)

    Su, Chang; Lu, Yang; Liu, Haoping

    2016-01-01

    N-acetylglucosamine (GlcNAc) exists ubiquitously as a component of the surface on a wide range of cells, from bacteria to humans. Many fungi are able to utilize environmental GlcNAc to support growth and induce cellular development, a property important for their survival in various host niches. However, how the GlcNAc signal is sensed and subsequently transduced is largely unknown. Here, we identify a gene that is essential for GlcNAc signalling (NGS1) in Candida albicans, a commensal and pathogenic yeast of humans. Ngs1 can bind GlcNAc through the N-terminal β-N-acetylglucosaminidase homology domain. This binding activates N-acetyltransferase activity in the C-terminal GCN5-related N-acetyltransferase domain, which is required for GlcNAc-induced promoter histone acetylation and transcription. Ngs1 is targeted to the promoters of GlcNAc-inducible genes constitutively by the transcription factor Rep1. Ngs1 is conserved in diverse fungi that have GlcNAc catabolic genes. Thus, fungi use Ngs1 as a GlcNAc-sensor and transducer for GlcNAc-induced transcription. PMID:27694804

  5. [Evaluation of a caffeine test for determining the phenotype of N-acetyltransferase].

    Science.gov (United States)

    Gascon, M P; Leemann, T; Dayer, P

    1987-12-05

    Xenobiotic acetylation by N-acetyltransferase is genetically controlled. This polymorphism governs the intestinal and liver metabolism of numerous amines. The use of caffeine, a ubiquitous and nontoxic amine, has been proposed as a probe for phenotyping. The aim of the present study is to evaluate this test and to identify the metabolite of caffeine used as substrate by the polymorphic enzyme. - A cup of coffee, tea or Coca-Cola is administered to fasting subjects. The molar ratio of two metabolites of caffeine (AFMU and 1X) is determined on a spot urine sample 4-6 hours later by means of a UV liquid chromatographic assay. In a reference population (n = 63), the distribution of molar ratios is trimodal with frequencies of 0.14, 0.35 and 0.51. These results correlate with those obtained by the classic isoniazid test. However, in vitro experiments in human liver subcellular fractions did not lead to the identification of a xanthine as the precursor of the acetylated metabolite.

  6. N-acetyltransferase-2 polymorphism in Parkinson's disease: the Rotterdam study

    NARCIS (Netherlands)

    B.S. Harhangi (Biswadjiet); B.A. Oostra (Ben); C.M. van Duijn (Cock); M.M.B. Breteler (Monique); P. Heutink (Peter); A. Hofman (Albert)

    1999-01-01

    textabstractThe N-acetyltransferase-2 gene (NAT-2) has been associated with Parkinson's disease. The genotype associated with slow acetylation has been reported to be increased in patients with Parkinson's disease. Three mutant alleles M1, M2, and M3 of NAT-2 were investigated in 80 patients with id

  7. N-acetyltransferase 2 polymorphism in Parkinson's disease. The Rotterdam study

    NARCIS (Netherlands)

    B.S. Harhangi (Biswadjiet); B.A. Oostra (Ben); P. Heutink (Peter); C.M. van Duijn (Cock); A. Hofman (Albert); M.M.B. Breteler (Monique)

    1999-01-01

    textabstractThe N-acetyltransferase-2 gene (NAT-2) has been associated with Parkinson's disease. The genotype associated with slow acetylation has been reported to be increased in patients with Parkinson's disease. Three mutant alleles M1, M2, and M3 of NAT-2 were investigated in 80 patients with id

  8. Orofacial clefts and spina bifida: N-acetyltransferase phenotype, maternal smoking, and medication use.

    NARCIS (Netherlands)

    Rooij, I.A.L.M. van; Groenen, P.; Drongelen, M. van; Morsche, R.H.M. te; Peters, W.H.M.; Steegers-Theunissen, R.P.M.

    2002-01-01

    BACKGROUND: Orofacial clefts and spina bifida are midline defects with a multifactorial etiology. Maternal smoking and medication use periconceptionally have been studied as risk factors for these malformations. The biotransformation enzyme N-acetyltransferase 2 (NAT2), plays a part in the

  9. N-acetyltransferase 1 in colon and rectal cancer cases from an industrialized area.

    Science.gov (United States)

    Roemer, Hermann C; Weistenhofer, Wobbeke; Lohlein, Dietrich; Geller, Frank; Blomeke, Brunhilde; Golka, Klaus

    2008-01-01

    Colon and rectal cancers are both associated with genetic as well as nutritional, occupational, and environmental factors. Aromatic amines and heterocyclic amines are established colorectal carcinogens. The polymorphic enzyme N-acetyltransferase 1 (NAT1) contributes to heterocyclic amine metabolism in the human colon. Thereby, NAT1 may influence the risk for development of colorectal cancer. The distribution of NAT1 genotypes was determined in 107 colon cancer cases, 77 rectal cancer cases, and 185 controls (suffering from nonmalignant diseases) by standard methods. In addition, possible occupational and nonoccupational risk factors were determined by a personal interview. Cancer cases and controls were derived from an area of former coal, iron, and steel industries, which is known for elevated colon cancer mortality. The proportions of NAT1*4/*4 genotype were 72% in controls, 75% in rectal cancer cases, and 72% in colon cancer cases. The proportions of the NAT1*4/*10 genotype were 17.8% in controls, 12.9% in rectal cancer cases, and 14% in colon cancer cases. Combinations of the determined NAT1 alleles *3/*3, *3/*10, *4/*3, *4/*11, *10/*10 and *11/*11 contributed to 10.2% of the genotypes in controls, 12.1% in rectal cancer cases, and 14% in colon cancer cases. In contrast to another study on healthy German volunteers, the NAT1*4/*4 genotype (wild type) is overrepresented. This might be due to the variation in the proportion of NAT1 alleles in the general population. The present study does not support a relevant impact of the NAT1 genotype on colorectal cancer risk development in the study area.

  10. Polymorphism of N-acetyltransferase 2 (NAT2) Gene Polymorphism in Shanghai population:Occupational and Non-occupational Bladder Cancer Patient Groups

    Institute of Scientific and Technical Information of China (English)

    QING-WEN MA; GUO-FANG LIN; JI-GANG CHEN; CUI-QING XIANG; WEI-CHAO GUO; KLAUS GOLKA; JIAN-HUA SHEN

    2004-01-01

    Arylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzidine exposed or non-exposed Chinese individuals, healthy subjects, subjects with bladder cancer of a former benzidine exposed cohort in Shanghai dyestuff industry and a group of bladder cancer patients without known occupational exposure to aromatic amines were genotyped for NAT2 gene polymorphism. Methods NAT2 genotyping was performed with a set of RFLP procedures at seven major polymorphic loci of gene coding area: G191A, C282T, T341C, C481T, G590A, A803G and G857A. Results The wild allele NAT2 *4 was the most prevalent allele (59%) in healthy individuals. The alleles NAT2*6A and NAT2*7B were also frequently observed (21% and 17%, respectively). In contrast to Caucasians, the percentage of slow acetylators was lower (12% in Chinese vs. 58% in Caucasians, P<0.001). No relevant differences were observed for homogenous rapid, heterogeneous rapid/slow and homogeneous slow acetylation genotypes between the healthy subjects and both groups of bladder cancer patients. Conclusion The present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups.

  11. Cigarette Smoking, N-Acetyltransferase 2 Acetylation Status, and Bladder Cancer Risk

    DEFF Research Database (Denmark)

    Marcus, P.M.; Hayes, R.B.; Vineis, P.

    2000-01-01

    Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder...... to assess multiplicative gene-environment interaction without inclusion of control subjects. A case-series interaction odds ratio (OR) > 1.0 indicates that the relationship of cigarette smoking and bladder cancer risk is stronger among slow acetylators as compared with rapid acetylators. We observed...

  12. Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.

    Science.gov (United States)

    Aboalroub, Adam A; Bachman, Ashleigh B; Zhang, Ziming; Keramisanou, Dimitra; Merkler, David J; Gelis, Ioannis

    2017-01-01

    The transfer of an acetyl group from acetyl-CoA to an acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it is established that the reaction proceeds through a sequential ordered mechanism, the role of the acetyl group in driving the ordered formation of binary and ternary complexes remains elusive. Herein, we show that CoA and acetyl-CoA alter the conformation of the substrate binding site of an arylalkylamine N-acetyltransferase (AANAT) to facilitate interaction with acceptor substrates. However, it is the presence of the acetyl group within the catalytic funnel that triggers high affinity binding. Acetyl group occupancy is relayed through a conserved salt bridge between the P-loop and the acceptor binding site, and is manifested as differential dynamics in the CoA and acetyl-CoA-bound states. The capacity of the acetyl group carried by an acceptor to promote its tight binding even in the absence of CoA, but also its mutually exclusive position to the acetyl group of acetyl-CoA underscore its importance in coordinating the progression of the catalytic cycle.

  13. A test method for the measurement of arylamines in stationary source emissions

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, M.R.; Pate, B.A.; Wright, R.S. [Research Triangle Institute, Research Triangle Park, NC (United States)] [and others

    1996-12-31

    Title III of the Clean Air Act Amendments of 1990 lists eighteen arylamines as hazardous air pollutants to be regulated. The eighteen arylamines range from semivolatile to almost nonvolatile, from almost water-insoluble to hygroscopic, from thermally quite stable to unstable, and from fairly toxic to confirmed human carcinogens. This paper presents a report on progress in the development of a method to measure this quite disparate group of compounds in stationary source emissions. The proposed method involves collection in an acidic aqueous solution, sorption of collected arylamines on a cation exchange resin, desorption of arylamines from the resin with a small volume of a basic solution, and separation and measurement by high pressure liquid chromatography with photodiode array (HPLC-PDA) detection. Evaluation of cation exchange resins and resin elution solvents and the analytical portions of the method are being conducted using a subset of eight arylamines: aniline, chloramben, 2,4-diaminotoluene, N,N-dimethylaniline, 3,3`-dimethylbenzidine, quinoline, o-toluidine, and trifluralin. Sorption on a solid-phase extraction resin (LC-SCX, Supelco) followed by elution off the resin with a 2.2 normal solution of ammonia in a 50:35:15 mixture of 1-butanol, 1-propanol, and water gave the best recoveries of the test compounds (except chloramben, which contains a carboxylic acid group and does not elute) from the acidified collection solution. The compounds were separated on an Alltech Alltima C18 5{mu}m, 150 {times} 4.6 mm HPLC column using solvent programming with acetonitrile and either water or an acetate/acetic acid pH 7 buffer. 1 fig., 3 tabs.

  14. A new arylalkylamine N-acetyltransferase in silkworm (Bombyx mori) affects integument pigmentation.

    Science.gov (United States)

    Long, Yaohang; Li, Jiaorong; Zhao, Tianfu; Li, Guannan; Zhu, Yong

    2015-04-01

    Dopamine is a precursor for melanin synthesis. Arylalkylamine N-acetyltransferase (AANAT) is involved in the melatonin formation in insects because it could catalyze the transformation from dopamine to dopamine-N-acetyldopamine. In this study, we identified a new AANAT gene in the silkworm (Bombyx mori) and assessed its role in the silkworm. The cDNA of this gene encodes 233 amino acids that shares 57 % amino acid identity with the Bm-iAANAT protein. We thus refer to this gene as Bm-iAANAT2. To investigate the role of Bm-iAANAT2, we constructed a transgenic interference system using a 3xp3 promoter to suppress the expression of Bm-iAANAT2 in the silkworm. We observed that melanin deposition occurs in the head and integument in transgenic lines. To verify the melanism pattern, dopamine content and the enzyme activity of AANAT were determined by high-performance liquid chromatography (HPLC). We found that an increase in dopamine levels affects melanism patterns on the heads of transgenic B. mori. A reduction in the enzyme activity of AANAT leads to changes in dopamine levels. We analyzed the expression of the Bm-iAANAT2 genes by qPCR and found that the expression of Bm-iAANAT2 gene is significantly lower in transgenic lines. Our results lead us to conclude that Bm-iAANAT2 is a new arylalkylamine N-acetyltransferase gene in the silkworm and is involved in the metabolism of the dopamine to avoid the generation of melanin.

  15. Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation.

    Science.gov (United States)

    Song, Wan Seok; Nam, Mi Sun; Namgung, Byeol; Yoon, Sung-il

    2015-03-20

    Campylobacter jejuni is a bacterium that uses flagella for motility and causes worldwide acute gastroenteritis in humans. The C. jejuni N-acetyltransferase PseH (cjPseH) is responsible for the third step in flagellin O-linked glycosylation and plays a key role in flagellar formation and motility. cjPseH transfers an acetyl group from an acetyl donor, acetyl coenzyme A (AcCoA), to the amino group of UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine to produce UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose. To elucidate the catalytic mechanism of cjPseH, crystal structures of cjPseH alone and in complex with AcCoA were determined at 1.95 Å resolution. cjPseH folds into a single-domain structure of a central β-sheet decorated by four α-helices with two continuously connected grooves. A deep groove (groove-A) accommodates the AcCoA molecule. Interestingly, the acetyl end of AcCoA points toward an open space in a neighboring shallow groove (groove-S), which is occupied by extra electron density that potentially serves as a pseudosubstrate, suggesting that the groove-S may provide a substrate-binding site. Structure-based comparative analysis suggests that cjPseH utilizes a unique catalytic mechanism of acetylation that has not been observed in other glycosylation-associated acetyltransferases. Thus, our studies on cjPseH will provide valuable information for the design of new antibiotics to treat C. jejuni-induced gastroenteritis.

  16. Molecular Evolution of Aralkylamine N-Acetyltransferase in Fish: A Genomic Survey

    Directory of Open Access Journals (Sweden)

    Jia Li

    2015-12-01

    Full Text Available All living organisms synchronize biological functions with environmental changes; melatonin plays a vital role in regulating daily and seasonal variations. Due to rhythmic activity of the timezyme aralkylamine N-acetyltransferase (AANAT, the blood level of melatonin increases at night and decreases during daytime. Whereas other vertebrates have a single form of AANAT, bony fishes possess various isoforms of aanat genes, though the reasons are still unclear. Here, we have taken advantage of multiple unpublished teleost aanat sequences to explore and expand our understanding of the molecular evolution of aanat in fish. Our results confirm that two rounds of whole-genome duplication (WGD led to the existence of three fish isoforms of aanat, i.e., aanat1a, aanat1b, and aanat2; in addition, gene loss led to the absence of some forms from certain special fish species. Furthermore, we suggest the different roles of two aanat1s in amphibious mudskippers, and speculate that the loss of aanat1a, may be related to terrestrial vision change. Several important sites of AANAT proteins and regulatory elements of aanat genes were analyzed for structural comparison and functional forecasting, respectively, which provides insights into the molecular evolution of the differences between AANAT1 and AANAT2.

  17. N-Acetyltransferase 2 genotype, exfoliated urothelial cells and benzidine exposure.

    Science.gov (United States)

    Ma, Qing-wen; Lin, Guo-fang; Chen, Ji-gang; Guo, Wei-Chao; Qin, Yi-qiu; Golka, Klaus; Shen, Jian-hua

    2012-01-01

    Most studies report an association of the slow N-acetyltransferase 2 (NAT2) status with elevated bladder cancer risk. In this study, NAT2 genotypes and the decades-long records of Papanicolaou's grading of exfoliated urothelial cells in a former benzidine-exposed cohort of the Shanghai dyestuff industry (29 bladder cancer patients; 307 non-cancer cohort members, some of them presenting different grades of pre-malignant alterations of exfoliated urothelial cells) were investigated. The cohort members had been enrolled in regular medical surveillance since mid-1980s. No overall increase of slow NAT2 genotypes in the former benzidine-exposed bladder cancer patients was found, compared with non-diseased members of the same cohort. A lower presentation of the homozygous wild genotype NAT2 4/4 was observed in bladder cancer patients, compared with non-diseased members with averaged Papanicolaou's grading (APG)3 II (OR=0.31, 95 percent CI 0.10-0.96, p=0.034) or with APG less than II (OR=0.36,95 percent CI 0.12-1.10, p=0.063). Nevertheless, neither a protective influence of rapid NAT2 genotypes on bladder cancer risk nor on pre-malignant cytological alterations could be confirmed by the present data.

  18. Structural characterization of a Gcn5-related N-acetyltransferase from Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Parul Srivastava

    Full Text Available The Gcn5-related N-acetyltransferases (GNATs are ubiquitously expressed in nature and perform a diverse range of cellular functions through the acetylation of small molecules and protein substrates. Using activated acetyl coenzyme A as a common acetyl donor, GNATs catalyse the transfer of an acetyl group to acceptor molecules including aminoglycoside antibiotics, glucosamine-6-phosphate, histones, serotonin and spermidine. There is often only very limited sequence conservation between members of the GNAT superfamily, in part, reflecting their capacity to bind a diverse array of substrates. In contrast, the secondary and tertiary structures are highly conserved, but then at the quaternary level there is further diversity, with GNATs shown to exist in monomeric, dimeric, or tetrameric states. Here we describe the X-ray crystallographic structure of a GNAT enzyme from Staphylococcus aureus with only low sequence identity to previously solved GNAT proteins. It contains many of the classical GNAT motifs, but lacks other hallmarks of the GNAT fold including the classic β-bulge splayed at the β-sheet interface. The protein is likely to be a dimer in solution based on analysis of the asymmetric unit within the crystal structure, homology with related GNAT family members, and size exclusion chromatography. The study provides the first high resolution structure of this enzyme, providing a strong platform for substrate and cofactor modelling, and structural/functional comparisons within this diverse enzyme superfamily.

  19. Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease.

    Science.gov (United States)

    Thangavelu, Bharani; Mutthamsetty, Vinay; Wang, Qinzhe; Viola, Ronald E

    2017-02-01

    Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-l-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms of aspartoacylase to adequately catalyze its breakdown. The membrane-associated enzyme responsible for the synthesis of NAA, aspartate N-acetyltransferase (ANAT), has recently been purified and examined (Wang et al., Prot Expr Purif. 2016;119:11). With the availability, for the first time, of a stable and soluble form of ANAT we can now report the identification of initial inhibitors against this biosynthetic enzyme, obtained from the screening of several focused compound libraries. Two core structures of these moderate binding compounds have subsequently been optimized, with the most potent inhibitors in these series possessing sub-micromolar inhibition constants (Ki values) against ANAT. Slowing the production of NAA via the inhibition of ANAT will lower the elevated levels of this metabolite and can potentially serve as a treatment option to moderate the symptoms of Canavan disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. N-Acetyltransferase 2 status and gastric cancer risk: a preliminary meta-analysis

    Directory of Open Access Journals (Sweden)

    Stefania Boccia

    2005-03-01

    Full Text Available

    In recent studies N- Acetyltransferase 2 (NAT2 genotype has been considered as a risk factor for developing gastric cancer, however with conflicting results among Asian and Caucasian populations. In order to clarify the influence of NAT2 slow acetylation status on gastric cancer risk, a preliminary meta-analysis of published case-control studies was undertaken.

    The primary outcome measure was the odds ratio (OR for the risk of gastric cancer associated with the NAT2 slow genotype using a random effects model. Pooling the results from the 5 studies identified (771 cases, 1083 controls, an overall OR for gastric cancer risk associated with the NAT2 slow genotype of 0.91 emerged (95% CI: 0.54-1.55.

    The result suggests that the NAT2 slow genotype has probably no effect on the risk of gastric cancer. Additional epidemiological studies, based on sample sizes that are commensurate with the detection of small genotypic risks, are required to confirm these findings. Future studies may also help to clarify whether geographic differences exist.

  1. Molecular Evolution of Multiple Arylalkylamine N-Acetyltransferase (AANAT in Fish

    Directory of Open Access Journals (Sweden)

    Bina Zilberman-Peled

    2011-05-01

    Full Text Available Arylalkylamine N-acetyltransferase (AANAT catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA to arylalkylamines, including indolethylamines and phenylethylamines. Multiple aanats are present in teleost fish as a result of whole genome and gene duplications. Fish aanat1a and aanat2 paralogs display different patterns of tissue expression and encode proteins with different substrate preference: AANAT1a is expressed in the retina, and acetylates both indolethylamines and phenylethylamines; while AANAT2 is expressed in the pineal gland, and preferentially acetylates indolethylamines. The two enzymes are therefore thought to serve different roles. Here, the molecular changes that led to their specialization were studied by investigating the structure-function relationships of AANATs in the gilthead seabream (sb, Sperus aurata. Acetylation activity of reciprocal mutated enzymes pointed to specific residues that contribute to substrate specificity of the enzymes. Inhibition tests followed by complementary analyses of the predicted three-dimensional models of the enzymes, suggested that both phenylethylamines and indolethylamines bind to the catalytic pocket of both enzymes. These results suggest that substrate selectivity of AANAT1a and AANAT2 is determined by the positioning of the substrate within the catalytic pocket, and its accessibility to catalysis. This illustrates the evolutionary process by which enzymes encoded by duplicated genes acquire different activities and play different biological roles.

  2. N-Acetyltransferase Mpr1 confers ethanol tolerance on Saccharomyces cerevisiae by reducing reactive oxygen species.

    Science.gov (United States)

    Du, Xiaoyi; Takagi, Hiroshi

    2007-07-01

    N-Acetyltransferase Mpr1 of Saccharomyces cerevisiae can reduce intracellular oxidation levels and protect yeast cells under oxidative stress, including H(2)O(2), heat-shock, or freeze-thaw treatment. Unlike many antioxidant enzyme genes induced in response to oxidative stress, the MPR1 gene seems to be constitutively expressed in yeast cells. Based on a recent report that ethanol toxicity is correlated with the production of reactive oxygen species (ROS), we examined here the role of Mpr1 under ethanol stress conditions. The null mutant of the MPR1 and MPR2 genes showed hypersensitivity to ethanol stress, and the expression of the MPR1 gene conferred stress tolerance. We also found that yeast cells exhibited increased ROS levels during exposure to ethanol stress, and that Mpr1 protects yeast cells from ethanol stress by reducing intracellular ROS levels. When the MPR1 gene was overexpressed in antioxidant enzyme-deficient mutants, increased resistance to H(2)O(2) or heat shock was observed in cells lacking the CTA1, CTT1, or GPX1 gene encoding catalase A, catalase T, or glutathione peroxidase, respectively. These results suggest that Mpr1 might compensate the function of enzymes that detoxify H(2)O(2). Hence, Mpr1 has promising potential for the breeding of novel ethanol-tolerant yeast strains.

  3. Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations.

    Science.gov (United States)

    Neuwald, Andrew F; Altschul, Stephen F

    2016-12-01

    Over evolutionary time, members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches. At the sequence level, such divergence appears as correlations that arise from residue patterns distinct to each subgroup. Such a superfamily may be viewed as a population of sequences corresponding to a complex, high-dimensional probability distribution. Here we model this distribution as hierarchical interrelated hidden Markov models (hiHMMs), which describe these sequence correlations implicitly. By characterizing such correlations one may hope to obtain information regarding functionally-relevant properties that have thus far evaded detection. To do so, we infer a hiHMM distribution from sequence data using Bayes' theorem and Markov chain Monte Carlo (MCMC) sampling, which is widely recognized as the most effective approach for characterizing a complex, high dimensional distribution. Other routines then map correlated residue patterns to available structures with a view to hypothesis generation. When applied to N-acetyltransferases, this reveals sequence and structural features indicative of functionally important, yet generally unknown biochemical properties. Even for sets of proteins for which nothing is known beyond unannotated sequences and structures, this can lead to helpful insights. We describe, for example, a putative coenzyme-A-induced-fit substrate binding mechanism mediated by arginine residue switching between salt bridge and π-π stacking interactions. A suite of programs implementing this approach is available (psed.igs.umaryland.edu).

  4. Genetic variants in microsomal epoxide hydrolase and N-acetyltransferase 2 in susceptibility of IBD in the Danish population

    DEFF Research Database (Denmark)

    Ernst, Anja; Andersen, Vibeke; Østergaard, Mette;

    induce or sustain an immune response. Changes in detoxification of substances that causes epithelial damage may confer susceptibility to IBD. Hence, polymorphic enzymes involved in the detoxification processes may be risk factors of IBD. Methods. The two biotransformation enzymes microsomal epoxide...... hydrolase and N-acetyltransferase 2 were genotyped using TaqMan based Real-Time PCR in 388 patients with Crohn's disease (CD), 565 patients with ulcerative colitis (UC) and 796 healthy Danish controls. Results. No association was found between low microsomal epoxide hydrolase activity or slow N......-acetyltransferase 2 acetylator status and IBD. An association between high activity of microsomal epoxide hydrolase and disease diagnosis before age 40 in CD with an OR of 2.2(1.1- 4.2) P=0.02) was found. No other phenotypic associations were found for the two enzymes and IBD, regarding age at onset, disease location...

  5. GENETIC POLYMORPHISMS IN HUMAN LIVER PHENOL SULFOTRANSFERASES INVOLVED IN THE BIOACTIVATION OF N-HYDROXY DERIVATIVES OF CARCINOGENIC ARYLAMINES AND HETEROCYCLIC AMINES. (R825280)

    Science.gov (United States)

    AbstractThree related forms of phenol sulfotransferase (PSULT), thermostable ST1A2 (SULT1A2hum) and ST1A3 (SULT1A1hum) and a thermolabile TL-PST (SULT1A3hum), are known to exist in human livers. Thermostable forms, whose activities are polymorphically distributed, hav...

  6. New N-Acetyltransferase Fold in the Structure and Mechanism of the Phosphonate Biosynthetic Enzyme FrbF

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Brian; Cobb, Ryan E.; DeSieno, Matthew A.; Zhao, Huimin; Nair, Satish K. (UIUC)

    2015-10-15

    The enzyme FrbF from Streptomyces rubellomurinus has attracted significant attention due to its role in the biosynthesis of the antimalarial phosphonate FR-900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. Despite the established function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity to any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we present the 2.0 {angstrom} resolution crystal structure of FrbF in complex with acetyl-CoA, which demonstrates a unique architecture that is distinct from those of canonical GNAT-like acetyltransferases. We also utilized the co-crystal structure to guide structure-function studies that identified the roles of putative active site residues in the acetyltransferase mechanism. The combined biochemical and structural analyses of FrbF provide insights into this previously uncharacterized family of N-acetyltransferases and also provide a molecular framework toward the production of novel N-acyl derivatives of FR-900098.

  7. Crystal structure and functional characterization of a glucosamine-6-phosphate N-acetyltransferase from Arabidopsis thaliana.

    Science.gov (United States)

    Riegler, Heike; Herter, Thomas; Grishkovskaya, Irina; Lude, Anja; Ryngajllo, Malgorzata; Bolger, Marie E; Essigmann, Bernd; Usadel, Björn

    2012-04-15

    GlcNAc (N-acetylglucosamine) is an essential part of the glycan chain in N-linked glycoproteins. It is a building block for polysaccharides such as chitin, and several glucosaminoglycans and proteins can be O-GlcNAcylated. The deacetylated form, glucosamine, is an integral part of GPI (glycosylphosphatidylinositol) anchors. Both are incorporated into polymers by glycosyltransferases that utilize UDP-GlcNAc. This UDP-sugar is synthesized in a short pathway comprising four steps starting from fructose 6-phosphate. GNA (glucosamine-6-phosphate N-acetyltransferase) catalyses the second of these four reactions in the de novo synthesis in eukaryotes. A phylogenetic analysis revealed that only one GNA isoform can be found in most of the species investigated and that the most likely Arabidopsis candidate is encoded by the gene At5g15770 (AtGNA). qPCR (quantitative PCR) revealed the ubiquitous expression of AtGNA in all organs of Arabidopsis plants. Heterologous expression of AtGNA showed that it is highly active between pH 7 and 8 and at temperatures of 30-40°C. It showed Km values of 231 μM for glucosamine 6-phosphate and 33 μM for acetyl-CoA respectively and a catalytic efficiency comparable with that of other GNAs characterized. The solved crystal structure of AtGNA at a resolution of 1.5 Å (1 Å=0.1 nm) revealed a very high structural similarity to crystallized GNA proteins from Homo sapiens and Saccharomyces cerevisiae despite less well conserved protein sequence identity.

  8. N-acetyltransferase 2 (NAT2 gene polymorphisms in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Borlak Juergen

    2006-03-01

    Full Text Available Abstract Background Parkinson's disease (PD is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2 gene leading to slow acetylation process have been associated with PD, but results are contradictory. Methods We analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q and c.857G>A (p.G286E, which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects. Results Overall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR of 1.32 (95% CI 1.12–1.54, p A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well. Conclusion We found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD.

  9. N-acetyltransferase 2, exposure to aromatic and heterocyclic amines, and receptor-defined breast cancer.

    Science.gov (United States)

    Rabstein, Sylvia; Brüning, Thomas; Harth, Volker; Fischer, Hans-Peter; Haas, Susanne; Weiss, Tobias; Spickenheuer, Anne; Pierl, Christiane; Justenhoven, Christina; Illig, Thomas; Vollmert, Caren; Baisch, Christian; Ko, Yon-Dschun; Hamann, Ute; Brauch, Hiltrud; Pesch, Beate

    2010-03-01

    The role of N-acetyltransferase 2 (NAT2) polymorphism in breast cancer is still unclear. We explored the associations between potential sources of exposure to aromatic and heterocyclic amines (AHA), acetylation status and receptor-defined breast cancer in 1020 incident cases and 1047 population controls of the German GENICA study. Acetylation status was assessed as slow or fast. Therefore, NAT2 haplotypes were estimated using genotype information from six NAT2 polymorphisms. Most probable haplotypes served as alleles for the deduction of NAT2 acetylation status. The risks of developing estrogen receptor alpha (ER) and progesterone receptor (PR)-positive or negative tumors were estimated for tobacco smoking, consumption of red meat, grilled food, coffee, and tea, as well as expert-rated occupational exposure to AHA with logistic regression conditional on age and adjusted for potential confounders. Joint effects of these factors and NAT2 acetylation status were investigated. Frequent consumption of grilled food and coffee showed higher risks in slow acetylators for receptor-negative tumors [grilled food: ER-: odds ratio (OR) 2.57, 95% confidence interval (CI) 1.07-6.14 for regular vs. rare; coffee: ER-: OR 2.55, 95% CI 1.22-5.33 for >or=4 vs. 0 cups/day]. We observed slightly higher risks for never smokers that are fast acetylators for receptor-positive tumors compared with slow acetylators (ER-: OR 1.32, 95% CI 1.00-1.73). Our results support differing risk patterns for receptor-defined breast cancer. However, the modifying role of NAT2 for receptor-defined breast cancer is difficult to interpret in the light of complex mixtures of exposure to AHA.

  10. N-Acetyltransferase 2 gene polymorphism in a group of senile dementia patients in Shanghai suburb

    Institute of Scientific and Technical Information of China (English)

    Wei-chao GUO; Guo-fang LIN; Yong-lin ZHA; Ke-jian LOU; Qing-wen MA; Jian-hua SHEN

    2004-01-01

    AIM: To investigate the possible association of hereditary polymorphism of N-acetyltransferase 2 (NAT2) gene with the susceptibility towards senile dementia in farmer population of Shanghai suburb. METHODS: NAT2 gene genotyping was performed at 7 major polymorphic loci (G191A, C282T, T341C, C481T, G590A, A803G, and .G857A) with a polymerase chain reaction-based restriction fragment length polymorphism based procedure in 2 groups of farmer subjects in Shanghai suburb. A group of 51 diagnosed dementia patients [comprising 29 sporadic Alzheimer disease(AD) patients and 22 sporadic vascular dementia (VD) patients] and a group of 112 healthy individuals were in the same area. RESULTS: The homogenous rapid genotypes (R/R, including*4/*4, *13/*13, and *4/*13) was found over-present in both groups of patients, compared with healthy individuals, for all farmer dementia patients, 52.9 %vs 33.0 %, P=0.016, OR (95 % CI): 2.28(1.16-4.48); for AD group only, 51.7 % vs 33.0 %, P=0.063, OR (95 %CI): 2.18 (0.95-4.97); for VD group 54.5 % vs 33.0 %, P=0.055, OR (95 % CI): 2.43 (0.96-2.43). The significant frequency difference of genotype *4/* 7B between farmer dementia patients and healthy individuals, and that of solo-alleles *13, and *7B were observed between the healthy individuals and both groups of dementia patients.CONCLUSION: Our data suggest the involvement of various NAT2 rapid-acetylating genotypes in the individual susceptibility to senile dementia. Variant genotypes of NAT2 might serve as a hereditary risk factor for AD and VD in Chinese population.

  11. Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Matthew, E.; Parfitt, A.G.; Sugden, D.; Engelhardt, D.L.; Zimmerman, E.A.; Klein, D.C.

    1984-02-01

    Studies of (/sup 3/H)diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot (Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture). Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the (/sup 3/H)diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.

  12. Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation

    Energy Technology Data Exchange (ETDEWEB)

    Song, Wan Seok; Nam, Mi Sun; Namgung, Byeol [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Yoon, Sung-il, E-mail: sungil@kangwon.ac.kr [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2015-03-20

    Campylobacter jejuni is a bacterium that uses flagella for motility and causes worldwide acute gastroenteritis in humans. The C. jejuni N-acetyltransferase PseH (cjPseH) is responsible for the third step in flagellin O-linked glycosylation and plays a key role in flagellar formation and motility. cjPseH transfers an acetyl group from an acetyl donor, acetyl coenzyme A (AcCoA), to the amino group of UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine to produce UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose. To elucidate the catalytic mechanism of cjPseH, crystal structures of cjPseH alone and in complex with AcCoA were determined at 1.95 Å resolution. cjPseH folds into a single-domain structure of a central β-sheet decorated by four α-helices with two continuously connected grooves. A deep groove (groove-A) accommodates the AcCoA molecule. Interestingly, the acetyl end of AcCoA points toward an open space in a neighboring shallow groove (groove-S), which is occupied by extra electron density that potentially serves as a pseudosubstrate, suggesting that the groove-S may provide a substrate-binding site. Structure-based comparative analysis suggests that cjPseH utilizes a unique catalytic mechanism of acetylation that has not been observed in other glycosylation-associated acetyltransferases. Thus, our studies on cjPseH will provide valuable information for the design of new antibiotics to treat C. jejuni-induced gastroenteritis. - Highlights: • cjPseH adopts a single-domain structure of a central β-sheet decorated by α-helices. • cjPseH features two continuously connected grooves on the protein surface. • Acetyl coenzyme A (AcCoA) binds into a deep groove of cjPseH in an ‘L’ shape. • The acetyl end of AcCoA points to a wide groove, a potential substrate-binding site.

  13. Toxicokinetics of novel psychoactive substances: characterization of N-acetyltransferase (NAT) isoenzymes involved in the phase II metabolism of 2C designer drugs.

    Science.gov (United States)

    Meyer, Markus R; Robert, Anja; Maurer, Hans H

    2014-06-05

    The 2,5-dimethoxyphenethylamine-derived designer drugs (so-called "2Cs") recently became of great importance on the illicit drug market as stimulating hallucinogens. They are distributed and consumed as "novel psychoactive substances" (NPS) without any safety testing at the forefront. As previous studies have shown, the 2Cs are mainly metabolized by O-demethylation, N-acetylation, or deamination. Therefore, the aim of this study was to elucidate the role of the recombinant human N-acetyltransferase (NAT) isoforms 1 and 2 in the phase II metabolism of 2Cs. For these studies, cDNA-expressed recombinant human NATs were used and formation of metabolites after incubation was measured using GC-MS. NAT2 could be shown to be the only isoform catalyzing the reaction in vitro, hence it should be the only relevant enzyme for in vivo acetylation. In general, all metabolite formation reactions followed classic Michaelis-Menten kinetics and the affinity to human NAT2 was increasing with the volume of the 4-substituent. In consequence, a slow acetylator phenotype or inhibition of NAT2 could lead to decreased N-acetylation and might lead to an increased risk of side effects caused by these novel psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Chloroplast-encoded serotonin N-acetyltransferase in the red alga Pyropia yezoensis: gene transition to the nucleus from chloroplasts.

    Science.gov (United States)

    Byeon, Yeong; Yool Lee, Hyoung; Choi, Dong-Woog; Back, Kyoungwhan

    2015-02-01

    Melatonin biosynthesis involves the N-acetylation of arylalkylamines such as serotonin, which is catalysed by serotonin N-acetyltransferase (SNAT), the penultimate enzyme of melatonin biosynthesis in both animals and plants. Here, we report the functional characterization of a putative N-acetyltransferase gene in the chloroplast genome of the alga laver (Pyropia yezoensis, formerly known as Porphyra yezoensis) with homology to the rice SNAT gene. To confirm that the putative Pyropia yezoensis SNAT (PySNAT) gene encodes an SNAT, we cloned the full-length chloroplastidic PySNAT gene by PCR and purified the recombinant PySNAT protein from Escherichia coli. PySNAT was 174 aa and had 50% amino acid identity with cyanobacteria SNAT. Purified recombinant PySNAT showed a peak activity at 55 °C with a K m of 467 µM and V max of 28 nmol min-1 mg(-1) of protein. Unlike other plant SNATs, PySNAT localized to the cytoplasm due to a lack of N-terminal chloroplast transit peptides. Melatonin was present at 0.16ng g(-1) of fresh mass but increased during heat stress. Phylogenetic analysis of the sequence suggested that PySNAT has evolved from the cyanobacteria SNAT gene via endosymbiotic gene transfer. Additionally, the chloroplast transit peptides of plant SNATs were acquired 1500 million years ago, concurrent with the appearance of green algae. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: Role of myeloperoxidase and arylamine free radicals.

    Science.gov (United States)

    Khan, Saifur R; Baghdasarian, Argishti; Nagar, Prarthna H; Fahlman, Richard; Jurasz, Paul; Michail, Karim; Aljuhani, Naif; Siraki, Arno G

    2015-09-01

    In this study, the cellular effects resulting from the metabolism of aminoglutethimide by myeloperoxidase were investigated. Human promyelocytic leukemia (HL-60) cells were treated with aminoglutethimide (AG), an arylamine drug that has a risk of adverse drug reactions, including drug-induced agranulocytosis. HL-60 cells contain abundant amounts of myeloperoxidase (MPO), a hemoprotein, which catalyzes one-electron oxidation of arylamines using H2O2 as a cofactor. Previous studies have shown that arylamine metabolism by MPO results in protein radical formation. The purpose of this study was to determine if pathways associated with a toxic response could be determined from conditions that produced protein radicals. Conditions for AG-induced protein radical formation (with minimal cytotoxicity) were optimized, and these conditions were used to carry out proteomic studies. We identified 43 proteins that were changed significantly upon AG treatment among which 18 were up-regulated and 25 were down-regulated. The quantitative proteomic data showed that AG peroxidative metabolism led to the down-regulation of critical anti-apoptotic proteins responsible for inhibiting the release of pro-apoptotic factors from the mitochondria as well as cytoskeletal proteins such as nuclear lamina. This overall pro-apoptotic response was confirmed with flow cytometry which demonstrated apoptosis to be the main mode of cell death, and this was attenuated by MPO inhibition. This response correlated with the intensity of AG-induced protein radical formation in HL-60 cells, which may play a role in cell death signaling mechanisms.

  16. Genetic variants in microsomal epoxide hydrolase and N-acetyltransferase 2 in susceptibility of IBD in the Danish population

    DEFF Research Database (Denmark)

    Ernst, Anja; Andersen, Vibeke; Østergaard, Mette

    , or severity of disease measured either as need for surgery or azathioprine treatment. Smoking was found to be a risk factor of CD (OR=1.8(1.4; 2.3) Psmoking being a protective factor regarding UC (0.7 (0.5-0.9) P=0.02) which is in agreement with previous findings in other study...... populations. Conclusion. Microsomal epoxide hydrolase and N-acetyltransferase 2 appear not to be important in susceptibility of IBD in the Danish population. Nor did we find convincing evidence of associations between the two polymorphic enzymes and phenotypic features in IBD. Smoking was found to be a risk...... factor of CD and a protective factor regarding UC. Being a complex disease, IBD are most likely dependent on an interaction between genetic and environmental factors....

  17. Structural and functional analysis of the yeast N-acetyltransferase Mpr1 involved in oxidative stress tolerance via proline metabolism.

    Science.gov (United States)

    Nasuno, Ryo; Hirano, Yoshinori; Itoh, Takafumi; Hakoshima, Toshio; Hibi, Takao; Takagi, Hiroshi

    2013-07-16

    Mpr1 (sigma1278b gene for proline-analog resistance 1), which was originally isolated as N-acetyltransferase detoxifying the proline analog L-azetidine-2-carboxylate, protects yeast cells from various oxidative stresses. Mpr1 mediates the L-proline and L-arginine metabolism by acetylating L-Δ(1)-pyrroline-5-carboxylate, leading to the L-arginine-dependent production of nitric oxide, which confers oxidative stress tolerance. Mpr1 belongs to the Gcn5-related N-acetyltransferase (GNAT) superfamily, but exhibits poor sequence homology with the GNAT enzymes and unique substrate specificity. Here, we present the X-ray crystal structure of Mpr1 and its complex with the substrate cis-4-hydroxy-L-proline at 1.9 and 2.3 Å resolution, respectively. Mpr1 is folded into α/β-structure with eight-stranded mixed β-sheets and six α-helices. The substrate binds to Asn135 and the backbone amide of Asn172 and Leu173, and the predicted acetyl-CoA-binding site is located near the backbone amide of Phe138 and the side chain of Asn178. Alanine substitution of Asn178, which can interact with the sulfur of acetyl-CoA, caused a large reduction in the apparent kcat value. The replacement of Asn135 led to a remarkable increase in the apparent Km value. These results indicate that Asn178 and Asn135 play an important role in catalysis and substrate recognition, respectively. Such a catalytic mechanism has not been reported in the GNAT proteins. Importantly, the amino acid substitutions in these residues increased the L-Δ(1)-pyrroline-5-carboxylate level in yeast cells exposed to heat stress, indicating that these residues are also crucial for its physiological functions. These studies provide some benefits of Mpr1 applications, such as the breeding of industrial yeasts and the development of antifungal drugs.

  18. Non-syndromic retinitis pigmentosa due to mutations in the mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT)

    Science.gov (United States)

    Haer-Wigman, Lonneke; Newman, Hadas; Leibu, Rina; Bax, Nathalie M.; Baris, Hagit N; Rizel, Leah; Banin, Eyal; Massarweh, Amir; Roosing, Susanne; Lefeber, Dirk J.; Zonneveld-Vrieling, Marijke N.; Isakov, Ofer; Shomron, Noam; Sharon, Dror; Den Hollander, Anneke I.; Hoyng, Carel B.; Cremers, Frans P.M.; Ben-Yosef, Tamar

    2015-01-01

    Retinitis pigmentosa (RP), the most common form of inherited retinal degeneration, is clinically and genetically heterogeneous and can appear as syndromic or non-syndromic. Mucopolysaccharidosis type IIIC (MPS IIIC) is a lethal disorder, caused by mutations in the heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) gene and characterized by progressive neurological deterioration, with retinal degeneration as a prominent feature. We identified HGSNAT mutations in six patients with non-syndromic RP. Whole exome sequencing (WES) in an Ashkenazi Jewish Israeli RP patient revealed a novel homozygous HGSNAT variant, c.370A>T, which leads to partial skipping of exon 3. Screening of 66 Ashkenazi RP index cases revealed an additional family with two siblings homozygous for c.370A>T. WES in three Dutch siblings with RP revealed a complex HGSNAT variant, c.[398G>C; 1843G>A] on one allele, and c.1843G>A on the other allele. HGSNAT activity levels in blood leukocytes of patients were reduced compared with healthy controls, but usually higher than those in MPS IIIC patients. All patients were diagnosed with non-syndromic RP and did not exhibit neurological deterioration, or any phenotypic features consistent with MPS IIIC. Furthermore, four of the patients were over 60 years old, exceeding by far the life expectancy of MPS IIIC patients. HGSNAT is highly expressed in the mouse retina, and we hypothesize that the retina requires higher HGSNAT activity to maintain proper function, compared with other tissues associated with MPS IIIC, such as the brain. This report broadens the spectrum of phenotypes associated with HGSNAT mutations and highlights the critical function of HGSNAT in the human retina. PMID:25859010

  19. N-acetyltransferase-2 and medical history in bladder cancer cases with a suspected occupational disease (BK 1301) in Germany.

    Science.gov (United States)

    Weistenhofer, Wobbeke; Blaszkewicz, Meinolf; Bolt, Hermann M; Golka, Klaus

    2008-01-01

    In 187 bladder cancer cases reported to the employers' liability insurance association in Germany as suspected cases of an occupational disease produced by aromatic amines, N- acetyltransferase-2 (NAT2) activity status, occupational exposure data, period of latency, and clinical parameters were determined. In 83 out of 187 cases surveyed within the period 1991-1999, the NAT2 acetylator status was investigated by determining the molar ratio of an acetylated and a nonacetylated caffeine metabolite in urine (phenotyping) and/or by NAT2 genotyping according to standard polymerase chain reaction (PCR) protocol. The proportion of slow NAT2 acetylators in the surveyed 83 bladder cancer cases was 67%. In the entire group of surveyed 187 cases, mean duration of exposure was 17.6 yr and mean period of latency was 34.7 yr. Occupational exposures to potential bladder carcinogens were observed in 73 occupations, including chemical industry (25%), and occupations as a painter and/or varnisher (23%) were most often encountered. In 12% of the surveyed bladder cancer cases, a second primary malignancy was observed. The NAT2 distribution observed in the 83 cases is comparable to the proportion in 40 occupationally exposed bladder cancer cases in a Department of Urology located close to a former German production site of benzidine-based azo dyes, but higher than in most studies involving NAT2 genetic status in bladder cancer cases.

  20. Prevalence of the N-Acetyltransferase (NAT2 gene polymorphism 282C>T in Peruvian population and health implications

    Directory of Open Access Journals (Sweden)

    Salazar-Granara Alberto

    2016-03-01

    Full Text Available Objective: To determine the frequency of the C282T polymorphism of the NAT2 gene (N acetyltransferase in Peruvian populations. Field work, focused on exploring genetic risk factor in Peruvian populations, which has influence in the response to drugs and malignancies aetiology. Material and Methods: Cross-sectional study. 166 voluntaries from Lima, Lambayeque, Apurimac, Puno, San Martin, Amazonas and Loreto were enrolled. The sampling was done by convenience and it was use the RFLP-PCR conventional technique was used. Results: The allele frequency were 54% (n=126 for C282 and 46% (n=106 for T282. For the T allele, by its orign , stand out 2 those which origins were Lima 42% (n=25, Amazonas 47% (n=16, San Martin 74% (n=28 and Apurimac 50% (n=13 (X , p>0.05. A global genotype frequency were 26.7% (n=31 for C282/C282, 56.0% (n=65 for C282/T282 and 17.2% (n=20 for T282/T282 (Hardy Weinberg Test p>0.05. By origin, Puno presented allelic imbalance (Hardy Weinberg test p0.05. Conclusion: The overall frequency of NAT2 allele T282 was 46%; San Martin had the highest prevalence (74%. The T282 allele is linked to neoplastic diseases and adverse reactions to anti-TB drugs, these results will be used for the application of pharmacogenetics in Peru

  1. Prevalence of the N-Acetyltransferase (NAT2 gene polymorphism 282C>T in Peruvian population and health implications

    Directory of Open Access Journals (Sweden)

    Salazar-Granara Alberto

    2016-01-01

    Full Text Available Objective: To determine the frequency of the C282T polymorphism of the NAT2 gene (N acetyltransferase in Peruvian populations. Field work, focused on exploring genetic risk factor in Peruvian populations, which has influence in the response to drugs and malignancies aetiology. Material and Methods: Cross-sectional study. 166 voluntaries from Lima, Lambayeque, Apurimac, Puno, San Martin, Amazonas and Loreto were enrolled. The sampling was done by convenience and it was use the RFLP-PCR conventional technique was used.Results: The allele frequency were 54% (n=126 for C282 and 46% (n=106 for T282. For the T allele, by its orign , stand out 2 those which origins were Lima 42% (n=25, Amazonas 47% (n=16, San Martin 74% (n=28 and Apurimac 50% (n=13 (X ,p>0.05. A global genotype frequency were 26.7% (n=31 for C282/C282, 56.0% (n=65 for C282/T282 and 17.2% (n=20 for T282/T282 (Hardy Weinberg Test p>0.05. By origin, Puno presented allelic imbalance (Hardy Weinberg test p0.05. Conclusion: The overall frequency of NAT2 allele T282 was 46%; San Martin had the highest prevalence (74%. The T282 allele is linked to neoplastic dis

  2. Melatonin production in Escherichia coli by dual expression of serotonin N-acetyltransferase and caffeic acid O-methyltransferase.

    Science.gov (United States)

    Byeon, Yeong; Back, Kyoungwhan

    2016-08-01

    Melatonin is a well-known bioactive molecule produced in animals and plants and a well-studied natural compound. Two enzymatic steps are required for the biosynthesis of melatonin from serotonin. First, serotonin N-acetyltransferase (SNAT) catalyzes serotonin to N-acetylserotonin (NAS) followed by the action of N-acetylserotonin O-methyltransferase (ASMT), resulting in the synthesis of O-methylated NAS, also known as melatonin. Attempts to document melatonin production in Escherichia coli have been unsuccessful to date due to either low enzyme activity or inactive ASMT expression. Here, we employed caffeic acid O-methyltransferase (COMT) instead of ASMT, as COMT is a multifunctional enzyme that has ASMT activity as well. Among several combinations of dual expression cassettes, recombinant E. coli that expressed sheep SNAT with rice COMT produced a high quantity of melatonin, which was measured in a culture medium (1.46 mg/L in response to 1 mM serotonin). This level was several orders of magnitude higher than that produced in transgenic rice and tomato overexpressing sheep SNAT and ASMT, respectively. This heterologous expression system can be widely employed to screen various putative SNAT or ASMT genes from animals and plants as well as to overproduce melatonin in various useful microorganisms.

  3. Association between N-Acetyltransferase 2 Polymorphism and Bladder Cancer Risk: a Meta-Analysis in a Single Ethnic Group.

    Science.gov (United States)

    Xu, Wan-Jiang; Wen, Li-Ping; Jiang, Xiang-Xin; Ye, Li-Yin; Meng, Fan-Hua; Guan, Sheng; Qian, Ying-Jun; Wei, Jing-Feng

    2017-02-01

    Many studies have evaluated the correlation between N-acetyltransferase 2 (NAT2) slow acetylation genotype and bladder cancer risk. However, the results are inconsistent and remain to be confirmed in each ethnic group. To assess the effects of NAT2 acetylation status on the risk of bladder cancer in the Chinese population, a meta-analysis was performed. Studies were identified using PubMed and Chinese databases through February 2016. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). This meta-analysis included 10 studies with 896 bladder cancer cases and 1188 controls. In the overall analysis, NAT2 slow acetylation phenotype was significantly associated with an increased risk of bladder cancer in the Chinese population (OR = 1.68, 95% CI = 1.11 - 2.53). In the subgroup analyses by geographic areas and sources of controls, significant risk was found in Mainland China (OR = 1.83, 95% CI = 1.04 - 3.20) and hospitalbased studies (OR = 1.74, 95% CI = 1.27 - 2.38), but not in Taiwan China. This meta-analysis suggested that the NAT2 slow acetylation genotype is associated with an increased bladder cancer risk in Chinese individuals.

  4. N-Acetylation of p-aminobenzoic acid and p-phenylenediamine in primary porcine urinary bladder epithelial cells and in the human urothelial cell line 5637.

    Science.gov (United States)

    Föllmann, Wolfram; Blaszkewicz, Meinolf; Behm, Claudia; Degen, Gisela H; Golka, Klaus

    2012-01-01

    N-Acetyltransferases (NAT) are important enzymes in the metabolism of certain carcinogenic arylamines, as N-acetylation decreases or prevents their bioactivation via N-hydroxylation. To study such processes in the bladder, cell culture models may be used, but metabolic competence needs to be characterized. This study focused on the N-acetylation capacity of two urothelial cell systems, using p-aminobenzoic acid (PABA) and the hair dye precursor p-phenylenediamine (PPD), two well-known substrates of the enzyme NAT1. The constitutive NAT1 activity was investigated using primary cultures of porcine urinary bladder epithelial cells (PUBEC) and in the human urothelial cell line 5637 to assess their suitability for further in vitro studies on PABA and PPD-induced toxicity. N-Acetylation of PABA and PPD was determined by high-performance liquid chromatography (HPLC) analysis in cytosols of the two cell systems upon incubation with various substrate levels for up to 60 min. The primary PUBEC revealed higher N-acetylation rates (2.5-fold for PABA, 5-fold for PPD) compared to the 5637 cell line, based on both PABA conversion to its acetylated metabolite and formation of mono- and diacetylated PPD. The urothelial cell systems may thus be useful as a tool for further studies on the N-acetylation of aromatic amines via NAT1.

  5. Catalytic Mechanism of Perosamine N-Acetyltransferase Revealed by High-Resolution X-ray Crystallographic Studies and Kinetic Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Thoden, James B.; Reinhardt, Laurie A.; Cook, Paul D.; Menden, Patrick; Cleland, W.W.; Holden, Hazel M. (UW); (Mount Union); (UW-MED)

    2012-09-17

    N-Acetylperosamine is an unusual dideoxysugar found in the O-antigens of some Gram-negative bacteria, including the pathogenic Escherichia coli strain O157:H7. The last step in its biosynthesis is catalyzed by PerB, an N-acetyltransferase belonging to the left-handed {beta}-helix superfamily of proteins. Here we describe a combined structural and functional investigation of PerB from Caulobacter crescentus. For this study, three structures were determined to 1.0 {angstrom} resolution or better: the enzyme in complex with CoA and GDP-perosamine, the protein with bound CoA and GDP-N-acetylperosamine, and the enzyme containing a tetrahedral transition state mimic bound in the active site. Each subunit of the trimeric enzyme folds into two distinct regions. The N-terminal domain is globular and dominated by a six-stranded mainly parallel {beta}-sheet. It provides most of the interactions between the protein and GDP-perosamine. The C-terminal domain consists of a left-handed {beta}-helix, which has nearly seven turns. This region provides the scaffold for CoA binding. On the basis of these high-resolution structures, site-directed mutant proteins were constructed to test the roles of His 141 and Asp 142 in the catalytic mechanism. Kinetic data and pH-rate profiles are indicative of His 141 serving as a general base. In addition, the backbone amide group of Gly 159 provides an oxyanion hole for stabilization of the tetrahedral transition state. The pH-rate profiles are also consistent with the GDP-linked amino sugar substrate entering the active site in its unprotonated form. Finally, for this investigation, we show that PerB can accept GDP-3-deoxyperosamine as an alternative substrate, thus representing the production of a novel trideoxysugar.

  6. Differential regulation of arylalkylamine N-acetyltransferase activity in chicken retinal ganglion cells by light and circadian clock.

    Science.gov (United States)

    Valdez, Diego J; Garbarino-Pico, Eduardo; Díaz, Nicolás M; Silvestre, David C; Guido, Mario E

    2012-10-01

    Retinal ganglion cells (RGCs) contain circadian clocks driving melatonin synthesis during the day, a subset of these cells acting as nonvisual photoreceptors sending photic information to the brain. In this work, the authors investigated the temporal and light regulation of arylalkylamine N-acetyltransferase (AA-NAT) activity, a key enzyme in melatonin synthesis. The authors first examined this activity in RGCs of wild-type chickens and compared it to that in photoreceptor cells (PRs) from animals maintained for 48 h in constant dark (DD), light (LL), or regular 12-h:12-h light-dark (LD) cycle. AA-NAT activity in RGCs displayed circadian rhythmicity, with highest levels during the subjective day in both DD and LL as well as in the light phase of the LD cycle. In contrast, AA-NAT activity in PRs exhibited the typical nocturnal peak in DD and LD, but no detectable oscillation was observed under LL, under which conditions the levels were basal at all times examined. A light pulse of 30-60 min significantly decreased AA-NAT activity in PRs during the subjective night, but had no effect on RGCs during the day or night. Intraocular injection of dopamine (50 nmol/eye) during the night to mimic the effect of light presented significant inhibition of AA-NAT activity in PRs compared to controls but had no effect on RGCs. The results clearly demonstrate that the regulation of the diurnal increase in AA-NAT activity in RGCs of chickens undergoes a different control mechanism from that observed in PRs, in which the endogenous clock, light, and dopamine exhibited differential effects.

  7. Cigarette smoking, N-acetyltransferase 2 genotypes, and breast cancer risk: pooled analysis and meta-analysis.

    Science.gov (United States)

    Ambrosone, Christine B; Kropp, Silke; Yang, Jun; Yao, Song; Shields, Peter G; Chang-Claude, Jenny

    2008-01-01

    Approximately 10 years ago, it was noted that smoking increased risk of breast cancer among women with N-acetyltransferase 2 (NAT2) slow acetylation genotypes. This report was followed by a number of studies to address this question. We pooled data from 10 existing studies and also conducted a meta-analysis of 13 studies published from 1996 to October 2006 that were conducted among women, were published in English, and had adequate information on smoking and NAT2 genotyping. Raw data were requested from authors. Unconditional logistic regression was done for pooled analysis, and random effect models was done for meta-analysis. Study heterogeneity was assessed, and sensitivity tests were done when subgroups were excluded from the analysis. In the pooled analysis, there was a significant interaction between smoking, NAT2 genotype, and risk of breast cancer [pack-years (continuous variable, P(interaction) = 0.03)], with higher pack-years significantly associated with an increased risk of breast cancer among women with NAT2 slow genotypes (pooled analysis relative risk, 1.49; 95% confidence interval, 1.08-2.04). These findings were supported by the meta-analysis including all studies; pack-years were significantly associated with risk among slow acetylators in a dose-dependent fashion (meta-analysis relative risk, 1.44; 95% confidence interval, 1.23-1.68 for > or =20 pack-years versus never smokers), but not among rapid acetylators. Similar relationships were noted for smoking status (ever, never) and duration of smoking. Our results show that cigarette smoking is associated with an increase in breast cancer risk among women with NAT2 slow acetylation genotypes. Because slow NAT2 genotypes are present in 50% to 60% of Caucasian populations, smoking is likely to play an important role in breast cancer etiology.

  8. Modification of N-acetyltransferases and glutathione S-transferases by coffee components: possible relevance for cancer risk.

    Science.gov (United States)

    Huber, Wolfgang W; Parzefall, Wolfram

    2005-01-01

    Enzymes of xenobiotic metabolism are involved in the activation and detoxification of carcinogens and can play a pivotal role in the susceptibility of individuals toward chemically induced cancer. Differences in such susceptibility are often related to genetically predetermined enzyme polymorphisms but may also be caused by enzyme induction or inhibition through environmental factors or in the frame of chemopreventive intervention. In this context, coffee consumption, as an important lifestyle factor, has been under thorough investigation. Whereas the data on a potential procarcinogenic effect in some organs remained inconclusive, epidemiology has clearly revealed coffee drinkers to be at a lower risk of developing cancers of the colon and the liver and possibly of several other organs. The underlying mechanisms of such chemoprotection, modifications of xenobiotic metabolism in particular, were further investigated in rodent and in vitro models, as a result of which several individual chemoprotectants out of the >1000 constituents of coffee were identified as well as some strongly metabolized individual carcinogens against which they specifically protected. This chapter discusses the chemoprotective effects of several coffee components and whole coffee in association with modifications of the usually protective glutathione-S-transferase (GST) and the more ambivalent N-acetyltransferase (NAT). A key role is played by kahweol and cafestol (K/C), two diterpenic constituents of the unfiltered beverage that were found to reduce mutagenesis/tumorigenesis by strongly metabolized compounds, such as 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, 7,12-dimethylbenz[a]anthracene, and aflatoxin B(1), and to cause various modifications of xenobiotic metabolism that were overwhelmingly beneficial, including induction of GST and inhibition of NAT. Other coffee components such as polyphenols and K/C-free coffee are also capable of increasing GST and partially of inhibiting NAT

  9. MicroRNAs in the pineal gland: miR-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase.

    Science.gov (United States)

    Clokie, Samuel J H; Lau, Pierre; Kim, Hyun Hee; Coon, Steven L; Klein, David C

    2012-07-20

    MicroRNAs (miRNAs) play a broad range of roles in biological regulation. In this study, rat pineal miRNAs were profiled for the first time, and their importance was evaluated by focusing on the main function of the pineal gland, melatonin synthesis. Massively parallel sequencing and related methods revealed the miRNA population is dominated by a small group of miRNAs as follows: ~75% is accounted for by 15 miRNAs; miR-182 represents 28%. In addition to miR-182, miR-183 and miR-96 are also highly enriched in the pineal gland, a distinctive pattern also found in the retina. This effort also identified previously unrecognized miRNAs and other small noncoding RNAs. Pineal miRNAs do not exhibit a marked night/day difference in abundance with few exceptions (e.g. 2-fold night/day differences in the abundance of miR-96 and miR-182); this contrasts sharply with the dynamic 24-h pattern that characterizes the pineal transcriptome. During development, the abundance of most pineal gland-enriched miRNAs increases; however, there is a marked decrease in at least one, miR-483. miR-483 is a likely regulator of melatonin synthesis, based on the following. It inhibits melatonin synthesis by pinealocytes in culture; it acts via predicted binding sites in the 3"-UTR of arylalkylamine N-acetyltransferase (Aanat) mRNA, the penultimate enzyme in melatonin synthesis, and it exhibits a developmental profile opposite to that of Aanat transcripts. Additionally, a miR-483 targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR-483 suppresses Aanat mRNA levels during development and that the developmental decrease in miR-483 abundance promotes melatonin synthesis.

  10. The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH2 in antibacterial activity

    OpenAIRE

    Yan, Xuxu; GAO Feng; Yotphan, Sirilata; Bakirtzian, Parseh; Auclair, Karine

    2007-01-01

    Aminoglycoside antibiotics act by binding to 16S rRNA. Resistance to these antibiotics occurs via drug modifications by enzymes such as aminoglycoside 6′-N-acetyltransferases (AAC(6′)s). We report here the regioselective and efficient synthesis of N-6′-acylated aminoglycosides and their use as probes to study AAC(6′)-Ii and aminoglycoside-RNA complexes. Our results emphasize the central role of N-6′ nucleophilicity for transformation by AAC(6′)-Ii and the importance of hydrogen bonding betwee...

  11. Structure-based molecular design for thermostabilization of N-acetyltransferase Mpr1 involved in a novel pathway of L-arginine synthesis in yeast.

    Science.gov (United States)

    Nasuno, Ryo; Hirase, Saeka; Norifune, Saki; Watanabe, Daisuke; Takagi, Hiroshi

    2016-02-01

    Previously, N-Acetyltransferase Mpr1 was suggested to be involved in a novel pathway of L-arginine biosynthesis in yeast. Our recent crystallographic analysis demonstrated that the overall structure of Mpr1 is a typical folding among proteins in the Gcn5-related N-acetyltransferase superfamily, and also provided clues to the design of mutations for improvement of the enzymatic functions. Here, we constructed new stable variants, Asn203Lys- and Asn203Arg-Mpr1, which exhibited 2.4-fold and 2.2-fold longer activity half-lives than wild-type Mpr1, respectively, by structure-based molecular design. The replacement of Asn203 with a basic amino acid was suggested to stabilize α-helix 2, which is important for the Mpr1 structure, probably by neutralizing its dipole. In addition, the combination of two amino acid substitutions at positions 65 and 203 in Mpr1, Phe65Leu, which was previously isolated by the screening from PCR random mutagenesis library of MPR1, and Asn203Lys or Asn203Arg, led to further stabilization of Mpr1. Our growth assay suggests that overexpression of the stable Mpr1 variants increase L-arginine synthesis in yeast cells. Our finding is the first report on the rational engineering of Mpr1 for thermostabilization and could be useful in the construction of new yeast strains with higher L-arginine synthetic activity and also improved fermentation ability.

  12. Base-oxidant promoted metal-free N-demethylation of arylamines

    Indian Academy of Sciences (India)

    VINAYAK BOTLA; CHIRANJEEVI BARREDDI; RAMANA V DAGGUPATI; CHANDRASEKHARAM MALAPAKA

    2016-09-01

    A metal-free oxidative N-demethylation of arylamines with triethylamine as a base and tert-butyl hydroperoxide (TBHP) as oxidant is reported in this paper. The reaction is general, practical, inexpensive, non-toxic, and the method followed is environmentally benign, with moderate to good yields.

  13. Palladium-catalyzed aerobic dehydrogenative aromatization of cyclohexanone imines to arylamines.

    Science.gov (United States)

    Hajra, Alakananda; Wei, Ye; Yoshikai, Naohiko

    2012-11-02

    Dehydrogenative aromatization of cyclohexanone imines to arylamines has been achieved using a palladium catalyst under aerobic conditions. The reaction is applicable to a variety of imines that are either preformed or generated in situ from cyclohexanone derivatives and aryl or alkylamines.

  14. Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

    Directory of Open Access Journals (Sweden)

    Jing Sun

    2012-10-01

    Full Text Available In the presence of p-toluenesulfonic acid as catalyst the domino reaction of arylamines, methyl propiolates and aromatic aldehydes in ethanol proceeded smoothly to give polysubstituted 1,2,3,4-tetrahydroquinolines in moderate yields. The reaction is believed to involve the Povarov reaction of in situ generated β-enamino ester with the in situ formed aromatic imine.

  15. Modifying effect of N-acetyltransferase 2 genotype on the association between systemic lupus erythematosus and consumption of alcohol and caffeine-rich beverages.

    Science.gov (United States)

    Kiyohara, Chikako; Washio, Masakazu; Horiuchi, Takahiko; Asami, Toyoko; Ide, Saburo; Atsumi, Tatsuya; Kobashi, Gen; Takahashi, Hiroki; Tada, Yoshifumi

    2014-07-01

    N-acetyltransferase 2 (NAT2) is involved in the metabolism of various environmental substances, both with and without carcinogenic potential. Alcoholic and nonalcoholic caffeine-rich beverages may be associated with markers of inflammation. Systemic lupus erythematosus (SLE) is a chronic, multifaceted inflammatory disease. We investigated the effects of alcoholic and nonalcoholic caffeine-rich beverages on risk of SLE and determined whether the effects were modified by NAT2 status. The NAT2 polymorphism was genotyped in 152 SLE cases and 427 healthy controls, all women and Japanese. We assessed effect modification by testing an interaction term for the NAT2 polymorphism and consumption of beverages. Consumption of black tea (odds ratio [OR] 1.88, 95% confidence interval [95% CI] 1.03-3.41) and coffee (OR 1.57, 95% CI 0.95-2.61), but not green tea, was associated with an increased risk of SLE, while alcohol use (OR 0.33, 95% CI 0.20-0.55) was associated with a decreased risk of SLE. There were significant interactions between the NAT2 polymorphism and either alcohol use (Pinteraction = 0.026) or consumption of black tea (Pinteraction = 0.048). The NAT2 polymorphism significantly modified the effects of alcohol use and black tea consumption on SLE, emphasizing the importance of incorporating genetic and metabolic information in studies on management of SLE. Additional studies are warranted to confirm the findings suggested in this study. Copyright © 2014 by the American College of Rheumatology.

  16. Small angle X-ray scattering data and structure factor fitting for the study of the quaternary structure of the spermidine N-acetyltransferase SpeG

    Directory of Open Access Journals (Sweden)

    Steven Weigand

    2016-03-01

    Full Text Available Here we describe the treatment of the small-angle X-ray Scattering (SAXS data used during SpeG quaternary structure study as part of the research article “Substrate induced allosteric change in the quaternary structure of the spermidine N-acetyltransferase SpeG” published in Journal of Molecular Biology [1]. These data were collected on two separate area detectors as separate dilution series of the SpeG and the SpeG with spermine samples along with data from their companion buffers. The data were radially integrated, corrected for incident beam variation, and scaled to absolute units. After subtraction of volume-fraction scaled buffer scattering and division by the SpeG concentration, multiple scattering curves free of an inter-molecular structure factor were derived from the dilution series. Rather than extrapolating to infinite dilution, the structure factor contribution was estimated by fitting to the full set of data provided by dividing the scattering curves of a dilution series by the curve from the most dilute sample in that series.

  17. Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)

    Science.gov (United States)

    Zhao, Minzhi; Li, Haiyun; Ma, Yan; Gong, He; Yang, Shu; Fang, Qiaojun; Hu, Zhiyuan

    2017-01-01

    Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes.

  18. Transgenic tobacco simultaneously overexpressing glyphosate N-acetyltransferase and 5-enolpyruvylshikimate-3-phosphate synthase are more resistant to glyphosate than those containing one gene.

    Science.gov (United States)

    Liu, Yunjun; Cao, Gaoyi; Chen, Rongrong; Zhang, Shengxue; Ren, Yuan; Lu, Wei; Wang, Jianhua; Wang, Guoying

    2015-08-01

    5-Enolpyruvylshikimate-3-phosphate synthase (EPSPS) and glyphosate N-acetyltransferase (GAT) can detoxify glyphosate by alleviating the suppression of shikimate pathway. In this study, we obtained transgenic tobacco plants overexpressing AM79 aroA, GAT, and both of them, respectively, to evaluate whether overexpression of both genes could confer transgenic plants with higher glyphosate resistance. The transgenic plants harboring GAT or AM79 aroA, respectively, showed good glyphosate resistance. As expected, the hybrid plants containing both GAT and AM79 aroA exhibited improved glyphosate resistance than the transgenic plants overexpressing only a single gene. When grown on media with high concentration of glyphosate, seedlings containing a single gene were severely inhibited, whereas plants expressing both genes were affected less. When transgenic plants grown in the greenhouse were sprayed with glyphosate, less damage was observed for the plants containing both genes. Metabolomics analysis showed that transgenic plants containing two genes could maintain the metabolism balance better than those containing one gene after glyphosate treatment. Glyphosate treatment did not lead to a huge increase of shikimate contents of tobacco leaves in transgenic plants overexpressing two genes, whereas significant increase of shikimate contents in transgenic plants containing only a single gene was observed. These results demonstrated that pyramiding both aroA and GAT in transgenic plants can enhance glyphosate resistance, and this strategy can be used for the development of transgenic glyphosate-resistant crops.

  19. Circadian dynamics of the cone-rod homeobox (CRX) transcription factor in the rat pineal gland and its role in regulation of arylalkylamine N-acetyltransferase (AANAT).

    Science.gov (United States)

    Rohde, Kristian; Rovsing, Louise; Ho, Anthony K; Møller, Morten; Rath, Martin F

    2014-08-01

    The cone-rod homeobox (Crx) gene encodes a transcription factor in the retina and pineal gland. Crx deficiency influences the pineal transcriptome, including a reduced expression of arylalkylamine N-acetyltransferase (Aanat), a key enzyme in nocturnal pineal melatonin production. However, previous functional studies on pineal Crx have been performed in melatonin-deficient mice. In this study, we have investigated the role of Crx in the melatonin-proficient rat pineal gland. The current study shows that pineal Crx transcript levels exhibit a circadian rhythm with a peak in the middle of the night, which is transferred into daily changes in CRX protein. The study further shows that the sympathetic innervation of the pineal gland controls the Crx rhythm. By use of adenovirus-mediated short hairpin RNA gene knockdown targeting Crx mRNA in primary rat pinealocyte cell culture, we here show that intact levels of Crx mRNA are required to obtain high levels of Aanat expression, whereas overexpression of Crx induces Aanat transcription in vitro. This regulatory function of Crx is further supported by circadian analysis of Aanat in the pineal gland of the Crx-knockout mouse. Our data indicate that the rhythmic nature of pineal CRX protein may directly modulate the daily profile of Aanat expression by inducing nighttime expression of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to its role in ensuring a correct tissue distribution of Aanat expression.

  20. Daily oscillation and photoresponses of clock gene, Clock, and clock-associated gene, arylalkylamine N-acetyltransferase gene transcriptions in the rat pineal gland.

    Science.gov (United States)

    Wang, Guo-Qing; Du, Yu-Zhen; Tong, Jian

    2007-01-01

    This study was conducted to investigate the circadian rhythms and light responses of Clock and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the environmental conditions of a 12 h light (05:00-17:00 h): 12 h-dark (17:00-05:00 h) cycle (LD) and constant darkness (DD). The pineal gland of Sprague-Dawley rats housed under a LD regime (n=42) for four weeks and of a regime (n=42) for eight weeks were sampled at six different times, every 4 h (n=7 animals per time point), during a 24 h period. Total RNA was extracted from each sample, and the semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine temporal changes in mRNA levels of Clock and NAT genes during different circadian or zeitgeber times. The data and parameters were analyzed by the cosine function software, Clock Lab software, and the amplitude F test was used to reveal the circadian rhythm. In the DD or LD condition, both the Clock and NAT mRNA levels in the pineal gland showed robust circadian oscillation (ppineal gland were significantly reduced (ppineal gland (p>0.05). These findings indicate that the transcriptions of Clock and NAT genes in the pineal gland not only show remarkably synchronous endogenous circadian rhythmic changes, but also respond to the ambient light signal in a reduced manner.

  1. [Circadian rhythms and light responses of clock gene and arylalkylamine N-acetyltransferase gene expressions in the pineal gland of rats].

    Science.gov (United States)

    Wang, Guo-Qing; Du, Yu-Zhen; Tong, Jian

    2005-02-25

    This study was to investigate the circadian rhythms and light responses of Clock gene and arylalkylamine N-acetyltransferase (NAT) gene expressions in the rat pineal gland under the 12 h-light : 12 h-dark cycle condition (LD) and constant darkness (DD). Sprague-Dawley rats housed under the light regime of LD (n=36) for 4 weeks and of DD (n=36) for 8 weeks were sampled for the pineal gland once a group (n=6) every 4 h in a circadian day. The total RNA was extracted from each sample and the semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was used to determine the temporal changes in mRNA levels of Clock and NAT genes during different circadian times or zeitgeber times. The data were analysed by the cosine function software, Clock Lab software and the amplitude F test was used to reveal the circadian rhythm. The main results obtained are as follows. (1) In DD or LD condition, both of Clock and NAT genes mRNA levels in the pineal gland showed robust circadian oscillation (Ppineal gland were significantly reduced (Ppineal gland (P> 0.05). These findings suggest that the expressions of Clock and NAT genes in the pineal gland not only show remarkably synchronous endogenous circadian rhythmic changes, but also response to the ambient light signal in a reduced manner.

  2. Eight hours of nocturnal 915 MHz radiofrequency identification (RFID) exposure reduces urinary levels of melatonin and its metabolite via pineal arylalkylamine N-acetyltransferase activity in male rats.

    Science.gov (United States)

    Kim, Hye Sun; Paik, Man-Jeong; Lee, Yu Hee; Lee, Yun-Sil; Choi, Hyung Do; Pack, Jeong-Ki; Kim, Nam; Ahn, Young Hwan

    2015-01-01

    We investigated the effects of whole-body exposure to the 915 MHz radiofrequency identification (RFID) on melatonin biosynthesis and the activity of rat pineal arylalkylamine N-acetyltransferase (AANAT). Rats were exposed to RFID (whole-body specific absorption rate, 4 W/kg) for 8 h/day, 5 days/week, for weeks during the nighttime. Total volume of urine excreted during a 24-h period was collected after RFID exposure. Urinary melatonin and 6-hydroxymelatonin sulfate (6-OHMS) was measured by gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), respectively. AANAT enzyme activity was measured using liquid biphasic dif-13 fusion assay. Protein levels and mRNA expression of AANAT was 14 measured by Western blot and reverse transcription polymerase 15 chain reaction (RT-PCR) analysis, respectively. Eight hours of nocturnal RFID exposure caused a significant reduction in both urinary melatonin (p = 0. 003) and 6-OHMS (p = 0. 026). Activity, protein levels, and mRNA expression of AANAT were suppressed by exposure to RFID (p RFID exposure can cause reductions in the levels of both urinary melatonin and 6-OHMS, possibly due to decreased melatonin biosynthesis via suppression of Aanat gene transcription in the rat pineal gland.

  3. Modifying CH3NH3PbBr3 nanocrystals with arylamines

    Science.gov (United States)

    Zhu, Ruimin; Liu, Heyuan; Shen, Li; Sun, Dejun; Li, Xiyou

    2017-04-01

    Chemically decorating CH3NH3PbBr3 with a group of para-substituted arylamine (R-An) was investigated, where R ranges from electron-withdrawing trifluoromethoxy(-CF3O), to hydrogen or electron-donating ethoxy (-EtO). Different ratios of R-An ammonium bromide and methylammonium bromide (MA) (R-An/MA=3/7, 4/6, 5/5, 6/4 and 7/3) were tested. XRD patterns revealed that the perovskite nanocomposite were cubic with good crystallinity. TEM and photoluminescence suggested that the perovskite nanocrystals were composed of 2D layered and 3D bulk structures. 1H NMR and TGA experiments revealed that the non-substituted aniline can readily adsorb to the surface of perovskite at any ratios between R-An and MA. But an EtOAn/MA ratio ≥1 is needed to anchor the EOAn molecules on the surface of perovskite. For the arylamine with the electron-withdrawing -CF3O group, it cannot adsorb to the surface of the perovskite at any concentrations. This result reveals that both steric hindrance and alkalinity can affect the anchoring of arylamine on the surface of CH3NH3PbBr3 perovskite. I-V curves of the perovskite nanocrystal films prepared by spin coating suggest that proper surface modification can increase the conductivity significantly.

  4. N-Acetyltransferase 2 and glutathione s-transferase M1 in colon and rectal cancer cases from an industrialized area.

    Science.gov (United States)

    Golka, Klaus; Roemer, Hermann C; Weistenhöfer, Wobbeke; Blaszkewicz, Meinolf; Hammad, Seddik; Reckwitz, Thomas; Loehlein, Dietrich; Hartel, Mark; Hengstler, Jan G; Geller, Frank

    2012-01-01

    Apart from genetics, nutrition, and environment, occupational factors also play an important role in colon and rectal cancer development. The aim of this study was to examine these cancer types in an area of former coal, iron, and steel industries, which was found to display an increased incidence of colon cancer mortality. N-Acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) genotypes were investigated in 108 colon cancer cases, 80 rectum cancer cases, and 188 controls (suffering from nonmalignant diseases). Further, in a pilot study, 28 colorectal cancer patients were NAT2 phenotyped by the caffeine test. Possible occupational and nonoccupational risk factors were investigated by a personal interview. The frequency of rapid NAT2 genotype was 35% in colon cancer cases, 47% in rectal cancer cases, and 42% in controls (GSTM1 0/0 genotype: 53, 46, and 47%, respectively). In the 29 patients with cancer in the ascending colon, 10% were of the rapid NAT2 genotype. In the pilot study the frequency of the rapid NAT2 phenotype was 49%. The only major professional group with an elevated risk was painters (colon cancer OR 2.48, 95% CI 0.4-15.23; rectal cancer OR 5.65, 95% CI 1.06-30.21). In contrast to early studies, in the present study the slow NAT2 status is overrepresented. As colorectal cancer is associated with nutrition and physical activity, present findings may be due to excessive physical heavy work and the resulting nutrition in this area.

  5. Refinement of the prediction of N-acetyltransferase 2 (NAT2) phenotypes with respect to enzyme activity and urinary bladder cancer risk.

    Science.gov (United States)

    Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Hengstler, Jan G; Golka, Klaus

    2013-12-01

    Polymorphisms of N-acetyltransferase 2 (NAT2) are well known to modify urinary bladder cancer risk as well as efficacy and toxicity of pharmaceuticals via reduction in the enzyme's acetylation capacity. Nevertheless, the discussion about optimal NAT2 phenotype prediction, particularly differentiation between different degrees of slow acetylation, is still controversial. Therefore, we investigated the impact of single nucleotide polymorphisms and their haplotypes on slow acetylation in vivo and on bladder cancer risk. For this purpose, we used a study cohort of 1,712 bladder cancer cases and 2,020 controls genotyped for NAT2 by RFLP-PCR and for the tagSNP rs1495741 by TaqMan(®) assay. A subgroup of 344 individuals was phenotyped by the caffeine test in vivo. We identified an 'ultra-slow' acetylator phenotype based on combined *6A/*6A, *6A/*7B and *7B/*7B genotypes containing the homozygous minor alleles of C282T (rs1041983, *6A, *7B) and G590A (rs1799930, *6A). 'Ultra-slow' acetylators have significantly about 32 and 46 % lower activities of caffeine metabolism compared with other slow acetylators and with the *5B/*5B genotypes, respectively (P < 0.01, both). The 'ultra-slow' genotype showed an association with bladder cancer risk in the univariate analysis (OR = 1.31, P = 0.012) and a trend adjusted for age, gender and smoking habits (OR = 1.22, P = 0.082). In contrast, slow acetylators in general were not associated with bladder cancer risk, neither in the univariate (OR = 1.02, P = 0.78) nor in the adjusted (OR = 0.98, P = 0.77) analysis. In conclusion, this study suggests that NAT2 phenotype prediction should be refined by consideration of an 'ultra-slow' acetylation genotype.

  6. Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1

    Directory of Open Access Journals (Sweden)

    Zhao MZ

    2017-03-01

    Full Text Available Minzhi Zhao,* Haiyun Li,* Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Abraxane (Abr, a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX. To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1, showed significant differential expression (P<0.05 in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. Keywords: quantitative proteomics, nano-drug, drug efficacy, lung cancer, molecular mechanisms, abraxane

  7. Moonlight affects mRNA abundance of arylalkylamine N-acetyltransferase in the retina of a lunar-synchronized spawner, the goldlined spinefoot.

    Science.gov (United States)

    Kashiwagi, Tomomi; Park, Yong-Ju; Park, Ji-Gweon; Imamura, Satoshi; Takeuchi, Yuki; Hur, Sung-Pyo; Takemura, Akihiro

    2013-11-01

    Melatonin synthesis in the pineal gland and retina shows a rhythmic fashion with high levels at night and is controlled by a rate-limiting enzyme, arylalkylamine N-acetyltransferase (AANAT). A previous study revealed that moonlight suppresses the plasma melatonin levels of the goldlined spinefoot (Siganus guttatus), which exhibits a lunar cycle in its reproductive activity and repeats gonadal development toward and spawning around the first quarter moon. Whether the retina of this species responds to moonlight is unknown. To clarify the photoperceptive ability of this species, we aimed to clone the full-length cDNA of Aanat1 (sgAanat1) from the retina and examine its transcriptional pattern under several daylight and moonlight regimes. The full-length sgAanat1 cDNA (1,038 bp) contained a reading frame encoding a protein of 225 amino acids, which was highly homologous to AANAT1 of other teleosts. Reverse transcription-polymerase chain reaction (PCR) analysis revealed that among the tissues tested, sgAanat1 fragments were expressed exclusively in the retina. Real-time quantitative PCR analysis revealed that sgAanat1 fluctuated with high abundance at night under light-dark cycle and at subjective night under constant darkness, but not under constant light. These results suggest that sgAanat1 is regulated by both the external light signal and internal clock system. The abundance of sgAanat1 in the retina was higher at the culmination time around new moon than full moon phase. Additionally, exposing fish to brightness around the full moon period suppressed sgAanat1 mRNA abundance. Thus, moonlight is perceived by fish and has an impact on melatonin fluctuation in the retina. © 2013 Wiley Periodicals, Inc.

  8. Molecular Structure of WlbB, a Bacterial N-Acetyltransferase Involved in the Biosynthesis of 2,3-Diacetamido-2,3-dideoxy-d-mannuronic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Thoden, James B.; Holden, Hazel M. (UW)

    2010-09-08

    The pathogenic bacteria Pseudomonas aeruginosa and Bordetella pertussis contain in their outer membranes the rare sugar 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid. Five enzymes are required for the biosynthesis of this sugar starting from UDP-N-acetylglucosamine. One of these, referred to as WlbB, is an N-acetyltransferase that converts UDP-2-acetamido-3-amino-2,3-dideoxy-D-glucuronic acid (UDP-GlcNAc3NA) to UDP-2,3-diacetamido-2,3-dideoxy-D-glucuronic acid (UDP-GlcNAc3NAcA). Here we report the three-dimensional structure of WlbB from Bordetella petrii. For this analysis, two ternary structures were determined to 1.43 {angstrom} resolution: one in which the protein was complexed with acetyl-CoA and UDP and the second in which the protein contained bound CoA and UDP-GlcNAc3NA. WlbB adopts a trimeric quaternary structure and belongs to the L{beta}H superfamily of N-acyltransferases. Each subunit contains 27 {beta}-strands, 23 of which form the canonical left-handed {beta}-helix. There are only two hydrogen bonds that occur between the protein and the GlcNAc3NA moiety, one between O{sup {delta}1} of Asn 84 and the sugar C-3{prime} amino group and the second between the backbone amide group of Arg 94 and the sugar C-5{prime} carboxylate. The sugar C-3{prime} amino group is ideally positioned in the active site to attack the si face of acetyl-CoA. Given that there are no protein side chains that can function as general bases within the GlcNAc3NA binding pocket, a reaction mechanism is proposed for WlbB whereby the sulfur of CoA ultimately functions as the proton acceptor required for catalysis.

  9. Mild conditions for deuteration of primary and secondary arylamines for the synthesis of deuterated optoelectronic organic molecules.

    Science.gov (United States)

    Krause-Heuer, Anwen M; Yepuri, Nageshwar R; Darwish, Tamim A; Holden, Peter J

    2014-11-13

    Deuterated arylamines demonstrate great potential for use in optoelectronic devices, but their widespread utility requires a method for large-scale synthesis. The incorporation of these deuterated materials into optoelectronic devices also provides the opportunity for studies of the functioning device using neutron reflectometry based on the difference in the scattering length density between protonated and deuterated compounds. Here we report mild deuteration conditions utilising standard laboratory glassware for the deuteration of: diphenylamine, N-phenylnaphthylamine, N-phenyl-o-phenylenediamine and 1-naphthylamine (via H/D exchange in D2O at 80 °C, catalysed by Pt/C and Pd/C). These conditions were not successful in the deuteration of triphenylamine or N,N-dimethylaniline, suggesting that these mild conditions are not suitable for the deuteration of tertiary arylamines, but are likely to be applicable for the deuteration of other primary and secondary arylamines. The deuterated arylamines can then be used for synthesis of larger organic molecules or polymers with optoelectronic applications.

  10. Mild Conditions for Deuteration of Primary and Secondary Arylamines for the Synthesis of Deuterated Optoelectronic Organic Molecules

    Directory of Open Access Journals (Sweden)

    Anwen M. Krause-Heuer

    2014-11-01

    Full Text Available Deuterated arylamines demonstrate great potential for use in optoelectronic devices, but their widespread utility requires a method for large-scale synthesis. The incorporation of these deuterated materials into optoelectronic devices also provides the opportunity for studies of the functioning device using neutron reflectometry based on the difference in the scattering length density between protonated and deuterated compounds. Here we report mild deuteration conditions utilising standard laboratory glassware for the deuteration of: diphenylamine, N-phenylnaphthylamine, N-phenyl-o-phenylenediamine and 1-naphthylamine (via H/D exchange in D2O at 80 °C, catalysed by Pt/C and Pd/C. These conditions were not successful in the deuteration of triphenylamine or N,N-dimethylaniline, suggesting that these mild conditions are not suitable for the deuteration of tertiary arylamines, but are likely to be applicable for the deuteration of other primary and secondary arylamines. The deuterated arylamines can then be used for synthesis of larger organic molecules or polymers with optoelectronic applications.

  11. Tetraphenylmethane-Arylamine Hole-Transporting Materials for Perovskite Solar Cells.

    Science.gov (United States)

    Liu, Xuepeng; Kong, Fantai; Cheng, Tai; Chen, Wangchao; Tan, Zhan'ao; Yu, Ting; Guo, Fuling; Chen, Jian; Yao, Jianxi; Dai, Songyuan

    2017-03-09

    A new class of hole-transporting materials (HTM) containing tetraphenylmethane (TPM) core have been developed. After thermal, charge carrier mobility, and contact angle tests, it was found that TPA-TPM (TPA: arylamine derivates side group) showed higher glass-transition temperature and larger water-contact angle than spiro-OMeTAD with comparable hole mobility. Photoluminescence and impedance spectroscopy studies indicate that TPA-TPM's hole-extraction ability is comparable to that of spiro-OMeTAD. SEM and AFM results suggest that TPA-TPM has a smooth surface. When TPA-TPM is used in mesoscopic perovskite solar cells, power conversion efficiency comparable to that of spiro-OMeTAD is achieved. Notably, the perovskite solar cells employing TPA-TPM show better long-term stability than that of spiro-OMeTAD. Moreover, TPA-TPM can be prepared from relatively inexpensive raw materials with a facile synthetic route. The results demonstrate that TPM-arylamines are a new class of HTMs for efficient and stable perovskite solar cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Pharmacogenomics, biochemistry, toxicology, microbiology and cancer research in one go.

    Science.gov (United States)

    Rodrigues-Lima, Fernando; Dairou, Julien; Laurieri, Nicola; Busi, Florent; Dupret, Jean-Marie

    2011-08-01

    Arylamine N-acetyltransferases (NATs) are phase II xenobiotic metabolizing enzymes playing a key role in the detoxification and metabolic activation of aromatic amine xenobiotics. The triennial International NAT Workshop has been an important academic meeting where developments in the study of NATs and aromatic amine metabolism have been presented. The 2010 Workshop took place in University Paris Diderot Paris, France. Topics included: structures and functions of eukaryotic and prokaryotic NATs, gene regulation and expression of human NATs, polymorphisms and their effects, arylamine metabolism and toxicity. Nomenclature issues were also discussed.

  13. Chromosomal aberrations in humans induced by urban air pollution: influence of DNA repair and polymorphisms of glutathione S-transferase M1 and N-acetyltransferase 2

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, H; Gamborg, M O

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes as a biomar...

  14. Synthesis and characterization of arylamine derivatives of rauwolscine as molecular probes for alpha 2-adrenergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lanier, S.M.; Graham, R.M.; Hess, H.J.; Grodski, A.; Repaske, M.G.; Nunnari, J.M.; Limbird, L.E.; Homcy, C.J.

    1987-06-01

    The selective alpha 2-adrenergic receptor antagonist rauwolscine was structurally modified to yield a series of arylamine carboxamide derivatives, which were investigated as potential molecular probes for the localization and structural characterization of alpha 2-adrenergic receptors. The arylamine carboxamides differ in the number of carbon atoms separating the reactive phenyl moiety from the fused ring structure of the parent compound, rauwolscine carboxylate. Competitive inhibition studies with (/sup 3/H)rauwolscine in rat kidney membranes indicate that the affinity for the carboxamide derivatives is inversely related to the length of the carbon spacer arm with rauwolscine 4-aminophenyl carboxamide exhibiting the highest affinity (Kd = 2.3 +/- 0.2 nM). Radioiodination of rau-AMPC yields a ligand, /sup 125/I-rau-AMPC, which binds to rat kidney alpha 2-adrenergic receptors with high affinity, as determined by both kinetic analysis (Kd = k2/k1 = 0.016 min-1/2.1 X 10(7) M-1 min-1 = 0.76 nM) and equilibrium binding studies (Kd = 0.78 +/- 0.16 nM). /sup 125/I-rau-AMPC was quantitatively converted to the photolabile arylazide derivative 17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-azido-3-(/sup 125/I)iodophenyl) carboxamide (/sup 125/I-rau-AZPC). In a partially purified receptor preparation from porcine brain, this compound photolabels a major (Mr = 62,000) peptide. The labeling of this peptide is inhibited by adrenergic agonists and antagonists with a rank order of potency consistent with an alpha 2-adrenergic receptor binding site. Both /sup 125/I-rau-AMPC and the photolabile arylazide derivative, /sup 125/I-rau-AZPC, should prove useful as molecular probes for the structural and biochemical characterization of alpha 2-adrenergic receptors.

  15. Lewis acid catalyzed cyclization of glycals/2-deoxy-D-ribose with arylamines: additional findings on product structure and reaction diastereoselectivity.

    Science.gov (United States)

    Du, Chengtang; Li, Fulong; Zhang, Xuefeng; Hu, Wenxiang; Yao, Qizheng; Zhang, Ao

    2011-11-01

    The cyclization reactions of arylamines with 2-deoxy-D-ribose or glycals were reinvestigated in the current report. In the montmorillonite KSF- or InCl(3)-initiated reactions of 2-deoxy-D-ribose with arylamines, a pair of diastereomeric tetrahydro-2H-pyran-fused tetrahydroquinolines was obtained in a nearly 1:1 ratio where the structure of one diastereomer was incorrectly assigned in the literature. Meanwhile, the diastereoselectivity in InBr(3)-catalyzed cyclization of glycals with arylamines was also incorrectly reported previously. It was found that high diastereomeric selectivity was achieved only when a C5-substituted glycal was used; otherwise, a pair of diastereomers was obtained in moderate yield with 1:1 diastereomeric ratio. Furthermore, tetrahydrofuran-fused tetrahydroquinolines 5b and 5b' were also prepared successfully by using TBDPS-protected ribose as the glycal precursor and montmorillonite KSF as the activator.

  16. In vitro effects of steroid hormones on arylalkylamine N-acetyltransferase (AA-NAT) activity in the pineal of fish, Clarias gariepinus (Burchell, 1822) during different phases of breeding cycle.

    Science.gov (United States)

    Yanthan, L; Gupta, B B P

    2007-08-01

    In vitro effects of gonadal hormones (testosterone, 17beta-estradiol estriol and estrone) and corticosteroid hormones (corticosterone and cortisol) were studied on arylalklyamine N-acetyltransferase (AA-NAT) activity in the pineal organ of the fish, C. gariepinus during quiescent, progressive, breeding and regressive phases of its annual breeding cycle. The pineals were collected under dim red light, maintained in organ culture for 7 hr and incubated with three concentrations (10(-6), 10(-5) and 10(-4) M) of hormones for 6 hr. The treatments with gonadal hormones and corticosteroid hormones inhibited pineal AA-NAT activity in a dose-dependent manner during all the phases of the breeding cycle. AA-NAT activity was comparatively more sensitive to the inhibitory effects of the gonadal hormones during the regressive phase and less sensitive during the quiescent phase. Further, the enzyme activity was more sensitive to the inhibitory effects of corticosteroid hormones (corticosterone and cortisol) during the breeding phase and less sensitive during the quiescent phase. These findings seem to suggest that gonadal hormones and corticosteroid hormones have direct inhibitory influence on AA-NAT activity and, hence melatonin synthesis in the photoreceptive pineal organ of C. gariepinus.

  17. Low melatonin production by suppression of either serotonin N-acetyltransferase or N-acetylserotonin methyltransferase in rice causes seedling growth retardation with yield penalty, abiotic stress susceptibility, and enhanced coleoptile growth under anoxic conditions.

    Science.gov (United States)

    Byeon, Yeong; Back, Kyoungwhan

    2016-04-01

    Serotonin N-acetyltransferase (SNAT) and N-acetylserotonin methyltransferase (ASMT) are the last two key enzymes for melatonin biosynthesis in living organisms. In this study, we demonstrated that transgenic rice (Oryza sativa L.) plants, in which expression of either endogenous SNAT or ASMT was suppressed, had reduced melatonin synthesis, confirming that both SNAT and ASMT are functionally involved in melatonin synthesis. The melatonin-deficient SNAT rice had retarded seedling growth, which was partially restored by exogenous melatonin application, suggesting melatonin's role in seedling growth. In addition, the plants were more sensitive to various abiotic stresses, including salt and cold, compared with the wild type. Melatonin-deficient SNAT rice had increased coleoptile growth under anoxic conditions, indicating that melatonin also inversely regulates plant growth under anaerobic conditions with the concomitant high expression of alcohol dehydrogenase genes. Similarly, the melatonin-deficient ASMT rice exhibited accelerated senescence in detached flag leaves, as well as significantly reduced yield. These loss-of-function studies on the melatonin biosynthetic genes confirmed most previous pharmacological reports that melatonin not only promotes plant growth but also mitigates various abiotic stresses.

  18. Synthesis of methyltrioxorhenium(VII) arylamine complexes and mono- and bis(ortho)-chelated arylaminorhenium(VII) trioxides

    NARCIS (Netherlands)

    Koten, G. van; Rietveld, M.H.P.; Nagelholt, L.; Grove, D.M.; Veldman, N.; Spek, A.L.; Rauch, M.U.; Hermann, W.

    1997-01-01

    From the reaction of MeReO{3} with the neutral arylamine C{6}H{5}CH{2}NMe{2} and the aryldiamine C{6}H{4}(CH{2}NMe{2}){2}-1, 3, have been isolated in good yields the 1/1 adduct complex [MeReO{3}.C{6}H{5}CH{2}NMe{2}], 1, and the21 adduct complex [(MeReO{3}){2} . C{6}H{4}(CH{2}NMe{2}){2}-1,3], 2,

  19. FeCl2-promoted cleavage of the unactivated C-C bond of alkylarenes and polystyrene: direct synthesis of arylamines.

    Science.gov (United States)

    Qin, Chong; Shen, Tao; Tang, Conghui; Jiao, Ning

    2012-07-09

    Ironing it out: an efficient and convenient nitrogenation strategy involving C-C bond cleavage for the straightforward synthesis of versatile arylamines is presented. Various alkyl azides and alkylarenes, including the common industrial by-product cumene, react using this protocol. Moreover, this method provides a potential strategy for the degradation of polystyrene.

  20. Effect of dark exposure in the middle of the day on Period1, Period2, and arylalkylamine N-acetyltransferase mRNA levels in the rat suprachiasmatic nucleus and pineal gland.

    Science.gov (United States)

    Fukuhara, Chiaki

    2004-11-04

    The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains a central circadian pacemaker, which adjusts circadian rhythms within the body to environmental light-dark cycles. It has been shown that dark exposure in the day causes phase shifts in circadian rhythms, but it does not induce changes in the melatonin levels in the pineal gland. In this study, we examined the effect of dark exposure on two "circadian clock" genes Period1 and Period2 mRNA levels in the rat SCN, and on Period1, Period2, and arylalkylamine N-acetyltransferase (Aa-Nat, the rate-limiting enzyme in melatonin synthesis) gene expression in the pineal gland. Period1 and Period2 mRNA levels were significantly decreased in the SCN after 0.5 and 2 h, respectively, therefore suggesting that changes in those mRNA levels may be the part of the mechanisms of dark-induced phase shifts. Period1 and Aa-Nat mRNA levels in the pineal gland were not affected by darkness, but Period2 was moderately affected. Since Period1 and Aa-Nat mRNA levels in the pineal gland did not respond to dark stimulation, we further examined whether the pineal gland itself is capable of responding to adrenergic stimulation at this time of the day. Isoproterenol significantly induced Period1 and Aa-Nat mRNA levels; however, it did not affect Period2. Although previous studies have reported that during the day the SCN "gates" the dark information reaching the pineal, our data demonstrate that dark information may reach the pineal during the daytime.

  1. Palladium-catalyzed cross coupling reaction of N-alkoxyimidoyl bromides and its application to one-pot synthesis of N-arylamines.

    Science.gov (United States)

    Ueda, Masafumi; Sugita, Shoichi; Aoi, Naoki; Sato, Aoi; Ikeda, Yuki; Ito, Yuta; Miyoshi, Tetsuya; Naito, Takeaki; Miyata, Okiko

    2011-01-01

    The synthetic utility of N-alkoxyimidoyl halides is demonstrated using the palladium-catalyzed cross-coupling reaction. The Sonogashira and Suzuki-Miyaura coupling reactions of N-alkoxyimidoyl bromides produced versatile ketoxime ethers in good to excellent yields. A one-pot reaction of the imidoyl bromides with arylboronic acid and allylmagnesium bromide to produce N-arylamines via Suzuki-Miyaura coupling followed by domino reaction involving sequential addition-eliminative rearrangement-addition reactions was developed.

  2. Unravelling the structural-electronic impact of arylamine electron-donating antennas on the performances of efficient ruthenium sensitizers for dye-sensitized solar cells

    Science.gov (United States)

    Chen, Wang-Chao; Kong, Fan-Tai; Ghadari, Rahim; Li, Zhao-Qian; Guo, Fu-Ling; Liu, Xue-Peng; Huang, Yang; Yu, Ting; Hayat, Tasawar; Dai, Song-Yuan

    2017-04-01

    We report a systematic research to understand the structural-electronic impact of the arylamine electron-donating antennas on the performances of the ruthenium complexes for dye-sensitized solar cells. Three ruthenium complexes functionalized with different arylamine electron-donating antennas (N,N-diethyl-aniline in RC-31, julolidine in RC-32 and N,N-dibenzyl-aniline in RC-36) are designed and synthesized. The photoelectric properties of RC dyes exhibit apparent discrepancy, which are ascribed to different structural nature and electronic delocalization ability of these arylamine electron-donating system. In conjunction with TiO2 microspheres photoanode and a typical coadsorbent DPA, the devices sensitized by RC-36 achieve the best conversion efficiency of 10.23%. The UV-Vis absorption, electrochemical measurement, incident photon-to-current conversion efficiency and transient absorption spectra confirm that the excellent performance of RC-36 is induced by synergistically structural-electronic impacts from enhanced absorption capacity and well-tuned electronic characteristics. These observations provide valuable insights into the molecular engineering methodology based on fine tuning structural-electronic impact of electron-donating antenna in efficient ruthenium sensitizers.

  3. RELATIONSHIP BETWEEN GENETIC POLYMORPHISMS OF N- ACETYLTRANSFERASE 2 AND SUSCEPTIBILITY OF BREAST CANCER IN SHANDONG DISTRICT%山东地区NAT2基因多态性与乳腺癌易感性的研究

    Institute of Scientific and Technical Information of China (English)

    王萍玉; 谢书阳; 张超; 高宗华

    2011-01-01

    [目的]研究NAT2基因多态性与乳腺癌易感性的关系.[方法]采用1:1配对病例-对照研究,对山东地区100例乳腺癌患者和100例健康对照者采用聚合酶链反应-限制性片段长度多态性分析(PCR- RFLP),检测NAT2基因多态性,分析NAT2基因多态性与乳腺癌易感性之间的关系.[结果]携带NAT2/5B等位基因者患乳腺癌 危险性增加(OR=2.38, 95%CI=1.54~3.67);幔基因型者患乳腺癌的危险性是快基因型者2.28倍(OR=2.28,95%CI=1.12~4.63);是中间基因型者2.14倍(OR=2.14,95%CI=1.08~4.24);慢型乙酰化患乳腺癌的危险性是快型乙酰化的2.11倍(OR=2.11, 95%CI=1.15-3.88).[结论]NAT2基因多态性在乳腺癌的遗传发病机制中起重要作用,携带NAT2/5B等位基因、慢基因型及慢型乙酰化能增加患乳腺癌的易感性.%[Objective] To evaluate the possible relationship between N-acetyltransferase 2 (NAT2) polymorphisms and breast cancer. [Methods] In the 1: 1 matched case-control study, NAT2 genotypes were determined by PCR-RFLP method in 100 patients with breast cancer and 100 healthy controls. The possible relationship between NAT2 polymorphisms and lung cancer risk was analyzed. [Results] NAT2*5B allele was associated with an increased risk of breast cancer (odds ratio (OR) 2.38 (95% confidence interval (95%Cl) 1.54-3.67; slow genotype was 2.28 times to rapid genotype (OR = 2.28, 95%CI= 1.12-4.63) and 2.14 times to intermediate genotype (OR - 2.14, 95%C/=1.08-4.24); and NAT2 slow acetylates increased risk of breast cancer (OR = 2.11, 95%C/ = 1.15-3.88). [Conclusion] These findings suggest that NAT2 genetic polymorphism may be associated with breast cancer susceptibility. People with NAT2*5B allele or NAT2 slow genotype or NAT2 slow acetylates have higher breast cancer risk.

  4. Metabolic activation of three arylamines and two organophosphorus insecticides by coriander (Coriandrum sativum) a common edible vegetable.

    Science.gov (United States)

    Cortés-Eslava, J; Gómez-Arroyo, S; Villalobos-Pietrini, R; Espinosa-Aguirre, J J

    2001-12-15

    Organophosphorus insecticides and arylamines, widely distributed in the environment, can be activated into mutagens by plants. Plant activation of three aromatic amines, 4-nitro-o-phenylenediamine (NOP), m-phenylenediamine (m-PDA) and 2-aminofluorene (2AF), and two organophosphorus insecticides, dimethoate and methyl parathion has been the focus of this study. The plant cell/microbe coincubation assay was used employing coriander (Coriandrum sativum) suspended cell cultures as the activating system. Interestingly, this vegetable is included in the Mexican diet and ingested generally uncooked and could have epidemiological consequences. As a genetic end point, the Salmonella typhimurium tester strain TA98 was used. Protein contents, as well as peroxidase activity and peroxidase activity inhibited by diethyldithiocarbamate (DEDTC) of coriander cultures were determined after the coculture. Coriander cells highly activated three aromatic amines, NOP, m-PDA and 2-AF to mutagenic products detected in Salmonella. On the other hand, insecticides were only lightly activated, probably because peroxidase activity of coriander cells was inhibited, corroborated by DEDTC peroxidase inhibition. In all the assays, NOP was the more potent mutagenic compound. The results demonstrated that coriander cells were metabolically competent and suitable for a plant cell microbe coincubation assay, developed to analyze the promutagen activation by plant systems and can be used as a indicator of potential genetic effects.

  5. Power Conversion Efficiency of Arylamine Organic Dyes for Dye-Sensitized Solar Cells (DSSCs Explicit to Cobalt Electrolyte: Understanding the Structural Attributes Using a Direct QSPR Approach

    Directory of Open Access Journals (Sweden)

    Supratik Kar

    2016-12-01

    Full Text Available Post silicon solar cell era involves light-absorbing dyes for dye-sensitized solar systems (DSSCs. Therefore, there is great interest in the design of competent organic dyes for DSSCs with high power conversion efficiency (PCE to bypass some of the disadvantages of silicon-based solar cell technologies, such as high cost, heavy weight, limited silicon resources, and production methods that lead to high environmental pollution. The DSSC has the unique feature of a distance-dependent electron transfer step. This depends on the relative position of the sensitized organic dye in the metal oxide composite system. In the present work, we developed quantitative structure-property relationship (QSPR models to set up the quantitative relationship between the overall PCE and quantum chemical molecular descriptors. They were calculated from density functional theory (DFT and time-dependent DFT (TD-DFT methods as well as from DRAGON software. This allows for understanding the basic electron transfer mechanism along with the structural attributes of arylamine-organic dye sensitizers for the DSSCs explicit to cobalt electrolyte. The identified properties and structural fragments are particularly valuable for guiding time-saving synthetic efforts for development of efficient arylamine organic dyes with improved power conversion efficiency.

  6. Convergent Theoretical Prediction of Reactive Oxidant Structures in Diiron Arylamine Oxygenases AurF and CmlI: Peroxo or Hydroperoxo?

    Science.gov (United States)

    Wang, Chao; Chen, Hui

    2017-09-20

    AurF and CmlI are currently the only two known diiron arylamine oxygenases. On the basis of extensive quantum mechanical/molecular mechanical (QM/MM) spectroscopic and mechanistic modelings, here we predict that the key oxygenated intermediates in AurF and CmlI, so-called P, are uniformly hydroperoxo species having similar structures. As a basis for mechanistic unification in AurF and CmlI, the proposed diferric-hydroperoxo P is calculated to be able to promote the arylamine N-oxygenation with highly accessible kinetics. This convergent μ-η(0):η(2) structural assignment of P's in AurF and CmlI can rationalize many conundrums for P, including the different Mössbauer spectroscopic parameters, low O-O vibrational frequency, ambiphilic reactivity, and inertness toward C-H activation. In view of the very limited knowledge about hydroperoxo species in diiron enzymes, the novel diferric-hydroperoxo-mediated N-oxygenation mechanism revealed in this work opens up a new avenue for understanding the O2 activation mode in nature. For elucidating the structures of transient oxidants for diiron enzymes, the promising approach of QM/MM Mössbauer spectroscopic modeling is highlighted as a key problem solver in mechanistic enzymatic research.

  7. Synthesis and characterization of some water soluble Zn(II) complexes with (E)-N-(pyridin-2-ylmethylene)arylamines that regulate tumour cell death by interacting with DNA.

    Science.gov (United States)

    Basu Baul, Tushar S; Kundu, Sajal; Linden, Anthony; Raviprakash, Nune; Manna, Sunil K; Guedes da Silva, M Fátima C

    2014-01-21

    The synthesis and spectroscopic properties of nine water soluble zinc(II) complexes of (E)-N-(pyridin-2-ylmethylene)arylamines (L(n)) with the general formula [Zn(X)2(L(n))] (X = Cl(-), Br(-), I(-); (1-8)) and [Zn(μ-N3)(N3)(L(3))]2 (9) are reported. The complexes were characterized by elemental analysis and their spectroscopic properties were studied using UV-Visible, fluorescence, IR and (1)H NMR spectroscopies. The solid state structures of zinc(II) complexes 2-4 and 6-9 were established by single crystal X-ray crystallography. The majority of the structures are mononuclear with tetra-coordinate zinc centres (2-4, 6 and 7) except where L carries an additional donor atom capable of coordinating zinc (8), in which case the zinc atom has a distorted square pyramidal geometry. The centrosymmetric molecule of [Zn(μ-N3)(N3)(L(3))]2 (9) is binuclear with the zinc atoms in a trigonal bipyramidal coordination environment. In general, the dichlorozinc derivatives 1, 3-5 and 8 exhibited moderately elevated in vitro cytotoxic potency towards the human epithelial cervical carcinoma (HeLa) cell line, with 4 as the best performer (IC50 value of 18 μM). Apoptosis-inducing activity, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, showed that the zinc complexes interacted with DNA and thereby interfered the DNA binding of several transcription factors to its promoter sites, thus inhibiting gene transcription required for the biological activity of cells.

  8. 大鼠松果体Clock基因和芳烷脘N-乙酰基转移酶基因的昼夜节律性表达及光照影响%Circadian rhythms and light responses of clock gene and arylalkylamine N-acetyltransferase gene expressions in the pineal gland of rats

    Institute of Scientific and Technical Information of China (English)

    王国卿; 杜玉珍; 童建

    2005-01-01

    探讨12 h光照、12 h黑暗交替(12 h-light:12 h-dark cycle,LD)及持续黑暗(constant darkness,DD)光制下松果体Clock基因和芳烷脘N-乙酰基转移酶基因(arylalkylamine N-acetyltransferase gene,NAT)是否存在昼夜节律性表达及其光反应变化.Sprague-Dawley大鼠在LD和DD光制下分别被饲养4周(n=36)和8周(n=36)后,在一昼夜内每隔4 h采集一组松果体组织(n=6),提取总RNA,用竞争性定量RT-PCR测定不同昼夜时点样品中Clock及NAT基因的mRNA相对表达量,通过余弦法和ClockLab软件获取节律参数,并经振幅检验是否存在昼夜节律.结果如下:(1)在DD或LD光制下,松果体Clock和NAT基因mRNA的表达均呈现夜高昼低的节律性振荡(P<0.05).(2)与DD光制下比较,LD光制下松果体Clock和NAT基因的表达振幅及峰值相的mRNA水平均降低(P<0.05).(3)在DD或LD光制下,Clock和NAT基因之间显示相似的节律性表达(P>0.05).结果表明,Clock和NAT基因在松果体中存在同步的内源性昼夜节律表达,光照作用可使其表达下调.

  9. Palladium-catalyzed coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates: a general method for the preparation of primary arylamines.

    Science.gov (United States)

    Vo, Giang D; Hartwig, John F

    2009-08-12

    We report that the complex generated from Pd[P(o-tol)(3)](2) and the alkylbisphosphine CyPF-t-Bu is a highly active and selective catalyst for the coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates. The couplings of ammonia with this catalyst conducted with a solution of ammonia in dioxane form primary arylamines from a variety of aryl electrophiles in high yields. Catalyst loadings as low as 0.1 mol % were sufficient for reactions of many aryl chlorides and bromides. In the presence of this catalyst, aryl sulfonates also coupled with ammonia for the first time in high yields. A comparison of reactions in the presence of this catalyst versus those in the presence of existing copper and palladium systems revealed a complementary, if not broader, substrate scope. The utility of this method to generate amides, imides, and carbamates is illustrated by a one-pot synthesis of a small library of these carbonyl compounds from aryl bromides and chlorides, ammonia, and acid chlorides or anhydrides. Mechanistic studies show that reactions conducted with the combination of Pd[P(o-tol)(3)](2) and CyPF-t-Bu as catalyst occur with faster rates and higher yields than those conducted with CyPF-t-Bu and palladiun(II) as catalyst precursors because of the low concentration of active catalyst that is generated from the combination of palladium(II), ammonia, and base.

  10. Nano MgBi₂O₄: A Novel Green Catalyst for the One-step Cascade Condensation of Arylamines, Acetone and Isatins in Water

    Indian Academy of Sciences (India)

    KOBRA NIKOOFAR; ZAHRA KHADEMI; MARYAM HAGHIGHI

    2016-11-01

    Nano-size MgBi₂O₄ has been synthesized for the first time via a simple co-precipitation method using the surfactant N-cetyl-N, N,N-trimethylammonium bromide (CTAB). Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray powder diffraction (XRD) techniques were employed to characterize the nano-catalyst. Additionally, the reactivity of the prepared nanoparticles was investigated in the synthesis of 1'-aryl-2'-(2-oxoindolin-3-yl)spiro[indoline-3,5'-pyrroline]-2,3'-diones in a one-pot, one-step and pseudo four-component condensation of arylamine, acetone, and isatins at 50◦C in water. Five new compounds were synthesized and identified. This procedure has various advantages such as, short reaction times, mild eco-friendly conditions and excellent yields to prepare a novel class of heteroaromatic compounds. MgBi₂O₄ possess superior qualities such as easy and economic preparation procedure and handling, stability, and non-toxicity. Its reusability has also been examined upto 4 runs without activity loss.

  11. N-Acetyltransferase 1 Polymorphism and Breast Cancer Risk

    Science.gov (United States)

    2011-10-01

    deoxyribosides supplemented with 10% fetal bovine serum (Hyclone, Logan, UT), 100 units/mL penicillin (Lonza), 100 mg/mL streptomycin (Lonza), and 2 mM...supplemented with 10% fetal bovine serum (Hyclone), 100 units/mL penicillin (Lonza), 100 mg/mL streptomycin (Lonza), and 2 mM L-glutamine (Lonza...are hypersensitive to bulky DNA lesions, were obtained from the ATCC (catalog number: CRL-1865). Unless otherwise noted, cells were incubated at 37

  12. New di(hetero)aryl)ethers and Di(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, growth inhibitory activity on tumor cell lines and non tumor cells, effects on cell cycle and on apoptosis

    OpenAIRE

    Queiroz, Maria João R. P.; Peixoto, Daniela; Ricardo C. Calhelha; Soares, Pedro; Santos,Tiago; Raquel T. Lima; Campos, Joana F.; Abreu, Rui M. V.; Isabel C. F. R. Ferreira; Vasconcelos, M. Helena

    2014-01-01

    The thienopyridine skeleton has been reported as having interesting biological activities namely antitumor[1,2] antiangiogenic.[3A] New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing 7-position of the thieno[3,2-bJpyridine, using copper (C-O) or palladium (C-N) catalyzed couplings, respectively, of the 7-t>rolmo: thieno[3,2-bJpyridine (1) with ortho, meta and para fluoro or methoxy phenols and anilines.

  13. 以芳香胺玻璃为载体的固定化的胆固醇脂酶和胆固醇氧化酶%Cholesterol Esterase and Cholesterol Oxidase Immobilized onto Arylamine Glass Beads

    Institute of Scientific and Technical Information of China (English)

    VoMalik; S.Singh; 等

    2002-01-01

    Cholesterol esterase (Cease) from bovine pancreas and cholesterol oxidasc (COD) from Bravibacterium recombinant type have been innobilized individually and co-immobilized onto arylamine glass (pore diameter 55nm) through the process of diazotization. Cease and COD retained 92.65% and 85.54% of the initial activity with conjugation yields of 7.2 mg/g and 8.3mg/g support respectively when imnobilized individually on arylamine glass beads, but retained 89.58% of the initial activity with a conjugation yield of 2.9 mg/g support when co-immobilized on the same support. The effects of pH, temperature, time of incubation, substrate concentration, serum inorganic salts & metabolites, thermal stability, storage stability in cold and reusability on the immobilized enzymes were studied and compared with those of free enzymes. The analytic use of both individually immobilized and co-immobilized enzymes in discrete analysis of total and free cholesterol in serum is demonstrated.

  14. Influences of Hypoxic-ischemic Brain Damage on Pineal Arylalkylamine-N-acetyltransferase mRNA Expression and Plasma Melatonin Level in Neonatal Rats%缺氧缺血对新生大鼠松果体芳香烷基胺-N-乙酰基转移酶

    Institute of Scientific and Technical Information of China (English)

    丁欣; 姜善雨; 冯星; 何军; 孙斌; 朱雪明

    2011-01-01

    Objective To elucidate the influences of hypoxic-ischemic brain damage (HIBD) on pineal function of melatonin synthesis and explore the possible significance of pineal function alterations in HIBD.Methods Sixty seven-day-old rats were randomly divided into 2 groups: the HIBD group and sham-operated group.Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to measure the melatonin-synthetase-arylalkylamine-N-acetyltransferase (AANAT) mRNA expressions in pineal gland.Radioimmunoassay (RIA) was used to measure the plasma melatonin levels.Results ( 1 ) The AANAT mRNA expression 6 h, 12 h, 24 h after HIBD were lower than those in the corresponding sham-operated groups( P <0.05 or 0.01 ) ,and no significant difference was found among different time points in the sham-operated groups; (2) The plasma melatonin levels 12 h, 24 h after HIBD were lower than those in the corresponding sham-operated groups.The melatonin levels at different time points in the sham-operated group were similar.Conclusions Pineal melatonin-synthesis is impaired on early stage of HIBD.Alternation of the protective process of endogenous MLT might be involved in pathogenic mechanism of early HIBD.%目的 了解缺氧缺血性脑损伤(HIBD)对松果体芳香烷基胺-N-乙酰基转移酶(AANAT)mRNA表达和血浆褪黑素(MLT)含量的影响,探讨松果体功能改变在HIBD中的意义.方法 选取7日龄SD大鼠60只随机分成HIBD模型组和假手术组.HIBD模型组按改良Levine法建立,然后用半定量逆转录聚合酶链反应(RT-PCR)和放免技术分别测定并比较两组缺氧缺血后0 h、6 h、12 h、24h、48 h松果体中AANAT mRNA的表达水平及血浆MLT的浓度.结果 (1)松果体中AANAT mRNA的表达在HIBD后6 h、12 h、24 h低于对应假手术组(P<0.05或<0.01);假手术组各时点之间AANAT mRNA的表达水平无明显变化(P>0.05).(2)血浆MLT浓度在HIBD后12 h、24 h均低于对应假手术组(P<0.01);假手术组

  15. 龙葵碱对HepG2细胞NAT1酶活性及动力学影响的研究%Study on the Effect of Solanine on N-acetyltransferase 1 Activity in HepG2

    Institute of Scientific and Technical Information of China (English)

    高世勇; 苏怡君; 季宇彬

    2011-01-01

    目的 探讨龙葵碱诱导HepG2细胞凋亡的芳香胺Ⅳ-乙酰化转移酶(NAT)1的影响.方法 采用高效液相色谱法(HPLC),以对氨基笨甲酸(PABA)为底物,以PABA被NAT1乙酰化为乙酰对氨基苯甲酸(Ac-PABA)的量反应NAT1酶的活性.观察不同浓度、不同时间龙葵碱对完整HepG2细胞NAT1酶活性的影响;龙葵碱对HepG2细胞细胞质中NAT1酶活性的影响;通过改变底物PABA浓度,采用双倒数作图法,以底物PABA浓度的倒数(1/S)对NAT1反应速率的倒数(1/V)作直线,得出回归方程,计算K和.结果 在NAT1酶活性测定中,龙葵碱能显著降低HepG2完整细胞NAT1的活性;龙葵碱能够降低HepG2细胞质内NAT1的活性;随着作用时间的增加Ac-PABA生成的量逐渐增加,但在相同作用时间段龙葵碱能显著降低Ac-PABA生成的量.动力学研究表明,以PABA为底物,对于HepG2完整细胞,阴性对照组的K和V分别为(1.04 x 10±8.36×10-5)mmol·L、(1.64×10±9.57×10)nmol·10cells,龙葵碱组的K和K分别为(1.06×10±6.97×10)mmol·L和(1.48×10±4.28×10)nmol·10cells·h.对于HepG2细胞质,阴性对照组的K和V分别为(3.32×10±2.35×10)mmol·L、(2.60×10±6.79×10)nmol·h·mg pro,龙葵碱组的K和K分别为(3.35×10±1.66×10)mmol·L和(2.22x10±8.12×10)nmol·h·mg(Pro),经统计学处理表明,对于HepG2完整细胞和细胞质,阴性对照组和龙葵碱组的K没有差异,而V差异显著结论 龙葵碱是HepG2细胞NAT1酶的非竞争性抑制剂.龙葵碱通过作用于NAT1与PABA结合位点以外的其他位点抑制NAT1酶的活性而诱导HepG2细胞凋亡.%OBJECTIVE To explore the relationship between N-acetyltransferase 1 activity and apoptosis inducing by solanine in HepG2 cell. METHODS The speed of PABA acetylation reaction mediated by NAT1 was teken as the indicator of the activity of NAT1 in intact HepG2 cells and their cytoplasm. HPLC was employed to determine the concentration of AC-PABA, the effects of different concentrations of

  16. The enhanced bladder cancer susceptibility of NAT2 slow acetylators towards aromatic amines: a review considering ethnic differences.

    Science.gov (United States)

    Golka, Klaus; Prior, Verena; Blaszkewicz, Meinolf; Bolt, Hermann M

    2002-03-10

    Human bladder cancer may be caused by exposure to aromatic amines. The polymorphic enzyme N-acetyltransferase 2 (NAT2) is involved in the metabolism of these compounds. Two classical studies on chemical workers in Europe, exposed in the past to aromatic amines like benzidine, unambiguously showed that the slow acetylator status is a genetic risk factor for arylamine-induced bladder cancer. In the former benzidine industry in Huddington, Great Britain, 22 of 23 exposed cases with bladder cancer, but only 57% of 95 local controls without bladder cancer were of the slow acetylator phenotype. In Leverkusen, Germany, 82% of 92 benzidine-exposed chemical workers with bladder cancer were of the slow acetylator phenotype, whereas only 48% of 331 chemical workers who had worked at that plant were of the slow acetylator phenotype. This is in line with several smaller studies, which also show an over-representation of the slow acetylator status in formerly arylamine-exposed subjects with bladder cancer. Some of these studies included also subjects that were exposed to aromatic amines by having applied dyes, paints and varnishes. These European findings are in contrast to a large study on Chinese workers occupationally exposed to aromatic amines. In this study, only five of 38 bladder cancer cases occupationally exposed to arylamines were of the slow acetylator genotype. This is much lower than the ratio of slow acetylators to the general population in China. This points to different mechanisms of susceptibility for bladder cancer upon exposure to aromatic amines between European (Caucasian) and Chinese populations.

  17. N-acetyltransferase-dependent activation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine: formation of 2-amino-1-methyl-6-(5-hydroxy)phenylimidazo [4,5-b]pyridine, a possible biomarker for the reactive dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lauritz; Alexander, J.

    2000-01-01

    -hydroxy-PhIP (N-OH-PhIP) with cytosol, acetyl coenzyme A (AcCoA) and 2'-deoxyguanosine for 24 h resulted in the formation of three different adducts: N-2-(deoxyguanosin-8-yl)-PhIP, N-2-(guanosin-8-yl) -PhIP and PhIP-xanthine. One additional product, 5-hydroxy-PhIP (5-OH-PhIP), was also identified...... in the incubation mixtures. 5-hydroxy-PhIP is formed as a degradation product of conjugates formed from N-acetoxy-PhIP and protein, glutathione or buffer constituents, A similar spectrum of products was obtained using 3'-phosphoadenosine-5'-phosphosulfate (PAPS) instead of acetyl CoA, Addition of glutathione (3 m...... dramatic effects, In addition, increasing the amount of N-OH-PhIP in the incubation mixture resulted in proportional increased amounts of total adducts and 5-OH-PhIP, Incubation of rat and human S9 with PhIP resulted in the formation of only traces of 5-OH-PhIP, Fortification with AcCoA clearly increased...

  18. AcEST: DK950447 [AcEST

    Lifescience Database Archive (English)

    Full Text Available 2_DANRE N-acetyltransferase ESCO2 OS=Danio rerio GN=esco2 PE=2 SV=1 Length...ss-Prot sp_hit_id Q8CIB9 Definition sp|Q8CIB9|ESCO2_MOUSE N-acetyltransferase ESCO2 OS=Mus musculus Align le...g significant alignments: (bits) Value sp|Q8CIB9|ESCO2_MOUSE N-acetyltransferase ESCO2 OS=Mus musculus ... 100 1e-20 sp|Q56NI9|ESCO...2_HUMAN N-acetyltransferase ESCO2 OS=Homo sapiens ... 92 2e-18 sp|Q5FWF5|ESCO...1_HUMAN N-acetyltransferase ESCO1 OS=Homo sapiens ... 92 2e-18 sp|Q5SPR8|ESCO2_DANRE N-acetyltransferase ESCO

  19. Structural Analysis of a Putative Aminoglycoside N-Acetyltransferase from Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Klimecka, Maria M.; Chruszcz, Maksymilian; Font, Jose; Skarina, Tatiana; Shumilin, Igor; Onopryienko, Olena; Porebski, Przemyslaw J.; Cymborowski, Marcin; Zimmerman, Matthew D.; Hasseman, Jeremy; Glomski, Ian J.; Lebioda, Lukasz; Savchenko, Alexei; Edwards, Aled; Minor, Wladek (SC); (Toronto); (UV)

    2012-02-15

    For the last decade, worldwide efforts for the treatment of anthrax infection have focused on developing effective vaccines. Patients that are already infected are still treated traditionally using different types of standard antimicrobial agents. The most popular are antibiotics such as tetracyclines and fluoroquinolones. While aminoglycosides appear to be less effective antimicrobial agents than other antibiotics, synthetic aminoglycosides have been shown to act as potent inhibitors of anthrax lethal factor and may have potential application as antitoxins. Here, we present a structural analysis of the BA2930 protein, a putative aminoglycoside acetyltransferase, which may be a component of the bacterium's aminoglycoside resistance mechanism. The determined structures revealed details of a fold characteristic only for one other protein structure in the Protein Data Bank, namely, YokD from Bacillus subtilis. Both BA2930 and YokD are members of the Antibiotic-NAT superfamily (PF02522). Sequential and structural analyses showed that residues conserved throughout the Antibiotic-NAT superfamily are responsible for the binding of the cofactor acetyl coenzyme A. The interaction of BA2930 with cofactors was characterized by both crystallographic and binding studies.

  20. N-acetyltransferase 2 polymorphisms and risk of esophageal cancer in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Liming Wang

    Full Text Available Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Genetic factors might play an important role in the carcinogenesis of esophageal squamous cell carcinoma (ESCC. We conducted a hospital-based case-control study to evaluate ten NAT2 tagging single nucleotide polymorphisms (SNPs on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction method. In the single locus analyses, there was a borderline statistically significant difference in genotype frequencies of NAT2 rs1565684 T>C SNP between the cases and the controls (p = 0.057. The NAT2 rs1565684 CC genotype was associated with a borderline significantly increased risk for ESCC (CC vs. TT: adjusted OR = 1.77, 95% CI = 0.97-3.21, p = 0.063 and CC vs. TT/TC: adjusted OR = 1.68, 95% CI = 0.93-3.04, p = 0.085. The association was evident among older patients and patients who never drunk. After the Bonferroni correction, in all comparison models, NAT2 rs1565684 T>C SNP was not associated with ESCC risk (p>0.05. For the other nine NAT2 SNPs, after Bonferroni correction, in all comparison models, the nine SNPs were also not associated with ESCC risk (p>0.05. Thus, nine NAT2 tagging SNPs were not associated with risk of ESCC. NAT2 rs1565684 T>C SNP might play a slight role in ESCC etiology. Additional, larger studies and tissue-specific biological characterization are required to confirm the current findings.

  1. Influence of heredity on human sensitivity to environmental chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.W. [Univ. of Michigan, Ann Arbor, MI (United States)

    1995-12-31

    Hereditary peculiarities in individual responses to environmental chemicals are a common occurrence in human populations. Genetic variation in glutathione S-transferase, CYP1A2, N-acetyltransferase, and paraoxonase exemplify the relationship of metabolic variation to individual susceptibility to cancer and other toxicants of environmental origin. Heritable receptor protein variants, a subset of proteins of enormous pharmacogenetic, potential that have not thus far been extensively explored form the pharmacogenetic standpoint, and also considered. Examples of interest that are considered include receptor variants associated with retinoic acid resistance in acute promyelocytic leukemia, with paradoxical responses to antiandrogens in prostate cancer, and with retinitis pigmentosa. Additional heritable protein variants of pharmacogenetic interest that result in antibiotic-induced deafness, glucocorticoid-remediable aldosteronism and hypertension, the long-QT syndrome, and beryllium-induced lung disease are also discussed. These traits demonstrate how knowledge of the molecular basis and mechanism of the variant response may contribute to its prevention in sensitive persons as well as to improved therapy for genetically conditioned disorders that arise form environmental chemicals. 99 refs.

  2. Xenobiotic metabolism capacities of human skin in comparison with a 3D-epidermis model and keratinocyte-based cell culture as in vitro alternatives for chemical testing: phase II enzymes.

    Science.gov (United States)

    Götz, Christine; Pfeiffer, Roland; Tigges, Julia; Ruwiedel, Karsten; Hübenthal, Ulrike; Merk, Hans F; Krutmann, Jean; Edwards, Robert J; Abel, Josef; Pease, Camilla; Goebel, Carsten; Hewitt, Nicola; Fritsche, Ellen

    2012-05-01

    The 7th Amendment to the EU Cosmetics Directive prohibits the use of animals in cosmetic testing for certain endpoints, such as genotoxicity. Therefore, skin in vitro models have to replace chemical testing in vivo. However, the metabolic competence neither of human skin nor of alternative in vitro models has so far been fully characterized, although skin is the first-pass organ for accidentally or purposely (cosmetics and pharmaceuticals) applied chemicals. Thus, there is an urgent need to understand the xenobiotic-metabolizing capacities of human skin and to compare these activities to models developed to replace animal testing. We have measured the activity of the phase II enzymes glutathione S-transferase, UDP-glucuronosyltransferase and N-acetyltransferase in ex vivo human skin, the 3D epidermal model EpiDerm 200 (EPI-200), immortalized keratinocyte-based cell lines (HaCaT and NCTC 2544) and primary normal human epidermal keratinocytes. We show that all three phase II enzymes are present and highly active in skin as compared to phase I. Human skin, therefore, represents a more detoxifying than activating organ. This work systematically compares the activities of three important phase II enzymes in four different in vitro models directly to human skin. We conclude from our studies that 3D epidermal models, like the EPI-200 employed here, are superior over monolayer cultures in mimicking human skin xenobiotic metabolism and thus better suited for dermatotoxicity testing. © 2012 John Wiley & Sons A/S.

  3. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

    Directory of Open Access Journals (Sweden)

    Sara Marcó

    2016-09-01

    Full Text Available Mucopolysaccharidosis type IIIC (MPSIIIC is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches.

  4. N-acetyltransferase 2 (NAT2 Gene Polymorphisms and the Effectiveness of Infertility Treatment in Patients with Peritoneal Endometriosis

    Directory of Open Access Journals (Sweden)

    Ekaterina D. Dubinskaya

    2014-03-01

    Full Text Available Today, infertility has become a global issue. WHO ranks it the fifth among the major diseases of those below 60 years, after alcoholism, depression, injuries and eyesight disorders. Numerous studies conducted on the problems of infertility in endometriosis still do not offer clear answers regarding the pathogenesis and mechanisms of this disease and its influences on fertility. According to the survey results, point mutations of the NAT2 gene (NAT2*5 and NAT2*6 have been identified in 75.6% of the patients with infertility problems and the peritoneal form of endometriosis, that create “slow” allelic variants, which exceed the average index in the population. The peculiarities of the NAT2 gene polymorphisms have been proven to be associated with the effectiveness of the infertility treatment of female patients with peritoneal endometriosis. In the group of non-pregnant patients, the presence of с.341Т>C, c.481C>T, c.590G>A and c.803A>G heterozygous point mutations are 73.2, 73.2, 5.4, and 62.5%, respectively. The significant difference in the comparison of the allelic polymorphism during the various stages of the endometriosis was not identified. At stage III-IV endometriosis the frequency of three and more point substitutions was significantly higher. NAT2 gene polymorphisms can find use as an additional criterion for predicting the effectiveness of the infertility treatment of patients with peritoneal endometriosis.

  5. N-acetyltransferase (nat) is a critical conjunct of photoperiodism between the circadian system and endocrine axis in Antheraea pernyi.

    Science.gov (United States)

    Mohamed, Ahmed A M; Wang, Qiushi; Bembenek, Jadwiga; Ichihara, Naoyuki; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

    2014-01-01

    Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16:8 (LD) and LD12:12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4 °C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNA(NAT) caused dysfunction of photoperiodism. dsRNA(PER) upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNA(NAT) decreased melatonin while dsRNA(PER) increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNA(NAT), to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism.

  6. Opposite effects of EGTA and neutral surfactants on the loss of chicken pineal serotonin N-acetyltransferase activity.

    Science.gov (United States)

    Rodriguez-Cabello, J C; Arpa, F; Agapito, M T; Recio, J M

    1990-01-01

    The effects of some general purpose drugs on the deactivation and activity measurement of the chicken pineal gland enzyme serotonin N-acetyl transferase (EC 2.3.1.5.) were studied. The drugs used were EGTA and two neutral surfactants, Nonidet P40 and Triton X-100. Enzyme activity showed significant variations ranging from 2.8 +/- 1.3 nmol/gland/h when Nonidet P40 was added to the homogenate buffer, to 31.8 +/- 1.7 nmol/gland/h when EGTA was present. This striking variation seemed to be caused by the ability of these compounds to modify the rate of NAT deactivation acting either as accelerating agents, as in the case of the detergents or as braking agent, as in the case of EGTA.

  7. N-acetyltransferase (nat is a critical conjunct of photoperiodism between the circadian system and endocrine axis in Antheraea pernyi.

    Directory of Open Access Journals (Sweden)

    Ahmed A M Mohamed

    Full Text Available Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16:8 (LD and LD12:12 (SD, and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4 °C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNA(NAT caused dysfunction of photoperiodism. dsRNA(PER upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNA(NAT decreased melatonin while dsRNA(PER increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNA(NAT, to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism.

  8. The elongation of primary cilia via the acetylation of α-tubulin by the treatment with lithium chloride in human fibroblast KD cells.

    Science.gov (United States)

    Nakakura, Takashi; Asano-Hoshino, Anshin; Suzuki, Takeshi; Arisawa, Kenjiro; Tanaka, Hideyuki; Sekino, Yoshihisa; Kiuchi, Yoshiko; Kawai, Kazuhiro; Hagiwara, Haruo

    2015-03-01

    Primary cilium, an organelle found on nearly every cell in the human body, typically serves as the mechanical sensor of the cell. Lithium ion is known to promote the elongation of primary cilia in a variety of cell types, but it is unknown whether lithium is involved in the acetylation of α-tubulin which is essential for the assembly of primary cilia. In order to reveal the relationship between the elongation of primary cilia with lithium and the acetylation of α-tubulin, we first observed the formation and structure of primary cilia in KD cells, a cell line deriving fibroblasts in human labium. Subsequently, by immunohistochemical and western blot analysis we elucidated that the length of primary cilia and acetylation of α-tubulin are regulated by lithium chloride (LiCl) in the medium in a time- and concentration-dependent manner. We next performed the RT-PCR, RNAi-based experiments and biochemical study using an inhibitor of glycogen synthase kinase-3βGSK-3β). We found that LiCl mobilizes the α-tubulin N-acetyltransferase 1 (αTAT1) in the signaling pathway mediating GSK-3β and adenylate cyclase III. In conclusion, our results suggested that LiCl treatments activate αTAT1 by the inhibition of GSK-3β and promote the α-tubulin acetylation, and then elongate the primary cilia.

  9. Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland.

    Science.gov (United States)

    Maronde, Erik; Saade, Anastasia; Ackermann, Katrin; Goubran-Botros, Hany; Pagan, Cecile; Bux, Roman; Bourgeron, Thomas; Dehghani, Faramarz; Stehle, Jörg H

    2011-08-01

    Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N-acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post-transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time-of-death groups (night/dawn/day/dusk) and analyzed for daytime-dependent changes in phosphorylated AANAT (p31T-AANAT) and in acetyl-serotonin-methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T-AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T-AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T-AANAT and ASMT were often found to colocalize in cellular rod-like structures that were also partly immunoreactive for the pinealocyte process-specific marker S-antigen (arrestin) in both, human and sheep pinealocytes. Protein-protein interaction studies with p31T-AANAT, ASMT, and S-antigen demonstrated a direct association and formation of robust complexes, involving also 14-3-3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T-AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species.

  10. Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Uzma Shahab

    Full Text Available BACKGROUND: The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP, a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl-4-aminobiphenyl (dG-C8-4ABP in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA. CONCLUSIONS/SIGNIFICANCE: This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.

  11. Daytime Unresponsiveness of the Human and Syrian Hamster Pineal to Adrenergic Stimulation

    Science.gov (United States)

    1989-01-01

    depresses nighttime melatonin content without changing N-acetyltransferase activity in the rat pineal gland . Neuroendocrinology 47, 55-60. Vaughan, G.M...exposure) raises pineal melatonin content; injection outside this sensitive period does not. (CajP-" This dramatic change in response of the pineal gland ...in rats , though the change is small in rats with functional pineal nerve endinvs. Ether anesthesia (G.M. Vaughan and J.P. Allen, unpublished results

  12. Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers

    Energy Technology Data Exchange (ETDEWEB)

    Doerrenhaus, Angelika; Roos, Peter H. [Institute for Occupational Physiology at the University Dortmund, Dortmund (Germany); Mueller, Tina [Institute for Occupational Physiology at the University Dortmund, Dortmund (Germany); University Dortmund, Department of Statistics, Mathematical Statistics with Applications in Biometrics, Dortmund (Germany)

    2007-01-15

    Polycyclic aromatic hydrocarbons, arylamines and nitrosamines, constituents of cigarette smoke, are known inducers of bladder cancer. The biochemical response of the target tissue, the bladder urothelium, following inhalation of cigarette smoke has not been studied so far. We used exfoliated transitional urothelial cells from human urine samples to analyze effects of smoking on induction of the cytochrome P450 enzyme CYP1A1. Samples of 40 subjects, including male and female smokers and non-smokers, were examined. A prerequisite for the immunofluorescence microscopic analysis of the cells was the enrichment of the urothelial cell population. This was achieved by a new method which is based on magnetic cell sorting exploiting specific binding of immobilized Griffonia simplicifolia lectin to the surface of urothelial cells. Immunostaining of the final cell preparation with a monoclonal antibody to CYP1A1 showed that about 6% of the urothelial cells of non-smokers stained positive for CYP1A1. However, this fraction of positive cells was more than 44% of the urothelial cells in samples from cigarette smokers. In spite of the individual variation, the difference was statistically significant. There were no gender-related differences in the portion of CYP1A1 expressing urothelial cells of smokers and non-smokers. In essence, we show for the first time that human urothelial cells respond to cigarette smoking by induction of CYP1A1. The approach opens new fields of mechanistic and biomarker research with respect to the pathogenetic processes of cancer development in the human bladder. (orig.)

  13. The role of para-aminophenol in acetaminophen-induced methemoglobinemia in dogs and cats.

    Science.gov (United States)

    McConkey, S E; Grant, D M; Cribb, A E

    2009-12-01

    Acetaminophen (APAP) overdose in most species is associated with hepatotoxicity because of the metabolite N-acetyl-p-benzoquinoneimine (NAPQI). In dogs and cats, APAP overdose primarily causes methemoglobinemia and hemolysis. Although NAPQI has been proposed as the responsible intermediate in dogs and cats, it lacks chemical or pharmacokinetic characteristics that favor methemoglobin formation. We hypothesized that para-aminophenol (PAP) rather than NAPQI induces methemoglobinemia and that deficient arylamine N-acetyltransferase (NAT) activity in dogs and cats contributes to this species-dependent methemoglobinemia. Erythrocytes from dogs, cats, mice, and rats were exposed in vitro to APAP, NAPQI, and PAP. Only PAP induced methemoglobin and it induced more methemoglobin formation in dog and cat than rat and mouse erythrocytes. PAP also induced more methemoglobin in erythrocytes from Nat1/Nat2 knockout mice than wildtype (WT) mouse erythrocytes (P dog and cat erythrocytes (P dogs and cats contributes to this species-dependent toxicity.

  14. Heritability of caffeine metabolism

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Tzvetkov, Mladen V; Strube, Jakob

    2016-01-01

    Heritability of caffeine pharmacokinetics and CYP1A2 activity is controversial. Here we analyzed the pharmacokinetics of caffeine, an in vivo probe drug for CYP1A2 and arylamine N-acetyltransferase 2 (NAT2) activity, in monozygotic and dizygotic twins. In the entire group, common and unique...... environmental effects explained most variation in caffeine AUC. Apparently, smoking and hormonal contraceptives masked the genetic effects on CYP1A2 activity. However, when excluding smokers and users of hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects and even in the entire...... group, 8% of caffeine AUC variation could be explained by a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the variation (99%) of NAT2 activity was explained by genetic effects. This study illustrates two very different situations in pharmacogenetics, from an almost exclusively...

  15. Active cigarette smoking and the risk of breast cancer at the level of N-acetyltransferase 2 (NAT2) gene polymorphisms.

    Science.gov (United States)

    Kasajova, Petra; Holubekova, Veronika; Mendelova, Andrea; Lasabova, Zora; Zubor, Pavol; Kudela, Erik; Biskupska-Bodova, Kristina; Danko, Jan

    2016-06-01

    The aim of our study was to assess the correlation between the tobacco exposure and NAT2 gene (rs1041983 C/T, rs1801280 T/C, rs1799930 G/A) polymorphisms in association with breast cancer development. We wanted to determine the prognostic clinical importance of these polymorphisms in association with smoking and breast cancer. For the detection of possible association between smoking, NAT2 gene polymorphisms, and the risk of breast cancer, we designed a case-controlled study with 198 patients enrolled, 98 breast cancer patients and 100 healthy controls. Ten milliliters of peripheral blood from the cubital vein was withdrawn from every patient. The HRM (high resolution melting) analysis was used for the detection of three abovementioned NAT2 gene polymorphisms. When comparing a group of women smoking more than 5 cigarettes a day with the patients smoking fewer than 5 cigarettes a day, we found out that if women were the carriers of aberrant AA genotype for rs1799930, the first group of women had higher risk of breast carcinoma than the second group. If patients were the carriers of aberrant TT genotype for rs1041983, for rs1801280CC genotype, and rs1799930AA genotype and they smoked more than 5 cigarettes a day, they had higher risk of malignant breast disease than never-smoking women. Our results confirm the hypothesis that NAT2 gene polymorphisms (rs1041983 C/T, rs1801280 T/C, and rs1799930 G/A) in association with long-period active smoking could be the possible individual risk-predicting factors for breast cancer development in the population of Slovak women.

  16. Structure and Active Stie Residues of Pg1D, an N-Acetyltransferase from the Bacillosamine Synthetic Pathway Required for N-Glycan Synthesis in Campylobacter jejuni

    Energy Technology Data Exchange (ETDEWEB)

    Rangarajan,E.; Ruane, K.; Sulea, T.; Watson, D.; Proteau, A.; Leclerc, S.; Cygler, M.; Matte, A.; Young, N.

    2008-01-01

    Campylobacter jejuni is highly unusual among bacteria in forming N-linked glycoproteins. The heptasaccharide produced by its pgl system is attached to protein Asn through its terminal 2, 4-diacetamido-2, 4,6-trideoxy-d-Glc (QuiNAc4NAc or N, N'-diacetylbacillosamine) moiety. The crucial, last part of this sugar's synthesis is the acetylation of UDP-2-acetamido-4-amino-2, 4,6-trideoxy-d-Glc by the enzyme PglD, with acetyl-CoA as a cosubstrate. We have determined the crystal structures of PglD in CoA-bound and unbound forms, refined to 1.8 and 1.75 Angstroms resolution, respectively. PglD is a trimer of subunits each comprised of two domains, an N-terminal {alpha}/{beta}-domain and a C-terminal left-handed {beta}-helix. Few structural differences accompany CoA binding, except in the C-terminal region following the {beta}-helix (residues 189-195), which adopts an extended structure in the unbound form and folds to extend the {beta}-helix upon binding CoA. Computational molecular docking suggests a different mode of nucleotide-sugar binding with respect to the acetyl-CoA donor, with the molecules arranged in an 'L-shape', compared with the 'in-line' orientation in related enzymes. Modeling indicates that the oxyanion intermediate would be stabilized by the NH group of Gly143', with His125' the most likely residue to function as a general base, removing H+ from the amino group prior to nucleophilic attack at the carbonyl carbon of acetyl-CoA. Site-specific mutations of active site residues confirmed the importance of His125', Glu124', and Asn118. We conclude that Asn118 exerts its function by stabilizing the intricate hydrogen bonding network within the active site and that Glu124' may function to increase the pKa of the putative general base, His125'.

  17. Circadian Dynamics of the Cone-Rod Homeobox (CRX) Transcription Factor in the Rat Pineal Gland and Its Role in Regulation of Arylalkylamine N-Acetyltransferase (AANAT)

    DEFF Research Database (Denmark)

    Rohde, Kristian; Rovsing, Louise; Ho, Anthony K

    2014-01-01

    that the rhythmic nature of pineal CRX protein may directly modulate the daily profile of Aanat expression by inducing nighttime expression of this enzyme, thus facilitating nocturnal melatonin synthesis in addition to its role in ensuring a correct tissue distribution of Aanat expression....

  18. Common polymorphisms in the microsomal epoxide hydrolase and N-acetyltransferase 2 genes in association with inflammatory bowel disease in the Danish population

    DEFF Research Database (Denmark)

    Ernst, Anja; Andersen, Vibeke; Ostergaard, Mette

    2011-01-01

    Chronic inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the intestinal mucosa. Reactive molecules play a central role in altering the intestinal permeability, which may induce or sustain an immune response. Changes in detoxification of substances that causes...

  19. Salmonella enterica Serovar Typhimurium blaPER-1-Carrying Plasmid pSTI1 Encodes an Extended-Spectrum Aminoglycoside 6′-N-Acetyltransferase of Type Ib

    OpenAIRE

    Casin, Isabelle; Hanau-Berçot, Beatrice; Podglajen, Isabelle; Vahaboglu, Haluk; Collatz, Ekkehard

    2003-01-01

    We have studied the aminoglycoside resistance gene, which confers high levels of resistance to both amikacin and gentamicin, that is carried by plasmid pSTI1 in the PER-1 β-lactamase-producing strain of Salmonella enterica serovar Typhimurium previously isolated in Turkey. This gene, called aac(6′)-Ib11, was found in a class 1 integron and codes for a protein of 188 amino acids, a fusion product between the N-terminal moiety (8 amino acids) of the signal peptide of the β-lactamase OXA-1 and t...

  20. AcEST: DK951697 [AcEST

    Lifescience Database Archive (English)

    Full Text Available transferase OS=Chlamydomona... 36 1.5 tr|Q00XM1|Q00XM1_OSTTA SMCA5_HUMAN SWI/SNF related matrix associ... 34... 5.6 tr|Q11KQ0|Q11KQ0_MESSB GCN5-related N-acetyltransferase OS=Mesor... 33 9.6 t

  1. SwissProt search result: AK241738 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241738 J065201C14 (Q5FWF5) N-acetyltransferase ESCO1 (EC 2.3.1.-) (Establishment ...of cohesion 1 homolog 1) (ECO1 homolog 1) (Establishment factor-like protein 1) (EFO1p) (hEFO1) ESCO1_HUMAN 1e-28 ...

  2. SwissProt search result: AK103812 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103812 J033147B21 (Q5FWF5) N-acetyltransferase ESCO1 (EC 2.3.1.-) (Establishment ...of cohesion 1 homolog 1) (ECO1 homolog 1) (Establishment factor-like protein 1) (EFO1p) (hEFO1) ESCO1_HUMAN 3e-14 ...

  3. SwissProt search result: AK068730 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK068730 J013159E18 (Q5FWF5) N-acetyltransferase ESCO1 (EC 2.3.1.-) (Establishment ...of cohesion 1 homolog 1) (ECO1 homolog 1) (Establishment factor-like protein 1) (EFO1p) (hEFO1) ESCO1_HUMAN 5e-28 ...

  4. Human See, Human Do.

    Science.gov (United States)

    Tomasello, Michael

    1997-01-01

    A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

  5. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  6. DNA adducts of the tobacco carcinogens 2-amino-9H-pyrido[2,3-b]indole and 4-aminobiphenyl are formed at environmental exposure levels and persist in human hepatocytes.

    Science.gov (United States)

    Nauwelaërs, Gwendoline; Bellamri, Medjda; Fessard, Valérie; Turesky, Robert J; Langouët, Sophie

    2013-09-16

    Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25-100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM-10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage

  7. Human Development, Human Evolution.

    Science.gov (United States)

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a…

  8. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards an

  9. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  10. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation ...... often mentioned post-human condition....

  11. 龙葵碱对人肝癌HepG2细胞N-乙酰基转移酶活性的影响%Effect of solanine on N-acetyltransferase activity in HepG2 cell

    Institute of Scientific and Technical Information of China (English)

    高世勇; 季字彬

    2008-01-01

    目的 探讨龙葵碱对HepG2细胞Ⅳ-乙酰基转移酶(NAT)活性的影响.方法 采用HPLC方法,以2-氨基芴(2-AF)为底物,以2-AF被NAT乙酰化为2-乙酰氨基芴(2-AAF)的量来反应NAT的活性.结果 龙葵碱能显著降低HepG2完整细胞NAT的活性;龙葵碱能够降低HepG2细胞质内NAT的活性,作用具有剂量依赖性.结论 龙葵碱通过抑制HepG2细胞NAT的活性发挥细胞毒作用.

  12. Circadian Expression of the Arylalkylamine N-acetyltransferase Gene in the Rat Pineal Gland%大鼠松果体N-乙酰转移酶基因的昼夜节律性表达

    Institute of Scientific and Technical Information of China (English)

    王国卿; 杜玉珍; 童建

    2005-01-01

    探讨12 h光照、12 h黑暗交替(LD)光制下松果体N-乙酰转移酶(NAT)基因的昼夜节律性表达.SD大鼠在LD光制下饲养4周后,在一昼夜内每隔4 h采集一组松果体组织,提取总RNA,进行竞争性定量RT-PCR,测定不同昼夜时点(ZT)样品中NAT基因mRNA的相对表达量.用余弦函数获取节律参数,并经振幅检验分析是否存在昼夜节律.结果表明松果体NAT基因mRNA表达呈现昼夜节律性振荡(P<0.05),峰值(mRNA水平为1.07±0.23)和谷值(mRNA水平为0.61±0.15)分别位于ZT16和ZT4,峰值相位-241.80±14.94,振幅0.23±0.13,中值0.84±0.11.证实LD光制下松果体NAT基因存在明显的昼低夜高节律性表达.

  13. Human microbiomics

    OpenAIRE

    Rajendhran, J.; P. Gunasekaran

    2010-01-01

    The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity has been demonstrated, which may pave the way for new prophylactic and therapeutic strategies such as bacteriotherapy. The sig...

  14. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  15. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  16. Digital Humanities

    DEFF Research Database (Denmark)

    Brügger, Niels

    2016-01-01

    the humanities for decades, starting with research fields such as humanities computing or computational linguistics in the 1950s, and later new media studies and internet studies. The historical development of digital humanities has been characterized by a focus on three successive, but co-existing types......Digital humanities is an umbrella term for theories, methodologies, and practices related to humanities scholarship that use the digital computer as an integrated and essential part of its research and teaching activities. The computer can be used for establishing, finding, collecting......, and preserving material to study, as an object of study in its own right, as an analytical tool, or for collaborating, and for disseminating results. The term "digital humanities" was coined around 2001, and gained currency within academia in the following years. However, computers had been used within...

  17. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  18. Role of melatonin in the induction and maintenance of sleep

    OpenAIRE

    Fourtillan, Jean B.

    2002-01-01

    Pharmacokinetic studies of melatonin in young and elderly human volunteers, and the measurement of hypnotic effects in chicks under alternate light-dark or permanent light conditions, show that melatonin is a bioprecursor of hypnotic acetyl metabolites produced by the enzymatic acetylation of both melatonin and 2-oxomelatonin under the control of serotonin N-acetyltransferases (NATs), which are present in the pineal gland. The acetyl metabolite of melatonin, which we call carbo2, is an N-acet...

  19. Human Rights and Human Nature

    Directory of Open Access Journals (Sweden)

    Vittorio Possenti

    2013-11-01

    Full Text Available There seems to be two different versions of human rights in Western tradition: say Rationalistic and Christian; the former adopted in revolutionary France, the latter highly developed in Renaissance Spain. Current relativistic criticisms attempt to deny the universality of human rights alleging that this theory has been created in Western countries or it has no strong justification, and therefore cannot have universal approach; but this objection can be dismissed with an alternative justification of human rights.

  20. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg

    2007-01-01

    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  1. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter

    2015-01-01

    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  2. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  3. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre

    2017-01-01

    , and true population genomic studies of Bronze Age populations. Among the emerging areas of aDNA research, the analysis of past epigenomes is set to provide more new insights into human adaptation and disease susceptibility through time. Starting as a mere curiosity, ancient human genetics has become...

  4. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  5. Teaching humanism.

    Science.gov (United States)

    Stern, David T; Cohen, Jordan J; Bruder, Ann; Packer, Barbara; Sole, Allison

    2008-01-01

    As the "passion that animates authentic professionalism," humanism must be infused into medical education and clinical care as a central feature of medicine's professionalism movement. In this article, we discuss a current definition of humanism in medicine. We will also provide detailed descriptions of educational programs intended to promote humanism at a number of medical schools in the United States (and beyond) and identify the key factors that make these programs effective. Common elements of programs that effectively teach humanism include: (1) opportunities for students to gain perspective in the lives of patients; (2) structured time for reflection on those experiences; and (3) focused mentoring to ensure that these events convert to positive, formative learning experiences. By describing educational experiences that both promote and sustain humanism in doctors, we hope to stimulate the thinking of other medical educators and to disseminate the impact of these innovative educational programs to help the profession meet its obligation to provide the public with humanistic physicians.

  6. Biotransformation of Trichoderma spp. and their tolerance to aromatic amines, a major class of pollutants.

    Science.gov (United States)

    Cocaign, Angélique; Bui, Linh-Chi; Silar, Philippe; Chan Ho Tong, Laetitia; Busi, Florent; Lamouri, Aazdine; Mougin, Christian; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Dairou, Julien

    2013-08-01

    Trichoderma spp. are cosmopolitan soil fungi that are highly resistant to many toxic compounds. Here, we show that Trichoderma virens and T. reesei are tolerant to aromatic amines (AA), a major class of pollutants including the highly toxic pesticide residue 3,4-dichloroaniline (3,4-DCA). In a previous study, we provided proof-of-concept remediation experiments in which another soil fungus, Podospora anserina, detoxifies 3,4-DCA through its arylamine N-acetyltransferase (NAT), a xenobiotic-metabolizing enzyme that enables acetyl coenzyme A-dependent detoxification of AA. To assess whether the N-acetylation pathway enables AA tolerance in Trichoderma spp., we cloned and characterized NATs from T. virens and T. reesei. We characterized recombinant enzymes by determining their catalytic efficiencies toward several toxic AA. Through a complementary approach, we also demonstrate that both Trichoderma species efficiently metabolize 3,4-DCA. Finally, we provide evidence that NAT-independent transformation is solely (in T. virens) or mainly (in T. reesei) responsible for the observed removal of 3,4-DCA. We conclude that T. virens and, to a lesser extent, T. reesei likely utilize another, unidentified, metabolic pathway for the detoxification of AA aside from acetylation. This is the first molecular and functional characterization of AA biotransformation in Trichoderma spp. Given the potential of Trichoderma for cleanup of contaminated soils, these results reveal new possibilities in the fungal remediation of AA-contaminated soil.

  7. Human Computation

    CERN Document Server

    CERN. Geneva

    2008-01-01

    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  8. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    In contemporary societies, the humanities are under constant pressure and have to justify their existence. In the ongoing debates, Humboldt’s ideals of ‘Bildung’ and ‘pure science’ are often used to justify the unique function of the humanities of ensuring free research and contributing to a vital...... philosophy. Contrary to Humboldt’s idea that the non-practical is the most practical in the long run, philosophical pragmatism recommends to the humanities to situate knowledge in practices and apply knowledge to practices....

  9. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  10. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    . The first section of this chapter outlines the complete cause-effect pathway, from emissions of toxic substances to intake by the population up to damages in terms of human health effects. Section 2 outlines the framework for assessing human toxicity in LCIA. Section 3 discusses the contributing substances......This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... – demonstrates the importance to account for both outdoor and indoor exposure, including consumer products. Analysing the variations in intake fraction (the fraction of the emitted or applied chemical that is taken in by the consumer and the general population), effect factor and characterisation factor across...

  11. Human influences

    NARCIS (Netherlands)

    Lanen, van H.A.J.; Kasparek, L.; Novicky, O.; Querner, E.P.; Fendeková, M.; Kupczyk, E.

    2004-01-01

    Human activities can cause drought, which was not previously reported (man-induced hydrological drought). Groundwater abstractions for domestic and industrial use are a well-known example of such an environmental change

  12. Human phantom

    CERN Multimedia

    CERN PhotoLab

    1973-01-01

    This human phantom has been received by CERN on loan from the State Committee of the USSR for the Utilization of Atomic Energy. It is used by the Health Physics Group to study personel radiation doses near the accelerators.

  13. Human expunction

    Science.gov (United States)

    Klee, Robert

    2017-10-01

    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  14. Human babesiosis.

    Science.gov (United States)

    Rożej-Bielicka, Wioletta; Stypułkowska-Misiurewicz, Hanna; Gołąb, Elżbieta

    2015-01-01

    Babesiosis is an emerging parasitic, anthropo-zoonotic tick-borne disease, seldom diagnosed in humans. Caused by Protozoa, Babesia (also called Piroplasma) intraerytrocytic piriform microorganism. Infection of vertebrates is transmitted by ticks. Out of more than 100 Babesia species/genotypes described so far, only some were diagnosed in infected humans, mostly B. microti, B. divergens and B. venatorum (Babesia sp. EU1). Infection in humans is often asymptomatic or mild but is of a particular risk for asplenic individuals, those with congenital or acquired immunodeficiencies, and elderly. Infections transmitted with blood and blood products raise concerns in hemotherapy. Epidemiological situation of babesiosis varies around the world. In Europe, no increase in the number of cases was reported, but in the USA its prevalence is increasing and extension of endemic areas is observed. The aim of this publication is to describe the problems connected with the current epidemiological situation, diagnosis and treatment of human babesiosis with regard to clinical status of patients.

  15. Human energy

    OpenAIRE

    2010-01-01

    In the midst of big-oil record profits and growing debate on global warming, the Chevron Corporation launched its “Human Energy” public relations campaign. In television commercials and print advertisements, Chevron portrays itself as a compassionate entity striving to solve the planet’s energy crisis. Yet, the first term in this corporate oxymoron misleadingly reframes the significance of the second, suggesting that the corporation has a renewed focus. In depicting Chevron as a green/human o...

  16. Human Echolocation

    OpenAIRE

    Teng, Santani

    2013-01-01

    The use of active natural echolocation as a mobility aid for blind humans has received increased scientific and popular attention in recent years (Engber, 2006; Kreiser, 2006; NPR, 2011), in part due to a focus on several blind individuals who have developed remarkable expertise. However, perhaps surprisingly, the history of empirical human echolocation research is not much younger than the era of echolocation research (cf. Griffin, 1958). Nevertheless, compared to its bat and cetacean count...

  17. Human ehrlichiosis

    Directory of Open Access Journals (Sweden)

    Đokić Milomir

    2006-01-01

    Full Text Available Background. Human ehrlichiosis is a newly recognized disease. It is a tick-borne disease caused by several bacterial species of the genhus Erlichia. These are small gram-negative pleomorphic cocci, that are obligatory intracellular bacteria. Tick Ixodes is the principle vector in Europe, and Amblyomma americanum in the United States. Bacterial organisms replicate in a tick, and are transmited from infected cells in a vector to the blood cells of animals or humans. Human ehrlichiosis is a name for a group of diseases caused by different species of Ehrlichia. One of them is the disease named human monocytic ehrlichiosis, caused by Ehrlichia chaffeensis, and the other is a human granulocytic ehrlichiosis caused by Anaplasma phagocytophilia. Case report. We reported a 23-year-old patient admitted for the clinical treatment with the symptoms of high febrility (above 40 °C, headache, vomiting, general weakness and exhaustion, but without data on a tick bite. The patient was treated with trimetoprim-sulfamethoxazole for a week when Ehrlichia chaffeensis was confirmed by the immunofluoroscence test, and the therapy contimed with doxacyclin. Conclusion. Human ehrlichiosis is also present in our country, so this disease should be considered everyday, especially in infectology practice.

  18. Scavenging of free-radical metabolites of aniline xenobiotics and drugs by amino acid derivatives: toxicological implications of radical-transfer reactions.

    Science.gov (United States)

    Michail, Karim; Baghdasarian, Argishti; Narwaley, Malyaj; Aljuhani, Naif; Siraki, Arno G

    2013-12-16

    We investigated a novel scavenging mechanism of arylamine free radicals by poly- and monoaminocarboxylates. Free radicals of arylamine xenobiotics and drugs did not react with oxygen in peroxidase-catalyzed reactions; however, they showed marked oxygen uptake in the presence of an aminocarboxylate. These free-radical intermediates were identified using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and electron paramagnetic resonance (EPR) spectrometry. Diethylenetriaminepentaacetic acid (DTPA), a polyaminocarboxylate, caused a concentration-dependent attenuation of N-centered radicals produced by the peroxidative metabolism of arylamines with the subsequent formation of secondary aliphatic carbon-centered radicals stemming from the cosubstrate molecule. Analogously, N,N-dimethylglycine (DMG) and N-methyliminodiacetate (MIDA), but not iminodiacetic acid (IDA), demonstrated a similar scavenging effect of arylamine-derived free radicals in a horseradish peroxidase/H2O2 system. Using human promyelocytic leukemia (HL-60) cell lysate as a model of human neutrophils, DTPA, MIDA, and DMG readily reduced anilinium cation radicals derived from the arylamines and gave rise to the corresponding carbon radicals. The rate of peroxidase-triggered polymerization of aniline was studied as a measure of nitrogen-radical scavenging. Although, IDA had no effect on the rate of aniline polymerization, this was almost nullified in the presence of DTPA and MIDA at half of the molar concentration of the aniline substrate, whereas a 20 molar excess of DMPO caused only a partial inhibition. Furthermore, the yield of formaldehyde, a specific reaction endproduct of the oxidation of aminocarboxylates by aniline free-radical metabolites, was quantitatively determined. Azobenzene, a specific reaction product of peroxidase-catalyzed free-radical dimerization of aniline, was fully abrogated in the presence of DTPA, as confirmed by GC/MS. Under aerobic conditions, a radical-transfer reaction

  19. [Human influenza].

    Science.gov (United States)

    Stock, Ingo

    2006-10-01

    Human influenza is one of the most common human infectious diseases, contributing to approximately one million deaths every year. In Germany, each year between 5.000 and 20.000 individuals die from severe influenza infections. In several countries, the morbidity and mortality of influenza is greatly underestimated. This is reflected by general low immunization rates. The emergence of avian influenza against the background of the scenario of a human influenza pandemic has revived public interest in the disease. According to the World Health Organisation, it is only the question on the beginning of a new influenza pandemic. The virus type of the new pandemic is still uncertain and it is also unclear, if a pandemic spread of the virus may be prevented by consistent controlling of avian influenza.

  20. [Humanized childbirth].

    Science.gov (United States)

    Kuo, Su-Chen

    2005-06-01

    Childbirth is a major event in a family. The expectant parent's perception of the childbirth experience influences his or her development as a parent. Making childbirth a positive and satisfying experience for women is the responsibility of health care providers. Women want to have physical and emotional privacy during labor and delivery, and to experience both in a friendly, comfortable environment. For women expected to undergo normal deliveries, humanized childbirth is one accessible approach. This article explores the definition and evolution of humanized childbirth and the care practice that it involves. It also explores birth plans and birth experiences, and the improvements necessary to routine labor practices to enable women to participate in decision making about their childbirth experiences. The author emphasizes that when health-care providers recognize the value of humanized childbirth and make changes accordingly, the dignity of women's childbirth experiences will be enhanced.

  1. Beyond Humanisms

    Directory of Open Access Journals (Sweden)

    Capurro, Rafael

    2012-01-01

    Full Text Available In the first part of this paper a short history of Western humanisms (Socrates, Pico della Mirandola, Descartes, Kant is presented. As far as these humanisms rest on a fixation of the ‘humanum’ they are metaphysical, although they might radically differ from each other. The second part deals with the present debate on trans- and posthumanism in the context of some breath-taking developments in science and technology.Angeletics, a theory of messengers and messages, intends to give an answer to the leading question of this paper, namely: ‘what does it mean to go beyond humanisms?’ The conclusion exposes briefly an ethics of hospitality and care from an angeletic perspective.

  2. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  3. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  4. Human Trafficking

    Science.gov (United States)

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  5. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  6. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  7. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    and self-reflective democracy. Contemporary humanities have adopted a new orientation towards practices, and it is not clear how this fits with the ideals of ‘Bildung’ and ‘pure science’. A possible theoretical framework for this orientation towards practices could be found in John Dewey’s pragmatic...

  8. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  9. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  10. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  11. Human paleoneurology

    CERN Document Server

    2015-01-01

    The book presents an integrative review of paleoneurology, the study of endocranial morphology in fossil species. The main focus is on showing how computed methods can be used to support advances in evolutionary neuroanatomy, paleoanthropology and archaeology and how they have contributed to creating a completely new perspective in cognitive neuroscience. Moreover, thanks to its multidisciplinary approach, the book addresses students and researchers approaching human paleoneurology from different angles and for different purposes, such as biologists, physicians, anthropologists, archaeologists

  12. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  13. Human universe

    CERN Document Server

    Cox, Brian

    2014-01-01

    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  14. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  15. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  16. Trifluoroacetic acid in 2,2,2-trifluoroethanol facilitates S(N)Ar reactions of heterocycles with arylamines.

    Science.gov (United States)

    Carbain, Benoit; Coxon, Christopher R; Lebraud, Honorine; Elliott, Kristopher J; Matheson, Christopher J; Meschini, Elisa; Roberts, Amy R; Turner, David M; Wong, Christopher; Cano, Celine; Griffin, Roger J; Hardcastle, Ian R; Golding, Bernard T

    2014-02-17

    Small-molecule drug discovery requires reliable synthetic methods for attaching amino compounds to heterocyclic scaffolds. Trifluoroacetic acid-2,2,2-trifluoroethanol (TFA-TFE) is as an effective combination for achieving SN Ar reactions between anilines and heterocycles (e.g., purines and pyrimidines) substituted with a leaving group (fluoro-, chloro-, bromo- or alkylsulfonyl). This method provides a variety of compounds containing a "kinase-privileged fragment" associated with potent inhibition of kinases. TFE is an advantageous solvent because of its low nucleophilicity, ease of removal and ability to solubilise polar substrates. Furthermore, TFE may assist the breakdown of the Meisenheimer-Jackson intermediate by solvating the leaving group. TFA is a necessary and effective acidic catalyst, which activates the heterocycle by N-protonation without deactivating the aniline by conversion into an anilinium species. The TFA-TFE methodology is compatible with a variety of functional groups and complements organometallic alternatives, which are often disadvantageous because of the expense of reagents, the frequent need to explore diverse sets of reaction conditions, and problems with product purification. In contrast, product isolation from TFA-TFE reactions is straightforward: evaporation of the reaction mixture, basification and chromatography affords analytically pure material. A total of 45 examples are described with seven discrete heterocyclic scaffolds and 2-, 3- and 4-substituted anilines giving product yields that are normally in the range 50-90 %. Reactions can be performed with either conventional heating or microwave irradiation, with the latter often giving improved yields.

  17. Effect of arylamine hole-transport units on the performance of blue polyspirobifulorene light-emitting diodes

    NARCIS (Netherlands)

    Abbaszadeh, D.; Nicolai, H.T.; Crəciun, N.I.; Blom, P.W.M.

    2014-01-01

    The operation of blue light-emitting diodes based on polyspirobifluorene with a varying number of N,N,N′,N′ tetraaryldiamino biphenyl (TAD) hole-transport units (HTUs) is investigated. Assuming that the electron transport is not affected by the incorporation of TAD units, model calculations predict

  18. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  19. Human steroidogenesis

    DEFF Research Database (Denmark)

    Andersen, Claus Y; Ezcurra, Diego

    2014-01-01

    steroid concentrations cause alterations in endometrial development, affecting oocyte viability in assisted reproductive technology. Furthermore, it has been proposed that elevated progesterone levels have a negative effect on the reproductive outcome of COS. This may arise from an asynchrony between...... reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

  20. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  1. Human Toxocariasis

    Directory of Open Access Journals (Sweden)

    Mehmet Burak Selek

    2013-09-01

    Full Text Available Human toxocariasis is an parasitic infection caused by the ingestion of larvae of dog nematode Toxocara canis and less frequently of cat nematode T.cati. Toxocara eggs, shed to environment by infected dogs' and cats' droppings, become infective by embryonation. Humans, particularly children, can be infected by accidentally ingesting embryonated Toxocara eggs. Larvae hatch in the small intestine, penetrate the intestinal wall and migrate to other parts of body via the bloodstream. It is generally a benign, asymptomatic, and self-limiting disease, although migrating larvae can cause damage to tissues and organs, especially brain involvement can cause severe morbidity. The two main clinical presentations of toxocariasis are visceral larva migrans (VLM (a systemic disease caused by larval migration through major organs and ocular larva migrans (OLM (a disease limited to the eyes and optic nerves. There are also two less-severe syndromes which have recently been described, one mainly in children (covert toxocariasis and the other mainly in adults (common toxocariasis. Diagnosis is usually made by clinical signs/symptoms, epidemiological background of the patient and the use of immunological methods (ELISA or western-blot. On the other hand definitive diagnosis is much more challenging, since it requires the demonstration of larvae via biopsy or autopsy. Most cases of toxocariasis clear up without any treatment. VLM is primarily treated with antihelmintic drugs, such as; albendazole or mebendazole. Treatment of OLM is more difficult and usually consists of measures to prevent progressive damage to the eye like steroids. Laser photocoagulation and cryoretinopexy may also be used to treat severe cases. Since eradicating T.canis infection is difficult due to the complexity of its life cycle, prevention of toxocariasis is always preferred. Toxocara eggs have a strong protective layer which makes the eggs able to survive in the environment for months or

  2. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  3. Frequency of NAT2 and GSTP1 polymorphisms in the Kazakh population

    Directory of Open Access Journals (Sweden)

    Aisha Iskakova

    2014-01-01

    Full Text Available Introduction: Phase II xenobiotic biotransformation enzymes perform detoxification of hydrophilic and often toxic Phase I products by glutathionetransferase (GST, UDP-glucuronosyltransferase (UDF, N-acetyltransferase (NAT families and other enzymes. GST protein family metabolizes a large number of electrophilic xenobiotics, including drugs, by conjugating them with glutathione. Arylamine-N-acetyltransferase (NAT catalyzes the acetylation of the aromatic and heterocyclic amines. Materials and methods: The current study has assessed the frequencies of NAT2 and GSTP1 genes polymorphisms in 326 healthy individuals from different regions of Kazakhstan by using Real-Time PCR and direct sequencing methods. Results: Allele frequencies were derived for NAT2*5 (0.54 and GSTP1 (0.27. GSTP1 alleles were in Hardy – Weinberg equilibrium (p > 0.05, while NAT2*5 (p = 0.00 were not.  The population differences between North, Northeast and South Kazakhstan regions were determined. Statistically significant differences in the frequency of genotypes were not found. Conclusion: Allelic polymorphisms of NAT2*5 and GSTP1 genes vary widely in different populations. Kazakh population was significantly different from Asian, Caucasoid, African-American and Hispanic ones by NAT2*5 and GSTP1 genes. Allelic variants of the NAT2*5 were detected with a low frequency in Asian populations. Allelic frequency in other world populations varies from 30 to 50%. The differences between Kazakh (0.54 and the world population were statistically significant (p < 0.05. The frequency of GSTP1 (rs1695 in the African American population is 42%. The frequency of GSTP1 in Asian populations varies from 11% to 23%, in Caucasoid populations it is about 30%. The differences between Kazakh population (0.27 and other populations selected from the literature were statistically significant (p < 0.05. The study of mutations in GSTP1 and NAT2 genes is necessary to assess the risk of the development of

  4. [Human papillomaviruses].

    Science.gov (United States)

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

  5. Human Development Report 1991: Financing Human Development

    OpenAIRE

    United Nations Development Programme, UNDP

    1991-01-01

    Lack of political commitment rather than financial resources is often the real barrier to human development. This is the main conclusion of Human Development Report 1991 - the second in a series of annual reports on the subject.

  6. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  7. Human-machine interactions

    Science.gov (United States)

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  8. Special Section: Human Rights

    Science.gov (United States)

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  9. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  10. Visualizing Humans by Computer.

    Science.gov (United States)

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  11. The Human/Machine Humanities: A Proposal

    Directory of Open Access Journals (Sweden)

    Ollivier Dyens

    2016-03-01

    Full Text Available What does it mean to be human in the 21st century? The pull of engineering on every aspect of our lives, the impact of machines on how we represent ourselves, the influence of computers on our understanding of free-will, individuality and species, and the effect of microorganisms on our behaviour are so great that one cannot discourse on humanity and humanities without considering their entanglement with technology and with the multiple new dimensions of reality that it opens up. The future of humanities should take into account AI, bacteria, software, viruses (both organic and inorganic, hardware, machine language, parasites, big data, monitors, pixels, swarms systems and the Internet. One cannot think of humanity and humanities as distinct from technology anymore.

  12. From Human Past to Human Future

    OpenAIRE

    Robert G. Bednarik

    2013-01-01

    This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic an...

  13. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  14. Has Human Evolution Stopped?

    OpenAIRE

    TEMPLETON, Alan R

    2010-01-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important ...

  15. Preference for human eyes in human infants.

    Science.gov (United States)

    Dupierrix, Eve; de Boisferon, Anne Hillairet; Méary, David; Lee, Kang; Quinn, Paul C; Di Giorgio, Elisa; Simion, Francesca; Tomonaga, Masaki; Pascalis, Olivier

    2014-07-01

    Despite evidence supporting an early attraction to human faces, the nature of the face representation in neonates and its development during the first year after birth remain poorly understood. One suggestion is that an early preference for human faces reflects an attraction toward human eyes because human eyes are distinctive compared with other animals. In accord with this proposal, prior empirical studies have demonstrated the importance of the eye region in face processing in adults and infants. However, an attraction for the human eye has never been shown directly in infants. The current study aimed to investigate whether an attraction for human eyes would be present in newborns and older infants. With the use of a preferential looking time paradigm, newborns and 3-, 6-, 9-, and 12-month-olds were simultaneously presented with a pair of nonhuman primate faces (chimpanzees and Barbary macaques) that differed only by the eyes, thereby pairing a face with original nonhuman primate eyes with the same face in which the eyes were replaced by human eyes. Our results revealed that no preference was observed in newborns, but a preference for nonhuman primate faces with human eyes emerged from 3months of age and remained stable thereafter. The findings are discussed in terms of how a preference for human eyes may emerge during the first few months after birth.

  16. Economics of human trafficking.

    Science.gov (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  17. An acetyltransferase conferring tolerance to toxic aromatic amine chemicals: molecular and functional studies.

    Science.gov (United States)

    Martins, Marta; Rodrigues-Lima, Fernando; Dairou, Julien; Lamouri, Aazdine; Malagnac, Fabienne; Silar, Philippe; Dupret, Jean-Marie

    2009-07-10

    Aromatic amines (AA) are a major class of environmental pollutants that have been shown to have genotoxic and cytotoxic potentials toward most living organisms. Fungi are able to tolerate a diverse range of chemical compounds including certain AA and have long been used as models to understand general biological processes. Deciphering the mechanisms underlying this tolerance may improve our understanding of the adaptation of organisms to stressful environments and pave the way for novel pharmaceutical and/or biotechnological applications. We have identified and characterized two arylamine N-acetyltransferase (NAT) enzymes (PaNAT1 and PaNAT2) from the model fungus Podospora anserina that acetylate a wide range of AA. Targeted gene disruption experiments revealed that PaNAT2 was required for the growth and survival of the fungus in the presence of toxic AA. Functional studies using the knock-out strains and chemically acetylated AA indicated that tolerance of P. anserina to toxic AA was due to the N-acetylation of these chemicals by PaNAT2. Moreover, we provide proof-of-concept remediation experiments where P. anserina, through its PaNAT2 enzyme, is able to detoxify the highly toxic pesticide residue 3,4-dichloroaniline in experimentally contaminated soil samples. Overall, our data show that a single xenobiotic-metabolizing enzyme can mediate tolerance to a major class of pollutants in a eukaryotic species. These findings expand the understanding of the role of xenobiotic-metabolizing enzyme and in particular of NATs in the adaptation of organisms to their chemical environment and provide a basis for new systems for the bioremediation of contaminated soils.

  18. Status Asetilator Gen NAT2 pada Pasien Tuberkulosis dan Tuberkulosis dengan Diabetes Melitus di Kupang, Nusa Tenggara Timur

    Directory of Open Access Journals (Sweden)

    Alvinsyah Adhityo Pramono

    2017-03-01

    Full Text Available Indonesia is the second highest country with TB patients in the world. Diabetes mellitus (DM is a comorbid of TB. Arylamine N-acetyltransferase 2 (NAT2, encoded by the NAT2 gene, is an enzyme that metabolizes isoniazid (INH. NAT2 gene has some polimorphysims that may play a role in INH acetylating process. Those who are slow acetylators may develop liver intoxication as a consequence of slow INH metabolism process. Slow acetylator TBDM patients may complicate both TB and DM treatment, causing them to be less optimal. The aim of this study was to explore the acetylator status of TBDM patients in Kupang, Indonesia. A cross-sectional study was conducted by obtaining DNA of 122 TB patients in Kupang in June–November 2011. NAT2 gene was amplified and sequenced to determine the acetylator status. There were 5 TB patients who had a glucose serum level of >200mg/dL and was catagorized as TBDM. Result showed that there was 1 TBDM patient who was a rapid acetylator (NAT2*4/NAT2*4, 2 patients as intermediate acetylators (NAT2*13A/NAT2*6J, and 2 patients as slow acetylators (NAT2*5/NAT2*5G, NAT2*6A/ NAT2*6A, NAT2*7B/ NAT2*7B. Meanwhile,  there were 2 TB patients who was rapid acetylators (NAT2*4/NAT2*4 and 3 patients as intermediate acetylators (NAT2*4/NAT2*6A, NAT2*13A/NAT2*6J. Slow NAT2 acetylator TBDM patients potentially face more problems during therapy. As INH may cause liver intoxication, these patients may also experience unoptimum DM treatment. Therefore, it is strongly recommended to do a study on the role of pharmacogenomics in TBDM.

  19. Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Unissa, Ameeruddin Nusrath; Subbian, Selvakumar; Hanna, Luke Elizabeth; Selvakumar, Nagamiah

    2016-11-01

    Isoniazid (INH) is one of the most active compounds used to treat tuberculosis (TB) worldwide. In addition, INH has been used as a prophylactic drug for individuals with latent Mycobacterium tuberculosis (MTB) infection to prevent reactivation of disease. Importantly, the definition of multidrug resistance (MDR) in TB is based on the resistance of MTB strains to INH and rifampicin (RIF). Despite its simple chemical structure, the mechanism of action of INH is very complex and involves several different concepts. Many pathways pertaining to macromolecular synthesis are affected, notably mycolic acid synthesis. The pro-drug INH is activated by catalase-peroxidase (KatG), and the active INH products are targeted by enzymes namely, enoyl acyl carrier protein (ACP) reductase (InhA) and beta-ketoacyl ACP synthase (KasA). In contrast, INH is inactivated by arylamine N-acetyltransferases (NATs). Consequently, the molecular mechanisms of INH resistance involve several genes in multiple biosynthetic networks and pathways. Mutation in the katG gene is the major cause for INH resistance, followed by inhA, ahpC, kasA, ndh, iniABC,fadE, furA, Rv1592c and Rv1772. The recent association of efflux genes with INH resistance has also gained considerable attention. Interestingly, substitutions have also been observed in nat, fabD, and accD recently in resistant isolates. Understanding the mechanisms operating behind INH action and resistance would enable better detection of INH resistance. This information would aid novel drug design strategies. Herein we review all mechanisms known to potentially contribute to the complexity of INH action and mechanisms of resistance in MTB, with insights into methods for detection of INH resistance as well as their limitations.

  20. Human assisted robotic exploration

    Science.gov (United States)

    Files, B. T.; Canady, J.; Warnell, G.; Stump, E.; Nothwang, W. D.; Marathe, A. R.

    2016-05-01

    In support of achieving better performance on autonomous mapping and exploration tasks by incorporating human input, we seek here to first characterize humans' ability to recognize locations from limited visual information. Such a characterization is critical to the design of a human-in-the-loop system faced with deciding whether and when human input is useful. In this work, we develop a novel and practical place-recognition task that presents humans with video clips captured by a navigating ground robot. Using this task, we find experimentally that human performance does not seem to depend on factors such as clip length or familiarity with the scene and also that there is significant variability across subjects. Moreover, we find that humans significantly outperform a state-of-the-art computational solution to this problem, suggesting the utility of incorporating human input in autonomous mapping and exploration techniques.

  1. Human Use Index (Future)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  2. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... Directory Cancer Prevention Overview Research Human Papillomavirus (HPV) Vaccines On This Page What are human papillomaviruses? Which ... infections? Can HPV infections be prevented? What HPV vaccines are available? Who should get the HPV vaccines? ...

  3. Human Use Index

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  4. Telling the Human Story.

    Science.gov (United States)

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  5. Human Services Offices

    Data.gov (United States)

    Fairfax County, Virginia — This data contains point features representing the human services offices within Fairfax County.“HS_Region” is the office for each human services region, “DFS_Area”...

  6. Human Resource Accounting System

    Science.gov (United States)

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  7. The Growing Human Population.

    Science.gov (United States)

    Keyfitz, Nathan

    1989-01-01

    Discusses the issue of human population. Illustrates the projections of the growing human population in terms of developed and less developed countries. Describes the family planning programs in several countries. Lists three references for further reading. (YP)

  8. Human bites (image)

    Science.gov (United States)

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  9. Monogenic human obesity syndromes

    National Research Council Canada - National Science Library

    Farooqi, I S; O'Rahilly, S

    2004-01-01

    .... This chapter will consider the human monogenic obesity syndromes that have been characterized to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  10. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007......) article 'Visualizing the mind: Looking at Titian's Flaying of Marsyas', addressing features of the painting not commented on by Hart, and supplementing Hart's (Kleinian) theoretical frame by involving Didier Anzieu's 'skin ego', Slavoj Zizek's concept of the 'non-human', Giorgio Agamben's term...

  11. Human productivity program definition

    Science.gov (United States)

    Cramer, D. B.

    1985-01-01

    The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

  12. Human Resource Management System

    OpenAIRE

    Navaz, A. S. Syed; Fiaz, A. S. Syed; Prabhadevi, C.; V.Sangeetha; Gopalakrishnan,S.

    2013-01-01

    The paper titled HUMAN RESOURCE MANAGEMENT SYSTEM is basically concerned with managing the Administrator of HUMAN RESOURCE Department in a company. A Human Resource Management System, refers to the systems and processes at the intersection between human resource management and information technology. It merges HRM as a discipline and in particular its basic HR activities and processes with the information technology field, whereas the programming of data processing systems evolved into standa...

  13. Human nature and enhancement.

    Science.gov (United States)

    Buchanan, Allen

    2009-03-01

    Appeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good. I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.

  14. Human Document Project

    NARCIS (Netherlands)

    Vries, de J.; Abelmann, L.; Manz, A.; Elwenspoek, M.C.

    2012-01-01

    “The Human Document Project” is a project which tries to answer all of the questions related to preserving information about the human race for tens of generations of humans to come or maybe even for a future intelligence which can emerge in the coming thousands of years. This document mainly focuss

  15. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  16. Has human evolution stopped?

    Science.gov (United States)

    Templeton, Alan R

    2010-07-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  17. (Human) Resourcing For CI

    DEFF Research Database (Denmark)

    Jørgensen, Frances; S., Jacob; Kofoed, Lise Busk

    2005-01-01

    More and more, the ability to compete in today’s market is viewed as being dependent on human capital. One of the most challenging aspects of human resource management involves supplying the organization with the human capital necessary to fulfill its objectives. This task becomes especially...

  18. Human Machine Learning Symbiosis

    Science.gov (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.

    2017-01-01

    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  19. Monogenic human obesity.

    Science.gov (United States)

    Farooqi, I Sadaf

    2008-01-01

    We and others have identified several single gene defects that disrupt the molecules in the leptinmelanocortin pathway causing severe obesity in humans. In this review, we consider these human monogenic obesity syndromes and discuss how far the characterisation of these patients has informed our understanding of the physiological role of leptin and the melanocortins in the regulation of human body weight and neuroendocrine function.

  20. From Human Past to Human Future

    Directory of Open Access Journals (Sweden)

    Robert G. Bednarik

    2013-01-01

    Full Text Available This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic and neural detriments and pathologies. Uniformitarian reasoning based on ontogenic homology suggests that the cognitive abilities of hominins are consistently underrated in the unstable orthodoxies of Pleistocene archaeology. A scientifically guided review establishes developmental trajectories defining recent changes in the human genome and its expressions, which then form the basis of attempts to extrapolate from them into the future. It is suggested that continuing and perhaps accelerating unfavorable genetic changes to the human species, rather than existential threats such as massive disasters, pandemics, or astrophysical events, may become the ultimate peril of humanity.

  1. Humanity at the Edge

    DEFF Research Database (Denmark)

    Svendsen, Mette N.; Gjødsbøl, Iben M.; Dam, Mie S.

    2017-01-01

    At the heart of anthropology and the social sciences lies a notion of human existence according to which humans and animals share the basic need for food, but only humans have the capacity for morality. Based on fieldwork in a pig laboratory, a neonatal intensive care unit (NICU), and a dementia ...... human and animal value and agency with approaches that focus on human experience and virtue ethics, we argue that ‘the human’ at stake in the moral laboratory of feeding precarious lives puts ‘the human’ in anthropology at disposal for moral experimentation....

  2. Jordan Adjusted Human Development

    OpenAIRE

    Ababsa, Myriam

    2014-01-01

    Jordan Human Development Index (HDI) and Adjusted Human Development Index (IHDI) In 1990, the United Nations Development Programme designed a Human Development Index composed of life expectancy at birth, level of education and gross domestic product (GDP) per capita. In 2011, the UNDP ranked Jordan 95th out of 187 countries with a human development index of 0.698, up from 0.591 in 1990, making it the leading medium-range country for human development (fig. VIII.1). In 2010, the inequality adj...

  3. Human Beings And Water

    OpenAIRE

    2016-01-01

    The writer of this paper on this writing is talking about the human beings and water. Water is one of the very fundamentally things that human beings need to keep their lives. Human beings sometimes do not realise that the water is very important for them because they actually cannot live their lives without the present of water. Human beings can keep their lives without rice, but cannot without water. For instances the use of water for human beings are domestic use, cooking, washing, bathing...

  4. Human rights and bioethics.

    Science.gov (United States)

    Barilan, Y M; Brusa, M

    2008-05-01

    In the first part of this article we survey the concept of human rights from a philosophical perspective and especially in relation to the "right to healthcare". It is argued that regardless of meta-ethical debates on the nature of rights, the ethos and language of moral deliberation associated with human rights is indispensable to any ethics that places the victim and the sufferer in its centre. In the second part we discuss the rise of the "right to privacy", particularly in the USA, as an attempt to make the element of personal free will dominate over the element of basic human interest within the structure of rights and when different rights seem to conflict. We conclude by discussing the relationship of human rights with moral values beyond the realm of rights, mainly human dignity, free will, human rationality and response to basic human needs.

  5. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula.

  6. Human Capital and Sustainability

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2011-01-01

    Full Text Available A study of sustainability needs to consider the role of all forms of capital—natural, biological, social, technological, financial, cultural—and the complex ways in which they interact. All forms of capital derive their value, utility and application from human mental awareness, creativity and social innovation. This makes human capital, including social capital, the central determinant of resource productivity and sustainability. Humanity has entered the Anthropocene Epoch in which human changes have become the predominant factor in evolution. Humanity is itself evolving from animal physicality to social vitality to mental individuality. This transition has profound bearing on human productive capabilities, adaptability, creativity and values, the organization of economy, public policy, social awareness and life styles that determine sustainability. This article examines the linkages between population, economic development, employment, education, health, social equity, cultural values, energy intensity and sustainability in the context of evolving human consciousness. It concludes that development of human capital is the critical determinant of long-term sustainability and that efforts to accelerate the evolution of human consciousness and emergence of mentally self-conscious individuals will be the most effective approach for ensuring a sustainable future. Education is the primary lever. Human choice matters.

  7. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  8. Human organ markets and inherent human dignity.

    Science.gov (United States)

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept.

  9. Chimeras and human dignity.

    Science.gov (United States)

    de Melo-Martín, Inmaculada

    2008-12-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman chimera research threaten human dignity and those who argue that such threat does not exist fail to make their case. I first introduce some of the arguments that have been offered supporting the claim that the creation of certain sorts of chimeras threatens or violates human dignity. I next present opponents' assessments of such arguments. Finally I critically analyze both the critics' and the supporters' claims about whether chimera research threatens human dignity.

  10. Human Performance in Space

    Science.gov (United States)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  11. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  12. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research......Todays expanding digital landscape constitutes an important research object as well as the research environment for the Humanities at the beginning of the 21st century. Taking this state of affairs as a starting point this inaugural lecture presents a vision for how the digital affects...

  13. Advancing Human Rights

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The National Human Rights Action Plan of China (2012-2015) was initiated after the successful conclusion of the National Human Rights Action Plan of China (2009-2010).The Chinese government in late July published an assessment report on the implementation of the plan,elaborating on the full implementation of China's first-ever national program on human rights development,which was drafted in April 2009.

  14. Human hemoglobin genetics

    Energy Technology Data Exchange (ETDEWEB)

    Honig, G.R.; Adams, J.G.

    1986-01-01

    This book contains the following 10 chapters: Introduction; The Human Hemoglobins; The Human Globin Genes; Hemoglobin Synthesis and Globin Gene Expression; The Globin Gene Mutations - A. Mechanisms and Classification; The Globin Gene Mutations - B. Their Phenotypes and Clinical Expression; The Genetics of the Human Globin Gene Loci: Formal Genetics and Gene Linkage; The Geographic Distribution of Globin Gene Variation; Labortory Identification, Screening, Education, and Counseling for Abnormal Hemoglobins and Thalassemias; and Approaches to the Treatment of the Hemoglobin Disorders.

  15. Modern Human Capital Management

    OpenAIRE

    Feldberger, Madita

    2008-01-01

    Title: Modern Human Capital Management Seminar date: 30th of May 2008 Course: Master thesis in Business Administration, 15 ECTS Authors: Madita Feldberger Supervisor: Lars Svensson Keywords: Human capital, SWOT Analysis, Strategic Map, Balanced Scorecard Research Problem: Despite of the success of Human Capital Management (HCM) in research it did not arrive yet in the HR departments of many companies. Numerous firms even have problems to set their strategic goals with focus on HR. The HR Bala...

  16. Robotics for Human Exploration

    Science.gov (United States)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  17. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  18. Human Performance Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — Biochemistry:Improvements in energy metabolism, muscular strength and endurance capacity have a basis in biochemical and molecular adaptations within the human body....

  19. Extraterritorial Human Rights Obligations

    DEFF Research Database (Denmark)

    Amsinck Boie, Hans Nikolaj; Torp, Kristian

    adequately be addressed without including the approach to the problem taken in practice; Corporate Social Responsibility, CSR. The book therefore draws upon the concept of CSR and the approaches developed here and discusses whether states may utilize the CSR-based concept of human rights due diligence...... to fulfil their possible obligations to protect against human rights violations by corporations.......The book addresses the issue of corporate respect for human rights by examining if and how states are obligated to ensure that corporations originating from their jurisdiction respect human rights when they operate abroad. The existence of such a duty is much debated by academics at national...

  20. The psychology of humanness.

    Science.gov (United States)

    Haslam, Nick; Loughnan, Steve; Holland, Elise

    2013-01-01

    This chapter explores the ways in which the concept of "humanness" illuminates a wide and fascinating variety of psychological phenomena. After introducing the concept--everyday understandings of what it is to be human--we present a model of the diverse ways in which humanness can be denied to people. According to this model people may be perceived as lacking uniquely human characteristics, and thus likened to animals, or as lacking human nature, and thus likened to inanimate objects. Both of these forms of dehumanization occur with varying degrees of subtlety, from the explicit uses of derogatory animal metaphors, to stereotypes that ascribe lesser humanness or simpler minds to particular groups, to nonconscious associations between certain humans and nonhumans. After reviewing research on dehumanization through the lens of our model we examine additional topics that the psychology of humanness clarifies, notably the perception of nonhuman animals and the objectification of women. Humanness emerges as a concept that runs an integrating thread through a variety of research literatures.

  1. The Human Toolmaker

    OpenAIRE

    Kassuba, Tanja; Kastner, Sabine

    2014-01-01

    Do you enjoy building airplanes, cars, houses, or robots with Lego blocks? Humans are the only animal species that can create complicated constructions from simple Lego blocks – our Lego building ability is “human-specific,” since it is only found in human beings. What would our closest relatives, apes or monkeys, do with a box of Lego blocks? They would probably chew on them, and lose interest when they find out that they are not edible! Why are humans the only Lego builders in the animal ki...

  2. Photography after the Human

    OpenAIRE

    Zylinska, Joanna

    2016-01-01

    How can we visualise and subsequently reimagine the abstraction that is the extinction of human species while there is still time? The article addresses this question by considering the existence of images – and, in particular, light-induced mechanical images known as photographs – after the human. The “after the human” designation does not just refer to the material disappearance of the human in some kind of distant future, but also to the present imagining of the disappearance of the human ...

  3. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...... in pharmacological management of chronic atrial fibrillation....

  4. 大鼠松果体N-乙酰基转移酶基因的内源性昼夜表达规律%Endogenous Circadian Expression of the Arylalkylamine N-acetyltransferase Gene in the Pineal Gland of Rat

    Institute of Scientific and Technical Information of China (English)

    王国卿; 傅春玲; 李建祥; 杜玉珍; 童建

    2007-01-01

    目的 探讨大鼠松果体N-乙酰基转移酶(NAT)基因的内源性昼夜节律表达.方法 SD大鼠在持续黑暗(DD)光制下饲养8周后,在一昼夜内每隔4h采集一组松果体组织,提取总RNA,进行竞争性定量RT-PCR,测定不同昼夜时点(CT)样品中NAT基因mRNA的相对表达量,用余弦函数软件获取节律参数,并经振幅F检验分析是否存在昼夜节律.结果 松果体NAT基因mRNA的表达呈现明显的内源性节律振荡(P<0.05),峰值(mRNA水平为1.42±0.11)和谷值(mRNA水平为0.56±0.18)分别位于CT17和CT5,峰值相位-260.85±9.45,振幅0.44±0.09,中值0.99±0.12.结论 大鼠松果体NAT基因存在明显的内源性昼夜节律表达,其转录水平在主观黑夜高于主观白天.

  5. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research...

  6. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  7. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century

  8. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  9. Human Capital and Retirement

    NARCIS (Netherlands)

    P. Alders

    1999-01-01

    textabstractThis paper investigates the relation between human capital and retirement when the age of retirement is endogenous. This relation is examined in a life-cycle earnings model. An employee works full time until retirement. The worker accumulates human capital by training- on-the-job and by

  10. Cohabitation: Humans & Agriculture

    NARCIS (Netherlands)

    Woodington, W.

    2012-01-01

    This "designers' manual" is made during the TIDO-course AR0531 Smart & Bioclimatic Design. Cohabitation of humans and agriculture can be used to improve building climate, human health and the state of the world. It affects building design and requires new building components. This manual explains w

  11. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  12. Human Resource Accounting

    Science.gov (United States)

    Woodruff, Robert L., Jr.

    1973-01-01

    An interview is reported which discussed the implications for the hiring, recruiting, screening and development of employees in the light of human resource accounting, here defined as the identification, accumulation and dissemination of information about human resources in dollar terms. (SA)

  13. Hooking Kids with Humanities.

    Science.gov (United States)

    Anstead, Neil L.

    1993-01-01

    Humanitas is part of Collaboratives for Humanities and Arts Teaching (CHART), a nationwide network funded primarily by the Rockefeller Foundation. In 11 large school districts and numerous rural districts, high school teachers, academics, artists, and business and community leaders are cooperating to promote teaching of the arts and humanities.…

  14. The Human Technology

    DEFF Research Database (Denmark)

    Fausing, Bent

    with fundamental human values like intuition, vision and sensing; all the qualities the technology, the industrialisation and rationalisation, or in short modernity, has been criticized for having taken away from human existence. What technology has taken away now comes back through new technology as an aid...

  15. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  16. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  17. Human Rights Guaranteed

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Report says China’s human rights plan successfully implemented According to a detailed assessment report published by China’s State Council Information Office (SCIO),all the measures outlined in the National Human Rights Action Plan of China (2009-10) had been successfully put into place by the end of 2010.

  18. Defects in Human Nature

    Institute of Scientific and Technical Information of China (English)

    黄靓

    2008-01-01

    By tracing the defects of society back to the defects of human nature, humanity's essence is proved to be inherent evil. Man's natural tendency to do evil remain harnessed through the controls and conventions imposed by civilization, however, when rules or civilization are weakened, man' s dark side is unleashed.

  19. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  20. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues its first white paper on human resources The Chinese Government issued a white paper on its human resources on September 10, highlighting the country’s policies to cope with employment pressures and a lack of "high-level innovative talents.

  1. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  2. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  3. Damping Effect of Humans

    DEFF Research Database (Denmark)

    Pedersen, Lars

    Passive humans (sitting or standing) might well be present on flooring-systems, footbridges or other structures that carry humans. An active croud of people might generate structural vibrations, and these might be problematic. The passive crowd of people, however, will interact with the structural...

  4. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  5. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  6. Human Resource Construction

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Centering on strategic objective of reform and development,CIAE formulated its objectives in human resource construction for the 13th Five-year Plan period,and achieved new apparent progress in human resource construction in 2015.1 Implementation of"LONGMA Project"

  7. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  8. Human Rights Improving

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues a white paper on its human rights,highlighting freedom of speech on the Interne The Chinese Government released a white paper on its human rights in 2009 on September 26,highlighting the role of Internet freedom and the country’s efforts in safeguarding citizens’legitimate civil and political rights.

  9. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century lib

  10. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... a shared interdisciplinary research and educational collaboration. As a creative research initiative it focuses on change and innovative thinking. The innovativeness is a result of the strongly interdisciplinary perspective which is at the heart of Designing Human Technologies. Designing Human Technologies...

  11. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...... der mellem Human Relations (Hawthorne-eksperimenter ne) og Neo-Human Relations (behovsteorierne), men i denne fremstilling bruges Human Relations som en samlebetegnelse for begge disse – noget forskellige – forskningstraditioner. De har i dag opnået stor udbredelse og er praktisk talt obligatorisk...

  12. Human to Human Transmission of Brucella Melitensis

    Directory of Open Access Journals (Sweden)

    Patrice Vigeant

    1995-01-01

    Full Text Available Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely mode of transmission in this case.

  13. Human to Human Transmission of Brucella Melitensis

    OpenAIRE

    Patrice Vigeant; Jack Mendelson; Miller, Mark A.

    1995-01-01

    Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely ...

  14. Archaea on human skin.

    Directory of Open Access Journals (Sweden)

    Alexander J Probst

    Full Text Available The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.

  15. Human Power Empirically Explored

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, A.J.

    2011-01-18

    Harvesting energy from the users' muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are convenient and can be environmentally and economically beneficial. This work provides insight into the knowledge required to design human-powered energy systems in consumer products from a scientific perspective. It shows the developments of human-powered products from the first introduction of the BayGen Freeplay radio in 1995 till current products and provides an overview and analysis of 211 human-powered products currently on the market. Although human power is generally perceived as beneficial for the environment, this thesis shows that achieving environmental benefit is only feasible when the environmental impact of additional materials in the energy conversion system is well balanced with the energy demands of the products functionality. User testing with existing products showed a preference for speeds in the range of 70 to 190 rpm for crank lengths from 32 to 95 mm. The muscular input power varied from 5 to 21 W. The analysis of twenty graduation projects from the Faculty of Industrial Design Engineering in the field of human-powered products, offers an interesting set of additional practice based design recommendations. The knowledge based approach of human power is very powerful to support the design of human-powered products. There is substantial potential for improvements in the domains energy conversion, ergonomics and environment. This makes that human power, when applied properly, is environmentally and economically competitive over a wider range of applications than thought previously.

  16. Human pancreas development.

    Science.gov (United States)

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  17. Enhancing human capacities

    CERN Document Server

    Savulescu, Julian; Kahane, Guy

    2011-01-01

    Enhancing Human Capacities is the first to review the very latest scientific developments in human enhancement. It is unique in its examination of the ethical and policy implications of these technologies from a broad range of perspectives. Presents a rich range of perspectives on enhancement from world leading ethicists and scientists from Europe and North America The most comprehensive volume yet on the science and ethics of human enhancement Unique in providing a detailed overview of current and expected scientific advances in this area Discusses both general conceptual and ethical issues

  18. Aluminium in human sweat.

    Science.gov (United States)

    Minshall, Clare; Nadal, Jodie; Exley, Christopher

    2014-01-01

    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  20. Human dignity and bioethics

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš

    2013-01-01

    Full Text Available By opening the field of bioethics followed a new wave of intense debate on the theological, philosophical and legal significance of the concept of human dignity . Exactly ten years ago (December 2003 American bioethicist Ruth Maclin has proposed to divest ourselves of the concept of human dignity because it is vague, useless and redundant and that, without any loss, we can replace it by the ethical principle of personal autonomy. Her article was followed by harsh reactions and opposite views. What is this term in so broad, almost inflationary and opposite use is not a reason to deprive him, but, on the contrary, it shows how important it is and that it should be determined at least outline. As universal values and general concept, the human dignity has no pre-defined and narrow, precise meaning. It is more an evaluation horizon, the guiding principle and regulatory ideas that must constantly define and codify by many guaranted human rights and fundamental freedoms. As generic notion of each reasonable law, it is their foundation and a common denominator, legitimising basis of natural but also of positive law. As intrinsic and static value which means the humaneness, the humanity it is absolute, inherent to every human being without distinction and conditioning, as a unique and unrepeatable creation. In this meaning, the dignity is the obligation and limitation of the state, society and each of us. As an ethical and dynamic category, it is not given to us, but it is assign to us, and it is not in us, but always before us, as a guide of our actions in accordance with virtues, to treat ourselves, each other and the nature in a human way. The century in which we live is named the century of molecular biology and genetic engineering because of the enormous potential but also risks to human dignity. Because of that human dignity has become a central principle in all international documents relating to the human genome, genetics and bioethics, adopted

  1. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  2. Human Capital Tracking Tool -

    Data.gov (United States)

    Department of Transportation — AVS is now required to collect, track, and report on data from the following Flight, Business and Workforce Plan. The Human Resource Management’s Performance Target...

  3. Human Research Program

    Data.gov (United States)

    National Aeronautics and Space Administration — Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance...

  4. Human Papillomavirus (HPV)

    Science.gov (United States)

    ... Español Text Size Email Print Share Human Papillomavirus (HPV) Page Content Article Body According to the Centers ... and how to prevent it. How to Prevent HPV: There are 3 types of HPV vaccine: Cervarix , ...

  5. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  6. Human Emotion Recognition System

    Directory of Open Access Journals (Sweden)

    Dilbag Singh

    2012-08-01

    Full Text Available This paper discusses the application of feature extraction of facial expressions with combination of neural network for the recognition of different facial emotions (happy, sad, angry, fear, surprised, neutral etc... Humans are capable of producing thousands of facial actions during communication that vary in complexity, intensity, and meaning. This paper analyses the limitations with existing system Emotion recognition using brain activity. In this paper by using an existing simulator I have achieved 97 percent accurate results and it is easy and simplest way than Emotion recognition using brain activity system. Purposed system depends upon human face as we know face also reflects the human brain activities or emotions. In this paper neural network has been used for better results. In the end of paper comparisons of existing Human Emotion Recognition System has been made with new one.

  7. Humanism vs. Behaviorism

    Science.gov (United States)

    Hunter, Madeline

    1977-01-01

    Author argues that humanism and behaviorism are not necessarily exclusive of one another, and that principles of behaviorism, when thoughtfully applied, can lead to the achievement of humanistic goals. (RW)

  8. Bridging Humanism and Behaviorism.

    Science.gov (United States)

    Chu, Lily

    1980-01-01

    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  9. BIOETHICS AND HUMAN CLONING

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2011-12-01

    Full Text Available In this paper the authors analyze the process of negotiating and beginning of the United Nations Declaration on Human Cloning as well as the paragraphs of the very Declaration. The negotiation was originally conceived as a clear bioethical debate that should have led to a general agreement to ban human cloning. However, more often it had been discussed about human rights, cultural, civil and religious differences between people and about priorities in case of eventual conflicts between different value systems. In the end, a non-binding Declaration on Human Cloning had been adopted, full of numerous compromises and ambiguous formulations, that relativized the original intention of proposer states. According to authors, it would have been better if bioethical discussion and eventual regulations on cloning mentioned in the following text had been left over to certain professional bodies, and only after the public had been fully informed about it should relevant supranational organizations have taken that into consideration.

  10. Human Resource Planning

    Science.gov (United States)

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  11. Viruses and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  12. CHINESE OF HUMANITY

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Humanism Education in Language Class,Innovative model university English teaching,Analysis on Information Literacy of College English Teachers Based On Net Environment,Cultural Differences between E-C Idioms and Teaching of English Idioms

  13. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  14. Will Technology Humanize Us?

    Science.gov (United States)

    Snider, Robert C.

    1972-01-01

    The author considers the question of whether technology will cause humanization or dehumanization in the schools. He concludes that we can not stop tecchnology; we can only give it direction and purpose. (Author/MS)

  15. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    YIN PUMIN

    2010-01-01

    @@ The Chinese Government issued a white paper on its human resources on September I0, highlighting the coun-try's policies to cope with employ-ment pressures and a lack of "high-level innovative talents."

  16. Statement on Human Cloning

    Science.gov (United States)

    ... ban on efforts to implant a human cloned embryo for the purpose of reproduction. The scientific evidence ... stem cell research, including the use of nuclear transplantation techniques (also known as research or therapeutic cloning), ...

  17. Science and Humanism

    Science.gov (United States)

    Auger, Pierre

    1971-01-01

    Science and humanism are separated so completely as to bring about the creation of two cultures quite distinct from each other within contemporary civilization. Pragmatic, rational attitudes are needed on both sides to bring them together. (DF)

  18. Re-investigation of the concordance of human NAT2 phenotypes and genotypes.

    Science.gov (United States)

    Bolt, Hermann M; Selinski, Silvia; Dannappel, Doris; Blaszkewicz, Meinolf; Golka, Klaus

    2005-04-01

    A comparative study of N-acetyltransferase 2 (NAT2) genotyping and phenotyping (caffeine test method) was performed on 211 persons to elucidate apparent discrepancies in the assignment of NAT2*12 and NAT2*13 alleles which occur in the literature. The study used the standard procedures of genotyping (two PCR runs and application of seven restriction enzymes) and phenotyping (determination of the two caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1X)), as documented in detail and validated by the Deutsche Forschungsgemeinschaft. The data were consistent with an AFMU/1X molar ratio of 0.85 as cut-off point (antimode) between phenotypically slow and rapid acetylators. Under this provision, several R/S allele combinations did not comply, either fully or partly, with their associated phenotypes. In particular, there was a wide phenotypic overlap of the alleged rapid allele combination groups (i) NAT2*12A/*5A; NAT2*12C/*5D; NAT2*4/*5B, (ii) NAT2*13/*6B; NAT2*4/*6A, and (iii) NAT2*13/*7A; NAT2*4/*7B. These groups obviously contained both phenotypically rapid and slow acetylators. If one assumes that the presence of one "wild type" allele NAT2*4 defines a rapid acetylator the assignment of the alleles NAT2*12A, NAT2*12C, and NAT*13 as determinants of a rapid acetylator phenotype must be questioned. This refers in particular to the nucleotide changes A803G (NAT2*12A, NAT2*12C) and C282T (NAT2*13). Based on discussions in the literature and the data presented here, there is accumulating evidence that current assignments of the NAT2*12 and NAT2*13 alleles as determinants of a rapid acetylator state should be reconsidered.

  19. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  20. [Demography and human ecology].

    Science.gov (United States)

    Nazareth, J M

    1993-01-01

    At the end of the 19th century the German biologist Ernest Haekel was the first scientist to use the term ecology, which was defined as the study of relationships of organisms or groups of organisms with the environment and indicated the interdependence of the living world, including plants, animals, and humans. This concept also indicates a continuous process of adaptation of organisms to their external environment. The basic concepts of scientific ecology, which developed at the end of the 19th century, can be attributed to Darwin: the relationships between living beings and the notion of the process of adaptation to their environment. The term human ecology appeared in the early 1920s. Human ecology embodies fundamental ideas: biotype, habitat, community, biocenosis, ecosystem, biomass, interchange and equilibrium, and circulation of energy. The accumulated knowledge about human ecology is broken down using the criteria of topography (ecology of humid forests, deserts, lakes, etc.); followed by the appearance of species; and the variants of classical division: auto ecology (influence of external factors on living beings) and sinecology (the study of groups of associated organisms, i.e., natural, animal, and vegetation communities). The species are considered on the basis of equality or sinecology (all of them have the same interests), while in human ecology a species is determined by its relation to a reference group--autoecology or anthropocentric ecology. In 1911, J. Thompson bridged the gap between biological knowledge and social sciences; in 1921, H. Barrows identified human ecology as a component of geography; in 1925, L. Bernard presented the classification of ecosystems; and in 1936, Ezra Park published his work, Human Ecology, followed in 1945 by the emergence of the Chicago school. Demography and human ecology are intimately connected because population is the result of natural and migratory movements, therefore the two sciences require a methodology

  1. Human Resources Accounting

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 21 st century will be the epoch of knowled ge economy. Knowledge economy is to develop economy on the basis of knowledge will surely become the major resources of economy development. Therefore, human resources accounting which provides such information as the ebb and follow of hu man resources investment, the size of the human resources employment, will bec ome the main stream of accounting the time of knowledge economy. To face China 's reality, to develop economy, and to flourish enterprise...

  2. Human motricity and health

    Directory of Open Access Journals (Sweden)

    Manuel Sérgio Vieira e Cunha

    2008-06-01

    Full Text Available If human motricity science intends to study motor conduct (or actions in which the human being pursues transcendence (or surmounting, it inevitably relates to the large realm of health. What are the aspects it evinces? Transdisciplinarity, solidarity among the various knowledge types (including poetical, complexity, (where the physical is integrated but surmounted and the firm belief that to be healthy is to have in ourselves, alive and working, the capacity for surmounting anything.

  3. Human Happiness Is Sensuous

    Institute of Scientific and Technical Information of China (English)

    吕静

    2003-01-01

    All human happiness is biological happiness. That is strictly scientific. At the risk of being misunderstood. I must make it clearer: all human happiness is sensuous happiness. The spiritualists will misunderstand me. I am sure; the spiritualists and materialists must forever misunderstand each other, because they don’t talk the same language, or mean by the same word different things. Are we, too, in this problem

  4. Evolution and human sexuality.

    Science.gov (United States)

    Gray, Peter B

    2013-12-01

    The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory.

  5. Meeting human needs

    Science.gov (United States)

    Nicogossian, Arnauld E.

    1992-01-01

    The degree of autonomy of future long duration manned missions will emphasize interactions between human operators and automated systems aimed at the most effective allocations of tasks between humans and machines. Knowledge of crewmembers' physical status, encompassing both capabilities and limitations, will also be critical during EVA and planetary roving missions; psychological evaluation and support, with a view to both individual health and group cohesion and productivity, may become a critical consideration. Attention is here given to crewmembers' medical and psychological vulnerabilities.

  6. Human bites - self-care

    Science.gov (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  7. Testing for Human Immunodeficiency Virus

    Science.gov (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  8. A WORLD BEYOND HUMAN

    Directory of Open Access Journals (Sweden)

    David Abram

    2013-12-01

    Full Text Available From an initial project to investigate the relationship between magic and traditional medicine as practiced by shamans in Southern rural Asia, the focus of attention gradually shifted to an awareness of the negotiation traditional medicine people or shamans exert between the human community and the larger community of beings. This attentiveness to a more-than-human world does not occur at a supernatural domain above nature or inside her personal self but is the result of the shaman’s special ability to project her consciousness horizontally to other forms of sensibility with which human existence is interwoven. The ecological function of the shaman is to maintain a constant balance between what is taken and what is given from the human community to the larger community. The spirits of indigenous cultures are not defined in opposition to materiality but are essentially those modes of intelligence or awareness that do not possess a human form. By exploring different landscapes, and the sensibility living in them, a new sensitivity is awoken that allows for communication with those intelligences. However, the drowning of these other voices in Western culture, which reduces otherness to an object, creates an uneasiness that is hardly perceived except as an inability to interact with anything more-than-human and its dire consequences in the form of “civilization’s” destructive behavior.

  9. Genomics of human longevity.

    Science.gov (United States)

    Slagboom, P E; Beekman, M; Passtoors, W M; Deelen, J; Vaarhorst, A A M; Boer, J M; van den Akker, E B; van Heemst, D; de Craen, A J M; Maier, A B; Rozing, M; Mooijaart, S P; Heijmans, B T; Westendorp, R G J

    2011-01-12

    In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial metabolic and cellular features of long-lived families resemble those in animals for whom the lifespan is extended by applying genetic manipulation and, especially, dietary restriction. Candidate gene studies in humans support the notion that human orthologues from longevity genes identified in lower species do contribute to longevity but that the influence of the genetic variants involved is small. Here we discuss how an integration of novel study designs, labour-intensive biobanking, deep phenotyping and genomic research may provide insights into the mechanisms that drive human longevity and healthy ageing, beyond the associations usually provided by molecular and genetic epidemiology. Although prospective studies of humans from the cradle to the grave have never been performed, it is feasible to extract life histories from different cohorts jointly covering the molecular changes that occur with age from early development all the way up to the age at death. By the integration of research in different study cohorts, and with research in animal models, biological research into human longevity is thus making considerable progress.

  10. Human Milk Fortification.

    Science.gov (United States)

    Simmer, Karen

    2015-01-01

    Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15-20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers' instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed composition while monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks' corrected gestational age or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population.

  11. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  12. Pt/PIC催化还原芳香硝基化合物制备芳胺%Pt/PIC catalyzed hydrogenation of aromatic nitro compounds to arylamine

    Institute of Scientific and Technical Information of China (English)

    张渊; 张瑞; 黄军; 朱福和

    2012-01-01

    制备了一种多孔离子型高聚物(简称离聚物PIC),利用扫描电镜、透射电镜等一系列手段对离聚物PIC的形貌、结构进行表征,并制备负载型纳米铂催化剂(Pt/PIC)用于温和条件下芳胺(如对苯二胺、邻苯二胺、2-溴苯胺等)的合成实验中。实验表明:在1 atm H2条件下,该Pt/PIC催化剂对于芳香硝基化合物还原氢化反应具有高的催化活性和选择性,尤其是还原性基团如醛基、酮基、氰基,在氢化还原相应硝基芳基化合物过程中未受影响,且高产率得到相应芳胺。%A porous ionic copolymer(PIC) was prepared and characterized by SEM,BET,and TEM.The morphology and structure was investigated.And a supported Pt nano-catalyst(Pt/PIC) was prepared and used for the synthesis of anilines(such as p-phenylenediamine,o-diaminobenzene,2-Bromoaniline,et al.) under mild conditions.The study results showed that Pt/PIC catalyst was highly active and selective for the hydrogenation of nitro aromatic compounds under 1 atm H2.Reducible groups such as aldehyde,ketone and nitrile were not attacked during the hydrogenation of the corresponding nitro compounds,and the corresponding anilines were obtained with high yield.

  13. Power Conversion Efficiency of Arylamine Organic Dyes for Dye-Sensitized Solar Cells (DSSCs) Explicit to Cobalt Electrolyte: Understanding the Structural Attributes Using a Direct QSPR Approach

    OpenAIRE

    Supratik Kar; Juganta K. Roy; Danuta Leszczynska; Jerzy Leszczynski

    2016-01-01

    Post silicon solar cell era involves light-absorbing dyes for dye-sensitized solar systems (DSSCs). Therefore, there is great interest in the design of competent organic dyes for DSSCs with high power conversion efficiency (PCE) to bypass some of the disadvantages of silicon-based solar cell technologies, such as high cost, heavy weight, limited silicon resources, and production methods that lead to high environmental pollution. The DSSC has the unique feature of a distance-dependent electron...

  14. Quantitative analysis of the guest-concentration dependence of the mobility in a disordered fluorene-arylamine host-guest system in the guest-to-guest regime

    NARCIS (Netherlands)

    Nicolai, H.T.; Hof, A.J.; Lu, M.; Blom, P.W.M.; Vries, R.J. de; Coehoorn, R.

    2011-01-01

    The charge transport in a polyspirobifluorene derivative with copolymerized N,N,N',N'-tetraaryldiamino biphenyl (TAD) hole transport units is investigated as a function of the TAD content. For TAD concentrations larger than 5, guest-to-guest transport is observed. It is demonstrated that in this

  15. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  16. Why Geo-Humanities

    Science.gov (United States)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  17. [Human ehrlichiosis. Review].

    Science.gov (United States)

    Arraga-Alvarado, C

    1994-12-01

    Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 Ehrlichia canis has been known as a cause of illness in dogs and other canine species, and for a few years it was related with human disease. In 1990, Ehrlichia chaffeensis was isolated from a man suspected of having ehrlichiosis. Partial sequencing of the rRNAS from the human isolate and E. canis, indicated that they are 98.7% related. More recently (May 1994) an "human granulocytic ehrlichiosis" have been reported in USA. PCR amplification and sequence of 16S rDNA, showed that the human isolate was virtually identical to those reported for E. phagocytophila y E. equi, organisms that cause ehrlichiosis in rumiant and in horses. Most patients shows fever, headache, malaise, nausea or vomiting, anorexia and in a minority of cases rash is present. Some of them have complications such as pulmonary infiltrates, gastrointestinal problems, renal dysfunction or failure, hepatoesplenomegaly, neurologic abnormalities, DIC and some times death. Leucopenia, thrombocytopenia and elevated liver enzyme values have been common findings. Tetracycline and cloramphenicol have been using in adults and children as especific theraphy.

  18. The human serum metabolome.

    Directory of Open Access Journals (Sweden)

    Nikolaos Psychogios

    Full Text Available Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca.

  19. Humanity and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available So far our open access publishing company MDPI (Multidisciplinary Digital Publishing Institute has published mainly science, medicine and technology journals. To become a multidisciplinary publisher, we launched the journal Sustainability [1]. More recently, we started to run several social science journals, including Societies [2], Religions [3], Administrative Sciences [4] and Behavioral Sciences [5]. Today we published the first paper [6] of the inaugural issue of Humanities (ISSN 2076-0787. This will be an international open access journal, publishing scholarly papers of high quality across all humanities disciplines. As a publisher, I would like to publish journals surrounding the topics of sustainability and I believe the humanities as a discipline of academic studies are very important. As a scientist, I believed science and technology will only benefit human beings. I was raised in a small village, living a very primitive life in a peasant family: no electricity, no machines, of course no TV and no refrigerator. Now, the life of my children is completely different. Even my own life has completely changed. I have witnessed very rapid changes: more and more machines are used to consume mineral resources and energy and to pollute the environment, in order to produce more and more powerful machines (we are also launching a journal titled Machines, in which the relationship between Man and machine should be an interesting topic.. Machines are more and more like human individuals consuming resources themselves (we are launching a journal titled Resources. [...

  20. NOOSPHERE HUMAN COMMUNITY

    Directory of Open Access Journals (Sweden)

    Novozhilova Elena Olegovna

    2013-01-01

    Full Text Available The author dwells upon typical features of noosphere human communities, assessing prospects and hazards of genetic engineering, namely of recombinant DNA technology. Background: Socio-historical ecology ushers in a new approach to studying society in its relation to nature. This interrelation is regarded as a series of socio-ecological transformations ending up in certain types of socio-ecological systems being formed. One of such historical types is represented by a noosphere human community [1]. Results: A number of characteristic features of this kind of community have been outlined, namely: its existence and functioning on global scale, major role of information in making up social wealth, creation of living matter. Conclusion: The noosphere human community is currently the latest stage in the sequence of historical types of socio-ecological systems. Widespread use of information and genetic technology may enable noosphere people to create in future a totally man-made world superseding evolutionary biosphere.

  1. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    , men også arbejdssociologien, arbejdspsykologien og human resource development. Den første retning udsprang af de såkaldte Hawthorne-eksperimenter og psykologen Elton Mayos bearbejdelse af resultaterne derfra. Den anden er en løsere gruppering bestående af navne som Abraham Maslow og Frederick Herzberg......Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...

  2. [Human pulmonary trichomonoses].

    Science.gov (United States)

    Duboucher, Christophe; Caby, Stéphanie; Chabé, Magali; Gantois, Nausicaa; Delgado-Viscogliosi, Pilar; Pierce, Raymond; Capron, Monique; Dei-Cas, Eduardo; Viscogliosi, Eric

    2007-05-01

    Colonization of human lungs by various Trichomonas species is a frequent occurrence, but is unknown to most physicians. At this site of infection, the parasite develops into an amoeboid form that renders it unrecognizable. For this reason it has been overlooked until recently. Morphological identification is not feasible under these conditions and molecular tools provide the only means of identification. The species involved are not restricted to Trichomonas tenax, a saprophyte of the mouth that is usually cited in the rare cases of pleuropulmonary trichomoniasis reported in the literature. The recent discovery of species previously unknown in humans raises further questions, including the zoonotic potential of these microorganisms and the existence of species of animal origin that have adapted to humans. Anaerobiosis in poorly ventilated alveolar lumen, rather than immunodepression, seems to be the factor that promotes proliferation of this parasite. The diagnosis of trichomoniasis and its treatment by specific drugs will make it possible to evaluate the pathogenicity of these parasites.

  3. Scientists and Human Rights

    Science.gov (United States)

    Makdisi, Yousef

    2012-02-01

    The American Physical Society has a long history of involvement in defense of human rights. The Committee on International Freedom of Scientists was formed in the mid seventies as a subcommittee within the Panel On Public Affairs ``to deal with matters of an international nature that endangers the abilities of scientists to function as scientists'' and by 1980 it was established as an independent committee. In this presentation I will describe some aspects of the early history and the impetus that led to such an advocacy, the methods employed then and how they evolved to the present CIFS responsibility ``for monitoring concerns regarding human rights for scientists throughout the world''. I will also describe the current approach and some sample cases the committee has pursued recently, the interaction with other human rights organizations, and touch upon some venues through which the community can engage to help in this noble cause.

  4. Helicopter human factors

    Science.gov (United States)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  5. Human Systems Design Criteria

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1982-01-01

    the necessary functional qualities but also the needed human qualities. The author's main argument is, that the design process should be a dialectical synthesis of the two points of view: Man as a System Component, and System as Man's Environment. Based on a man's presentation of the state of the art a set...... of design criteria is suggested and their relevance discussed. The point is to focus on the operator rather than on the computer. The crucial question is not to program the computer to work on its own conditions, but to “program” the operator to function on human conditions.......This paper deals with the problem of designing more humanised computer systems. This problem can be formally described as the need for defining human design criteria, which — if used in the design process - will secure that the systems designed get the relevant qualities. That is not only...

  6. Reflections on humanizing biomedicine.

    Science.gov (United States)

    Marcum, James A

    2008-01-01

    Although biomedicine is responsible for the "miracles" of modern medicine, paradoxically it has also led to a quality-of-care crisis in which many patients feel disenfranchised from the health-care industry. To address this crisis, several medical commentators make an appeal for humanizing biomedicine, which has led to shifts in the philosophical boundaries of medical knowledge and practice. In this paper, the metaphysical, epistemological, and ethical boundaries of biomedicine and its humanized versions are investigated and compared to one another. Biomedicine is founded on a metaphysical position of mechanistic monism, an epistemology of objective knowing, and an ethic of emotionally detached concern. In humanizing modern medicine, these boundaries are often shifted to a metaphysical position of dualism/holism, an epistemology of subject knowing, and an ethic of empathic care. In a concluding section, the question is discussed whether these shifts in the philosophical boundaries are adequate to resolve the quality-of-care crisis.

  7. HUMAN MISSION OF EDUCATION

    Directory of Open Access Journals (Sweden)

    Suzana Miovska Spaseva

    2013-06-01

    Full Text Available The article examines the complex role and great responsibility of the education today in development of the moral strength and human values of the children and youth. At the beginning of the article the author reconsiders the pedagogical ideas of Maria Montessori and her concept of education for peace as an instrument for reconstruction of the society and for improvement of the human living. Than the analysis of the moral values in the contemporary society is made and several issues and dilemmas are discussed referring the value disorientation of the youth and the importance of the models of adult’s moral behavior in their search for personal identity. On the basis of this analysis, the human dimension of the education is elaborated enhancing the need for its understanding as support of development, which is based on several crucial elements: love, freedom and spirit of community.

  8. (Human) Resourcing For CI

    DEFF Research Database (Denmark)

    Jørgensen, Frances; S., Jacob; Kofoed, Lise Busk

    2005-01-01

    More and more, the ability to compete in today’s market is viewed as being dependent on human capital. One of the most challenging aspects of human resource management involves supplying the organization with the human capital necessary to fulfill its objectives. This task becomes especially...... challenging in organizations involved in change processes such as Continuous Improvement (CI), as the technical skills traditionally valued are no longer adequate. These companies are faced with the question: “What competencies should our employees possess in order to contribute to our success, given...... the change processes in which we are engaged?” Without a clear picture of the types of competencies required to implement CI, it is impossible for companies to make informed decisions regarding recruitment, hiring, and training of their workforce. The objective of this paper is therefore to define...

  9. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... and technologies relating to performances and experiences, urban design, climate adaptation, etc. The research takes a process-oriented and participatory approach and involves interaction between different user interests and designs. It is based on empirical, typical case- and action research-oriented studies...

  10. Abortion and human rights.

    Science.gov (United States)

    Shaw, Dorothy

    2010-10-01

    Abortion has been a reality in women's lives since the beginning of recorded history, typically with a high risk of fatal consequences, until the last century when evolutions in the field of medicine, including techniques of safe abortion and effective methods of family planning, could have ended the need to seek unsafe abortion. The context of women's lives globally is an important but often ignored variable, increasingly recognised in evolving human rights especially related to gender and reproduction. International and regional human rights instruments are being invoked where national laws result in violations of human rights such as health and life. The individual right to conscientious objection must be respected and better understood, and is not absolute. Health professional organisations have a role to play in clarifying responsibilities consistent with national laws and respecting reproductive rights. Seeking common ground using evidence rather than polarised opinion can assist the future focus.

  11. Human-Robot Interaction

    Science.gov (United States)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta

    2012-01-01

    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  12. Human immune system variation.

    Science.gov (United States)

    Brodin, Petter; Davis, Mark M

    2017-01-01

    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

  13. [Human rights and procreation].

    Science.gov (United States)

    Leroy, F

    1990-04-01

    The impact of procreation on freedom, health and welfare of human beings, is considerable. This relationship, however, is not mirrored in texts devoted to Human Rights. This omission obviously implies a neglect of women's and children's rights. The history of anticonceptive methods exemplifies the struggle for these rights. This conquest, which has lasted two hundred years, is far from completed. Because of the demographic outbreak in Third World countries, an ideological conflict has appeared between first generation Human Rights concerned with individual freedom ("rights of") and those of second generation aiming at social fairness ("rights to"). Adequate political and economic adjustment between North and South is a prerequisite to any balanced compromise that would resolve this conflict through democratic, albeit intensive, birth control.

  14. Monogenic obesity in humans.

    Science.gov (United States)

    Farooqi, I Sadaf; O'Rahilly, Stephen

    2005-01-01

    Until relatively recently, the small number of identifiable inherited human diseases associated with marked obesity were complex, pleiotropic developmental disorders, the molecular basis for which were entirely obscure. The molecular basis for many of these complex syndromes, such as Bardet Beidl syndrome, has been revealed, providing novel insights into processes essential for human hypothalamic function and energy balance. In addition to these discoveries, which were the fruits of positional cloning, the molecular constituents of the signaling pathways responsible for the control of mammalian energy homeostasis have been identified, largely through the study of natural or artificial mutations in mice. We discuss the increasing number of human disorders that result from genetic disruption of the leptin-melanocortin pathways that have been identified. Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged.

  15. Monogenic human obesity syndromes.

    Science.gov (United States)

    Farooqi, I S

    2006-01-01

    Over the past decade we have witnessed a major increase in the scale of scientific activity devoted to the study of energy balance and obesity. This explosion of interest has, to a large extent, been driven by the identification of genes responsible for murine obesity syndromes, and the novel physiological pathways revealed by those genetic discoveries. Others and we have also recently identified several single gene defects causing severe human obesity. Many of these defects have been in molecules identical or similar to those identified as a cause of obesity in rodents. I will review the human monogenic obesity syndromes that have been characterised to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  16. Social cognition in humans

    DEFF Research Database (Denmark)

    Frith, Christopher; Frith, Uta

    2007-01-01

    We review a diversity of studies of human social interaction and highlight the importance of social signals. We also discuss recent findings from social cognitive neuroscience that explore the brain basis of the capacity for processing social signals. These signals enable us to learn about...... the world from others, to learn about other people, and to create a shared social world. Social signals can be processed automatically by the receiver and may be unconsciously emitted by the sender. These signals are non-verbal and are responsible for social learning in the first year of life. Social...... signals can also be processed consciously and this allows automatic processing to be modulated and overruled. Evidence for this higher-level social processing is abundant from about 18 months of age in humans, while evidence is sparse for non-human animals. We suggest that deliberate social signalling...

  17. Lung cancer in Asian women - the environment and genes

    Energy Technology Data Exchange (ETDEWEB)

    Lam, W.K. [University of Hong Kong, Pokfulam (China). Queen Mary Hospital

    2005-09-15

    The mortality rate of lung cancer in Asian women has increased significantly in the past few decades. Environmental factors include tobacco smoke (active and environmental), other indoor pollutions (cooking oil vapours, coal burning, fungus spores), diet, and infections. Active tobacco smoking is not the major factor. Cooking oil vapours associated with high temperature wok cooking and indoor coal burning for heating and cooking in unvented homes, particularly in rural areas, are risk factors for Chinese women. Chronic benign respiratory diseases due to the fungus Microsporum canis probably accounts for the high incidence of lung cancer in northern Thai women at Sarapee. Diets rich in fruits, leafy green vegetables, and vitamin A are protective, while cured meat (Chinese sausage, pressed duck and cured pork), deep-fried cooking, and chili increased the risk. Tuberculosis is associated with lung cancer. Also, a Taiwanese study showed that the odds ratio of papillomavirus (HPV) 16/18 infection in non-smoking female lung cancer patients was 10.1, strongly suggesting a causative role. Genetic factors have also been studied in Chinese women, including human leucocyte antigens, K-ras oncogene activation, p53 mutation, polymorphisms of phase I activating enzymes (cytochrome P450, N-acetyltransferase slow acetylator status), and phase II detoxifying enzymes (glutathione-S-transferases, N-acetyltransferase rapid acetylator status).

  18. The crystal structure of Rv1347c, a putative antibiotic resistance protein from Mycobacterium tuberculosis, reveals a GCN5-related fold and suggests an alternative function in siderophore biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Card, G L; Peterson, N A; Smith, C A; Rupp, B; Schick, B M; Baker, E N

    2005-02-15

    Mycobacterium tuberculosis, the cause of TB, is a devastating human pathogen. The emergence of multi-drug resistance in recent years has prompted a search for new drug targets and for a better understanding of mechanisms of resistance. Here we focus on the gene product of an open reading frame from M. tuberculosis, Rv1347c, which is annotated as a putative aminoglycoside N-acetyltransferase. The Rv1347c protein does not show this activity, however, and we show from its crystal structure, coupled with functional and bioinformatic data, that its most likely role is in the biosynthesis of mycobactin, the M. tuberculosis siderophore. The crystal structure of Rv1347c was determined by MAD phasing from selenomethionine-substituted protein and refined at 2.2 {angstrom} resolution (R = 0.227, R{sub free} = 0.257). The protein is monomeric, with a fold that places it in the GCN5-related N-acetyltransferase (GNAT) family of acyltransferases. Features of the structure are an acylCoA binding site that is shared with other GNAT family members, and an adjacent hydrophobic channel leading to the surface that could accommodate long-chain acyl groups. Modeling the postulated substrate, the N{sup {var_epsilon}}-hydroxylysine side chain of mycobactin, into the acceptor substrate binding groove identifies two residues at the active site, His130 and Asp168, that have putative roles in substrate binding and catalysis.

  19. Human Security Agendas

    Institute of Scientific and Technical Information of China (English)

    Alan Hunter

    2012-01-01

    Ⅰ.IntroductionThe need for governments and international organisations to gain a better understanding of "security" is ever more urgent.For example in the conflict in Libya in early 2011,many security dilemmas were visible:the protection of Libyan civilians,the security of the regime,whether and how the UN or NATO should intervene,whether Europe would be threatened with a massive refugee flow,how to protect or evacuate foreign citizens (including Chinese),how to secure food and medical supplies in the midst of armed conflict.Such events may be termed "complex emergencies" which often raise legal, military and humanitarian issues simultaneously.International law and practice do not provide clear guidelines on such situations,and responses can be random,contingent on a variety of factors.Traditional concepts of security,for example protection of national borders,are certainly still relevant and legally enforceable,but more sophisticated concepts are needed to respond to security dilemmas in today's globalised world.Human security as a concept was first developed within the UN system in the 1990s,and set out,for example,in Human Security Now [1] The first section of this paper tracks the development of Human Security discourse,and also examines the broadening of the "security"concept in recent years.The second section reports on institutions with a specific interest in Human Security,for example within the UN system and in universities.The third section acknowledges some critiques of the Human Security paradigm.The last section reports on new directions that may enrich the Human Security agenda.

  20. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  1. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...

  2. On human health.

    Science.gov (United States)

    van Spijk, Piet

    2015-05-01

    If it is true that health is a priority objective of medicine, then medical practice can only be successful if the meaning of the term "health" is known. Various attempts have been made over the years to define health. This paper proposes a new definition. In addition to current health concepts, it also takes into account the distinction between specifically human (great) health and health as the absence of disease and illness-i.e. small health. The feeling of leading a life that makes sense plays a key role in determining specifically human great health.

  3. Handbook of human computation

    CERN Document Server

    Michelucci, Pietro

    2013-01-01

    This volume addresses the emerging area of human computation, The chapters, written by leading international researchers, explore existing and future opportunities to combine the respective strengths of both humans and machines in order to create powerful problem-solving capabilities. The book bridges scientific communities, capturing and integrating the unique perspective and achievements of each. It coalesces contributions from industry and across related disciplines in order to motivate, define, and anticipate the future of this exciting new frontier in science and cultural evolution. Reade

  4. When computers were human

    CERN Document Server

    Grier, David Alan

    2013-01-01

    Before Palm Pilots and iPods, PCs and laptops, the term ""computer"" referred to the people who did scientific calculations by hand. These workers were neither calculating geniuses nor idiot savants but knowledgeable people who, in other circumstances, might have become scientists in their own right. When Computers Were Human represents the first in-depth account of this little-known, 200-year epoch in the history of science and technology. Beginning with the story of his own grandmother, who was trained as a human computer, David Alan Grier provides a poignant introduction to the wider wo

  5. We Are Human Beings

    Science.gov (United States)

    McGee, Andrew

    2016-01-01

    In this paper, I examine Jeff McMahan’s arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients. PMID:26810918

  6. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W

    2010-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...... to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival...... - and healthy survival - to even greater ages....

  7. Understanding digital humanities

    CERN Document Server

    Berry, D

    2012-01-01

    The application of new computational techniques and visualisation technologies in the Arts and Humanities are resulting in fresh approaches and methodologies for the study of new and traditional corpora. This 'computational turn' takes the methods and techniques from computer science to create innovative means of close and distant reading. This book discusses the implications and applications of 'Digital Humanities' and the questions raised when using algorithmic techniques. Key researchers in the field provide a comprehensive introduction to important debates surrounding issues such as th

  8. Artificial human vision.

    Science.gov (United States)

    Dowling, Jason

    2005-01-01

    Can vision be restored to the blind? As early as 1929 it was discovered that stimulating the visual cortex of an individual led to the perception of spots of light, known as phosphenes [1] . The aim of artificial human vision systems is to attempt to utilize the perception of phosphenes to provide a useful substitute for normal vision. Currently, four locations for electrical stimulation are being investigated; behind the retina (subretinal), in front of the retina (epiretinal), the optic nerve and the visual cortex (using intra- and surface electrodes). This review discusses artificial human vision technology and requirements, and reviews the current development projects.

  9. Post-human Viewing

    DEFF Research Database (Denmark)

    Blaagaard, Bolette

    2013-01-01

    to become part of a global cultural flow, thus calling into question the physical connection between viewer and image. This article analyses what happens to that connection when not only the image but also the physical body is mediated and challenged in post-human relations, and examines the ensuing ethical...... implications. The author takes photojournalism and, in particular, mobile phone footage as a starting point for an exploration of the (post-human) body as evidence and sign of authenticity in the modern age of digital communications and journalism....

  10. Ayahuasca and human destiny.

    Science.gov (United States)

    McKenna, Dennis J

    2005-06-01

    In this essay, the author shares his personal reflections gleaned from a lifetime of research with ayahuasca, and speculates on the societal, political, planetary, and evolutionary implications of humanity's aeons-old symbiosis with this shamanic plant. The thesis is developed that at this critical historical juncture, ayahuasca has developed a strategy to broadcast its message to a wider world--a reflection of the urgent need to avert global ecological catastrophe. While ayahuasca has much to teach us, the critical question is, will humanity hear it, and heed it, in time?

  11. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  12. Pragmatic Challenges to Human Rights

    DEFF Research Database (Denmark)

    Schaumburg-Müller, Sten

    2007-01-01

    Pragmatism offers a platform for posing relevant questions. This article uses a pragmatic point of departure to question a natural law conception of human rights and to take a closer look at three pressing human rights problems: The human rights situation in states with little or no state capacity......; the revision and adaptation of human rights law; and the not straightforward relationship betweemn human rights and democracy....

  13. Human automation integration

    NARCIS (Netherlands)

    Barnes, M.; Cosenzo, K.; Galster, s.; Hollnagel, E.; Miller, C.; Parasuraman, R.; Reising, J.; Taylor, R.; Breda, L. van

    2007-01-01

    Many versions of future concept of operations (CONOPS) rely heavily on UMVs. The pressure to take the human out of immediate control of these vehicles is being driven by several factors. These factors include a reduction in cost for the production and maintenance of the vehicle, operational viabilit

  14. Human Work Interaction Design

    DEFF Research Database (Denmark)

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID frame-work, and a sample of 54 papers from workshops, conferences and journals from the period 2009-2014. We group the papers into six topical groups, and then ...

  15. Human Work Interaction Design

    DEFF Research Database (Denmark)

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID framework, and a sample of 54 HWID related papers from workshops, conferences and journals from the period 2009–2014. We group the papers into six topical group...

  16. Biotechnologies and Human Dignity

    Science.gov (United States)

    Sweet, William; Masciulli, Joseph

    2011-01-01

    In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the…

  17. Predictors of human rotation.

    Science.gov (United States)

    Stochl, Jan; Croudace, Tim

    2013-01-01

    Why some humans prefer to rotate clockwise rather than anticlockwise is not well understood. This study aims to identify the predictors of the preferred rotation direction in humans. The variables hypothesised to influence rotation preference include handedness, footedness, sex, brain hemisphere lateralisation, and the Coriolis effect (which results from geospatial location on the Earth). An online questionnaire allowed us to analyse data from 1526 respondents in 97 countries. Factor analysis showed that the direction of rotation should be studied separately for local and global movements. Handedness, footedness, and the item hypothesised to measure brain hemisphere lateralisation are predictors of rotation direction for both global and local movements. Sex is a predictor of the direction of global rotation movements but not local ones, and both sexes tend to rotate clockwise. Geospatial location does not predict the preferred direction of rotation. Our study confirms previous findings concerning the influence of handedness, footedness, and sex on human rotation; our study also provides new insight into the underlying structure of human rotation movements and excludes the Coriolis effect as a predictor of rotation.

  18. Humanizing science education

    Science.gov (United States)

    Donnelly, James F.

    2004-09-01

    This paper argues that the diverse curriculum reform agendas associated with science education are strongly and critically associated with the educational characteristics of the humanities. The article begins with a survey of interpretations of the distinctive contribution which the humanities make to educational purposes. From this survey four general characteristics of the humanities are identified: an appeal to an autonomous self with the right and capacity to make independent judgements and interpretations; indeterminacy in the subject matter of these judgements and interpretations; a focus on meaning, in the context of human responses, actions, and relationships, and especially on the ethical, aesthetic, and purposive; and finally, the possibility of commonality in standards of judgement and interpretation, under conditions of indeterminacy. Inquiry and science technology and society (STS) orientated curriculum development agendas within science education are explored in the light of this analysis. It is argued that the four characteristics identified are central to the educational purposes of these and other less prominent modes of curriculum development in science, though not unproblematically so. In the light of this discussion the prognosis and challenges for science curriculum development are explored.

  19. Learning to Be Human

    Science.gov (United States)

    Macmurray, John

    2012-01-01

    This article presents "Learning to be Human", which John Macmurray delivered on 5 May 1958 as the annual public lecture at Moray House College of Education, now part of Edinburgh University. The key themes of the paper are ones to which Macmurray returned again and again in both his educational and his philosophical writing for over 40 years and…

  20. Human memory search

    NARCIS (Netherlands)

    Davelaar, E.J.; Raaijmakers, J.G.W.; Hills, T.T.; Robbins, T.W.; Todd, P.M.

    2012-01-01

    The importance of understanding human memory search is hard to exaggerate: we build and live our lives based on what whe remember. This chapter explores the characteristics of memory search, with special emphasis on the use of retrieval cues. We introduce the dependent measures that are obtained

  1. Human Memory: The Basics

    Science.gov (United States)

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  2. Parasites and human evolution.

    Science.gov (United States)

    Perry, George H

    2014-01-01

    Our understanding of human evolutionary and population history can be advanced by ecological and evolutionary studies of our parasites. Many parasites flourish only in the presence of very specific human behaviors and in specific habitats, are wholly dependent on us, and have evolved with us for thousands or millions of years. Therefore, by asking when and how we first acquired those parasites, under which environmental and cultural conditions we are the most susceptible, and how the parasites have evolved and adapted to us and we in response to them, we can gain considerable insight into our own evolutionary history. As examples, the tapeworm life cycle is dependent on our consumption of meat, the divergence of body and head lice may have been subsequent to the development of clothing, and malaria hyperendemicity may be associated with agriculture. Thus, the evolutionary and population histories of these parasites are likely intertwined with critical aspects of human biology and culture. Here I review the mechanics of these and multiple other parasite proxies for human evolutionary history and discuss how they currently complement our fossil, archeological, molecular, linguistic, historical, and ethnographic records. I also highlight potential future applications of this promising model for the field of evolutionary anthropology.

  3. Antihumanism in the Humanities.

    Science.gov (United States)

    Schwartz, Joel

    1990-01-01

    Analyzes the antihumanistic elements of Jacques Derrida's theory of deconstruction. Argues that the modern French intellectuals, including Foucault, Derrida, and Lacan, have had an antihumanistic effect on the American social sciences and humanities by rejecting the existence of truth, morality, and rationality. (FMW)

  4. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  5. Human thimet oligopeptidase.

    Science.gov (United States)

    Dando, P M; Brown, M A; Barrett, A J

    1993-01-01

    We have purified human thimet oligopeptidase to homogeneity from erythrocytes, and compared it with the enzyme from rat testis and chicken liver. An antiserum raised against rat thimet oligopeptidase also recognized the human and chicken enzymes, suggesting that the structure of the enzyme has been strongly conserved in evolution. Consistent with this, the properties of the human enzyme were very similar to those for the other species. Thus human thimet oligopeptidase also is a thiol-dependent metallo-oligopeptidase with M(r) about 75,000. Specificity for cleavage of a number of peptides was indistinguishable from that of the rat enzyme, but Ki values for the four potent reversible inhibitors tested were lower. In discussing the results, we consider the determinants of the complex substrate specificity of thimet oligopeptidase. We question whether substrates containing more than 17 amino acid residues are cleaved, as has been suggested. We also point out that the favourable location of a proline residue and a free C-terminus in the substrate may be as important as the hydrophobic residues in the P2, P1 and P3' positions that have been emphasized in the past. Images Figure 1 PMID:8373360

  6. Visible Human Project

    Science.gov (United States)

    ... Library of Medicine thanks the men and the women who will their body to science, thereby enabling medical research and development. Further Information General Information A description of The Visible Human Project ® image data and how to obtain it (includes license ...

  7. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  8. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies dif

  9. Human Power Empirically Explored

    NARCIS (Netherlands)

    Jansen, A.J.

    2011-01-01

    Harvesting energy from the users’ muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are conven

  10. Narratology beyond the Human

    Directory of Open Access Journals (Sweden)

    David Herman

    2014-12-01

    Full Text Available This essay uses Lauren Groff’s 2011 short story “Above and Below” to explore aspects of a narratology beyond the human, considering how ideas developed by scholars of narrative bear on questions about the nature and scope of human-animal relationships in the larger biosphere. Bringing Groff’s text into dialogue with the concept of “self-narratives” as developed by Kenneth J. Gergen and Mary M. Gergen, anthropological research on the ontologies projected by the members of different cultures, and ideas from literary narratology, I discuss how the structure and narration of Groff’s story reveal a fault line between two competing ontologies in the culture of modernity, one parsimonious and the other prolific when it comes to allocating possibilities for selfhood across species lines. More generally, in addition to illuminating how a given self-narrative locates the human agent in a transspecies constellation of selves, a narratology beyond the human can assist with the construction of new, more sustainable individual and collective self-narratives that situate the self within wider webs of creatural life.

  11. Communicating Humanism Nonverbally.

    Science.gov (United States)

    Hillison, John

    1983-01-01

    Discusses the importance of nonverbal communication by counselors in expressing humanistic feeling. Notes that facial expression (i.e., smiling) provides immediate feedback to the observer; use of space (i.e., close proximity) communicates warmth and humaneness; and tone of voice can complement spoken words and give them more meaning. (WAS)

  12. Cultivating human nature

    NARCIS (Netherlands)

    Derksen, Maarten

    2007-01-01

    Evolutionary psychology claims to offer a unified perspective on human nature and culture, which can serve to further the integration of psychology and the social sciences. I describe four approaches to evolutionary psychology, and note increasing attention to the agency of the individual in constru

  13. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  14. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  15. Lessons in Human Relations.

    Science.gov (United States)

    Glenn, Joanne Lozar

    2003-01-01

    Explores the importance of relationship literacy--the ability to create good relationships with others--in the next economy and offers perspectives on how business education instructors can help students develop and improve their human relations skills for business success. (Author/JOW)

  16. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  17. Human health and groundwater

    Science.gov (United States)

    The high quality of most groundwaters, consequent upon the self-purification capacity of subsurface strata, has long been a key factor in human health and wellbeing. More than 50% of the world’s population now rely on groundwater for their supply of drinking water – and in most circumstances a prope...

  18. Humanizing the Secondary School.

    Science.gov (United States)

    Hamilton, Norman K., Ed.; Saylor, J. Galen, Ed.

    These papers, presented during ASCD-sponsored conference, confront educators with issues in and alternatives for making secondary schools a more humanizing experience for students. The contributors and their articles are: Norman K. Hamilton, "Alternatives in Secondary Education"; Thornton B. Monez and Norman L. Bussiere, "The High School in Human…

  19. Humanism in Education

    Science.gov (United States)

    Armstrong, Michael

    2015-01-01

    This is the text of Michael Armstrong's address to the Brian Simon Centenary conference, held at the Institute of Education on 26 March 2015. Michael Armstrong celebrates the humanism that underlay Brian's belief in a common system of education, democratic and non-selective, and finds its counterpart in the creative practice of school children.

  20. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1995-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  1. Hauntings of Human Nature

    DEFF Research Database (Denmark)

    Clasen, Mathias

    2017-01-01

    The central conflicts of Stephen King’s horror novel The Shining are rooted in human nature and reflect evolutionarily recurrent adaptive problems—the problem of balancing conflicting evolved motives, such as motives for selfish status striving versus motives for affiliative nurturing behavior...

  2. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  3. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies

  4. Human Memory: The Basics

    Science.gov (United States)

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  5. Designers of Human Settlements

    Science.gov (United States)

    Cliff, Ursula

    1976-01-01

    Reviewed herein are the ideas of nine men who have addressed themselves to the problems of human settlements in this century. The ideas reviewed include those of Arnold Toynbee, Lewis Mumford, Hassan Fathy, Buckminster Fuller, Constantinos Doxiadis, Charles Correa, Paul Mwaluko, Robert McNamara and John F. C. Turner. (BT)

  6. The human myotendinous junction

    DEFF Research Database (Denmark)

    Knudsen, A B; Larsen, M; Mackey, Abigail

    2015-01-01

    The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never ...

  7. Haptocorrin in humans

    DEFF Research Database (Denmark)

    Mørkbak, Anne Louise; Nexo, Ebba; Poulsen, Steen Seier

    2007-01-01

    knowledge concerning its function and its distribution in adult and foetal life is limited. In this study, we present data on the tissue expression of haptocorrin and on the relation between analogues on haptocorrin and vitamin B(12) status in humans. Methods: Polyclonal antibodies towards haptocorrin were...

  8. Strengthening Career Human Agency

    Science.gov (United States)

    Chen, Charles P.

    2006-01-01

    Rooted in A. Bandura's (1982, 2001b) social cognitive theory, the notion of human agency has received considerable attention in vocational and career psychology for the last 2 decades, especially with the recent emergence of social constructivist thinking in the field. This article continues in the same direction. In reviewing the notion of human…

  9. Humanism in Education

    Science.gov (United States)

    Armstrong, Michael

    2015-01-01

    This is the text of Michael Armstrong's address to the Brian Simon Centenary conference, held at the Institute of Education on 26 March 2015. Michael Armstrong celebrates the humanism that underlay Brian's belief in a common system of education, democratic and non-selective, and finds its counterpart in the creative practice of school children.

  10. Animal and Human Communication.

    Science.gov (United States)

    Rummel, Lynda

    Several misconceptions regarding the status of human communication systems relative to the systems of other animals are discussed in this paper. Arguments are offered supporting the expansion of the communication discipline to include the study of the communication systems of other species. The "communicative continuity" view which ranks…

  11. Conceptualizations of Human Environments

    Science.gov (United States)

    Moos, Rudolf H.

    1973-01-01

    Presents six major methods by which characteristics of environments have been related to indexes of human functioning: (1) ecological dimensions; (2) behavior settings; (3) dimensions of organizational structure; and, (4) dimensions identifying the collective personal and/or behavioral characteristics of the milieu inhabitants; and two others.…

  12. Radar: Human Safety Net

    Science.gov (United States)

    Ritz, John M.

    2016-01-01

    Radar is a technology that can be used to detect distant objects not visible to the human eye. A predecessor of radar, called the telemobiloscope, was first used to detect ships in the fog in 1904 off the German coast. Many scientists have worked on the development and refinement of radar (Hertz with electromagnetic waves; Popov with determining…

  13. Human Influenza Virus Infections.

    Science.gov (United States)

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  14. Selenium and Human Health

    Directory of Open Access Journals (Sweden)

    M Abedi

    2013-04-01

    Full Text Available Introduction: Selenium is an essential element for human health and it is toxic at high concentrations. Selenium is a constituent component of selenoproteins that have enzymatic and structural roles in human biochemistry. Selenium is a best antioxidant and catalyst for production of thyroid hormone. This element has the key role in the immune function; prevention of AIDS progression and the deactivity of toxins. Furthermore, selenium is essential for sperm motility and can reduce abortions. Selenium deficiency was also associated with adverse mood states. The findings regarding cardiovascular disease risk related to selenium deficiency is unclear, though other conditions such as vascular inflammation, oxidative stress and selenium deficiency can cause this disease too. Moreover, consuming of 60 mg of selenium per day may be associated with reduction of cancer risk. In this study, a review of studies has been performed on the biochemical function of selenium toxicity, and its effects on human health. Furthermore, certain identified cancers associated with selenium have been discussed to absorb more attention to the status of this element and also as a guide for further studies. Selenium plays the dual character (useful and harmful in human health, and then it is necessary to determine the concentration of this element in body fluids and tissues. An appropriate method for routine measurement of selenium in clinical laboratories is electro thermal atomic absorption spectrometry (ETAAS with very low detection limit and good precision.

  15. Towards International Humanism

    Science.gov (United States)

    Huxley, Julian

    1971-01-01

    The basic task before the educational profession today is to study and understand the evolutionary-humanist revolution, to follow up its educational implications; and to enable as many as possible of the world's growing minds to be illuminated by its new vision of human destiny. (Author/JB)

  16. Recombinant human milk proteins.

    Science.gov (United States)

    Lönnerdal, Bo

    2006-01-01

    Human milk provides proteins that benefit newborn infants. They not only provide amino acids, but also facilitate the absorption of nutrients, stimulate growth and development of the intestine, modulate immune function, and aid in the digestion of other nutrients. Breastfed infants have a lower prevalence of infections than formula-fed infants. Since many women in industrialized countries choose not to breastfeed, and an increasing proportion of women in developing countries are advised not to breastfeed because of the risk of HIV transmission, incorporation of recombinant human milk proteins into infant foods is likely to be beneficial. We are expressing human milk proteins known to have anti-infective activity in rice. Since rice is a normal constituent of the diet of infants and children, limited purification of the proteins is required. Lactoferrin has antimicrobial and iron-binding activities. Lysozyme is an enzyme that is bactericidal and also acts synergistically with lactoferrin. These recombinant proteins have biological activities identical to their native counterparts. They are equally resistant to heat processing, which is necessary for food applications, and to acid and proteolytic enzymes which are needed to maintain their biological activity in the gastrointestinal tract of infants. These recombinant human milk proteins may be incorporated into infant formulas, baby foods and complementary foods, and used with the goal to reduce infectious diseases.

  17. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of hu

  18. Disability and Human Supports

    Directory of Open Access Journals (Sweden)

    Jeff McNair

    2015-01-01

    Full Text Available This article provides a brief overview of models of disability growing out of the field of disability studies and leading to a call for interventions going beyond a simply medical model approach. A brief discussion of human supports/services is provided such that readers engaged in the development of services/supports can base them on best principles.

  19. Human herpesviruses and MS

    DEFF Research Database (Denmark)

    Christensen, Tove

    2007-01-01

    Environmental factors operate on a background of genetic susceptibility in MS pathogenesis; the human herpesviruses (HHV) are likely candidates for such factors. HHV share a number of properties: they are almost ubiquitous, they are highly prevalent worldwide, they all cause latent infections...

  20. Children Are Human Beings

    Science.gov (United States)

    Bossard, James H. S.

    2017-01-01

    The basic assumption underlying this article is that the really significant changes in human history are those that occur, not in the mechanical gadgets which men use nor in the institutionalized arrangements by which they live, but in their attitudes and in the values which they accept. The revolutions of the past that have had the greatest…

  1. Ubiquitous Human Computing

    OpenAIRE

    Zittrain, Jonathan L.

    2008-01-01

    Ubiquitous computing means network connectivity everywhere, linking devices and systems as small as a thumb tack and as large as a worldwide product distribution chain. What could happen when people are so readily networked? This short essay explores issues arising from two possible emerging models of ubiquitous human computing: fungible networked brainpower and collective personal vital sign monitoring.

  2. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Lopes, Arminda; Ørngreen, Rikke

    This book constitutes the thoroughly refereed post-conference proceedings of the Third IFIP WG 13.6 Working Conference on Human Work Interaction Design, HWID 2012, held in Copenhagen, Denmark, in December 2012. The 16 revised papers presented were carefully selected for inclusion in this volume...

  3. Human-Centered Aspects

    NARCIS (Netherlands)

    Kulyk, O.; Kosara, R.; Urquiza, J.; Wassink, I.; Kerren, A.; Ebert, A.; Meyer, J.

    2007-01-01

    Humans have remarkable perceptual capabilities. These capabilities are heavily underestimated in current visualizations. Often, this is due to the lack of an in-depth user study to set the requirements for optimal visualizations. The designer does not understand what kind of information should be vi

  4. Human Learning and Memory

    Science.gov (United States)

    Lieberman, David A.

    2012-01-01

    This innovative textbook is the first to integrate learning and memory, behaviour, and cognition. It focuses on fascinating human research in both memory and learning (while also bringing in important animal studies) and brings the reader up to date with the latest developments in the subject. Students are encouraged to think critically: key…

  5. Making Human Beings Human: Bioecological Perspectives on Human Development. The SAGE Program on Applied Developmental Science

    Science.gov (United States)

    Bronfenbrenner, Urie, Ed.

    2004-01-01

    To a greater extent than any other species, human beings create the environments that, in turn, shape their own development. This book endeavors to demonstrate that human beings can also develop those environments to optimize their most constructive genetic potentials. What makes human beings human, therefore, is both the potential to shape their…

  6. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  7. Human-Robot Interaction

    Science.gov (United States)

    Sandor, Aniko; Cross, E. Vincent, II; Chang, Mai Lee

    2015-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces affect the human's ability to perform tasks effectively and efficiently when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. For efficient and effective remote navigation of a rover, a human operator needs to be aware of the robot's environment. However, during teleoperation, operators may get information about the environment only through a robot's front-mounted camera causing a keyhole effect. The keyhole effect reduces situation awareness which may manifest in navigation issues such as higher number of collisions, missing critical aspects of the environment, or reduced speed. One way to compensate for the keyhole effect and the ambiguities operators experience when they teleoperate a robot is adding multiple cameras and including the robot chassis in the camera view. Augmented reality, such as overlays, can also enhance the way a person sees objects in the environment or in camera views by making them more visible. Scenes can be augmented with integrated telemetry, procedures, or map information. Furthermore, the addition of an exocentric (i.e., third-person) field of view from a camera placed in the robot's environment may provide operators with the additional information needed to gain spatial awareness of the robot. Two research studies investigated possible mitigation approaches to address the keyhole effect: 1) combining the inclusion of the robot chassis in the camera view with augmented reality overlays, and 2) modifying the camera

  8. Helicopter Human Factors

    Science.gov (United States)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  9. Helicopter Human Factors

    Science.gov (United States)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  10. The science of unitary human beings and interpretive human science.

    Science.gov (United States)

    Reeder, F

    1993-01-01

    Natural science and human science are identified as the bases of most nursing theories and research programs. Natural science has been disclaimed by Martha Rogers as the philosophy of science that undergirds her work. The question remains, is the science of unitary human beings an interpretive human science? The author explores the works of Rogers through a dialectic with two human scientists' works. Wilhelm Dilthey's works represent the founding or traditional view, and Jurgen Habermas' works represent a contemporary, reconstructionist view. The ways Rogerian thought contributes to human studies but is distinct from traditional and reconstructionist human sciences are illuminated.

  11. Digitalization of the human mind

    Directory of Open Access Journals (Sweden)

    Mr.Sc. Drita Mehmeti

    2013-06-01

    Full Text Available The human faces with various problems already in its first steps in live, and carriers of such life situations are found in various ages which bring new currents in the way of life. Starting from the ancient Greek thought, the human and its mind made the centre of the world, already orienting the Western thought towards the study of the human mind (namely human reason, since it made the key tool for human survival. Although human problems have been discussed throughout various ages, they have not been able to resolve in full the human problems, and therefore, the same issues were taken by the representatives of the socalled “critical theory”, who used the theory to criticize the way of live Western civilization was offering, known as digitalization of the human mind. The human problems are addressed in a poly-dimensional manner. The factors affecting the human mind are: industrial civilization, technical progress, automation, overtly influence of machinery on humans, substitution of cultural values, which in sum have developed a new World Order, where the ruler is technology. In the modern world, the human fails to recognize himself, since he is out of himself and lives according to the rules set forth by the “remote control”. In the flow of this kind of livelihood, human alienates, or in other words, the human goes out of himself, trying to adapt maximally to the requirements of the new way of life.

  12. Human Integration Design Processes (HIDP)

    Science.gov (United States)

    Boyer, Jennifer

    2014-01-01

    The purpose of the Human Integration Design Processes (HIDP) document is to provide human-systems integration design processes, including methodologies and best practices that NASA has used to meet human systems and human rating requirements for developing crewed spacecraft. HIDP content is framed around human-centered design methodologies and processes in support of human-system integration requirements and human rating. NASA-STD-3001, Space Flight Human-System Standard, is a two-volume set of National Aeronautics and Space Administration (NASA) Agency-level standards established by the Office of the Chief Health and Medical Officer, directed at minimizing health and performance risks for flight crews in human space flight programs. Volume 1 of NASA-STD-3001, Crew Health, sets standards for fitness for duty, space flight permissible exposure limits, permissible outcome limits, levels of medical care, medical diagnosis, intervention, treatment and care, and countermeasures. Volume 2 of NASASTD- 3001, Human Factors, Habitability, and Environmental Health, focuses on human physical and cognitive capabilities and limitations and defines standards for spacecraft (including orbiters, habitats, and suits), internal environments, facilities, payloads, and related equipment, hardware, and software with which the crew interfaces during space operations. The NASA Procedural Requirements (NPR) 8705.2B, Human-Rating Requirements for Space Systems, specifies the Agency's human-rating processes, procedures, and requirements. The HIDP was written to share NASA's knowledge of processes directed toward achieving human certification of a spacecraft through implementation of human-systems integration requirements. Although the HIDP speaks directly to implementation of NASA-STD-3001 and NPR 8705.2B requirements, the human-centered design, evaluation, and design processes described in this document can be applied to any set of human-systems requirements and are independent of reference

  13. The effects of human resource flexibility on human resources development

    Directory of Open Access Journals (Sweden)

    SeidMehdi Veise

    2014-08-01

    Full Text Available Human resources are the primary factor for development of competitiveness and innovation and reaching competitive advantage and they try to improve corporate capabilities through various characteristics such as value creation, scarcity and difficulty of imitation. This paper investigates the effect of human resource flexibility and its dimensions on human resource development and its dimensions. The survey was conducted using descriptive-correlation method that intended to describe how human resource flexibility was effective on human resource development. Questionnaire was tool of data collection. The statistical population included one hundred employees of the Electric Company in Ilam province, thus census method was used. Reliability of the questionnaire was measured via Cronbach's alpha equal to 0.96. The findings revealed that flexibility and its dimensions were effective on human resource development and dimensions of it. As a result, human resource flexibility should be considered for development of human resources and employees with the highest flexibility should be selected.

  14. Survey Relationship between Human Resources Roles and Human Resources Competencies

    Directory of Open Access Journals (Sweden)

    Hasan Darvish

    2012-09-01

    Full Text Available This study evaluates relationship between Human resources roles and Human resources competencies in Iranian Petroleum Company. For this study, we were looking for answers to these questions: What are the new required Human Resources competencies For Contemporary organizations? And For Gain these competencies what roles should be played by Human Resources? The study had one main hypothesis and four minor hypotheses. Research method was descriptive, and regression and correlation tests were used to determine the relationship between variables. The populations of this study were managers of Iranian Petroleum Company. This Research showed that Human resources roles have significant effect on Human resources competencies; Strategic partner, Employee champion, and Change agent had significant relationship with all of Human resource competencies; Administrative expert had not significant relationship with none of the Human resource competencies.

  15. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    morphine via high pressure liquid chromatography (HPLC). The HPLC peak corresponding to an authentic morphine standard had its morphine level determined via radioimmune assay. The identity of this material was established by Q-TOF-MS analysis. RESULTS: Each glioma exhibited an endogenous morphine presence....... Tumor extractions demonstrated a molecular mass of 286.14 da, identical to authentic morphine. Subsequent fragmentation analysis of this molecule revealed fragment masses of 129.01 da, 183.09 da and 201.07 da, corresponding to authentic morphine fragments. This material was not found in any......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  16. [PALEOPATHOLOGY OF HUMAN REMAINS].

    Science.gov (United States)

    Minozzi, Simona; Fornaciari, Gino

    2015-01-01

    Many diseases induce alterations in the human skeleton, leaving traces of their presence in ancient remains. Paleopathological examination of human remains not only allows the study of the history and evolution of the disease, but also the reconstruction of health conditions in the past populations. This paper describes the most interesting diseases observed in skeletal samples from the Roman Imperial Age necropoles found in urban and suburban areas of Rome during archaeological excavations in the last decades. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumours, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, the palaeopathological study allowed to highlight the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

  17. Human Actions Made Tangible

    DEFF Research Database (Denmark)

    Buur, Jacob; Caglio, Agnese; Jensen, Lars Christian

    2014-01-01

    projects, it remains a challenge to investigate in detail how people interact with all of their body. Analysis of full-body movement is time consuming, notation techniques are rare, and findings are difficult to share between members of a design team. In this paper we propose tangible video analysis......, a method developed to engage people from different backgrounds in collaboratively analysing videos with the help of physical objects. We will present one of these tools, Action Scrabble, for analysing temporal organisation of human actions. We work with a case of skilled forklift truck driving....... By backtracking our design research experiments, we will unfold how and why the tangible tool succeeds in engaging designers with varied analysis experience to collaboratively focus on human action structures – and even find video analysis fun!...

  18. Philanthropy and Human Rights

    DEFF Research Database (Denmark)

    Larsen, Øjvind

    2013-01-01

    written about philanthropy from a political, sociological, anthropological and managerial perspective. However, an essential question remains: what does philanthropy mean? In a Greek context, philanthropy is connected to a friendly act towards one’s owns close connections such as family or fellow citizens......, and normally utilized to promote one’s own prestige in the city-state. In Roman context, universal humanism, humanitas, was invented. This universal perspective was also supported by Christianity. It is this universal concept of philanthropy which is the foundation for the different philanthropic traditions...... in Germany, England, France and USA. In each tradition is developed special features of the concept of philanthropy. The four traditions are summarized in the UN universal human rights, which has become the common normative reference for global philanthropy. In this way philanthropy has become, in a modern...

  19. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    2015-01-01

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of transnational business governance interactions (TBGI) analytical framework.1 The article identifies and discusses dimensions of interaction...... and components of regulatory governance which characterize the Guiding Principles, focusing in particular on rule formation and implementation. The article notes that the Guiding Principles actively enrolled other actors for the rule-making process, ensuring support in a politically and legally volatile field...... in several areas of relevance to transnational business governance interaction and indicates the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational business governance suggests that this form...

  20. Business and Human Rights

    DEFF Research Database (Denmark)

    Buhmann, Karin

    This article analyses the United Nations (UN) Guidelines on Business and Human Rights adopted in 2011 by the UN Human Rights Council from the perspective of Transnational Business Governance Interactions (TBGI) analytical framework (Eberlein et al. 2014). The article identifies and discusses...... dimensions of interaction and components of regulatory governance which characterise the Guiding Principles, focusing in particular on the rule formation and implementation. The article notes that the Guiding Principles actively enrolled other actors for the rule-making process ensuring support...... that the UN Guiding Principles are unique in several respects of relevance to transnational business governance interaction and indicate the relevance of the TBGI approach to public regulatory transnational business governance initiatives. The analysis of the Guiding Principles as interactional transnational...

  1. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...... and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus...

  2. Ancient human microbiomes.

    Science.gov (United States)

    Warinner, Christina; Speller, Camilla; Collins, Matthew J; Lewis, Cecil M

    2015-02-01

    Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and we therefore lack a foundation for characterizing this change. High-throughput sequencing has opened up new opportunities in the field of paleomicrobiology, allowing us to investigate the evolution of the complex microbial ecologies that inhabit our bodies. By focusing on recent coprolite and dental calculus research, we explore how emerging research on ancient human microbiomes is changing the way we think about ancient disease and how archaeological studies can contribute to a medical understanding of health and nutrition today.

  3. Is human fecundity changing?

    DEFF Research Database (Denmark)

    Smarr, Melissa M; Sapra, Katherine J; Gemmill, Alison

    2017-01-01

    Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is, therefore, fundamental for understanding human health at the population level. Given the absence of a population (bio)marker, fecundity is assessed indirectly by various individual-based (e.g. semen...... quality, ovulation) or couple-based (e.g. time-to-pregnancy) endpoints. Population monitoring of fecundity is challenging, and often defaults to relying on rates of births (fertility) or adverse outcomes such as genitourinary malformations and reproductive site cancers. In light of reported declines...... in semen quality and fertility rates in some global regions among other changes, the question as to whether human fecundity is changing needs investigation. We review existing data and novel methodological approaches aimed at answering this question from a transdisciplinary perspective. The existing...

  4. Serotonin in human skin

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Qiying Gong; Guiming Li

    2005-01-01

    In this review the authors summarize data of a potential role for serotonin in human skin physiology and pathology. The uncovering of endogenous serotonin synthesis and its transformation to melatonin underlines a putative important role of this pathway in melanocyte physiology and pathology. Pathways of the biosynthesis and biodegradation of serotonin have been characterized in human beings and its major cellular populations. Moreover, receptors of serotonin are expressed on keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. And the widespread expression of a cutaneous seorotoninergic system indicates considerable selectivity of action to facilitate intra-, auto-, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner. Melatonin, in turn, can also act as a hormone, neurotransmitter, cytokine, biological modifier and immunomodulator. Thus, Serotonin local synthesis and cellular localization could thus become of great importance in the diagnosis and management of cutaneous pathology.

  5. Posthumanism: beyond humanism?

    Science.gov (United States)

    Valera, Luca

    2014-01-01

    The focal point of posthumanism consists not as such in an a-critical acceptance of the technological promises - like there is for transhumanism - but in a total contamination and hybridization of human beings with other living beings and machines (these are the two main forms of contamination). The change of perspective untaken by posthumanism would be, thus, a paradigmatic shift in anthropology. As with ecologism, posthumanism, in order to obtain total contamination and man's openness to otherness, proposes the elimination and the fluidification of boundaries, thus even denying man's identity, and, with it, the very possibility of openness. However, by denying the identity, one denies the condition of possibility of thought, just as it has been manifested in history until now: hence we understand how, primarily, posthumanism is not configured as an adequate philosophical reflection, but as a narrative that takes origin from certain requirements, which are eminently human, and that discloses its deeply anthropogenic roots.

  6. Human-Forest Relationships

    DEFF Research Database (Denmark)

    Ritter, Eva; Dauksta, D.

    2012-01-01

    The relationship between human beings and forests has been important for the development of society. It is based on various productive, ecological, social and cultural functions of forests. The cultural functions, including the spiritual and symbolic role of forests, are often not addressed...... problems. To achieve a deeper understanding of the dependency of society on forests, it is necessary to recognise the role of forests in our consciousness of being human. Giving a historical overview about the cultural bonds between people and forests, the first part of the paper puts focus on non-productive...... with the same attention as the other functions. The aim of this paper is to put a stronger emphasis on the fact that the acknowledgement of cultural bonds is needed in the discussion of sustainable development. Forest should not only be considered as a technical means to solve environmental and economic...

  7. Animals, Humans and Sociability

    Directory of Open Access Journals (Sweden)

    Enrica Tedeschi

    2016-06-01

    Full Text Available This article discusses animal studies from the point of view of sociability as an “inter-subjective field of action” and as an agent and builder of society (“doing society”. In sociology, the zoological connection has availed of the theory of borders and critical realism, but, above all, of constructionism, in its interactionist and ethno-methodological sense and both focused on social micro-interaction. The construction of the identity of social actors (both human and animal is especially evident in interaction regarding play, games, sport, daily life and work. In these spheres, analyses shed light on ambivalent and contradictory human experiences that clash with the dominant culture, while highlighting practical resistance against speciesism, which it is well worth to bring to the attention of future research, using open, mixed methodologies.

  8. Fractionating human intelligence.

    Science.gov (United States)

    Hampshire, Adam; Highfield, Roger R; Parkin, Beth L; Owen, Adrian M

    2012-12-20

    What makes one person more intellectually able than another? Can the entire distribution of human intelligence be accounted for by just one general factor? Is intelligence supported by a single neural system? Here, we provide a perspective on human intelligence that takes into account how general abilities or "factors" reflect the functional organization of the brain. By comparing factor models of individual differences in performance with factor models of brain functional organization, we demonstrate that different components of intelligence have their analogs in distinct brain networks. Using simulations based on neuroimaging data, we show that the higher-order factor "g" is accounted for by cognitive tasks corecruiting multiple networks. Finally, we confirm the independence of these components of intelligence by dissociating them using questionnaire variables. We propose that intelligence is an emergent property of anatomically distinct cognitive systems, each of which has its own capacity.

  9. Hyaluronan in human malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: Veli-Matti.Kosma@uef.fi [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  10. Strategies of Human Mating

    Directory of Open Access Journals (Sweden)

    David M. Buss

    2006-12-01

    Full Text Available Modern humans have inherited the mating strategies that led to the success of their ancestors. These strategies include long-term mating, short-term mating, extra-pair mating, mate poaching, and mate guarding. This article presents empirical evidence supporting evolution-based hypotheses about the complexities of these mating strategies. Since men and women historically confronted different adaptive problems in the mating domain, the sexes differ profoundly in evolved strategic solutions. These differences include possessing different mate preferences, different desires for short-term mating, and differences in the triggers that evoke sexual jealousy. The study of human mating is one of the “success stories” of evolutionary psychology.

  11. Human herpesvirus 8 – A novel human pathogen

    Directory of Open Access Journals (Sweden)

    Edelman Daniel C

    2005-09-01

    Full Text Available Abstract In 1994, Chang and Moore reported on the latest of the gammaherpesviruses to infect humans, human herpesvirus 8 (HHV-8 1. This novel herpesvirus has and continues to present challenges to define its scope of involvement in human disease. In this review, aspects of HHV-8 infection are discussed, such as, the human immune response, viral pathogenesis and transmission, viral disease entities, and the virus's epidemiology with an emphasis on HHV-8 diagnostics.

  12. Den humane teknologi

    DEFF Research Database (Denmark)

    Fausing, Bent

    2008-01-01

    Artiklen undersøger hverdagsæstetikkens forestillinger om teknologi i tv-reklamer, nærmere bestemt to mobiltelefoner fra Nokia. Nokias slogan er som bekendt: "Nokia -connecting people". Hvilken funktion tilskrives denne succes-teknologi via billeder, narrativer, lyde, interaktioner og affekter? M...... så ofte nævnte post-humane tilstand, er konklusionen. Udgivelsesdato: 14.9.08...

  13. Den humane teknologi

    DEFF Research Database (Denmark)

    Fausing, Bent

    2008-01-01

    Artiklen undersøger hverdagsæstetikkens forestillinger om teknologi i tv-reklamer, nærmere bestemt to mobiltelefoner fra Nokia. Nokias slogan er som bekendt: "Nokia -connecting people". Hvilken funktion tilskrives denne succes-teknologi via billeder, narrativer, lyde, interaktioner og affekter? M...... så ofte nævnte post-humane tilstand, er konklusionen. Udgivelsesdato: 14.9.08...

  14. Retroviruses and human disease.

    OpenAIRE

    1987-01-01

    Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Qu...

  15. [The process of humanization].

    Science.gov (United States)

    Durali, T

    1999-01-01

    As Stefan Zweig expressed the situation of mankind succinctly: There are key moments in history (Sternstunden der Menschheit). Because of their paramount importance their events are minimal. Moreover, among them there are those which are greater in calibre than the ones quoted in Stefan Zweig's Sternstunden der Menschheit. These are the turning points of history. At first glance we can enumerate four major events: first and foremost, the enormous shift of certain communities from food-gathering to agriculture around 8000 BC mainly in Southwest Asia (Mesopotamia). Second, the introduction of the writing system at circa 3500 BC by the Sumerians again in Southwest Asia. Last but not least that tremendous innovation, maybe the greatest in history, once more in western Asia, the emergence of monotheistic religions based on revelation, and the origination of philosophy-science within the realm of the Antique Aegean civilization. Man's basic reality is biotic. He shares this very particularity with all other living beings of this world. Livingness, so far as we know, is a peculiarity of our planet, the Earth. The unfolding of livingness and ultimately the emergence of man as a living being is apparently covered by evolution. Hominization is the biotic, whereas humanization represents the cultural (or spiritual) aspect of becoming the human being. Hominization and humanization complement one another to bring about the human wholeness. Hominization, or put it in another way, the evolutionary aspect is, indeed, not the beginning of the story. There still remains a lower layer, in the ontological sense of the team, to be tackled; and that is the physical one. Just as with every living thing, man's most fundamental building blocks are of a physico-chemical-i.e. subatomic, atomic and molecular-nature.

  16. Ancient human microbiomes

    OpenAIRE

    Warinner, C.; Speller, C; Collins, M.; Lewis Jr., C.

    2015-01-01

    Very recently, we discovered a vast new microbial self: the human microbiome. Our native microbiota interface with our biology and culture to influence our health, behavior, and quality of life, and yet we know very little about their origin, evolution, or ecology. With the advent of industrialization, globalization, and modern sanitation, it is intuitive that we have changed our relationship with microbes, but we have little information about the ancestral state of our microbiome, and theref...

  17. Recombinant Human Enterovirus 71

    OpenAIRE

    2004-01-01

    Two human enterovirus 71 (HEV71) isolates were identified from hand, foot and mouth disease patients with genome sequences that had high similarity to HEV71 (>93%) at 5´ UTR, P1, and P2 and coxsackievirus A16 (CV-A16, >85%) at P3 and 3´UTR. Intertypic recombination is likely to have occurred between HEV71 and CV-A16 or an as-yet to be described CV-A16-like virus.

  18. Strategic Human Resources Management

    OpenAIRE

    Marta Muqaj

    2016-01-01

    Strategic Human Resources Management (SHRM) represents an important and sensitive aspect of the functioning and development of a company, business, institution, state, public or private agency of a country. SHRM is based on a point of view of the psychological practices, especially by investing on empowerment, broad training and teamwork. This way it remains the primary resource to maintain stability and competitiveness. SHRM has lately evolved on fast and secure steps, and the transformation...

  19. Structure of Human Adenovirus

    OpenAIRE

    Nemerow, Glen R.; Phoebe L Stewart; Reddy, Vijay S.

    2012-01-01

    A detailed structural analysis of the entire human adenovirus capsid has been stymied by the complexity and size of this 150 MDa macromolecular complex. Over the past 10 years, the steady improvements in viral genome manipulation concomitant with advances in crystallographic techniques and data processing software has allowed structure determination of this virus by X-ray diffraction at 3.5 Å resolution. The virus structure revealed the location, folds, and interactions of major and minor (ce...

  20. Understanding Human Carboxylesterase 2

    OpenAIRE

    Lamego, Joana

    2012-01-01

    Dissertation presented to obtain the Ph.D degree in Engineering and Technology Sciences, Biotechnology The first barrier oral drugs and prodrugs encounter prior to reaching an organism’s systemic circulation is the gastrointestinal (GI) tract, specifically the intestine, which is the primary section for absorption. Therefore, it is fundamental to understand the permeability of the therapeutic agent as well as its potential metabolism by human enterocytes, since biotransformatio...

  1. Literature as a Humanity

    Science.gov (United States)

    Levi, Albert William

    1976-01-01

    Attempts a brief summary of the American critical scene for the period 1935-1965 in order to indicate the serial prominence of 1) a sociological, 2) a New-Critical, and 3) a Marxist moment in literary criticism. Sets out to assert that for any literary work to be taught as a humanity is to bring to bear upon it the arts of communication,…

  2. Human Islet Amyloid Polypeptide

    DEFF Research Database (Denmark)

    Kosicka, Iga

    2014-01-01

    Diabetes mellitus type II is a metabolic disease affecting millions of people worldwide. The disease is associated with occurence of insoluble, fibrillar, protein aggregates in islets of Langerhans in the pancreas - islet amyloid. The main constituent of these protein fibers is the human islet...... of diabetes type II, while revealing the structure(s) of islet amyloid fibrils is necessary for potential design of therapeutic agents....

  3. Is dissection humane?

    OpenAIRE

    Hasan, Tabinda

    2011-01-01

    Dissection is being jeopardized in the modern medical education. It has unrelentingly faced the lashes of time and has been the scapegoat for numerous convenient curricula reforms and subjective biases. The cadaver is unparallel in establishing core knowledge among the medical community and it needs to be appreciated in a new light in the “cyber anatomy” realm of today. This article elucidates the medical and ethical validity of continuing human body dissection in medicine which outweighs all...

  4. Multichannel Human Body Communication

    Science.gov (United States)

    Przystup, Piotr; Bujnowski, Adam; Wtorek, Jerzy

    2016-01-01

    Human Body Communication is an attractive alternative for traditional wireless communication (Bluetooth, ZigBee) in case of Body Sensor Networks. Low power, high data rates and data security makes it ideal solution for medical applications. In this paper, signal attenuation for different frequencies, using FR4 electrodes, has been investigated. Performance of single and multichannel transmission with frequency modulation of analog signal has been tested. Experiment results show that HBC is a feasible solution for transmitting data between BSN nodes.

  5. Science and Human Experience

    Science.gov (United States)

    Cooper, Leon N.

    2015-01-01

    Part I. Science and Society: 1. Science and human experience; 2. Does science undermine our values?; 3. Can science serve mankind?; 4. Modern science and contemporary discomfort: metaphor and reality; 5. Faith and science; 6. Art and science; 7. Fraud in science; 8. Why study science? The keys to the cathedral; 9. Is evolution a theory? A modest proposal; 10. The silence of the second; 11. Introduction to Copenhagen; 12. The unpaid debt; Part II. Thought and Consciousness: 13. Source and limits of human intellect; 14. Neural networks; 15. Thought and mental experience: the Turing test; 16. Mind as machine: will we rubbish human experience?; 17. Memory and memories: a physicist's approach to the brain; 18. On the problem of consciousness; Part III. On the Nature and Limits of Science: 19. What is a good theory?; 20. Shall we deconstruct science?; 21. Visible and invisible in physical theory; 22. Experience and order; 23. The language of physics; 24. The structure of space; 25. Superconductivity and other insoluble problems; 26. From gravity to light and consciousness: does science have limits?

  6. Oxytocin promotes human ethnocentrism.

    Science.gov (United States)

    De Dreu, Carsten K W; Greer, Lindred L; Van Kleef, Gerben A; Shalvi, Shaul; Handgraaf, Michel J J

    2011-01-25

    Human ethnocentrism--the tendency to view one's group as centrally important and superior to other groups--creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate "love drug" or "cuddle chemical" and suggest that oxytocin has a role in the emergence of intergroup conflict and violence.

  7. Human Viruses and Cancer

    Directory of Open Access Journals (Sweden)

    Abigail Morales-Sánchez

    2014-10-01

    Full Text Available The first human tumor virus was discovered in the middle of the last century by Anthony Epstein, Bert Achong and Yvonne Barr in African pediatric patients with Burkitt’s lymphoma. To date, seven viruses -EBV, KSHV, high-risk HPV, MCPV, HBV, HCV and HTLV1- have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide. Viral oncogenic mechanisms generally include: generation of genomic instability, increase in the rate of cell proliferation, resistance to apoptosis, alterations in DNA repair mechanisms and cell polarity changes, which often coexist with evasion mechanisms of the antiviral immune response. Viral agents also indirectly contribute to the development of cancer mainly through immunosuppression or chronic inflammation, but also through chronic antigenic stimulation. There is also evidence that viruses can modulate the malignant properties of an established tumor. In the present work, causation criteria for viruses and cancer will be described, as well as the viral agents that comply with these criteria in human tumors, their epidemiological and biological characteristics, the molecular mechanisms by which they induce cellular transformation and their associated cancers.

  8. Psychophysics of human echolocation.

    Science.gov (United States)

    Schörnich, Sven; Wallmeier, Ludwig; Gessele, Nikodemus; Nagy, Andreas; Schranner, Michael; Kish, Daniel; Wiegrebe, Lutz

    2013-01-01

    The skills of some blind humans orienting in their environment through the auditory analysis of reflections from self-generated sounds have received only little scientific attention to date. Here we present data from a series of formal psychophysical experiments with sighted subjects trained to evaluate features of a virtual echo-acoustic space, allowing for rigid and fine-grain control of the stimulus parameters. The data show how subjects shape both their vocalisations and auditory analysis of the echoes to serve specific echo-acoustic tasks. First, we show that humans can echo-acoustically discriminate target distances with a resolution of less than 1 m for reference distances above 3.4 m. For a reference distance of 1.7 m, corresponding to an echo delay of only 10 ms, distance JNDs were typically around 0.5 m. Second, we explore the interplay between the precedence effect and echolocation. We show that the strong perceptual asymmetry between lead and lag is weakened during echolocation. Finally, we show that through the auditory analysis of self-generated sounds, subjects discriminate room-size changes as small as 10%.In summary, the current data confirm the practical efficacy of human echolocation, and they provide a rigid psychophysical basis for addressing its neural foundations.

  9. Mapping the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Cantor, Charles R.

    1989-06-01

    The following pages aim to lay a foundation for understanding the excitement surrounding the ''human genome project,'' as well as to convey a flavor of the ongoing efforts and plans at the Human Genome Center at the Lawrence Berkeley Laboratory. Our own work, of course, is only part of a broad international effort that will dramatically enhance our understanding of human molecular genetics before the end of this century. In this country, the bulk of the effort will be carried out under the auspices of the Department of Energy and the National Institutes of Health, but significant contributions have already been made both by nonprofit private foundations and by private corporation. The respective roles of the DOE and the NIH are being coordinated by an inter-agency committee, the aims of which are to emphasize the strengths of each agency, to facilitate cooperation, and to avoid unnecessary duplication of effort. The NIH, for example, will continue its crucial work in medical genetics and in mapping the genomes of nonhuman species. The DOE, on the other hand, has unique experience in managing large projects, and its national laboratories are repositories of expertise in physics, engineering, and computer science, as well as the life sciences. The tools and techniques the project will ultimately rely on are thus likely to be developed in multidisciplinary efforts at laboratories like LBL. Accordingly, we at LBL take great pride in this enterprise -- an enterprise that will eventually transform our understanding of ourselves.

  10. Cocoa and human health.

    Science.gov (United States)

    Ellam, Samantha; Williamson, Gary

    2013-01-01

    Cocoa is a dry, powdered, nonfat component product prepared from the seeds of the Theobroma cacao L. tree and is a common ingredient of many food products, particularly chocolate. Nutritionally, cocoa contains biologically active substances that may affect human health: flavonoids (epicatechin and oligomeric procyanidins), theobromine, and magnesium. Theobromine and epicatechin are absorbed efficiently in the small intestine, and the nature of their conjugates and metabolites are now known. Oligomeric procyanidins are poorly absorbed in the small intestine, but catabolites are very efficiently absorbed after microbial biotransformation in the colon. A significant number of studies, using in vitro and in vivo approaches, on the effects of cocoa and its constituent flavonoids have been conducted. Most human intervention studies have been performed on cocoa as an ingredient, whereas many in vitro studies have been performed on individual components. Approximately 70 human intervention studies have been carried out on cocoa and cocoa-containing products over the past 12 years, with a variety of endpoints. These studies indicate that the most robust biomarkers affected are endothelial function, blood pressure, and cholesterol level. Mechanistically, supporting evidence shows that epicatechin affects nitric oxide synthesis and breakdown (via inhibition of nicotinamide adenine di-nucleotide phosphate oxidase) and the substrate arginine (via inhibition of arginase), among other targets. Evidence further supports cocoa as a biologically active ingredient with potential benefits on biomarkers related to cardiovascular disease. However, the calorie and sugar content of chocolate and its contribution to the total diet should be taken into account in intervention studies.

  11. Human African trypanosomiasis.

    Science.gov (United States)

    Lejon, Veerle; Bentivoglio, Marina; Franco, José Ramon

    2013-01-01

    Human African trypanosomiasis or sleeping sickness is a neglected tropical disease that affects populations in sub-Saharan Africa. The disease is caused by infection with the gambiense and rhodesiense subspecies of the extracellular parasite Trypanosoma brucei, and is transmitted to humans by bites of infected tsetse flies. The disease evolves in two stages, the hemolymphatic and meningoencephalitic stages, the latter being defined by central nervous system infection after trypanosomal traversal of the blood-brain barrier. African trypanosomiasis, which leads to severe neuroinflammation, is fatal without treatment, but the available drugs are toxic and complicated to administer. The choice of medication is determined by the infecting parasite subspecies and disease stage. Clinical features include a constellation of nonspecific symptoms and signs with evolving neurological and psychiatric alterations and characteristic sleep-wake disturbances. Because of the clinical profile variability and insidiously progressive central nervous system involvement, disease staging is currently based on cerebrospinal fluid examination, which is usually performed after the finding of trypanosomes in blood or other body fluids. No vaccine being available, control of human African trypanosomiasis relies on diagnosis and treatment of infected patients, assisted by vector control. Better diagnostic tools and safer, easy to use drugs are needed to facilitate elimination of the disease.

  12. Human evolution and cognition.

    Science.gov (United States)

    Tattersall, Ian

    2010-09-01

    Human beings are distinguished from all other organisms by their symbolic way of processing information about the world. This unique cognitive style is qualitatively different from all the earlier hominid cognitive styles, and is not simply an improved version of them. The hominid fossil and archaeological records show clearly that biological and technological innovations have typically been highly sporadic, and totally out of phase, since the invention of stone tools some 2.5 million years ago. They also confirm that this pattern applied in the arrival of modern cognition: the anatomically recognizable species Homo sapiens was well established long before any population of it began to show indications of behaving symbolically. This places the origin of symbolic thought in the realms of exaptation, whereby new structures come into existence before being recruited to new uses, and of emergence, whereby entire new levels of complexity are achieved through new combinations of attributes unremarkable in themselves. Both these phenomena involve entirely routine evolutionary processes; special as we human beings may consider ourselves, there was nothing special about the way we came into existence. Modern human cognition is a very recent acquisition; and its emergence ushered in an entirely new pattern of technological (and other behavioral) innovation, in which constant change results from the ceaseless exploration of the potential inherent in our new capacity.

  13. Securing Humanity - Situating 'Human Security' as Concept and Discourse

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2005-01-01

    markdownabstractAbstract The label ‘human security’ (HS) has attracted much attention since the 1994 Human Development Report, but there are numerous conflicting definitions and agendas and widespread scepticism. The Ogata-Sen Commission report Human Security Now has proposed a unified yet

  14. Securing Humanity - Situating 'Human Security' as Concept and Discourse

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2005-01-01

    markdownabstractAbstract The label ‘human security’ (HS) has attracted much attention since the 1994 Human Development Report, but there are numerous conflicting definitions and agendas and widespread scepticism. The Ogata-Sen Commission report Human Security Now has proposed a unified yet flexibl

  15. Human to human transmission of arthropod-borne pathogens

    NARCIS (Netherlands)

    Martina, Byron E.; Barzon, Luisa; Pijlman, Gorben P.; Fuente, de la José; Rizzoli, Annapaola; Wammes, Linda J.; Takken, Willem; Rij, van Ronald P.; Papa, Anna

    2017-01-01

    Human-to-human (H2H) transmitted arthropod-borne pathogens are a growing burden worldwide, with malaria and dengue being the most common mosquito-borne H2H transmitted diseases. The ability of vectors to get infected by humans during a blood meal to further propel an epidemic depends on complex i

  16. Human dignity according to international instruments on human rights

    Directory of Open Access Journals (Sweden)

    José Pablo Alzina de Aguilar

    2011-01-01

    Full Text Available According to international instruments on human rights, the dignity of the human person is the foundation of human rights, and both human dignity and human rights are inherent to the human being, universal and inviolable. This understanding of human dignity is not a fruitless truism, but the solid foundation on which to build a world community under the rule of the new ius gentium: the International Law for Humankind. Moreover, it is the clue to answer many questions raised by the new world of globalization and of the exponential growth of international rules.Consequently, there is a need to a common doctrine on a notion of human dignity which will allow the implementation and adjudication of the aforementioned instruments, at the service of the human person and in conformity with the juridical conscience which they reflect. Philosophy of Law concepts which can be traced back to Aristotle provide that notion. According to these concepts, the demanding nature of “human dignity” sustains the notion of “legal personhood”, and both notions pertain to the realm of Law and Right, not of Morale and Values. Thus, human dignity and human rights are and must be, respectively, a basic principle and a necessary part of any Law system, including international law

  17. Human-centered Computing: Toward a Human Revolution

    OpenAIRE

    Jaimes, Alejandro; Gatica-Perez, Daniel; Sebe, Nicu; Thomas S. Huang

    2007-01-01

    Human-centered computing studies the design, development, and deployment of mixed-initiative human-computer systems. HCC is emerging from the convergence of multiple disciplines that are concerned both with understanding human beings and with the design of computational artifacts.

  18. Human Provenancing: It's Elemental…

    Science.gov (United States)

    Meier-Augenstein, Wolfram; Kemp

    2009-04-01

    Forensic science already uses a variety of methods often in combination to determine a deceased person's identity if neither personal effects nor next of kin (or close friends) can positively identify the victim. While disciplines such as forensic anthropology are able to work from a blank canvass as it were and can provide information on age, gender and ethnical grouping, techniques such as DNA profiling do rely on finding a match either in a database or a comparative sample presumed to be an ante-mortem sample of the victim or from a putative relation. Chances for either to succeed would be greatly enhanced if information gained from a forensic anthropological examination and, circumstances permitting a facial reconstruction could be linked to another technique that can work from a blank canvass or at least does not require comparison to a subject specific database. With the help of isotope ratio mass spectrometry even the very atoms from which a body is made can be used to say something about a person that will help to focus human identification using traditional techniques such as DNA, fingerprints and odontology. Stable isotope fingerprinting works on the basis that almost all chemical elements and in particular the so-called light elements such as carbon (C) that comprise most of the human body occur naturally in different forms, namely isotopes. 2H isotope abundance values recorded by the human body through food and drink ultimately reflect averaged isotopic composition of precipitation or ground water. Stable isotope analysis of 2H isotopic composition in different human tissue such as hair, nails, bone and teeth enables us to construct a time resolved isotopic profile or ‘fingerprint' that may not necessarily permit direct identification of a murder victim or mass disaster victim but in conjunction with forensic anthropological information will provide sufficient intelligence to construct a profile for intelligence lead identification stating where a

  19. Administrative Aspects of Human Experimentation.

    Science.gov (United States)

    Irvine, George W.

    1992-01-01

    The following administrative aspects of scientific experimentation with human subjects are discussed: the definition of human experimentation; the distinction between experimentation and treatment; investigator responsibility; documentation; the elements and principles of informed consent; and the administrator's role in establishing and…

  20. Consolidated Human Activities Database (CHAD)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Consolidated Human Activity Database (CHAD) contains data obtained from human activity studies that were collected at city, state, and national levels. CHAD is...