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Sample records for association study implicates

  1. The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D.;

    2008-01-01

    BACKGROUND: Schizophrenia is a highly heritable complex psychiatric disorder with an underlying pathophysiology that is still not well understood. Metaanalyses of schizophrenia linkage studies indicate numerous but rather large disease-associated genomic regions, whereas accumulating gene......- and protein expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently...... not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling...

  2. Results of Associated Implication Algebra on a Partial Ordered Set

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Some sufficient and necessary conditions that implication algebra on a partial ordered set is associated implication algebra are obtained, and the relation between lattice H implication algebra and associated implication algebra is discussed. Also, the concept of filter is proposed with some basic properties being studied.

  3. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.;

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  4. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; Cair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutdiffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ove

  5. Evidence for increased recombination near the human insulin gene: implication for disease association studies

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarti, A.; Elbein, S.C.; Permutt, M.A.

    1986-02-01

    Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq I, HincII, and Sac I) and a previously identified DNA length polymorphism (5'FP), all at the insulin locus, have been studied in US Blacks, African Blacks, Caucasians, and Pima Indians. Black populations are polymorphic for all five markers, whereas the other groups are polymorphic for Rsa I, Taq I, and 5'FP only. The data suggest that approx. = 1 in 550 base pairs is variant in this region. The polymorphisms, even though located within 20 kilobases, display low levels of nonrandom association. Population genetic analysis suggests that recombination within this 20-kilobase segment occurs 24 times more frequently than expected if crossing-over occurred uniformly throughout the human genome. These findings suggest that population association between DNA polymorphisms and disease susceptibility genes near the insulin gene or structural mutations in the insulin gene will be weak. Thus, population studies would probably require large sample sizes to detect association. However, the low levels of nonrandom association increase the information content of the locus for linkage studies, which is the best alternative for discovering disease susceptibility genes.

  6. Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies.

    Science.gov (United States)

    Templeton, A R; Weiss, K M; Nickerson, D A; Boerwinkle, E; Sing, C F

    2000-01-01

    Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3' region should have general utility in most human populations, but the 5' SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region. PMID:11063700

  7. A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.

    Science.gov (United States)

    Davies, G; Harris, S E; Reynolds, C A; Payton, A; Knight, H M; Liewald, D C; Lopez, L M; Luciano, M; Gow, A J; Corley, J; Henderson, R; Murray, C; Pattie, A; Fox, H C; Redmond, P; Lutz, M W; Chiba-Falek, O; Linnertz, C; Saith, S; Haggarty, P; McNeill, G; Ke, X; Ollier, W; Horan, M; Roses, A D; Ponting, C P; Porteous, D J; Tenesa, A; Pickles, A; Starr, J M; Whalley, L J; Pedersen, N L; Pendleton, N; Visscher, P M; Deary, I J

    2014-01-01

    Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear. PMID:23207651

  8. Population structure and linkage disequilibrium in oat (Avena sativa L.): implications for genome-wide association studies.

    Science.gov (United States)

    Newell, M A; Cook, D; Tinker, N A; Jannink, J-L

    2011-02-01

    The level of population structure and the extent of linkage disequilibrium (LD) can have large impacts on the power, resolution, and design of genome-wide association studies (GWAS) in plants. Until recently, the topics of LD and population structure have not been explored in oat due to the lack of a high-throughput, high-density marker system. The objectives of this research were to survey the level of population structure and the extent of LD in oat germplasm and determine their implications for GWAS. In total, 1,205 lines and 402 diversity array technology (DArT) markers were used to explore population structure. Principal component analysis and model-based cluster analysis of these data indicated that, for the lines used in this study, relatively weak population structure exists. To explore LD decay, map distances of 2,225 linked DArT marker pairs were compared with LD (estimated as r²). Results showed that LD between linked markers decayed rapidly to r² = 0.2 for marker pairs with a map distance of 1.0 centi-Morgan (cM). For GWAS, we suggest a minimum of one marker every cM, but higher densities of markers should increase marker-QTL association and therefore detection power. Additionally, it was found that LD was relatively consistent across the majority of germplasm clusters. These findings suggest that GWAS in oat can include germplasm with diverse origins and backgrounds. The results from this research demonstrate the feasibility of GWAS and related analyses in oat.

  9. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

    Science.gov (United States)

    Sellgren, CM; Kegel, ME; Bergen, SE; Ekman, CJ; Olsson, S; Larsson, M; Vawter, MP; Backlund, L; Sullivan, PF; Sklar, P; Smoller, JW; Magnusson, PKE; Hultman, CM; Walther-Jallow, L; Svensson, CI; Lichtenstein, P; Schalling, M; Engberg, G; Erhardt, S; Landén, M

    2016-01-01

    Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant—associated with reduced SNX7 expression—to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1β and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder. PMID:23459468

  10. A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder

    Science.gov (United States)

    Sellgren, C M; Kegel, M E; Bergen, S E; Ekman, C J; Olsson, S; Larsson, M; Vawter, M P; Backlund, L; Sullivan, P F; Sklar, P; Smoller, J W; Magnusson, P K E; Hultman, C M; Walther-Jallow, L; Svensson, C I; Lichtenstein, P; Schalling, M; Engberg, G; Erhardt, S; Landén, M

    2016-01-01

    Elevated cerebrospinal fluid (CSF) levels of the glia-derived N-methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA) have consistently been implicated in schizophrenia and bipolar disorder. Here, we conducted a genome-wide association study based on CSF KYNA in bipolar disorder and found support for an association with a common variant within 1p21.3. After replication in an independent cohort, we linked this genetic variant—associated with reduced SNX7 expression—to positive psychotic symptoms and executive function deficits in bipolar disorder. A series of post-mortem brain tissue and in vitro experiments suggested SNX7 downregulation to result in a caspase-8-driven activation of interleukin-1β and a subsequent induction of the brain kynurenine pathway. The current study demonstrates the potential of using biomarkers in genetic studies of psychiatric disorders, and may help to identify novel drug targets in bipolar disorder. PMID:26666201

  11. Genome-wide association study knowledge-driven pathway analysis of alcohol dependence implicates the calcium signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Li Danni; Li Jinming; Guo Yanfang

    2014-01-01

    Background Alcohol dependence (AD) is a serious and common public health problem.The identification of genes that contribute to the AD variation will improve our understanding of the genetic mechanism underlying this complex disease.Previous genome-wide association studies (GWAS) and candidate gene genetic association studies identified individual genes as candidates for alcohol phenotypes,but efforts to generate an integrated view of accumulative genetic variants and pathways under alcohol drinking are lacking.Methods We applied enrichment gene set analysis to existing genetic association results to identify pertinent pathways to AD in this study.A total of 1 438 SNPs (P <1.0×10-3) associated to alcohol drinking related traits have been collected from 31 studies (10 candidate gene association studies,19 GWAS of SNPs,and 2 GWAS of copy number variants).Results Among all of the KEGG pathways,the calcium signaling pathway (hsa04020) showed the most significant enrichment of associations (21 genes) to alcohol consumption phenotypes (P=5.4×10-5).Furthermore,the calcium signaling pathway is the only pathway that turned out to be significant after multiple test adjustments,achieving Bonferroni P value of 0.8×10-3 and FDR value of 0.6×10-2,respectively.Interestingly,the calcium signaling pathway was previously found to be essential to regulate brain function,and genes in this pathway link to a depressive effect of alcohol consumption on the body.Conclusions Our findings,together with previous biological evidence,suggest the importance of gene polymorphisms of calcium signaling pathway to AD susceptibility.Still,further investigations are warranted to uncover the role of this pathway in AD and related traits.

  12. A genome-wide association study of Cloninger's temperament scales: Implications for the evolutionary genetics of personality

    NARCIS (Netherlands)

    Verweij, C.J.H.; Zietsch, B.P.; Medland, S.E.; Gordon, S.D.; Benyamin, B.; Nyholt, D.R.; McEvoy, B.P.; Sullivan, P.F.; Heath, A.C.; Madden, P.A.F.; Henders, A.K.; Montgomery, G.W.; Martin, N.G.; Wray, N.R.

    2010-01-01

    Variation in personality traits is 30-60% attributed to genetic influences. Attempts to unravel these genetic influences at the molecular level have, so far, been inconclusive. We performed the first genome-wide association study of Cloninger's temperament scales in a sample of 5117 individuals, in

  13. Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity

    DEFF Research Database (Denmark)

    Hägg, Sara; Ganna, Andrea; Van Der Laan, Sander W;

    2015-01-01

    ) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci......To date, genome-wide association studies (GWASs) have identified >100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions...... with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation...

  14. Genome-Wide Association Study Reveals Genetic Architecture of Eating Behaviors in Pigs and its Implications for Humans Obesity by Comparative Genome Mapping

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage;

    2013-01-01

    for geneticimprovement of pig feed efficiency. The results of pig-human comparative genemapping revealed some important genomic regions and/or genes on the humangenome that may influence eating behavior in human and consequently affect thedevelopment of obesity and metabolic syndromes. This is the first......This study was aimed at identifying genomic regions controlling feeding behaviors inDanish Duroc boars and its potential implications for eating behaviors in humans.Individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of dailyvisits to feeder (NVD), time spent to eat...... per visit (TPV), mean feed intake per visit(FPV) and mean feed intake rate (FR) were available on 1130 boars. All boars weregenotyped using the Illumina Porcine SNP60 BeadChip. The association analyseswere performed using the GenABEL package in R. Sixteen SNPs had moderategenome-wide significant (p...

  15. Spatial and temporal associations of road traffic noise and air pollution in London: Implications for epidemiological studies.

    Science.gov (United States)

    Fecht, Daniela; Hansell, Anna L; Morley, David; Dajnak, David; Vienneau, Danielle; Beevers, Sean; Toledano, Mireille B; Kelly, Frank J; Anderson, H Ross; Gulliver, John

    2016-03-01

    Road traffic gives rise to noise and air pollution exposures, both of which are associated with adverse health effects especially for cardiovascular disease, but mechanisms may differ. Understanding the variability in correlations between these pollutants is essential to understand better their separate and joint effects on human health. We explored associations between modelled noise and air pollutants using different spatial units and area characteristics in London in 2003-2010. We modelled annual average exposures to road traffic noise (LAeq,24h, Lden, LAeq,16h, Lnight) for ~190,000 postcode centroids in London using the UK Calculation of Road Traffic Noise (CRTN) method. We used a dispersion model (KCLurban) to model nitrogen dioxide, nitrogen oxide, ozone, total and the traffic-only component of particulate matter ≤2.5μm and ≤10μm. We analysed noise and air pollution correlations at the postcode level (~50 people), postcodes stratified by London Boroughs (~240,000 people), neighbourhoods (Lower layer Super Output Areas) (~1600 people), 1km grid squares, air pollution tertiles, 50m, 100m and 200m in distance from major roads and by deprivation tertiles. Across all London postcodes, we observed overall moderate correlations between modelled noise and air pollution that were stable over time (Spearman's rho range: |0.34-0.55|). Correlations, however, varied considerably depending on the spatial unit: largest ranges were seen in neighbourhoods and 1km grid squares (both Spearman's rho range: |0.01-0.87|) and was less for Boroughs (Spearman's rho range: |0.21-0.78|). There was little difference in correlations between exposure tertiles, distance from road or deprivation tertiles. Associations between noise and air pollution at the relevant geographical unit of analysis need to be carefully considered in any epidemiological analysis, in particular in complex urban areas. Low correlations near roads, however, suggest that independent effects of road noise and

  16. Spatial and temporal associations of road traffic noise and air pollution in London: Implications for epidemiological studies.

    Science.gov (United States)

    Fecht, Daniela; Hansell, Anna L; Morley, David; Dajnak, David; Vienneau, Danielle; Beevers, Sean; Toledano, Mireille B; Kelly, Frank J; Anderson, H Ross; Gulliver, John

    2016-03-01

    Road traffic gives rise to noise and air pollution exposures, both of which are associated with adverse health effects especially for cardiovascular disease, but mechanisms may differ. Understanding the variability in correlations between these pollutants is essential to understand better their separate and joint effects on human health. We explored associations between modelled noise and air pollutants using different spatial units and area characteristics in London in 2003-2010. We modelled annual average exposures to road traffic noise (LAeq,24h, Lden, LAeq,16h, Lnight) for ~190,000 postcode centroids in London using the UK Calculation of Road Traffic Noise (CRTN) method. We used a dispersion model (KCLurban) to model nitrogen dioxide, nitrogen oxide, ozone, total and the traffic-only component of particulate matter ≤2.5μm and ≤10μm. We analysed noise and air pollution correlations at the postcode level (~50 people), postcodes stratified by London Boroughs (~240,000 people), neighbourhoods (Lower layer Super Output Areas) (~1600 people), 1km grid squares, air pollution tertiles, 50m, 100m and 200m in distance from major roads and by deprivation tertiles. Across all London postcodes, we observed overall moderate correlations between modelled noise and air pollution that were stable over time (Spearman's rho range: |0.34-0.55|). Correlations, however, varied considerably depending on the spatial unit: largest ranges were seen in neighbourhoods and 1km grid squares (both Spearman's rho range: |0.01-0.87|) and was less for Boroughs (Spearman's rho range: |0.21-0.78|). There was little difference in correlations between exposure tertiles, distance from road or deprivation tertiles. Associations between noise and air pollution at the relevant geographical unit of analysis need to be carefully considered in any epidemiological analysis, in particular in complex urban areas. Low correlations near roads, however, suggest that independent effects of road noise and

  17. Huntington's disease: implications of associated cellular radiosensitivity

    International Nuclear Information System (INIS)

    Ionizing radiation sensitivity was studied in a series of Huntington's Disease (HD) patients and controls by measurement of radiation-induced chromosome aberrations in lymphocytes and by clonogenic survival of lymphoblastoid cell lines. As a group, HD patients were found to be significantly more radioisensitive than controls (p<0.001), but there was an overlap between values for the two groups such that an absolute distinction is not possible. These data are consistent with an association between HD and radiosensitivity but not with identity between HD and a radiosensitive phenotype, so that cellular radiosensitivity cannot be used for individual diagnosis. Analysis of three families including 5 HD patients and 11 first-degree relatives confirmed this conclusion and demonstrated that even within a given family presymptomatic diagnosis cannot be based on measurement of radiosensitivity. However, the common association of cellular radiosensitivity with HD probands and their families provides a potential lead to the identification of HD gene(s) and so to an eventual understanding of the aetiopathogenesis of this disease at the molecular level. (author)

  18. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    NARCIS (Netherlands)

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N.; Saleheen, Danish; Lehne, Benjamin; Leach, Irene Mateo; Drong, Alexander W.; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R.; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S.; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L.; Esko, Tonu; Go, Min Jin; Harris, Sarah E.; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E.; Li, Huaixing; Mok, Zuan Yu; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F. R.; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Alves, Alexessander Da Silva Couto; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C.; Kim, Yun Kyoung; Koivula, Robert W.; Luan, Jian'an; Lyytikainen, Leo-Pekka; Nguyen, Quang N.; Pereira, Mark A.; Postmus, Iris; Raitakari, Olli T.; Bryan, Molly Scannell; Scott, Robert A.; Sorice, Rossella; Tragante, Vinicius; Traglia, Michela; White, Jon; Yamamoto, Ken; Zhang, Yonghong; Adair, Linda S.; Ahmed, Alauddin; Akiyama, Koichi; Asif, Rasheed; Aung, Tin; Barroso, Ines; Bjonnes, Andrew; Braun, Timothy R.; Cai, Hui; Chang, Li-Ching; Chen, Chien-Hsiun; Cheng, Ching-Yu; Chong, Yap-Seng; Collins, Rory; Courtney, Regina; Davies, Gail; Delgado, Graciela; Do, Loi D.; Doevendans, Pieter A.; Gansevoort, Ron T.; Gao, Yu-Tang; Grammer, Tanja B.; Grarup, Niels; Grewal, Jagvir; Gu, Dongfeng; Wander, Gurpreet S.; Hartikainen, Anna-Liisa; Hazen, Stanley L.; He, Jing; Heng, Chew-Kiat; Hixson, James E.; Hofman, Albert; Hsu, Chris; Huang, Wei; Husemoen, Lise L. N.; Hwang, Joo-Yeon; Ichihara, Sahoko; Igase, Michiya; Isono, Masato; Justesen, Johanne M.; Katsuy, Tomohiro; Kibriya, Muhammad G.; Kim, Young Jin; Kishimoto, Miyako; Koh, Woon-Puay; Kohara, Katsuhiko; Kumari, Meena; Kwek, Kenneth; Lee, Nanette R.; Lee, Jeannette; Liao, Jiemin; Lieb, Wolfgang; Liewald, David C. M.; Matsubara, Tatsuaki; Matsushita, Yumi; Meitinger, Thomas; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Mononen, Nina; Mueller-Nurasyid, Martina; Nabika, Toru; Nakashima, Eitaro; Ng, Hong Kiat; Nikus, Kjell; Nutile, Teresa; Ohkubo, Takayoshi; Ohnaka, Keizo; Parish, Sarah; Paternoster, Lavinia; Peng, Hao; Peters, Annette; Pham, Son T.; Pinidiyapathirage, Mohitha J.; Rahman, Mahfuzar; Rakugi, Hiromi; Rolandsson, Olov; Rozario, Michelle Ann; Ruggiero, Daniela; Sala, Cinzia F.; Sarju, Ralhan; Shimokawa, Kazuro; Snieder, Harold; Sparso, Thomas; Spiering, Wilko; Starr, John M.; Stott, David J.; Stram, Daniel O.; Sugiyama, Takao; Szymczak, Silke; Tang, W. H. Wilson; Tong, Lin; Trompet, Stella; Turjanmaa, Vaino; Ueshima, Hirotsugu; Uitterlinden, Andre G.; Umemura, Satoshi; Vaarasmaki, Marja; van Dam, Rob M.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.; Viikari, Jorma S.; Waldenberger, Melanie; Wang, Yiqin; Wang, Aili; Wilson, Rory; Wong, Tien-Yin; Xiang, Yong-Bing; Yamaguchi, Shuhei; Ye, Xingwang; Young, Robin D.; Young, Terri L.; Yuan, Jian-Min; Zhou, Xueya; Asselbergs, Folkert W.; Ciullo, Marina; Clarke, Robert; Deloukas, Panos; Franke, Andre; Franks, Paul W.; Franks, Steve; Friedlander, Yechiel; Gross, Myron D.; Guo, Zhirong; Hansen, Torben; Jarvelin, Marjo-Riitta; Jorgensen, Torben; Jukema, J. Wouter; Kahonen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimaki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J.; Sorensen, Thorkild I. A.; Takayanagi, Ryoichi; Toniolo, Daniela; Ahsan, Habibul; Allayee, Hooman; Chen, Yuan-Tsong; Danesh, John; Deary, Ian J.; Franco, Oscar H.; Franke, Lude; Heijman, Bastiaan T.; Holbrook, Joanna D.; Isaacs, Aaron; Kim, Bong-Jo; Lin, Xu; Liu, Jianjun; Maerz, Winfried; Metspalu, Andres; Mohlke, Karen L.; Sanghera, Dharambir K.; Shu, Xiao-Ou; van Meurs, Joyce B. J.; Vithana, Eranga; Wickremasinghe, Ananda R.; Wijmenga, Cisca; Wolffenbuttel, Bruce H. W.; Yokota, Mitsuhiro; Zheng, Wei; Zhu, Dingliang; Vineis, Paolo; Kyrtopoulos, Soterios A.; Kleinjans, Jos C. S.; McCarthy, Mark I.; Soong, Richie; Gieger, Christian; Scott, James; Teo, Yik-Ying; He, Jiang; Elliott, Paul; Tai, E. Shyong; van der Harst, Pim; Kooner, Jaspal S.; Chambers, John C.; Doevendans, PAFM

    2015-01-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21

  19. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    NARCIS (Netherlands)

    N. Kato (Norihiro); M. Loh (Marie); F. Takeuchi (Fumihiko); N. Verweij (Niek); X. Wang (Xu); W. Zhang (Weihua); T. NKelly (Tanika); D. Saleheen; B. Lehne (Benjamin); I.M. Leach (Irene Mateo); A. Drong (Alexander); J. Abbott (James); S. Wahl (Simone); S.-T. Tan (Sian-Tsung); W.R. Scott (William R.); G. Campanella (Gianluca); M. Chadeau-Hyam (Marc); U. Afzal (Uzma); T.S. Ahluwalia (Tarunveer Singh); M.J. Bonder (Marc Jan); P. Chen (Ping); A. Dehghan (Abbas); T.L. Edwards (Todd L.); T. Esko (Tõnu); M.J. Go (Min Jin); S.E. Harris (Sarah); J. Hartiala (Jaana); S. Kasela (Silva); A. Kasturiratne (Anuradhani); C.C. Khor; M.E. Kleber (Marcus); H. Li (Huaixing); Z.Y. Mok (Zuan Yu); M. Nakatochi (Masahiro); N.S. Sapari (Nur Sabrina); R. Saxena (Richa); A.F. Stewart (Alexandre F.); L. Stolk (Lisette); Y. Tabara (Yasuharu); A.L. Teh (Ai Ling); Y. Wu (Ying); J.-Y. Wu (Jer-Yuarn); Y. Zhang (Yi); I. Aits (Imke); A. Da Silva Couto Alves (Alexessander); S. Das; R. Dorajoo (Rajkumar); J. CHopewell (Jemma); Y.K. Kim (Yun Kyoung); R. WKoivula (Robert); J. Luan (Jian'An); L.-P. Lyytikäinen (Leo-Pekka); Q. NNguyen (Quang); M.A. Pereira (Mark A); D. Postmus (Douwe); O. TRaitakari (Olli); M. Scannell Bryan (Molly); R.A. Scott (Robert); R. Sorice; V. Tragante (Vinicius); M. Traglia (Michela); J. White (Jon); K. Yamamoto (Ken); Y. Zhang (Yonghong); L.S. Adair (Linda); A. Ahmed (Alauddin); K. Akiyama (Koichi); R. Asif (Rasheed); T. Aung (Tin); I. Barroso (Inês); A. Bjonnes (Andrew); T.R. Braun (Timothy R.); H. Cai (Hui); L.-C. Chang (Li-Ching); C.-H. Chen; C-Y. Cheng (Ching-Yu); Y.-S. Chong (Yap-Seng); F.S. Collins (Francis); R. Courtney (Regina); G. Davies (Gail); G. Delgado; L.D. Do (Loi D.); P.A. Doevendans (Pieter); R.T. Gansevoort (Ron); Y. Gao; T.B. Grammer (Tanja B); N. Grarup (Niels); J. Grewal (Jagvir); D. Gu (D.); G. SWander (Gurpreet); A.L. Hartikainen; S.L. Hazen (Stanley); J. He (Jing); C.K. Heng (Chew-Kiat); E.J.A. Hixso (E. James Ames); A. Hofman (Albert); C. Hsu (Chris); W. Huang (Wei); L.L.N. Husemoen (Lise Lotte); J.-Y. Hwang (Joo-Yeon); S. Ichihara (Sahoko); M. Igase (Michiya); M. Isono (Masato); J.M. Justesen (Johanne M.); T. Katsuya (Tomohiro); M. GKibriya (Muhammad); Y.J. Kim; M. Kishimoto (Miyako); W.-P. Koh (Woon-Puay); K. Kohara (Katsuhiko); M. Kumari (Meena); K. Kwek (Kenneth); N.R. Lee (Nanette); J. Lee (Jeannette); J. Liao (Jie); W. Lieb (Wolfgang); D.C. Liewald (David C.); T. Matsubara (Tatsuaki); Y. Matsushita (Yumi); T. Meitinger (Thomas); E. Mihailov (Evelin); L. Milani (Lili); R. Mills (Rebecca); K. Mononen (Kari); M. Müller-Nurasyid (Martina); T. Nabika (Toru); E. Nakashima (Eitaro); H.K. Ng (Hong Kiat); K. Nikus (Kjell); T. Nutile; T. Ohkubo (Takayoshi); K. Ohnaka (Keizo); S. Parish (Sarah); L. Paternoster (Lavinia); H. Peng (Hao); A. Peters (Annette); S. TPham (Son); M.J. Pinidiyapathirage (Mohitha J.); M. Rahman (Mahfuzar); H. Rakugi (Hiromi); O. Rolandsson (Olov); M.A. Rozario (Michelle Ann); D. Ruggiero; C. Sala (Cinzia); R. Sarju (Ralhan); K. Shimokawa (Kazuro); H. Snieder (Harold); T. Sparsø (Thomas); W. Spiering (Wilko); J.M. Starr (John); D.J. Stott (David J.); D. OStram (Daniel); T. Sugiyama (Takao); S. Szymczak (Silke); W.H.W. Tang (W.H. Wilson); L. Tong (Lin); S. Trompet (Stella); V. Turjanmaa (Väinö); H. Ueshima (Hirotsugu); A.G. Uitterlinden (André); S. Umemura (Satoshi); M. Vaarasmaki (Marja); R.M. Dam (Rob Mvan); W.H. van Gilst (Wiek); D.J. van Veldhuisen (Dirk); J. Viikari (Jorma); M. Waldenberger (Melanie); Y. Wang (Yiqin); A. Wang (Aili); R. Wilson (Rory); T.-Y. Wong (Tien-Yin); Y.-B. Xiang (Yong-Bing); S. Yamaguchi (Shuhei); X. Ye (Xingwang); R. Young (Robin); T.L. Young (Terri); J.-M. Yuan (Jian-Min); X. Zhou (Xueya); F.W. Asselbergs (Folkert); M. Ciullo; R. Clarke (Robert); P. Deloukas (Panagiotis); A. Franke (Andre); W.F. Paul (W. Frank); S. Franks (Steve); Y. Friedlander (Yechiel); M.D. Gross (Myron D.); Z. Guo (Zhirong); T. Hansen (T.); M.-R. Jarvelin (Marjo-Riitta); T. Jørgensen (Torben); J.W. Jukema (Jan Wouter); M. Kähönen (Mika); H. Kajio (Hiroshi); M. Kivimaki (Mika); J.-Y. Lee (Jong-Young); T. Lehtimäki (Terho); A. Linneberg (Allan); T. Miki (Tetsuro); O. Pedersen (Oluf); N.J. Samani (Nilesh); T.I.A. Sørensen (Thorkild); R. Takayanagi (Ryoichi); D. Toniolo (Daniela); H. Ahsan (Habibul); H. Allayee (Hooman); Y.-T. Chen (Yuan-Tsong); J. Danesh (John); I.J. Deary (Ian J.); O.H. Franco (Oscar); L. Franke (Lude); B. THeijman (Bastiaan); J.D. Holbrook (Joanna D.); A.J. Isaacs (Aaron); B.-J. Kim (Bong-Jo); X. Lin (Xu); J. Liu (Jianjun); W. März (Winfried); A. Metspalu (Andres); K.L. Mohlke (Karen); K. Sangher; D. Harambir (Dharambir); X.-O. Shu (Xiao-Ou); J.B.J. van Meurs (Joyce); E.N. Vithana (Eranga); A.R. Wickremasinghe (Ananda); C. Wijmenga (Cisca); B.H.W. Wolffenbuttel (Bruce H.W.); M. Yokota (Mitsuhiro); W. Zheng (Wei); D. Zhu (Dingliang); P. Vineis (Paolo); S.A. Kyrtopoulos (Soterios A.); J.C.S. Kleinjans (Jos C.S.); M.I. McCarthy (Mark); R. Soong (Richie); C. Gieger (Christian); J. Scott (James); Y.Y. Teo (Yik Ying); J. He (Jiang); P. Elliott (Paul); E.S. Tai (Shyong); P. van der Harst (Pim); J.S. Kooner (Jaspal S.); J.C. Chambers (John)

    2015-01-01

    textabstractWe carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10 -11 to 5

  20. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

    DEFF Research Database (Denmark)

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko;

    2015-01-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(...

  1. Cerebral Microbleeds: Detection, Associations and Clinical Implications.

    Science.gov (United States)

    Yakushiji, Yusuke

    2015-01-01

    Vigorous investigations for cerebral microbleeds (CMBs) have been made since the late 1990s. CMBs on paramagnetic-sensitive magnetic resonance sequences correspond pathologically to clusters of hemosiderin-laden macrophages and have emerged as an important new imaging marker of cerebral small vessel disease, including intracerebral hemorrhage (ICH). The prevalence of CMBs varies according to the specific disease settings (stroke subtypes and dementing disorders) and is highest (60%) in ICH patients. The associations of CMBs with aging, hypertension and apolipoprotein E genotype are consistent with the two major underlying pathogeneses of CMBs: hypertensive arteriopathy and cerebral amyloid angiopathy (CAA). The distributional patterns of CMBs might help us to understand the predominant small vessel disease pathogenesis in the brain; the strictly lobar type of CMBs often reflects the presence of advanced CAA, while the other types of CMBs, such as 'deep or infratentorial CMBs', including the mixed type, are strongly associated with hypertension. CMBs might be associated with cognitive function (especially executive function), gait performance, and cerebrovascular events (spontaneous, antithrombotic drug-related or post-thrombolysis ICH). In the field of CAA, an understanding of CAA-related CMBs might help to guide decision making with regard to new therapeutic approaches, including the use of monoclonal antibodies against vascular amyloid. These concepts of CMBs might allow us to advance research on ICH as well as for dementia. PMID:26587900

  2. Association of neighbourhood residence and preferences with the built environment, work-related travel behaviours, and health implications for employed adults: Findings from the URBAN study

    OpenAIRE

    Badland, Hannah M; Oliver, Melody; Kearns, Robin A.; Mavoa, Suzanne; Witten, Karen; Duncan, Mitch J.; Batty, G David

    2012-01-01

    Although the neighbourhoods and health field is well established, the relationships between neighbourhood selection, neighbourhood preference, work-related travel behaviours, and transport infrastructure have not been fully explored. It is likely that understanding these complex relationships more fully will inform urban policy development, and planning for neighbourhoods that support health behaviours. Accordingly, the objective of this study was to identify associations between these variab...

  3. Genome-wide association study for colorectal cancer identifies risk polymorphisms in German familial cases and implicates MAPK signalling pathways in disease susceptibility.

    Science.gov (United States)

    Lascorz, Jesús; Försti, Asta; Chen, Bowang; Buch, Stephan; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Schulmann, Karsten; Goecke, Timm; Kloor, Matthias; Engel, Cristoph; Büttner, Reinhard; Kunkel, Nelli; Weires, Marianne; Hoffmeister, Michael; Pardini, Barbara; Naccarati, Alessio; Vodickova, Ludmila; Novotny, Jan; Schreiber, Stefan; Krawczak, Michael; Bröring, Clemens D; Völzke, Henry; Schafmayer, Clemens; Vodicka, Pavel; Chang-Claude, Jenny; Brenner, Hermann; Burwinkel, Barbara; Propping, Peter; Hampe, Jochen; Hemminki, Kari

    2010-09-01

    Genetic susceptibility accounts for approximately 35% of all colorectal cancer (CRC). Ten common low-risk variants contributing to CRC risk have been identified through genome-wide association studies (GWASs). In our GWAS, 610 664 genotyped single-nucleotide polymorphisms (SNPs) passed the quality control filtering in 371 German familial CRC patients and 1263 controls, and replication studies were conducted in four additional case-control sets (4915 cases and 5607 controls). Known risk loci at 8q24.21 and 11q23 were confirmed, and a previously unreported association, rs12701937, located between the genes GLI3 (GLI family zinc finger 3) and INHBA (inhibin, beta A) [P = 1.1 x 10(-3), odds ratio (OR) 1.14, 95% confidence interval (CI) 1.05-1.23, dominant model in the combined cohort], was identified. The association was stronger in familial cases compared with unselected cases (P = 2.0 x 10(-4), OR 1.36, 95% CI 1.16-1.60, dominant model). Two other unreported SNPs, rs6038071, 40 kb upstream of CSNK2A1 (casein kinase 2, alpha 1 polypeptide) and an intronic marker in MYO3A (myosin IIIA), rs11014993, associated with CRC only in the familial CRC cases (P = 2.5 x 10(-3), recessive model, and P = 2.7 x 10(-4), dominant model). Three software tools successfully pointed to the overrepresentation of genes related to the mitogen-activated protein kinase (MAPK) signalling pathways among the 1340 most strongly associated markers from the GWAS (allelic P value genes involved in MAPK signalling events (P(trend) = 2.2 x 10(-16), OR(per allele) = 1.34, 95% CI 1.11-1.61).

  4. Pain Symptoms Associated with Opioid Use among Vulnerable Persons with HIV: An exploratory study with implications for palliative care and opioid abuse prevention.

    Science.gov (United States)

    Knowlton, Amy R; Nguyen, Trang Q; Robinson, Allysha C; Harrell, Paul T; Mitchell, Mary M

    2015-01-01

    Current or former injection drug users with human immunodeficiency virus (HIV) are at high risk for pain, which adversely affects their quality of life and may increase their risk for illicit drug use or relapse. We explored associations between pain symptoms and substance use among injection-drug-using study participants with HIV who had histories of heroin use. Using generalized estimating equations and controlling for prior substance use, we found that pain in each six-month period was associated with the use of heroin and prescription opioids, but not the use of nonopioid drugs or alcohol. Routine clinical assessment and improved management of pain symptoms may be needed for persons with HIV and a history of injection drug use, particularly those with chronic pain, for whom there is increased risk for heroin use.

  5. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

    Science.gov (United States)

    Kato, Norihiro; Loh, Marie; Takeuchi, Fumihiko; Verweij, Niek; Wang, Xu; Zhang, Weihua; Kelly, Tanika N; Saleheen, Danish; Lehne, Benjamin; Mateo Leach, Irene; Drong, Alexander W; Abbott, James; Wahl, Simone; Tan, Sian-Tsung; Scott, William R; Campanella, Gianluca; Chadeau-Hyam, Marc; Afzal, Uzma; Ahluwalia, Tarunveer S; Bonder, Marc Jan; Chen, Peng; Dehghan, Abbas; Edwards, Todd L; Esko, Tõnu; Go, Min Jin; Harris, Sarah E; Hartiala, Jaana; Kasela, Silva; Kasturiratne, Anuradhani; Khor, Chiea-Chuen; Kleber, Marcus E; Li, Huaixing; Mok, Zuan Yu; Nakatochi, Masahiro; Sapari, Nur Sabrina; Saxena, Richa; Stewart, Alexandre F R; Stolk, Lisette; Tabara, Yasuharu; Teh, Ai Ling; Wu, Ying; Wu, Jer-Yuarn; Zhang, Yi; Aits, Imke; Da Silva Couto Alves, Alexessander; Das, Shikta; Dorajoo, Rajkumar; Hopewell, Jemma C; Kim, Yun Kyoung; Koivula, Robert W; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Nguyen, Quang N; Pereira, Mark A; Postmus, Iris; Raitakari, Olli T; Bryan, Molly Scannell; Scott, Robert A; Sorice, Rossella; Tragante, Vinicius; Traglia, Michela; White, Jon; Yamamoto, Ken; Zhang, Yonghong; Adair, Linda S; Ahmed, Alauddin; Akiyama, Koichi; Asif, Rasheed; Aung, Tin; Barroso, Inês; Bjonnes, Andrew; Braun, Timothy R; Cai, Hui; Chang, Li-Ching; Chen, Chien-Hsiun; Cheng, Ching-Yu; Chong, Yap-Seng; Collins, Rory; Courtney, Regina; Davies, Gail; Delgado, Graciela; Do, Loi D; Doevendans, Pieter A; Gansevoort, Ron T; Gao, Yu-Tang; Grammer, Tanja B; Grarup, Niels; Grewal, Jagvir; Gu, Dongfeng; Wander, Gurpreet S; Hartikainen, Anna-Liisa; Hazen, Stanley L; He, Jing; Heng, Chew-Kiat; Hixson, James E; Hofman, Albert; Hsu, Chris; Huang, Wei; Husemoen, Lise L N; Hwang, Joo-Yeon; Ichihara, Sahoko; Igase, Michiya; Isono, Masato; Justesen, Johanne M; Katsuya, Tomohiro; Kibriya, Muhammad G; Kim, Young Jin; Kishimoto, Miyako; Koh, Woon-Puay; Kohara, Katsuhiko; Kumari, Meena; Kwek, Kenneth; Lee, Nanette R; Lee, Jeannette; Liao, Jiemin; Lieb, Wolfgang; Liewald, David C M; Matsubara, Tatsuaki; Matsushita, Yumi; Meitinger, Thomas; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Mononen, Nina; Müller-Nurasyid, Martina; Nabika, Toru; Nakashima, Eitaro; Ng, Hong Kiat; Nikus, Kjell; Nutile, Teresa; Ohkubo, Takayoshi; Ohnaka, Keizo; Parish, Sarah; Paternoster, Lavinia; Peng, Hao; Peters, Annette; Pham, Son T; Pinidiyapathirage, Mohitha J; Rahman, Mahfuzar; Rakugi, Hiromi; Rolandsson, Olov; Rozario, Michelle Ann; Ruggiero, Daniela; Sala, Cinzia F; Sarju, Ralhan; Shimokawa, Kazuro; Snieder, Harold; Sparsø, Thomas; Spiering, Wilko; Starr, John M; Stott, David J; Stram, Daniel O; Sugiyama, Takao; Szymczak, Silke; Tang, W H Wilson; Tong, Lin; Trompet, Stella; Turjanmaa, Väinö; Ueshima, Hirotsugu; Uitterlinden, André G; Umemura, Satoshi; Vaarasmaki, Marja; van Dam, Rob M; van Gilst, Wiek H; van Veldhuisen, Dirk J; Viikari, Jorma S; Waldenberger, Melanie; Wang, Yiqin; Wang, Aili; Wilson, Rory; Wong, Tien-Yin; Xiang, Yong-Bing; Yamaguchi, Shuhei; Ye, Xingwang; Young, Robin D; Young, Terri L; Yuan, Jian-Min; Zhou, Xueya; Asselbergs, Folkert W; Ciullo, Marina; Clarke, Robert; Deloukas, Panos; Franke, Andre; Franks, Paul W; Franks, Steve; Friedlander, Yechiel; Gross, Myron D; Guo, Zhirong; Hansen, Torben; Jarvelin, Marjo-Riitta; Jørgensen, Torben; Jukema, J Wouter; Kähönen, Mika; Kajio, Hiroshi; Kivimaki, Mika; Lee, Jong-Young; Lehtimäki, Terho; Linneberg, Allan; Miki, Tetsuro; Pedersen, Oluf; Samani, Nilesh J; Sørensen, Thorkild I A; Takayanagi, Ryoichi; Toniolo, Daniela; Ahsan, Habibul; Allayee, Hooman; Chen, Yuan-Tsong; Danesh, John; Deary, Ian J; Franco, Oscar H; Franke, Lude; Heijman, Bastiaan T; Holbrook, Joanna D; Isaacs, Aaron; Kim, Bong-Jo; Lin, Xu; Liu, Jianjun; März, Winfried; Metspalu, Andres; Mohlke, Karen L; Sanghera, Dharambir K; Shu, Xiao-Ou; van Meurs, Joyce B J; Vithana, Eranga; Wickremasinghe, Ananda R; Wijmenga, Cisca; Wolffenbuttel, Bruce H W; Yokota, Mitsuhiro; Zheng, Wei; Zhu, Dingliang; Vineis, Paolo; Kyrtopoulos, Soterios A; Kleinjans, Jos C S; McCarthy, Mark I; Soong, Richie; Gieger, Christian; Scott, James; Teo, Yik-Ying; He, Jiang; Elliott, Paul; Tai, E Shyong; van der Harst, Pim; Kooner, Jaspal S; Chambers, John C

    2015-11-01

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation. PMID:26390057

  6. Th17 response and autophagy - main pathways implicated in the development of inflammatory bowel disease by genome-wide association studies: new factors involved in inflammatory bowel disease susceptibility

    Directory of Open Access Journals (Sweden)

    Roberto Díaz-Peña

    2015-09-01

    Full Text Available Inflammatory bowel disease (IBD is an entity that mainly includes ulcerative colitis (UC and Crohn's disease (CD. Improved health care, diet changes, and higher industrialization are associated with an increase in IBD prevalence. This supports the central role of environmental factors in the pathology of this disease. However, IBD also shows a relevant genetic component as shown by high heritability. Classic genetic studies showed relevant associations between IBD susceptibility and genes involved in the immune response. This is consistent with prior theories about IBD development. According to these, contact of the immune system with a high number of harmless antigens from the diet and the bacterial flora should originate tolerance while preserving response against pathogens. Failure to achieve this balance may originate the typical inflammatory response associated with IBD. Recently, genome-wide association studies (GWASs have confirmed the implication of the immune system, particularly the Th17 immune response, previously associated to other autoimmune diseases, and of autophagy. In this paper, the mechanisms involved in these two relevant pathways and their potential role in the pathogenesis of IBD are reviewed.

  7. Genome wide linkage disequilibrium in Chinese asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm: implications for domestication history and genome wide association studies.

    Science.gov (United States)

    Xu, P; Wu, X; Wang, B; Luo, J; Liu, Y; Ehlers, J D; Close, T J; Roberts, P A; Lu, Z; Wang, S; Li, G

    2012-07-01

    Association mapping of important traits of crop plants relies on first understanding the extent and patterns of linkage disequilibrium (LD) in the particular germplasm being investigated. We characterize here the genetic diversity, population structure and genome wide LD patterns in a set of asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse collection of 99 asparagus bean and normal cowpea accessions were genotyped with 1127 expressed sequence tag-derived single nucleotide polymorphism markers (SNPs). The proportion of polymorphic SNPs across the collection was relatively low (39%), with an average number of SNPs per locus of 1.33. Bayesian population structure analysis indicated two subdivisions within the collection sampled that generally represented the 'standard vegetable' type (subgroup SV) and the 'non-standard vegetable' type (subgroup NSV), respectively. Level of LD (r(2)) was higher and extent of LD persisted longer in subgroup SV than in subgroup NSV, whereas LD decayed rapidly (0-2 cM) in both subgroups. LD decay distance varied among chromosomes, with the longest (≈ 5 cM) five times longer than the shortest (≈ 1 cM). Partitioning of LD variance into within- and between-subgroup components coupled with comparative LD decay analysis suggested that linkage group 5, 7 and 10 may have undergone the most intensive epistatic selection toward traits favorable for vegetable use. This work provides a first population genetic insight into domestication history of asparagus bean and demonstrates the feasibility of mapping complex traits by genome wide association study in asparagus bean using a currently available cowpea SNPs marker platform.

  8. Genome wide linkage disequilibrium in Chinese asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm: implications for domestication history and genome wide association studies.

    Science.gov (United States)

    Xu, P; Wu, X; Wang, B; Luo, J; Liu, Y; Ehlers, J D; Close, T J; Roberts, P A; Lu, Z; Wang, S; Li, G

    2012-07-01

    Association mapping of important traits of crop plants relies on first understanding the extent and patterns of linkage disequilibrium (LD) in the particular germplasm being investigated. We characterize here the genetic diversity, population structure and genome wide LD patterns in a set of asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse collection of 99 asparagus bean and normal cowpea accessions were genotyped with 1127 expressed sequence tag-derived single nucleotide polymorphism markers (SNPs). The proportion of polymorphic SNPs across the collection was relatively low (39%), with an average number of SNPs per locus of 1.33. Bayesian population structure analysis indicated two subdivisions within the collection sampled that generally represented the 'standard vegetable' type (subgroup SV) and the 'non-standard vegetable' type (subgroup NSV), respectively. Level of LD (r(2)) was higher and extent of LD persisted longer in subgroup SV than in subgroup NSV, whereas LD decayed rapidly (0-2 cM) in both subgroups. LD decay distance varied among chromosomes, with the longest (≈ 5 cM) five times longer than the shortest (≈ 1 cM). Partitioning of LD variance into within- and between-subgroup components coupled with comparative LD decay analysis suggested that linkage group 5, 7 and 10 may have undergone the most intensive epistatic selection toward traits favorable for vegetable use. This work provides a first population genetic insight into domestication history of asparagus bean and demonstrates the feasibility of mapping complex traits by genome wide association study in asparagus bean using a currently available cowpea SNPs marker platform. PMID:22378357

  9. Mobility behavior and environmental implications of trace elements associated with coal gangue: a case study at the Huainan Coalfield in China.

    Science.gov (United States)

    Chuncai, Zhou; Guijian, Liu; Dun, Wu; Ting, Fang; Ruwei, Wang; Xiang, Fan

    2014-01-01

    The potential environmental hazards posed by trace elements have assumed serious proportions due to their toxicity, bioavailability and geochemical behavior. The toxicity and mobility of trace elements in coal gangue is dependent on the elements' chemical properties, therefore, the quantification of the different forms of trace elements is more significant than the estimation of their total concentrations. In this study, the mobility behavior of trace elements in coal gangue from the Huainan Coalfield was studied to evaluate the potential eco-toxicity of the trace elements. Sequential extraction was employed to analyze the fractionation behavior of trace elements in coal gangue. The selected trace elements (As, Co, Cr, Cu, Mn, Ni, Se, Sn, V and Zn) are predominantly found in silicate-bound, sulfide-bound and carbonate-bound fractions. The correlation of the element concentration with ash yield, aluminum, calcium and iron-sulfur indicates that As, Co, Cu, Ni, Se and Zn in coal gangue are mainly associated with sulfide minerals, which could release from coal gangue easily and can disperse into the environment as a result of long-term natural weathering. The Risk Assessment Code reveals that the trace elements (Mn, Cr, Se, Ni, Zn, As and Cu) can pose serious environmental risks to the ecosystem. The fractionation profiles of other elements (Co, Sn and V) indicate no risk or low risk to the environment.

  10. Pedagogical Implications of Contrastive Studies

    Science.gov (United States)

    Marton, Waldemar

    1972-01-01

    Pessimism regarding pedagogical applications of contrastive studies, and reasons therefore, are described. Several misunderstandings believed to contribute to this pessimism, and several areas of controversy concerning uses of contrastive studies, are discussed. See FL 508 197 for availability. (RM)

  11. Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

    Directory of Open Access Journals (Sweden)

    T Bernard Bigdeli

    Full Text Available BACKGROUND: Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants. METHODS: We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects. These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted for each of five factor-derived scores based on the Operational Criteria Checklist for Psychotic Illness (delusions, hallucinations, mania, depression, and negative symptoms. Tests of association were conducted using the PDTPHASE and QPDTPHASE packages of UNPHASED. Empirical estimates of gene-wise significance were obtained by adaptive permutation of a the smallest observed P-value and b the threshold-truncated product of P-values for each locus. RESULTS: While no single variant was significant after LD-corrected Bonferroni-correction, our gene-dropping analyses identified loci which exceeded empirical significance criteria for both gene-based tests. Namely, R3HDML and C20orf39 are significantly associated with depressive symptoms of schizophrenia (P(emp<2×10⁻⁵ based on the minimum P-value and truncated-product methods, respectively. CONCLUSIONS: Using a gene-based approach to family-based association, R3HDML and C20orf39 were found to be significantly associated with clinical dimensions of schizophrenia. These findings demonstrate the efficacy of gene-based analysis and support previous evidence that chromosome 20 may harbor schizophrenia susceptibility or modifier loci.

  12. [Forensic Implications of Sleep-Associated Behavior Disorders].

    Science.gov (United States)

    Bumb, J M; Schredl, M; Dreßing, H

    2015-11-01

    Parasomnias represent a category of disorders that involve complex behaviors or emotional experiences, arising from or occurring during sleep, which might be also associated with (incomplete) awakening. These phenomena are classified as REM- or Non-REM-parasomnias. In particular the latter, including confusional arousal, sleepwalking and sleep terrors but also REM-sleep behavior disorder might result in criminal consequences. Using polysomnography, the pathophysiological mechanisms of these disorders have been investigated thoroughly. Nevertheless, in German literature, forensic implications of complex behaviors arising from sleep disorders have only been described insufficiently. Here we describe the most relevant parasomnias and also how to proceed in the context of forensic assessments. PMID:26633841

  13. Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2

    NARCIS (Netherlands)

    Huang, Jie; Huffman, Jennifer E.; Yamkauchi, Munekazu; Trompet, Stella; Asselbergs, Folkert W.; Sabater-Lleal, Maria; Tregouet, David-Alexandre; Chen, Wei-Min; Smith, Nicholas L.; Kleber, Marcus E.; Shin, So-Youn; Becker, Diane M.; Tang, Weihong; Dehghan, Abbas; Johnson, Andrew D.; Vinh Truong, [No Value; Folkersen, Lasse; Yang, Qiong; Oudot-Mellkah, Tiphaine; Buckley, Brendan M.; Moore, Jason H.; Williams, Frances M. K.; Campbell, Harry; Silbernagel, Guenther; Vitart, Veronique; Rudan, Igor; Tofler, Geoffrey H.; Navis, Gerjan J.; DeStefano, Anita; Wright, Alan F.; Chen, Ming-Huei; de Craen, Anton J. M.; Worrall, Bradford B.; Rudnicka, Alicja R.; Rumley, Ann; Bookman, Ebony B.; Psaty, Bruce M.; Chen, Fang; Keene, Keith L.; Franco, Oscar H.; Boehm, Bernhard O.; Uitterlinden, Andre G.; Carter, Angela M.; Jukema, J. Wouter; Sattar, Naveed; Bis, Joshua C.; Ikram, Mohammad A.; Sale, Michele M.; McKnight, Barbara; Fornage, Myriam; Ford, Ian; Taylor, Kent; Slagboom, P. Eline; McArdle, Wendy L.; Hsu, Fang-Chi; Franco-Cereceda, Anders; Goodall, Alison H.; Yanek, Lisa R.; Furie, Karen L.; Cushman, Mary; Hofman, Albert; Witteman, Jacqueline C. M.; Folsom, Aaron R.; Basu, Saonli; Matijevic, Nena; van Gilst, Wiek H.; Wilson, James F.; Westendorp, Rudi G. J.; Kathiresan, Sekar; Reilly, Muredach P.; Tracy, Russell P.; Polasek, Ozren; Winkelmann, Bernhard R.; Grant, Peter J.; Hillege, Hans L.; Cambien, Francois; Stott, David J.; Lowe, Gordon D.; Spector, Timothy D.; Meigs, James B.; Marz, Winfried; Eriksson, Per; Becker, Lewis C.; Morange, Pierre-Emmanuel; Soranzo, Nicole; Williams, Scott M.; Hayward, Caroline; van der Harst, Pim; Hamsten, Anders; Lowenstein, Charles J.; Strachan, David P.; O'Donnell, Christopher J.

    2014-01-01

    Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular d

  14. Immune activation in HIV-infected aging women on antiretrovirals--implications for age-associated comorbidities: a cross-sectional pilot study.

    Directory of Open Access Journals (Sweden)

    Maria L Alcaide

    Full Text Available Persistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages.Twenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163, microbial translocation (LPS and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10 were evaluated.T cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation.HIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls.

  15. Genome-wide association study reveals genetic architecture of eating behavior in pigs and its implications for humans obesity by comparative mapping

    DEFF Research Database (Denmark)

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage;

    2013-01-01

    are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome...... found to have moderate genome-wide significance (pgene on chromosome (SSC) 14 was very strongly associated with NVD. Thirty-six SNPs were located in genome regions where QTLs have previously been reported...... for behavior and/or feed intake traits in pigs. The regions: 64–65 Mb on SSC 1, 124–130 Mb on SSC 8, 63–68 Mb on SSC 11, 32–39 Mb and 59–60 Mb on SSC 12 harbored several signifcant SNPs. Synapse genes (GABRR2, PPP1R9B, SYT1, GABRR1, CADPS2, DLGAP2 and GOPC), dephosphorylation genes (PPM1E, DAPP1, PTPN18, PTPRZ...

  16. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.

    Directory of Open Access Journals (Sweden)

    Terje Raudsepp

    Full Text Available Impaired acrosomal reaction (IAR of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (PA and g.11040379C>A (p.166H>N in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44 and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.

  17. A genome-wide association study points out the causal implication of SOX9 in the sex-reversal phenotype in XX pigs.

    Directory of Open Access Journals (Sweden)

    Sarah Rousseau

    Full Text Available Among farm animals, pigs are known to show XX sex-reversal. In such cases the individuals are genetically female but exhibit a hermaphroditism, or a male phenotype. While the frequency of this congenital disease is quite low (less than 1%, the economic losses are significant for pig breeders. These losses result from sterility, urogenital infections and the carcasses being downgraded because of the risk of boar taint. It has been clearly demonstrated that the SRY gene is not involved in most cases of sex-reversal in pigs, and that autosomal recessive mutations remain to be discovered. A whole-genome scan analysis was performed in the French Large-White population to identify candidate genes: 38 families comprising the two non-affected parents and 1 to 11 sex-reversed full-sib piglets were genotyped with the PorcineSNP60 BeadChip. A Transmission Disequilibrium Test revealed a highly significant candidate region on SSC12 (most significant p-value<4.65.10(-10 containing the SOX9 gene. SOX9, one of the master genes involved in testis differentiation, was sequenced together with one of its main regulatory region Tesco. However, no causal mutations could be identified in either of the two sequenced regions. Further haplotype analyses did not identify a shared homozygous segment between the affected pigs, suggesting either a lack of power due to the SNP properties of the chip, or a second causative locus. Together with information from humans and mice, this study in pigs adds to the field of knowledge, which will lead to characterization of novel molecular mechanisms regulating sexual differentiation and dysregulation in cases of sex reversal.

  18. A Candidate Gene Association Study of 77 Polymorphisms in Migraine

    OpenAIRE

    Schürks, Markus; Kurth, Tobias; Buring, Julie E.; Zee, Robert Y.L.

    2009-01-01

    Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association....

  19. Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappa B signalling

    NARCIS (Netherlands)

    Trynka, G.; Zhernakova, A.; Romanos, J.; Franke, L.; Hunt, K. A.; Turner, G.; Bruinenberg, M.; Heap, G. A.; Platteel, M.; Ryan, A. W.; de Kovel, C.; Holmes, G. K. T.; Howdle, P. D.; Walters, J. R. F.; Sanders, D. S.; Mulder, C. J. J.; Mearin, M. L.; Verbeek, W. H. M.; Trimble, V.; Stevens, F. M.; Kelleher, D.; Barisani, D.; Bardella, M. T.; McManus, R.; van Heel, D. A.; Wijmenga, C.

    2009-01-01

    Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest associ

  20. RNAi screening in primary human hepatocytes of genes implicated in genome-wide association studies for roles in type 2 diabetes identifies roles for CAMK1D and CDKAL1, among others, in hepatic glucose regulation.

    Directory of Open Access Journals (Sweden)

    Steven Haney

    Full Text Available Genome-wide association (GWA studies have described a large number of new candidate genes that contribute to of Type 2 Diabetes (T2D. In some cases, small clusters of genes are implicated, rather than a single gene, and in all cases, the genetic contribution is not defined through the effects on a specific organ, such as the pancreas or liver. There is a significant need to develop and use human cell-based models to examine the effects these genes may have on glucose regulation. We describe the development of a primary human hepatocyte model that adjusts glucose disposition according to hormonal signals. This model was used to determine whether candidate genes identified in GWA studies regulate hepatic glucose disposition through siRNAs corresponding to the list of identified genes. We find that several genes affect the storage of glucose as glycogen (glycolytic response and/or affect the utilization of pyruvate, the critical step in gluconeogenesis. Of the genes that affect both of these processes, CAMK1D, TSPAN8 and KIF11 affect the localization of a mediator of both gluconeogenesis and glycolysis regulation, CRTC2, to the nucleus in response to glucagon. In addition, the gene CDKAL1 was observed to affect glycogen storage, and molecular experiments using mutant forms of CDK5, a putative target of CDKAL1, in HepG2 cells show that this is mediated by coordinate regulation of CDK5 and PKA on MEK, which ultimately regulates the phosphorylation of ribosomal protein S6, a critical step in the insulin signaling pathway.

  1. Food Avoidance and Food Modification Practices of Older Rural Adults: Association with Oral Health Status and Implications for Service Provision

    Science.gov (United States)

    Quandt, Sara A.; Chen, Haiying; Bell, Ronny A.; Savoca, Margaret R.; Anderson, Andrea M.; Leng, Xiaoyan; Kohrman, Teresa; Gilbert, Gregg H.; Arcury, Thomas A.

    2010-01-01

    Purpose: Dietary variation is important for health maintenance and disease prevention among older adults. However, oral health deficits impair ability to bite and chew foods. This study examines the association between oral health and foods avoided or modified in a multiethnic rural population of older adults. It considers implications for…

  2. Cluster formation in liverwort-associated methylobacteria and its implications

    Science.gov (United States)

    Kutschera, U.; Thomas, J.; Hornschuh, M.

    2007-08-01

    Pink-pigmented methylotropic bacteria of the genus Methylobacterium inhabit the surfaces of plant organs. In bryophytes, these methylobacteria enhance cell growth, but the nature of this plant-microbe interaction is largely unknown. In this study, methylobacteria were isolated from the upper surface of the free-living thalli of the liverwort Marchantia polymorpha L. Identification of one strain by 16S ribosomal RNA (rRNA) gene-targeted polymerase chain reaction (PCR) and other data show that these microbes represent an undescribed species of the genus Methylobacterium ( Methylobacterium sp.). The growth-promoting activity of these wild-type methylobacteria was tested and compared with that of the type strain Methylobacterium mesophilicum. Both types of methylobacteria stimulated surface expansion of isolated gemmae from Marchantia polymorpha by about 350%. When suspended in water, the liverwort-associated bacteria ( Methylobacterium sp.) formed dense clusters of up to 600 cells. In liquid cultures of Methylobacterium mesophilicum, single cells were observed, but no clustering occurred. We suggest that the liverwort-associated methylobacteria are co-evolved symbionts of the plants: Cluster formation may be a behavior that enhances the survival of the epiphytic microbes during periods of drought of these desiccation-tolerant lower plants.

  3. Persistent primitive hypoglossal artery associated with Chiari II malformation: Diagnosis and clinical implications

    Directory of Open Access Journals (Sweden)

    Gupta Mudit

    2010-01-01

    Full Text Available We present a case of persistent primitive hypoglossal artery (PPHA associated with Chiari II malformation and discuss the clinical implications. There has been one reported case of PPHA associated with Chiari 1 malformation, but none in association with Chiari II. Our patient also had a widened hypoglossal canal, with cerebrospinal fluid (CSF sac herniation through it.

  4. Persistent primitive hypoglossal artery associated with Chiari II malformation: Diagnosis and clinical implications

    International Nuclear Information System (INIS)

    We present a case of persistent primitive hypoglossal artery (PPHA) associated with Chiari II malformation and discuss the clinical implications. There has been one reported case of PPHA associated with Chiari 1 malformation, but none in association with Chiari II. Our patient also had a widened hypoglossal canal, with cerebrospinal fluid (CSF) sac herniation through it

  5. Fontan-associated liver disease: Implications for heart transplantation.

    Science.gov (United States)

    Greenway, Steven C; Crossland, David S; Hudson, Mark; Martin, Steven R; Myers, Robert P; Prieur, Tim; Hasan, Asif; Kirk, Richard

    2016-01-01

    Chronic liver diseases are associated with multiple complications, including cirrhosis, portal hypertension, ascites, synthetic dysfunction and hepatocellular carcinoma, and these processes are increasingly recognized in post-Fontan patients. Fontan-associated liver disease (FALD) can be defined as abnormalities in liver structure and function that result from the Fontan circulation and are not related to another disease process. FALD arises due to chronic congestion of the liver created by the elevated venous pressure and low cardiac output of the Fontan circulation, which may be superimposed on previous liver injury. Pathology studies have generally shown that FALD worsens as time post-Fontan increases, but the prevalence of FALD is not well defined because the majority of Fontan patients, even those with significant hepatic fibrosis, appear to be asymptomatic and biochemical or functional hepatic abnormalities are usually subtle or absent. Alternate non-invasive investigations, derived from the study of other chronic liver diseases, have been tested in small series of pediatric and adult Fontan patients, but they have been confounded by congestion and do not correlate well with liver biopsy findings. Liver disease can complicate Fontan circulatory failure and may even be significant enough to be considered a contraindication to heart transplantation or require combined heart-liver transplantation. The search for the optimal management strategy continues in the setting of increasing numbers of Fontan patients surviving to adulthood and being referred for heart transplantation. Thus, in this review we attempt to define the scope and significance of FALD and address transplant-related assessment and management of this challenging disorder. PMID:26586487

  6. Genome-wide association study identifies four loci associated with eruption of permanent teeth

    DEFF Research Database (Denmark)

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao;

    2011-01-01

    The sequence and timing of permanent tooth eruption is thought to be highly heritable and can have important implications for the risk of malocclusion, crowding, and periodontal disease. We conducted a genome-wide association study of number of permanent teeth erupted between age 6 and 14 years, ...

  7. Empirical studies of software design: Implications for SSEs

    Science.gov (United States)

    Krasner, Herb

    1988-01-01

    Implications for Software Engineering Environments (SEEs) are presented in viewgraph format for characteristics of projects studied; significant problems and crucial problem areas in software design for large systems; layered behavioral model of software processes; implications of field study results; software project as an ecological system; results of the LIFT study; information model of design exploration; software design strategies; results of the team design study; and a list of publications.

  8. HLA-B27 Positivity: associated health implications

    OpenAIRE

    Cox, C. L.; Gibbons, H.; Evans, P; Withers, T.; Titmus, K.

    2011-01-01

    HLA-B27 positivity makes the onset of autoimmune diseases such as uveitis, ankylosing spondylitis and Crohn's disease more likely to occur. Ankylosing spondylitis and Crohn's disease are two types of HLA-B27 positive diseases that demonstrate a direct association with uveitis. Although the possession of HLA-B27 positivity is not mandatory for autoimmune diseases such as uveitis to occur, HLA-B27 positivity not only makes it more likely but may modify the clinical picture in which a patient pr...

  9. Food Avoidance and Food Modification Practices of Older Rural Adults: Association With Oral Health Status and Implications for Service Provision

    OpenAIRE

    Quandt, Sara A.; Chen, Haiying; Bell, Ronny A; Savoca, Margaret R.; Anderson, Andrea M.; Leng, Xiaoyan; Kohrman, Teresa; Gilbert, Gregg H.; Arcury, Thomas A

    2009-01-01

    Purpose: Dietary variation is important for health maintenance and disease prevention among older adults. However, oral health deficits impair ability to bite and chew foods. This study examines the association between oral health and foods avoided or modified in a multiethnic rural population of older adults. It considers implications for nutrition and medical service provision to this population. Design and Methods: In-home interviews and oral examinations were conducted with 635 adults in ...

  10. SYSTEMIC INFLAMMATION IMPAIRS ATTENTION AND COGNITIVE FLEXIBILITY BUT NOT ASSOCIATIVE LEARNING IN AGED RATS: Possible Implications for Delirium

    OpenAIRE

    Culley, Deborah J.; Mary eSnayd; Baxter, Mark G.; Zhongcong eXie; In-Ho eLee; James eRudolph; Sharon eInouye; Edward eMarcantonio; Gregory eCrosby

    2014-01-01

    Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that system...

  11. Systemic Inflammation Impairs Attention and Cognitive Flexibility but Not Associative Learning in Aged Rats: Possible Implications for Delirium

    OpenAIRE

    Culley, Deborah J.; Snayd, Mary; Baxter, Mark G.; Xie, Zhongcong; Lee, In Ho; Rudolph, James; Inouye, Sharon K.; Marcantonio, Edward R.; Crosby, Gregory

    2014-01-01

    Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that system...

  12. Genome-wide association studies in pediatric endocrinology.

    Science.gov (United States)

    Dauber, Andrew; Hirschhorn, Joel N

    2011-01-01

    Genome-wide association (GWA) studies are a powerful tool for understanding the genetic underpinnings of human disease. In this article, we briefly review the role and findings of GWA studies in type 1 diabetes, stature, pubertal timing, obesity, and vitamin D deficiency. We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of novel therapeutic agents.

  13. Geochemical Implications of CO2 Leakage Associated with Geologic Storage: A Review

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, Omar R.; Qafoku, Nikolla; Cantrell, Kirk J.; Brown, Christopher F.

    2012-07-09

    Leakage from deep storage reservoirs is a major risk factor associated with geologic sequestration of carbon dioxide (CO2). Different scientific theories exist concerning the potential implications of such leakage for near-surface environments. The authors of this report reviewed the current literature on how CO2 leakage (from storage reservoirs) would likely impact the geochemistry of near surface environments such as potable water aquifers and the vadose zone. Experimental and modeling studies highlighted the potential for both beneficial (e.g., CO2 re sequestration or contaminant immobilization) and deleterious (e.g., contaminant mobilization) consequences of CO2 intrusion in these systems. Current knowledge gaps, including the role of CO2-induced changes in redox conditions, the influence of CO2 influx rate, gas composition, organic matter content and microorganisms are discussed in terms of their potential influence on pertinent geochemical processes and the potential for beneficial or deleterious outcomes. Geochemical modeling was used to systematically highlight why closing these knowledge gaps are pivotal. A framework for studying and assessing consequences associated with each factor is also presented in Section 5.6.

  14. Student Identity Considerations and Implications Associated with Socioscientific Issues Instruction

    Science.gov (United States)

    Ruzek, Mitchel James

    The purpose of this investigation was to explore how aspects of identity, perceived levels of controversy, and the strength of a student's attachment to their controversial identity relate to conceptual understanding and knowledge acquisition during socioscientific issues (SSI) based instruction in a biology classroom. The knowledge gained from this study will have the capacity to enhance our understanding of the role that attachment to identity plays during SSI negotiation. Additionally, insight was gained into the role played by aspects of identity in conceptual understanding of scientifically controversial topics during SSI based instruction. This study contributed to the existing knowledge base in science education by illuminating processes involved in socioscientific issue navigation among students of differing perceptions of controversy as well as students who held aspects of controversial identity that may or may not interact with the specific issues chosen. Students demonstrated evidence of variations of reasoning, justification, perception of controversy, and aspects of knowledge gain as they negotiated the issues of marijuana safety and fast food legality. Additionally, evidence was provided that showed general knowledge gain throughout the group during socioscientific issues instruction. It has been said that one of the appeals of the SSI instructional model is that is serves not only as a context for the delivery of content, but acts as a catalyst for various forms of epistemological beliefs and research into the development of conceptual and psychological knowledge structures (Zeidler, 2013). This investigation supports the deeper understanding of the contribution of controversy perception to epistemology as well as conceptual and psychological knowledge structures during SSI navigation.

  15. The Religious Implications of an Historical Approach to Jewish Studies.

    Science.gov (United States)

    Furst, Rachel

    This project examines the religious implications of an approach to "limmudei kodesh" (primarily the study of Talmud) and "halakhah" (an integration of academic scholarship with traditional Torah study and the evaluation of the educational pros and cons of a curriculum built on such a synthesis). In the concerted effort over the past century to…

  16. Association analysis of the extended MHC region in celiac disease implicates multiple independent susceptibility loci.

    Directory of Open Access Journals (Sweden)

    Richard Ahn

    Full Text Available Celiac disease is a common autoimmune disease caused by sensitivity to the dietary protein gluten. Forty loci have been implicated in the disease. All disease loci have been characterized as low-penetrance, with the exception of the high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but not sufficient to cause the disease. The very strong effects from the known HLA loci and the genetically complex nature of the major histocompatibility complex (MHC have precluded a thorough investigation of the region. The purpose of this study was to test the hypothesis that additional celiac disease loci exist within the extended MHC (xMHC. A set of 1898 SNPs was analyzed for association across the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected controls. Conditional recursive partitioning was used to create an informative indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was included in the association analysis to account for their effects. A linkage disequilibrium-based grouping procedure was utilized to estimate the number of independent celiac disease loci present in the xMHC after accounting for the known effects. There was significant statistical evidence for four new independent celiac disease loci within the classic MHC region. This study is the first comprehensive association analysis of the xMHC in celiac disease that specifically accounts for the known HLA disease genotypes and the genetic complexity of the region.

  17. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    Science.gov (United States)

    Tafti, Mehdi; Lammers, Gert J.; Dauvilliers, Yves; Overeem, Sebastiaan; Mayer, Geert; Nowak, Jacek; Pfister, Corinne; Dubois, Valérie; Eliaou, Jean-François; Eberhard, Hans-Peter; Liblau, Roland; Wierzbicka, Aleksandra; Geisler, Peter; Bassetti, Claudio L.; Mathis, Johannes; Lecendreux, Michel; Khatami, Ramin; Heinzer, Raphaël; Haba-Rubio, José; Feketeova, Eva; Baumann, Christian R.; Kutalik, Zoltán; Tiercy, Jean-Marie

    2016-01-01

    Study Objectives: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despite the strong association with HLA class II, there is no evidence for CD4+ T-cell-mediated mechanism in narcolepsy. Since neurons express class I and not class II molecules, the final effector immune cells involved might include class I-restricted CD8+ T-cells. Methods: HLA class I (A, B, and C) and II (DQB1) genotypes were analyzed in 944 European narcolepsy with cataplexy patients and in 4,043 control subjects matched by country of origin. All patients and controls were DQB1*06:02 positive and class I associations were conditioned on DQB1 alleles. Results: HLA-A*11:01 (OR = 1.49 [1.18–1.87] P = 7.0*10−4), C*04:01 (OR = 1.34 [1.10–1.63] P = 3.23*10−3), and B*35:01 (OR = 1.46 [1.13–1.89] P = 3.64*10−3) were associated with susceptibility to narcolepsy. Analysis of polymorphic class I amino-acids revealed even stronger associations with key antigen-binding residues HLA-A-Tyr9 (OR = 1.32 [1.15–1.52] P = 6.95*10−5) and HLA-C-Ser11 (OR = 1.34 [1.15–1.57] P = 2.43*10−4). Conclusions: Our findings provide a genetic basis for increased susceptibility to infectious factors or an immune cytotoxic mechanism in narcolepsy, potentially targeting hypocretin neurons. Citation: Tafti M, Lammers GJ, Dauvilliers Y, Overeem S, Mayer G, Nowak J, Pfister C, Dubois V, Eliaou JF, Eberhard HP, Liblau R, Wierzbicka A, Geisler P, Bassetti CL, Mathis J, Lecendreux M, Khatami R, Heinzer R, Haba-Rubio J, Feketeova E, Baumann CR, Kutalik Z, Tiercy JM. Narcolepsy-associated HLA class I alleles implicate cell-mediated cytotoxicity. SLEEP 2016;39(3):581–587. PMID:26518595

  18. Associations between Gun Violence Exposure, Gang Associations, and Youth Aggression: Implications for Prevention and Intervention Programs

    Directory of Open Access Journals (Sweden)

    Myriam Forster

    2015-01-01

    Full Text Available Using cross-sectional data collected from three middle schools in Southeast Los Angeles, we assessed the association of neighborhood violence exposure, gang associations, and social self-control with past week aggression in a sample of minority youth (n=164. Results from Poisson and logistic regression models showed that direct exposure to gun violence, having friends in gangs, and low social self control were all positively associated with past week aggression. Among girls, having gang affiliated family members was positively associated with aggression, whereas among boys having friends in gangs was associated with past week aggression. Subjective expectations of engagement in future interpersonal violence were associated with being male, having friends in gangs, and fear of neighborhood gun violence. We recommend that youth violence prevention and intervention programs address the impact of family, peers, and gun violence on student coping and identify students with low social self-control who could benefit from social and emotional skills training.

  19. Associations between Gun Violence Exposure, Gang Associations, and Youth Aggression: Implications for Prevention and Intervention Programs

    OpenAIRE

    Myriam Forster; Grigsby, Timothy J.; Unger, Jennifer B.; Steve Sussman

    2015-01-01

    Using cross-sectional data collected from three middle schools in Southeast Los Angeles, we assessed the association of neighborhood violence exposure, gang associations, and social self-control with past week aggression in a sample of minority youth (n=164). Results from Poisson and logistic regression models showed that direct exposure to gun violence, having friends in gangs, and low social self control were all positively associated with past week aggression. Among girls, having gang affi...

  20. Implications for cancer epidemiology of differences in dietary intake associated with alcohol consumption.

    Science.gov (United States)

    Hebert, J R; Kabat, G C

    1991-01-01

    Several dietary factors are thought to modify risk for cancers that are known to be associated with alcohol intake. In this study, we sought to identify and describe alcohol-related differences in dietary and nutritional factors that are potential independent predictors of cancer risk or effect modifiers or confounders of alcohol-cancer relationships. Data were obtained from a large hospital-based case-control study that was designed to estimate the cancer risk from various tobacco products. Study subjects consisted of 465 male and 300 female incident lung cancer cases and 870 male and 556 female hospitalized patient controls matched on age (+/- 5 yrs). Nutritional data were analyzed as log-transformed frequencies of 30 food items, 9 factor scores generated to describe overall patterns of dietary intake, and nutrient scores estimating daily intake of fat, vitamin A, fiber, and cholesterol. We observed many more significant differences in nutritional exposures by alcoholic beverage intake than would be expected merely by chance. For males, the most striking relationships included increased meat and egg consumption with increasing alcohol consumption and higher intake of cantaloupe and cold cereal among lighter drinkers. For females, we observed strong inverse relationships between alcohol consumption and reported intake of fruit, cold cereal, and ice cream. We also observed a direct association between alcohol and meat consumption, though it was weaker than that found among men. Findings based on factors and nutrients followed the pattern observed for the individual food items, with highest fat scores and lowest fruit scores among the heaviest drinkers. Implications for nutrient-alcohol interactions and statistical considerations are discussed. PMID:2038565

  1. Discursive Study of Religion : Approaches, Definitions, Implications

    NARCIS (Netherlands)

    von Stuckrad, Kocku

    2013-01-01

    The article explores recent approaches to historical analysis of discourse that have been developed in disciplines such as the sociology of knowledge and historical epistemology. These approaches have only sporadically been taken seriously in the academic study of religion, although they have a grea

  2. Genome-wide association study identifies five new schizophrenia loci

    OpenAIRE

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A; Scolnick, Edward; Cichon, Sven; St. Clair, David; Corvin, Aiden; Gurling, Hugh

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated ...

  3. Genome-wide association study identifies five new schizophrenia loci.

    OpenAIRE

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A; Scolnick, Edward; Cichon, Sven; St. Clair, David; Corvin, Aiden; Gurling, Hugh

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated ...

  4. Factors associated with uterine endometrial hyperplasia and pyometra in wild canids: implications for fertility.

    Science.gov (United States)

    Asa, Cheryl S; Bauman, Karen L; Devery, Sarah; Zordan, Martín; Camilo, Gerardo R; Boutelle, Sally; Moresco, Anneke

    2014-01-01

    The ability to safely and effectively manage reproduction is central to the success of AZA captive-breeding programs. Although the AZA Wildlife Contraception Center routinely monitors contraceptive safety, there have been no studies that compare the effects of contraceptive use to separation of males from females, the other option for preventing reproduction. We used retrospective medical records and pathology reports submitted by AZA and related facilities for the seven AZA-managed canid species to assess rates of uterine pathology relative to female reproductive life histories. Our results showed that the prevalence of both pyometra and endometrial hyperplasia (EH) was associated not only with treatment with the two most common contraceptives (Suprelorin® and MGA implants) but also with the number of years barren (i.e., not producing a litter and not contracepted). Rates of pyometra and EH were especially high in African painted dogs and red wolves, but lowest in swift and fennec foxes. The number of years producing a litter had a low association, suggesting it could be protective against uterine pathology. A more recently developed Suprelorin® protocol using Ovaban® to prevent the initial stimulation phase, followed by implant removal when reversal is desired, may be a safer contraceptive option. These results concerning the relationship between reproductive management and uterine health have important implications for AZA-managed programs, since the unsustainability of many captive populations may be due at least in part to infertility. Managing a female's reproductive lifespan to optimize or maintain fertility will require a reconsideration of how breeding recommendations are formulated. PMID:23553688

  5. Association between airborne PM2.5 chemical constituents and birth weight—implication of buffer exposure assignment

    International Nuclear Information System (INIS)

    Several papers reported associations between airborne fine particulate matter (PM2.5) and birth weight, though findings are inconsistent across studies. Conflicting results might be due to (1) different PM2.5 chemical structure across locations, and (2) various exposure assignment methods across studies even among the studies that use ambient monitors to assess exposure. We investigated associations between birth weight and PM2.5 chemical constituents, considering issues arising from choice of buffer size (i.e. distance between residence and pollution monitor). We estimated the association between each pollutant and term birth weight applying buffers of 5 to 30 km in Connecticut (2000–2006), in the New England region of the USA. We also investigated the implication of the choice of buffer size in relation to population characteristics, such as socioeconomic status. Results indicate that some PM2.5 chemical constituents, such as nitrate, are associated with lower birth weight and appear more harmful than other constituents. However, associations vary with buffer size and the implications of different buffer sizes may differ by pollutant. A homogeneous pollutant level within a certain distance is a common assumption in many environmental epidemiology studies, but the validity of this assumption may vary by pollutant. Furthermore, we found that areas close to monitors reflect more minority and lower socio-economic populations, which implies that different exposure approaches may result in different types of study populations. Our findings demonstrate that choosing an exposure method involves key tradeoffs of the impacts of exposure misclassification, sample size, and population characteristics. (letter)

  6. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    Science.gov (United States)

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. PMID:27492634

  7. Genome-Wide Association Studies for Polycystic Ovary Syndrome.

    Science.gov (United States)

    Liu, Hongbin; Zhao, Han; Chen, Zi-Jiang

    2016-07-01

    Over the past several years, the field of reproductive medicine has witnessed great advances in genome-wide association studies (GWASs) of polycystic ovary syndrome (PCOS), leading to identification of several promising genes involved in hormone action, type 2 diabetes, and cell proliferation. This review summarizes the key findings and discusses their potential implications with regard to genetic mechanisms of PCOS. Limitations of GWAS are evaluated, emphasizing the understanding of the reasons for variability in results between individual studies. Root causes of misinterpretations of GWASs are also addressed. Finally, the impact of GWAS on future directions of multi- and interdisciplinary studies is discussed. PMID:27513023

  8. Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Yue ePei

    2016-04-01

    Full Text Available Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the classical biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA, norepinephrine, epinephrine, serotonin (5-HT and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS, and hence referred to as trace amines (TAs, are now recognized to play significant neurophysiological and behavioural functions. At the turn of the century, the discovery of the trace amine-associated receptor 1 (TAAR1, a phylogenetically conserved G protein-coupled receptor that is responsive to both TAs, such as β-phenylethylamine, octopamine and tyramine, and structurally-related amphetamines, unveiled mechanisms of action for TAs other than interference with aminergic pathways, laying the foundations for deciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1. Although its molecular interactions and downstream targets have not been fully elucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates PKA and PKC signalling and interferes with the β-arrestin2-dependent pathway via G protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation, including Parkinson’s disease, schizophrenia, mood disorders and addiction. Indeed, the recent development of novel pharmacological tools targeting TAAR1 has uncovered the remarkable potential of TAAR1-based medications as new generation pharmacotherapies in neuropsychiatry. This review summarizes recent developments in the study of TAs and TAAR1, their intricate neurochemistry and

  9. Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications.

    Science.gov (United States)

    Pei, Yue; Asif-Malik, Aman; Canales, Juan J

    2016-01-01

    Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the "classical" biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA), norepinephrine, epinephrine, serotonin (5-HT), and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS), and hence referred to as "trace" amines (TAs), are now recognized to play significant neurophysiological and behavioral functions. At the turn of the century, the discovery of the trace amine-associated receptor 1 (TAAR1), a phylogenetically conserved G protein-coupled receptor that is responsive to both TAs, such as β-phenylethylamine, octopamine, and tyramine, and structurally-related amphetamines, unveiled mechanisms of action for TAs other than interference with aminergic pathways, laying the foundations for deciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1. Although, its molecular interactions and downstream targets have not been fully elucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates PKA and PKC signaling and interferes with the β-arrestin2-dependent pathway via G protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation, including Parkinson's disease, schizophrenia, mood disorders, and addiction. Indeed, the recent development of novel pharmacological tools targeting TAAR1 has uncovered the remarkable potential of TAAR1-based medications as new generation pharmacotherapies in neuropsychiatry. This review summarizes recent developments in the study of TAs and TAAR1, their intricate neurochemistry and

  10. Ventilator associated pneumonia and transfusion, is there really an association? (the NAVTRA study

    Directory of Open Access Journals (Sweden)

    Gonzalez Marco

    2006-07-01

    Full Text Available Abstract Background Anemic syndrome is a frequent problem in intensive care units. The most probable etiology is the suppression of the erythropoietin response due to the direct effects of cytokines, as well as frequent blood sampling. Transfusions are not free of complications, therefore transfusion reactions are estimated to occur in 2% of the total packed red blood cells (pRBCs transfused. In the past several years, several trials had tried to compare the restrictive with the more liberal use of transfusions, and they were found to be equally effective. Nosocomial pneumonia is the most common nosocomial infection in intensive care units; the prevalence is 47% with an attributive mortality of 33%. There are multiple risk factors for the development of nosocomial pneumonia. Colonization of the upper airways is the most important pathophysiological factor but there are other factors implicated like, sedation techniques, inappropriate use of antibiotics and recumbent positioning. A secondary analysis of the CRIT study describes transfusion therapy and its practices in the United States. They found that transfusion practice is an independent risk factor for the development of nosocomial pneumonia. Methods This is a multicenter, prospective cohort study in different intensive care units in Colombia. A total of 474 patients were selected who had more than 48 hours of mechanical ventilation. The primary objective is to try to demonstrate the hypothetical relationship between the use of transfusions and nosocomial pneumonia. Secondly, we will try to determine which other factors are implicated in the development of pneumonia in intensive care units and describe the incidence of pneumonia and transfusion practices. Discussion Ventilator associated pneumonia is a primary problem in the intensive care unit, multiple factors have been associated with its presence in this study we try to explore the possible association between pneumonia and transfusion

  11. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per;

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  12. Association of CHMP4B and Autophagy with Micronuclei: Implications for Cataract Formation

    Directory of Open Access Journals (Sweden)

    Antonia P. Sagona

    2014-01-01

    Full Text Available Autophagy is a mechanism of cellular self-degradation that is very important for cellular homeostasis and differentiation. Components of the endosomal sorting complex required for transport (ESCRT machinery are required for endosomal sorting and also for autophagy and the completion of cytokinesis. Here we show that the ESCRT-III subunit CHMP4B not only localizes to normal cytokinetic bridges but also to chromosome bridges and micronuclei, the latter surrounded by lysosomes and autophagosomes. Moreover, CHMP4B can be co-immunoprecipitated with chromatin. Interestingly, a CHMP4B mutation associated with autosomal dominant posterior polar cataract abolishes the ability of CHMP4B to localize to micronuclei. We propose that CHMP4B, through its association with chromatin, may participate in the autophagolysosomal degradation of micronuclei and other extranuclear chromatin. This may have implications for DNA degradation during lens cell differentiation, thus potentially protecting lens cells from cataract development.

  13. Age-associated epigenetic drift: implications, and a case of epigenetic thrift?

    Science.gov (United States)

    Teschendorff, Andrew E; West, James; Beck, Stephan

    2013-10-15

    It is now well established that the genomic landscape of DNA methylation (DNAm) gets altered as a function of age, a process we here call 'epigenetic drift'. The biological, functional, clinical and evolutionary significance of this epigenetic drift, however, remains unclear. We here provide a brief review of epigenetic drift, focusing on the potential implications for ageing, stem cell biology and disease risk prediction. It has been demonstrated that epigenetic drift affects most of the genome, suggesting a global deregulation of DNAm patterns with age. A component of this drift is tissue-specific, allowing remarkably accurate age-predictive models to be constructed. Another component is tissue-independent, targeting stem cell differentiation pathways and affecting stem cells, which may explain the observed decline of stem cell function with age. Age-associated increases in DNAm target developmental genes, overlapping those associated with environmental disease risk factors and with disease itself, notably cancer. In particular, cancers and precursor cancer lesions exhibit aggravated age DNAm signatures. Epigenetic drift is also influenced by genetic factors. Thus, drift emerges as a promising biomarker for premature or biological ageing, and could potentially be used in geriatrics for disease risk prediction. Finally, we propose, in the context of human evolution, that epigenetic drift may represent a case of epigenetic thrift, or bet-hedging. In summary, this review demonstrates the growing importance of the 'ageing epigenome', with potentially far-reaching implications for understanding the effect of age on stem cell function and differentiation, as well as for disease prevention.

  14. Cross-sectional study of morbidity, morbidity-associated factors and cost of treatment in Ngaoundere, Cameroon, with implications for health policy in developing countries and development assistance policy

    Directory of Open Access Journals (Sweden)

    Holtedahl Knut

    2002-04-01

    Full Text Available Abstract Background In a population-based epidemiological study in Ngaoundere, Cameroon, we studied cross-sectional child morbidity and the cost of necessary investigation and treatment. Methods Three teams of two to three health workers visited haphazardly selected households in all major housing quarters. We asked permission to enter for a health survey. Children with cough, fever or weight loss as well as sick adults were offered free-of-charge local hospital examination and treatment. Results From 177 households with 1777 persons, 51 (2.9% persons were referred. Thirty-five of them had an undiagnosed disease threatening individual health and in many cases also public health. Seven were hospitalised, including three adults with tuberculosis. Malnutrition was diagnosed in nine small children. Four patients had AIDS, seven had malaria. Average total cost for ambulant patients was 15 USD, for hospitalised patients 110 USD. In the households, almost half of the women 16–50 years of age had no schooling. Two per cent of women and nine per cent of men were daily smokers. Coughing children were more likely than non-coughing children to live in a household with at least one smoker (OR = 3.58, 95% CI 1.72 to 7.46, and they generally lived in more poor households (P = 0.018. Twelve of 16 children with weight loss were referred from households with a high poverty score. Conclusions Adult smoking and poverty affect children's health. The cost of hospitalisation or long-lasting therapy is beyond the means of most ordinary families. Diseases with severe consequences for public health, like tuberculosis, AIDS and malaria should have national programs with free, decentralised examination and treatment. Access to generic drugs is important. A major educational effort is needed to improve public health.

  15. A network based method for analysis of lncRNA-disease associations and prediction of lncRNAs implicated in diseases.

    Science.gov (United States)

    Yang, Xiaofei; Gao, Lin; Guo, Xingli; Shi, Xinghua; Wu, Hao; Song, Fei; Wang, Bingbo

    2014-01-01

    Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis. In this paper, we investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, we studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, we constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. We then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. Our algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, our results for Alzheimer's disease, pancreatic cancer, and gastric cancer were verified by other independent studies.

  16. Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease.

    Science.gov (United States)

    Pistollato, Francesca; Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

    2016-07-01

    Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD. PMID:27422503

  17. BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism.

    Science.gov (United States)

    Wang, Zhi-Qiang; Faddaoui, Adnen; Bachvarova, Magdalena; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Guillemette, Chantal; Gobeil, Stéphane; Macdonald, Elizabeth; Vanderhyden, Barbara; Bachvarov, Dimcho

    2015-10-13

    Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high-grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target.

  18. Body mass index and its association with lumbar disc herniation and sciatica: a large-scale, population-based study

    OpenAIRE

    Samartzis, D; Karppinen, JI; Luk, KDK; Cheung, KMC

    2014-01-01

    INTRODUCTION: This large-scale study addressed the association of body mass index (BMI), especially overweight / obesity with lumbar disc herniation, its global lumbar involvement and implications with sciatica that little of which is ...

  19. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  20. Genome-wide association studies in asthma: progress and pitfalls

    Directory of Open Access Journals (Sweden)

    March ME

    2015-01-01

    Full Text Available Michael E March,1 Patrick MA Sleiman,1,2 Hakon Hakonarson1,2 1Center for Applied Genomics, Children's Hospital of Philadelphia Research Institute, 2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Abstract: Genetic studies of asthma have revealed that there is considerable heritability to the phenotype. An extensive history of candidate-gene studies has identified a long list of genes associated with immune function that are potentially involved in asthma pathogenesis. However, many of the results of candidate-gene studies have failed to be replicated, leaving in question the true impact of the implicated biological pathways on asthma. With the advent of genome-wide association studies, geneticists are able to examine the association of hundreds of thousands of genetic markers with a phenotype, allowing the hypothesis-free identification of variants associated with disease. Many such studies examining asthma or related phenotypes have been published, and several themes have begun to emerge regarding the biological pathways underpinning asthma. The results of many genome-wide association studies have currently not been replicated, and the large sample sizes required for this experimental strategy invoke difficulties with sample stratification and phenotypic heterogeneity. Recently, large collaborative groups of researchers have formed consortia focused on asthma, with the goals of sharing material and data and standardizing diagnosis and experimental methods. Additionally, research has begun to focus on genetic variants that affect the response to asthma medications and on the biology that generates the heterogeneity in the asthma phenotype. As this work progresses, it will move asthma patients closer to more specific, personalized medicine. Keywords: asthma, genetics, GWAS, pharmacogenetics, biomarkers

  1. Periodontal Systemic Connections-Novel Associations-A Review of the Evidence with Implications for Medical Practitioners.

    Science.gov (United States)

    Kalakonda, Butchibabu; Koppolu, Pradeep; Baroudi, Kusai; Mishra, Ashank

    2016-04-01

    Periodontal diseases, considered as inflammatory diseases have proved to have a spectrum of systemic implications. Earliest research has associated periodontal disease with common systemic aliments such as hypertension, diabetes, osteoporosis, rheumatoid arthritis to name a few. The evolution of advanced diagnostic aids let researchers make vast inroads in linking periodontal diseases to systemic diseases like Alzheimer's disease (AD) and even Schizophrenia. Our aim was to review and critically evaluate comprehensive literature and provide knowledge to medical practitioners on these associations so as to pave way for closer interactions between medical and dental practitioners in implementing better health care. Electronic databases such as PubMed, Google Scholar and Cochrane databases were used as source of the data for relevant studies published from 2005 up to 2015 with the following keywords, "'Periodontal disease", "systemic conditions", "periodontal disease and Alzheimer's", "Periodontal disease and Schizophrenia", "Periodontal disease and Psoriasis" and "Periodontal disease and erectile dysfunction". The evidence presented ascertains that a reasonable and modest association does exist between Periodontal disease and Alzheimer's, Schizophrenia, Erectile dysfunction, as well as Psoriasis and thus establishes periodontal disease as a potential risk factor. PMID:27103910

  2. Insights into kidney diseases from genome-wide association studies.

    Science.gov (United States)

    Wuttke, Matthias; Köttgen, Anna

    2016-09-01

    Over the past decade, genome-wide association studies (GWAS) have considerably improved our understanding of the genetic basis of kidney function and disease. Population-based studies, used to investigate traits that define chronic kidney disease (CKD), have identified >50 genomic regions in which common genetic variants associate with estimated glomerular filtration rate or urinary albumin-to-creatinine ratio. Case-control studies, used to study specific CKD aetiologies, have yielded risk loci for specific kidney diseases such as IgA nephropathy and membranous nephropathy. In this Review, we summarize important findings from GWAS and clinical and experimental follow-up studies. We also compare risk allele frequency, effect sizes, and specificity in GWAS of CKD-defining traits and GWAS of specific CKD aetiologies and the implications for study design. Genomic regions identified in GWAS of CKD-defining traits can contain causal genes for monogenic kidney diseases. Population-based research on kidney function traits can therefore generate insights into more severe forms of kidney diseases. Experimental follow-up studies have begun to identify causal genes and variants, which are potential therapeutic targets, and suggest mechanisms underlying the high allele frequency of causal variants. GWAS are thus a useful approach to advance knowledge in nephrology.

  3. 77 FR 9946 - Draft Guidance for Industry on Drug Interaction Studies-Study Design, Data Analysis, Implications...

    Science.gov (United States)

    2012-02-21

    ... on Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and Labeling... entitled ``Drug Interaction Studies--Study Design, Data Analysis, Implications for Dosing, and Labeling... vivo studies, in vivo study design, and data analysis in the context of identifying potential...

  4. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Science.gov (United States)

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  5. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Directory of Open Access Journals (Sweden)

    Varun Warrier

    Full Text Available Asperger Syndrome (AS is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC, which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448 were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448 lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

  6. A Pooled Genome-Wide Association Study of Asperger Syndrome.

    Science.gov (United States)

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; Peltonen, Leena; Wheelwright, Sally; Allison, Carrie; Fisher, Simon E; Baron-Cohen, Simon

    2015-01-01

    Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision. PMID:26176695

  7. A Comparative Study of Sparse Associative Memories

    Science.gov (United States)

    Gripon, Vincent; Heusel, Judith; Löwe, Matthias; Vermet, Franck

    2016-07-01

    We study various models of associative memories with sparse information, i.e. a pattern to be stored is a random string of 0s and 1s with about log N 1s, only. We compare different synaptic weights, architectures and retrieval mechanisms to shed light on the influence of the various parameters on the storage capacity.

  8. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of the

  9. Associative visual agnosia: a case study.

    Science.gov (United States)

    Charnallet, A; Carbonnel, S; David, D; Moreaud, O

    2008-01-01

    We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study, an alternative account in the framework of (non abstractive) episodic models of memory.

  10. Factors associated with female genital mutilation in Burkina Faso and its policy implications

    Directory of Open Access Journals (Sweden)

    Chung Donna

    2011-05-01

    Full Text Available Abstract Background Female genital mutilation (FGM usually undertaken between the ages of 1-9 years and is widely practised in some part of Africa and by migrants from African countries in other parts of the world. Laws prohibit FGM in almost every country. FGM can cause immediate complications (pain, bleeding and infection and delayed complications (sexual, obstetric, psychological problems. Several factors have been associated with an increased likelihood of FGM. In Burkina Faso, the prevalence of FGM appears to have increased in recent years. Methods We investigated social, demographic and economic factors associated with FGM in Burkina Faso using the 2003 Demographic Health Survey (DHS. The DHS is a nationally representative cross-sectional survey (multistage stratified random sampling of households of women of reproductive age (15-49 years. Associations between potential risk factors and the prevalence of FGM were explored using χ2 and t-tests and Mann Whitney U-test as appropriate. Logistic regression modelling was used to investigate social, demographic and economic risk factors associated with FGM. Main outcome measures i whether a woman herself had had FGM; ii whether she had one or more daughters with FGM. Results Data were available on 12,049 women. Response rates by region were at least 90%. Women interviewed were representative of the underlying populations of the different regions of Burkina Faso. Seventy seven percent (9267 of the women interviewed had had FGM. 7336 women had a daughter of whom 2216 (30.2% had a daughter with FGM and 334 (4.5% said that they intended that their daughter should have it. Univariate analysis showed that age, religion, wealth, ethnicity, literacy, years of education, household affluence, region and who had responsibility for health care decisions in the household had (RHCD were all significantly related to the two outcomes (p Conclusions and Policy implications Factors associated with FGM are varied

  11. Quantifying Shark Distribution Patterns and Species-Habitat Associations: Implications of Marine Park Zoning

    OpenAIRE

    Mario Espinoza; Mike Cappo; Heupel, Michelle R.; Tobin, Andrew J.; Simpfendorfer, Colin A.

    2014-01-01

    Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21...

  12. Functional analysis of variance for association studies.

    Science.gov (United States)

    Vsevolozhskaya, Olga A; Zaykin, Dmitri V; Greenwood, Mark C; Wei, Changshuai; Lu, Qing

    2014-01-01

    While progress has been made in identifying common genetic variants associated with human diseases, for most of common complex diseases, the identified genetic variants only account for a small proportion of heritability. Challenges remain in finding additional unknown genetic variants predisposing to complex diseases. With the advance in next-generation sequencing technologies, sequencing studies have become commonplace in genetic research. The ongoing exome-sequencing and whole-genome-sequencing studies generate a massive amount of sequencing variants and allow researchers to comprehensively investigate their role in human diseases. The discovery of new disease-associated variants can be enhanced by utilizing powerful and computationally efficient statistical methods. In this paper, we propose a functional analysis of variance (FANOVA) method for testing an association of sequence variants in a genomic region with a qualitative trait. The FANOVA has a number of advantages: (1) it tests for a joint effect of gene variants, including both common and rare; (2) it fully utilizes linkage disequilibrium and genetic position information; and (3) allows for either protective or risk-increasing causal variants. Through simulations, we show that FANOVA outperform two popularly used methods - SKAT and a previously proposed method based on functional linear models (FLM), - especially if a sample size of a study is small and/or sequence variants have low to moderate effects. We conduct an empirical study by applying three methods (FANOVA, SKAT and FLM) to sequencing data from Dallas Heart Study. While SKAT and FLM respectively detected ANGPTL 4 and ANGPTL 3 associated with obesity, FANOVA was able to identify both genes associated with obesity. PMID:25244256

  13. Epidemiology of Epilepsy in Older Adults with an Intellectual Disability in Ireland: Associations and Service Implications

    Science.gov (United States)

    McCarron, Mary; O'Dwyer, Marie; Burke, Eilish; McGlinchey, Eimear; McCallion, Philip

    2014-01-01

    There are limited studies on the prevalence of epilepsy and co-morbid conditions in older adults with an ID. To begin to address this prevalence of epilepsy was estimated for participants in the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing. Associations with demographic variables and co morbid health conditions were…

  14. Buoyant Nanoparticles: Implications for Nano-Biointeractions in Cellular Studies.

    Science.gov (United States)

    Watson, C Y; DeLoid, G M; Pal, A; Demokritou, P

    2016-06-01

    In the safety and efficacy assessment of novel nanomaterials, the role of nanoparticle (NP) kinetics in in vitro studies is often ignored although it has significant implications in dosimetry, hazard ranking, and nanomedicine efficacy. It is demonstrated here that certain nanoparticles are buoyant due to low effective densities of their formed agglomerates in culture media, which alters particle transport and deposition, dose-response relationships, and underestimates toxicity and bioactivity. To investigate this phenomenon, this study determines the size distribution, effective density, and assesses fate and transport for a test buoyant NP (polypropylene). To enable accurate dose-response assessment, an inverted 96-well cell culture platform is developed in which adherent cells are incubated above the buoyant particle suspension. The effect of buoyancy is assessed by comparing dose-toxicity responses in human macrophages after 24 h incubation in conventional and inverted culture systems. In the conventional culture system, no adverse effects are observed at any NP concentration tested (up to 250 μg mL(-1) ), whereas dose-dependent decreases in viability and increases in reactive oxygen species are observed in the inverted system. This work sheds light on an unknown issue that plays a significant role in vitro hazard screening and proposes a standardized methodology for buoyant NP assessments. PMID:27135209

  15. Physiological Effects Associated with Quinoa Consumption and Implications for Research Involving Humans: a Review.

    Science.gov (United States)

    Simnadis, Thomas George; Tapsell, Linda C; Beck, Eleanor J

    2015-09-01

    Quinoa is a pseudo-grain consumed as a dietary staple in South America. In recent years, consumer demand for quinoa in the developed world has grown steadily. Its perceived health benefits have been cited as a driving force behind this trend, but there are very few human studies investigating the impact of quinoa consumption. The aim of this review was to identify physiological effects of quinoa consumption with potential for human health. A critical evaluation of animal model studies was conducted. The quality of identified studies was assessed using a methodological quality assessment tool and summative conclusions were drawn to guide the direction of future human research. The majority of studies were of fair quality. Purported physiological effects of quinoa consumption included decreased weight gain, improved lipid profile and improved capacity to respond to oxidative stress. These physiological effects were attributed to the presence of saponins, protein and 20-hydroxyecdysone in the quinoa seed. The implications of these findings are that human studies should investigate the impact of quinoa consumption on weight gain and lipid levels. The role of quinoa as an antioxidant is still unclear and requires further elucidation in animal models. PMID:26249220

  16. Fluid retention associated with imatinib treatment in patients with gastroenterol stromal: Quantitative radiologic assessment and implications for management

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Won; Shinagare, Atul B.; Krajewski, Katherine M.; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikihil H. [Dept. of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Pyo, Jun Hee [The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston (United States)

    2015-04-15

    We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.

  17. Study of Implications of FDI on Indian Economy

    Directory of Open Access Journals (Sweden)

    Srikant MISRA

    2012-12-01

    Full Text Available Foreign direct investment (FDI is always contributing in the positive growth toward the economy of one country due to the investment by another country or country’s personnel’s. The effectiveness and efficiency of Global economy depends upon the investor’s perception, if investment seen with the purpose of long terms investment in the social-economical development then it is said that the investment contributes positively towards global economy, if it is short term for the purpose of making profit then it may be less significant than that long term and disinvestment leads negative effect. The FDI may also be affected due to the governmental trade barriers and policies for the foreign investments and leads to less or more effective toward contribution in economy as well as GDP and GNP of the country.In this paper, our aim is to point out the negative and positive implications which affect the economic scenario and also measure the level of predominance by the factors for economic contribution of particular country with special reference to India. FDI seen as an important catalyst for economic growth in the developing countries, The main purpose of the study is to investigate the impact of FDI on economic growth in India, from the period of 1990 to 2010.This article will also be examined current international investment regime and their relation with Indian economy. This article hopes to find a new position for effectiveness and efficiency of Indian economy through integrated global market by FDI.

  18. A norovirus outbreak associated with consumption of NSW oysters: implications for quality assurance systems.

    Science.gov (United States)

    Huppatz, Clare; Munnoch, Sally A; Worgan, Tory; Merritt, Tony D; Dalton, Craig; Kelly, Paul M; Durrheim, David N

    2008-03-01

    Norovirus is a common cause of gastroenteritis outbreaks associated with raw shellfish consumption. In Australia there have been several reports of norovirus outbreaks associated with oysters despite the application of regulatory measures recommended by Food Standards Australia New Zealand. This study describes an outbreak of norovirus gastroenteritis following the consumption of New South Wales oysters. In September 2007, OzFoodNet conducted a cohort study of a gastroenteritis outbreak amongst people that had dined at a Port Macquarie restaurant. Illness was strongly associated with oyster consumption, with all cases having eaten oysters from the same lease (RR undefined, p quality assurance programs do not routinely test oysters for viral contamination that pose a risk to human health. It is recommended that the feasibility of testing oysters for norovirus, particularly after known faecal contamination of oyster leases, be assessed. PMID:18522310

  19. Genetic Risk Scores Implicated in Adult Bone Fragility Associate With Pediatric Bone Density.

    Science.gov (United States)

    Mitchell, Jonathan A; Chesi, Alessandra; Elci, Okan; McCormack, Shana E; Roy, Sani M; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

    2016-04-01

    Using adult identified bone mineral density (BMD) loci, we calculated genetic risk scores (GRS) to determine if they were associated with changes in BMD during childhood. Longitudinal data from the Bone Mineral Density in Childhood Study were analyzed (N = 798, 54% female, all European ancestry). Participants had up to 6 annual dual energy X-ray scans, from which areal BMD (aBMD) Z-scores for the spine, total hip, and femoral neck were estimated, as well as total body less head bone mineral content (TBLH-BMC) Z-scores. Sixty-three single-nucleotide polymorphisms (SNPs) were genotyped, and the percentage of BMD-lowering alleles carried was calculated (overall adult GRS). Subtype GRS that include SNPs associated with fracture risk, pediatric BMD, WNT signaling, RANK-RANKL-OPG, and mesenchymal stem cell differentiation were also calculated. Linear mixed effects models were used to test associations between each GRS and bone Z-scores, and if any association differed by sex and/or chronological age. The overall adult, fracture, and WNT signaling GRS were associated with lower Z-scores (eg, spine aBMD Z-score: βadult  = -0.04, p = 3.4 × 10(-7) ; βfracture = -0.02, p = 8.9 × 10(-6) ; βWNT  = -0.01, p = 3.9 × 10(-4) ). The overall adult GRS was more strongly associated with lower Z-scores in females (p-interaction ≤ 0.05 for all sites). The fracture GRS was more strongly associated with lower Z-scores with increasing age (p-interaction ≤ 0.05 for all sites). The WNT GRS associations remained consistent for both sexes and all ages (p-interaction > 0.05 for all sites). The RANK-RANKL-OPG GRS was more strongly associated in females with increasing age (p-interaction < 0.05 for all sites). The mesenchymal stem cell GRS was associated with lower total hip and femoral neck Z-scores, in both boys and girls, across all ages. No associations were observed between the pediatric GRS and bone Z-scores. In conclusion, adult identified BMD loci associated with BMD and

  20. Associative Visual Agnosia: A Case Study

    Directory of Open Access Journals (Sweden)

    A. Charnallet

    2008-01-01

    Full Text Available We report a case of massive associative visual agnosia. In the light of current theories of identification and semantic knowledge organization, a deficit involving both levels of structural description system and visual semantics must be assumed to explain the case. We suggest, in line with a previous case study [1], an alternative account in the framework of (non abstractive episodic models of memory [4].

  1. Microorganisms associated particulate matter: a preliminary study.

    Science.gov (United States)

    Alghamdi, Mansour A; Shamy, Magdy; Redal, Maria Ana; Khoder, Mamdouh; Awad, Abdel Hameed; Elserougy, Safaa

    2014-05-01

    This study aims to determine the microbiological quality of particulate matter (PM) in an urban area in Jeddah, Saudi Arabia, during December 2012 to April 2013. This was achieved by the determination of airborne bacteria, fungi, and actinobacteria associated PM10 and PM2.5, as well as their relationships with gaseous pollutants, O3, SO2 and NO2, and meteorological factors (T°C, RH% and Ws). High volume samplers with PM10 and PM2.5 selective sizes, and glass fiber filters were used to collect PM10 and PM2.5, respectively. The filters were suspended in buffer phosphate and aliquots were spread plated onto the surfaces of trypticase soy agar, malt extract agar, and starch casein agar media for counting of bacteria, fungi and actinobacteria-associated PM, respectively. PM10 and PM2.5 concentrations averaged 159.9 μg/m(3) and 60 μg/m(3), respectively, with the ratio of PM2.5/PM10 averaged ~0.4. The concentrations of O3, SO2 and NO2 averaged 35.73 μg/m(3), 38.1μg/m(3) and 52.5 μg/m(3), respectively. Fungi and actinobacteria associated PM were found in lower concentrations than bacteria. The sum of microbial loads was higher in PM10 than PM2.5, however a significant correlation (r=0.57, P ≤ 0.05) was found between the sum of microbial loads associated PM10 and PM2.5. Aspergillus fumigatus and Aspergillus niger were the common fungal types associated PM. Temperature significantly correlated with both PM10 (r=0.44), and PM2.5 (r=0.5). Significant negative correlations were found between O3 and PM2.5 (r=-0.47), and between SO2 with PM10 (r=-0.48). Wind speed positively correlated with airborne microorganisms associated PM. The regression model showed that the inverse PM2.5 concentration (1/PM2.5) was a significant determinant of fungal count associated PM. Chemical processes and environmental factors could affect properties of PM and in turn its biological quality.

  2. Gastroschisis and associated defects: an international study.

    LENUS (Irish Health Repository)

    Mastroiacovo, Pierpaolo

    2007-04-01

    Our objective was to evaluate the frequency and type of malformations associated with gastroschisis in a large pool of international data, to identify malformation patterns, and to evaluate the role of maternal age in non-isolated cases. Case-by-case information from 24 registries, all members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), were evaluated. After the exclusion of other abdominal wall defects cases were classified as: (a) isolated; (b) recognizable syndrome, chromosomal or not; (c) multiple congenital anomalies (MCA). Our results showed that out of 3,322 total cases 469 non-isolated cases were registered (14.1%): 41 chromosomal syndromes, 24 other syndromes, and 404 MCA. Among MCA four groups of anomalies were most frequent: CNS (4.5%), cardio-vascular (2.5%), limb (2.2%), and kidney anomalies (1.9%). No similar patterns emerged except two patterns resembling limb-body wall complex and OEIS. In both of them the gastroschisis could be however misclassified. Chromosomal trisomies and possibly non-syndromic MCA are associated with an older maternal age more than isolated cases. On consideration of our data and the most valid studies published in the literature, the best estimate of the proportion of gastroschisis associated with major unrelated defects is about 10%, with a few cases associated to recognizable syndromes. Recognized syndromes with gastroschisis seem to be so exceptional that the well documented and validated cases are worth being published as interesting case report. An appropriate case definition in etiological studies should include only isolated gastroschisis after an appropriate definition of isolated and non-isolated cases and a thorough case-by-case review.

  3. Multiple Intelligences (MI of Associate in Hotel and Restaurant Management Students & Its Implication to the Teaching of Oral Communication

    Directory of Open Access Journals (Sweden)

    Juvy G. Mojares

    2015-11-01

    Full Text Available A number of educators argue that MI helps students build positive attitudes toward learning in English class. A study says that “Students who are using their areas of strength to learn feel more competent and confident and enjoy the challenge of acquiring new information”. This study sought to find out the MI of selected Associate in Hotel and Restaurant Management (AHRMstudents. It also delved on the implication of MI to the teaching of the subject. The research design used was basically a descriptive method employing an adopted MI survey form administered to Oral Communication students. There were five sections of second year AHRM students. Out of 196 students, 111 were selected to answer the survey questions by the use of the combination of stratified random sampling and the Slovin’s formula. Results showed that the top three intelligences the respondents have based on their scores are intrapersonal, followed by bodily/kinesthetic and logical/mathematical intelligences; least of the intelligences are verbal/linguistic and visual/spatial.This implied that teaching of Oral Communication should nurture the intrapersonal intelligence and more importantly should enhance and develop the verbal strength of the AHRM students. Teaching should focus more on improving communication skills with others, and not just within themselves.

  4. Arab Teens Lifestyle Study (ATLS: objectives, design, methodology and implications

    Directory of Open Access Journals (Sweden)

    Musaiger AO; ATLS Research Group

    2011-12-01

    Full Text Available Hazzaa M Al-Hazzaa1,2, Abdulrahman O Musaiger3, ATLS Research Group1Exercise Physiology Laboratory, Department of Physical Education and Movement Sciences, College of Education, King Saud University, 2Scientific Board, Obesity Research Chair, King Saud University, Riyadh, Saudi Arabia; 3Arab Center for Nutrition, Manama, Bahrain, and Nutrition and Health Studies Unit, Deanship of Scientific Research, University of Bahrain, BahrainBackground: There is a lack of comparable data on physical activity, sedentary behavior, and dietary habits among Arab adolescents, which limits our understanding and interpretation of the relationship between obesity and lifestyle parameters. Therefore, we initiated the Arab Teens Lifestyle Study (ATLS. The ATLS is a multicenter collaborative project for assessing lifestyle habits of Arab adolescents. The objectives of the ATLS project were to investigate the prevalence rates for overweight and obesity, physical activity, sedentary activity and dietary habits among Arab adolescents, and to examine the interrelationships between these lifestyle variables. This paper reports on the objectives, design, methodology, and implications of the ATLS.Design/Methods: The ATLS is a school-based cross-sectional study involving 9182 randomly selected secondary-school students (14–19 years from major Arab cities, using a multistage stratified sampling technique. The participating Arab cities included Riyadh, Jeddah, and Al-Khobar (Saudi Arabia, Bahrain, Dubai (United Arab Emirates, Kuwait, Amman (Jordan, Mosel (Iraq, Muscat (Oman, Tunisia (Tunisia and Kenitra (Morocco. Measured variables included anthropometric measurements, physical activity, sedentary behavior, sleep duration, and dietary habits.Discussion: The ATLS project will provide a unique opportunity to collect and analyze important lifestyle information from Arab adolescents using standardized procedures. This is the first time a collaborative Arab project will

  5. BigR, a Transcriptional Repressor from Plant-Associated Bacteria, Regulates an Operon Implicated in Biofilm Growth▿

    OpenAIRE

    Barbosa, Rosicler L.; Benedetti, Celso E.

    2007-01-01

    Xylella fastidiosa is a plant pathogen that colonizes the xylem vessels, causing vascular occlusion due to bacterial biofilm growth. However, little is known about the molecular mechanisms driving biofilm formation in Xylella-plant interactions. Here we show that BigR (for “biofilm growth-associated repressor”) is a novel helix-turn-helix repressor that controls the transcription of an operon implicated in biofilm growth. This operon, which encodes BigR, membrane proteins, and an unusual beta...

  6. First Amendment Implications of Harassment Rules to Be Studied.

    Science.gov (United States)

    Jaschik, Scott

    1994-01-01

    The Department of Education, criticized by colleges for its guidelines on investigating racial harassment and hate-speech charges, will issue a new policy on First Amendment implications of such inquiries. A major issue is school responsibility for racial harassment by diverse populations over whom colleges may have little control. (MSE)

  7. Diagnostic implications of associated defects in patients with typical orofacial clefts

    Directory of Open Access Journals (Sweden)

    Isabella L. Monlleó

    2015-10-01

    Full Text Available ABSTRACT OBJECTIVES: To describe prevalence of associated defects and clinical-genetic characteristics of patients with typical orofacial clefts seen at a reference genetic service. METHODS: Descriptive study conducted between September of 2009 and July of 2014. Two experienced dysmorphologists personally collected and coded clinical data using a validated, standard multicenter protocol. Syndromic cases were defined by the presence of four or more minor defects, one or more major defects, or recognition of a specific syndrome. Fisher's exact and Kruskal-Wallis tests were used for statistics. RESULTS: Among 141 subjects, associated defects were found in 133 (93%, and 84 (59.5% were assigned as syndromic. Cleft palate was statistically associated with a greater number of minor defects (p < 0.0012 and syndromic assignment (p < 0.001. Syndromic group was associated with low birth weight (p < 0.04 and less access to surgical treatment (p < 0.002. There was no statistical difference between syndromic and non-syndromic groups regarding gender (p < 0.55, maternal age of 35 years and above (p < 0.50, alcohol (p < 0.50 and tobacco consumption (p < 0.11, consanguinity (p < 0.59, recurrence (p < 0.08, average number of pregnancies (p < 0.32, and offspring (p < 0.35. CONCLUSIONS: There is a lack of information on syndromic clefts. The classification system for phenotype assignment adopted in this study has facilitated recognition of high prevalence of associated defects and syndromic cases. This system may be a useful strategy to gather homogeneous samples, to elect appropriate technologies for etiologic and genotype-phenotype approaches, and to assist with multiprofessional care and genetic counseling.

  8. Gendered risk perceptions associated with human-wildlife conflict: implications for participatory conservation.

    Science.gov (United States)

    Gore, Meredith L; Kahler, Jessica S

    2012-01-01

    This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1) gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC) in a participatory conservation context, and (2) highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2) to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38) to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting) dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities. PMID:22403722

  9. Gendered risk perceptions associated with human-wildlife conflict: implications for participatory conservation.

    Directory of Open Access Journals (Sweden)

    Meredith L Gore

    Full Text Available This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1 gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC in a participatory conservation context, and (2 highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal conservancies in Caprivi, Namibia served as case study sites. We analyzed data from focus groups (n = 2 to create gendered concept maps about risks to wildlife and livelihoods and any associations of those risks with HWC, and semi-structured interviews (n = 76; men = 38, women = 38 to measure explicit risk attitudes associated with HWC. Concept maps indicated some divergent perceptions in how groups characterized risks to wildlife and livelihoods; however, not only were identified risks to wildlife (e.g., pollution, hunting dissimilar in some instances, descriptions of risks varied as well. Study groups reported similar risk perceptions associated with HWC with the exception of worry associated with HWC effects on local livelihoods. Gendered differences in risk perceptions may signal different priorities or incentives to participate in efforts to resolve HWC-related risks. Thus, although shared goals and interests may seem to be an obvious reason for cooperative wildlife management, it is not always obvious that management goals are shared. Opportunity exists to move beyond thinking about gender as an explanatory variable for understanding how different groups think about participating in conservation activities.

  10. The implications of trade liberalization for diet and health: a case study from Central America

    Directory of Open Access Journals (Sweden)

    Hawkes Corinna

    2009-07-01

    Full Text Available Abstract Background Central America has undergone extensive trade liberalization over the past two decades, and has recently signed a Free Trade Agreement with the United States. The region is also experiencing a dual burden of malnutrition with the growth of dietary patterns associated with the global 'nutrition transition'. This study describes the relationship between trade liberalization policies and food imports and availability, and draws implications for diet and health, using Central America as a case study region. Methods Changes in tariff and non-tariff barriers for each country were documented, and compared with time-series graphs of import, production and availability data to show the outcome of changes in trade policy in relation to food imports and food availability. Results Changes in trade policy in Central America have directly affected food imports and availability via three avenues. First, the lowering of trade barriers has promoted availability by facilitating higher imports of a wide range of foods. Second, trade liberalization has affected food availability through promoting domestic meat production. Third, reductions in barriers to investment appear to be critical in expansion of processed food markets. This suggests that changes in trade policies have facilitated rising availability and consumption of meat, dairy products, processed foods and temperate (imported fruits in Central America. Conclusion This study indicates that the policies of trade liberalization in Central American countries over the past two decades, particularly in relation to the United States, have implications for health in the region. Specifically, they have been a factor in facilitating the "nutrition transition", which is associated with rising rates of obesity and chronic diseases such as cardiovascular disease and cancer. Given the significant cost of chronic disease for the health care system, individuals and the wider community, it is critical

  11. Mutations in presenilin 2 and its implications in Alzheimer’s disease and other dementia-associated disorders

    Directory of Open Access Journals (Sweden)

    Cai Y

    2015-07-01

    Full Text Available Yan Cai,1 Seong Soo A An,1 SangYun Kim2 1Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, 2Department of Neurology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, South Korea Abstract: Alzheimer’s disease (AD is the most common form of dementia. Mutations in the genes encoding presenilin 1 (PSEN1, presenilin 2 (PSEN2, and amyloid precursor protein have been identified as the main genetic causes of familial AD. To date, more than 200 mutations have been described worldwide in PSEN1, which is highly homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We performed a systematic review of studies describing the mutations identified in PSEN2. Most PSEN2 mutations were detected in European and in African populations. Only two were found in Korean populations. Interestingly, PSEN2 mutations appeared not only in AD patients but also in patients with other disorders, including frontotemporal dementia, dementia with Lewy bodies, breast cancer, dilated cardiomyopathy, and Parkinson’s disease with dementia. Here, we have summarized the PSEN2 mutations and the potential implications of these mutations in dementia-associated disorders. Keywords: mutations in presenilin 2, Alzheimer’s disease

  12. Genome-wide association study identifies five new schizophrenia loci.

    LENUS (Irish Health Repository)

    Ripke, Stephan

    2011-10-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).

  13. The Association between Dietary Energy Density and Type 2 Diabetes in Europe : Results from the EPIC-InterAct Study

    NARCIS (Netherlands)

    van den Berg, Saskia W.; van der A, Daphne L.; Spijkerman, Annemieke M. W.; van Woudenbergh, Geertruida J.; Tijhuis, Mariken J.; Amiano, Pilar; Ardanaz, Eva; Beulens, Joline W. J.; Boeing, Heiner; Clavel-Chapelon, Francoise; Crowe, Francesca L.; de Lauzon-Guillain, Blandine; Fagherazzi, Guy; Franks, Paul W.; Freisling, Heinz; Gonzalez, Carlos; Grioni, Sara; Halkjaer, Jytte; Maria Huerta, Jose; Huybrechts, Inge; Kaaks, Rudolf; Khaw, Kay Tee; Masala, Giovanna; Nilsson, Peter M.; Overvad, Kim; Panico, Salvatore; Ramon Quiros, J.; Rolandsson, Olov; Sacerdote, Carlotta; Sanchez, Maria-Jose; Schulze, Matthias B.; Slimani, Nadia; Struijk, Ellen A.; Tjonneland, Anne; Tumino, Rosario; Sharp, Stephen J.; Langenberg, Claudia; Forouhi, Nita G.; Feskens, Edith J. M.; Riboli, Elio; Wareham, Nicholas J.

    2013-01-01

    Background: Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited evidence exists. Therefore, we investigated the association

  14. The association between dietary energy density and type 2 diabetes in Europe: results form the EPIC-InterAct Study

    NARCIS (Netherlands)

    The InterAct Consortium, A.; Groenendijk-van Woudenbergh, G.J.; Feskens, E.J.M.

    2013-01-01

    Background Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited evidence exists. Therefore, we investigated the association

  15. HPV Literacy and Associated Factors Among Hmong American Immigrants: Implications for Reducing Cervical Cancer Disparity.

    Science.gov (United States)

    Beltran, Raiza; Simms, Tina; Lee, Hee Yun; Kwon, Melissa

    2016-06-01

    Previous studies show that certain minority and ethnic communities experience low human papillomavirus (HPV) vaccination rates despite a higher cervical cancer burden. HPV is known to be responsible for almost all cervical cancer cases. Hmong Americans, a growing Asian American population, appear to be at increased risk. The cervical cancer incidence rate among Hmong American women is three times higher than other Asian/Pacific Islanders and more than four times higher than Non-Hispanic Whites. Despite such alarming statistics, there is limited research focusing on HPV literacy and its associated factors in the Hmong American community. This study's objectives are to investigate: (1) the level of HPV knowledge among Hmong Americans; (2) HPV vaccination initiation and completion rates of Hmong Americans; and (3) factors associated with HPV literacy in the Hmong American community. Andersen's Behavioral Model of Health Services Use was used as the study's theoretical framework. A self-administered paper and online health survey was completed by192 Hmong Americans living in a major metropolitan area in Minnesota. Results revealed a mean score of 4.76 (SD 1.67) for the 7-item questionnaire measuring HPV knowledge. The HPV vaccination initiation rate was 46.3 % (n = 56), with 32.7 % completing the recommended three doses. Multiple regression analysis found that participants' level of education, number of doctor visits, and cervical cancer screening literacy were significantly associated with HPV knowledge. This study's results indicate the important role of health providers in educating Hmong Americans patients about HPV and cervical cancer prevention to decrease the cervical cancer burden in this high-risk population. PMID:26696118

  16. Implications of flexible work systems for work studies.

    Science.gov (United States)

    Kogi, K

    1997-12-01

    The relationship between changing work systems and work study methods is discussed by focusing on a recent trend toward more flexible work systems in different countries. These systems are commonly characterized by (a) uncoupling of working hours from business hours, (b) combining different atypical work forms and (c) individualized work patterns. Increased flexibility in working patterns is demanded because business hours may be covered by different workers and because special arrangements become necessary for unpopular shifts or linking separate jobs. Changes in work systems seem more successful when they are associated with (a) multiskilled work, (b) independent task implementation, (c) networked communication, (d) balanced or adjusted workload, and (e) accommodation of workers' preferences. Special attention is drawn to safety and health concerns and work-life effects. Many intervention studies done for work improvement are paying attention to multifaceted work aspects, locally available options, and participation by people. All these elements are important because prepackaged solutions do not exist. The following three views seem especially useful for action-oriented work studies: 1) Look at multiple aspects of the work, including work content and atypical work forms; 2) Know worker preferences and available options; and 3) Take into account work elements that may not be well defined, but important from local points of view. It is envisioned that these studies can provide support for a well-informed participatory process of work system changes in each local context.

  17. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies.

    Directory of Open Access Journals (Sweden)

    Martin Köbel

    2008-12-01

    Full Text Available BACKGROUND: Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. METHODS AND FINDINGS: In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1 in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognostic marker in the entire cohort (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.2%-2.4% but is not of prognostic significance within any subtype. Prognostic associations can even show an inverse correlation within the entire cohort, when compared to a specific subtype. For example, WT1 is more frequently expressed in high-grade serous carcinomas, an aggressive subtype, and is an unfavourable prognostic marker within the entire cohort of ovarian carcinomas (RR 1.7, 95% CI 1

  18. Urban river restoration: implications on channel sedimentation patterns and associated ecosystem and human health

    Science.gov (United States)

    Gibbs, H.; Gurnell, A.; Heppell, K.; Spencer, K.

    2012-04-01

    the restored as opposed to the unrestored stretch at both sites, and this difference persisted after standardisation to loading/m2 of channel to account for differing channel dimensions. Metal concentrations at the two sites were analysed using sediment quality guidelines to assess the potential impact upon both the aquatic ecosystem (Environment Agency draft freshwater quality guidelines, 2008) and human health (Dutch Intervention Values for human, plant and/or animal life, 2009). Greater exceedances occurred for the ecological rather than the human health guidelines. Cu, Ni, Pb and Zn were of greatest concern in terms of ecological sediment quality at Sutcliffe Park and Pb and Zn at Chinbrook Meadows. At Sutcliffe Park a greater proportion of samples exceeded the Predicted Effects Level (PEL) in the restored as opposed to the unrestored stretch; conversely at Chinbrook Meadows a greater proportion of samples in the unrestored stretch as opposed to the restored stretch exceeded the PEL. In terms of human health, exceedances only occurred for Cu and Zn at Sutcliffe Park, with the greater proportion being in the restored stretch. The results from this research will have implications for the design, management and maintenance of restored urban rivers in terms of fine sediment accumulation assessment, its quality and the associated potential impact upon ecosystem and human health.

  19. Divergent associations of height with cardiometabolic disease and cancer: epidemiology, pathophysiology, and global implications.

    Science.gov (United States)

    Stefan, Norbert; Häring, Hans-Ulrich; Hu, Frank B; Schulze, Matthias B

    2016-05-01

    Among chronic non-communicable diseases, cardiometabolic diseases and cancer are the most important causes of morbidity and mortality worldwide. Although high BMI and waist circumference, as estimates of total and abdominal fat mass, are now accepted as predictors of the increasing incidence of these diseases, adult height, which also predicts mortality, has been neglected. Interestingly, increasing evidence suggests that height is associated with lower cardiometabolic risk, but higher cancer risk, associations supported by mendelian randomisation studies. Understanding the complex epidemiology, biology, and pathophysiology related to height, and its association with cardiometabolic diseases and cancer, is becoming even more important because average adult height has increased substantially in many countries during recent generations. Among the mechanisms driving the increase in height and linking height with cardiometabolic diseases and cancer are insulin and insulin-like growth factor signalling pathways. These pathways are thought to be activated by overnutrition, especially increased intake of milk, dairy products, and other animal proteins during different stages of child development. Limiting overnutrition during pregnancy, early childhood, and puberty would avoid not only obesity, but also accelerated growth in children-and thus might reduce risk of cancer in adulthood. PMID:26827112

  20. Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages

    OpenAIRE

    Markakis, Konstantinos P.; Koropouli, Maria K.; Grammenou-Savvoglou, Stavroula; van Winden, Ewoud C.; Dimitriou, Andromaxi A.; Demopoulos, Constantinos A.; Tselepis, Alexandros D; Kotsifaki, Eleni E.

    2010-01-01

    Recognition and uptake of oxidized LDL (oxLDL) by scavenger receptors of macrophages and foam cell formation are mediated by the oxidatively modified apolipoprotein B (ApoB) and lipid moiety of oxLDL. A great amount of oxidized phosphatidylcholine (oxPC) of oxLDL is hydrolyzed at the sn-2 position by lipoprotein associated phospholipase A2 (Lp-PLA2) to lysophosphatidylcholine and small oxidation products. This study examines the involvement of Lp-PLA2 in the uptake of oxLDL by mouse peritonea...

  1. Calcium intake and hypertension among obese adults in United States: associations and implications explored.

    Science.gov (United States)

    Chen, Y; Strasser, S; Cao, Y; Wang, K-S; Zheng, S

    2015-09-01

    The relationship between calcium intake and hypertension is receiving increased research attention. The prevalence of hypertension is high among the obese populations. Calcium is a mineral that influences blood pressure. The aim of the study was to examine the association between calcium intake and hypertension in a large nationally representative sample of obese American adults. A total of 14,408 obese adults aged 20 years or older were obtained from the 1999-2010 National Health and Nutrition Examination Survey. Analysis of variance and linear regression models were used to examine relationships between calcium intake and systolic blood pressure (SBP) as well as diastolic blood pressure (DBP). Multiple logistic regression models were used to examine the association between calcium intake and hypertension after adjusting for potential confounders and interactions, including: age, race, education level, alcohol use, smoking, diabetes status, sodium intake and potassium intake. Calcium intake was significantly lower for the hypertensive group compared with the normotensive group (Pobese female young adults aged 20-44 years and among non-diabetic obese adults. Based on ordinary linear regression analysis, a significant inverse relationship was detected, SBP and DBP decreased if calcium intake increased (SBP: regression coefficient estimate=-0.015, Pintake was negatively associated with the probability of hypertension (odds ratio (OR)=0.81, 95% confidence interval (CI): 0.74-0.87, Pintake in youngest adults (age 20-44 years) had the lowest likelihood of hypertension (OR=0.77, 95% CI: 0.64-0.93, Pintake and probability of hypertension was stronger among females (OR: 0.68, 95% CI: 0.55-0.84, Pobese adults. The protective effect of calcium intake and hypertension was found significantly in obese non-diabetic adults (OR: OR=0.77, 95% CI: 0.67-0.89, Pobese diabetic adults. SBP, DBP and calcium intake were log transformed for both ordinary linear regression analysis and

  2. Quantifying shark distribution patterns and species-habitat associations: implications of marine park zoning.

    Directory of Open Access Journals (Sweden)

    Mario Espinoza

    Full Text Available Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS along the entire Great Barrier Reef Marine Park (GBRMP over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances. Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation

  3. Quantifying shark distribution patterns and species-habitat associations: implications of marine park zoning.

    Science.gov (United States)

    Espinoza, Mario; Cappo, Mike; Heupel, Michelle R; Tobin, Andrew J; Simpfendorfer, Colin A

    2014-01-01

    Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances). Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites) relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation approaches. PMID

  4. Quantifying shark distribution patterns and species-habitat associations: implications of marine park zoning.

    Science.gov (United States)

    Espinoza, Mario; Cappo, Mike; Heupel, Michelle R; Tobin, Andrew J; Simpfendorfer, Colin A

    2014-01-01

    Quantifying shark distribution patterns and species-specific habitat associations in response to geographic and environmental drivers is critical to assessing risk of exposure to fishing, habitat degradation, and the effects of climate change. The present study examined shark distribution patterns, species-habitat associations, and marine reserve use with baited remote underwater video stations (BRUVS) along the entire Great Barrier Reef Marine Park (GBRMP) over a ten year period. Overall, 21 species of sharks from five families and two orders were recorded. Grey reef Carcharhinus amblyrhynchos, silvertip C. albimarginatus, tiger Galeocerdo cuvier, and sliteye Loxodon macrorhinus sharks were the most abundant species (>64% of shark abundances). Multivariate regression trees showed that hard coral cover produced the primary split separating shark assemblages. Four indicator species had consistently higher abundances and contributed to explaining most of the differences in shark assemblages: C. amblyrhynchos, C. albimarginatus, G. cuvier, and whitetip reef Triaenodon obesus sharks. Relative distance along the GBRMP had the greatest influence on shark occurrence and species richness, which increased at both ends of the sampling range (southern and northern sites) relative to intermediate latitudes. Hard coral cover and distance across the shelf were also important predictors of shark distribution. The relative abundance of sharks was significantly higher in non-fished sites, highlighting the conservation value and benefits of the GBRMP zoning. However, our results also showed that hard coral cover had a large effect on the abundance of reef-associated shark species, indicating that coral reef health may be important for the success of marine protected areas. Therefore, understanding shark distribution patterns, species-habitat associations, and the drivers responsible for those patterns is essential for developing sound management and conservation approaches.

  5. Spatial scales of foraging in fallow deer: Implications for associational effects in plant defences

    Science.gov (United States)

    Rautio, Pasi; Kesti, Kari; Bergvall, Ulrika A.; Tuomi, Juha; Leimar, Olof

    2008-07-01

    Large herbivores select food at several spatial scales: plant communities are chosen at a landscape scale, plant patches are chosen within a plant community, and individual plants within a patch. Foraging decision at the patch level can result in associational effects in plant communities and populations. Several studies have shown that herbivore attack and consumption rates may not only depend on a plant's own defence traits, but also on the defence traits of its neighbours. In the present experiment we investigated whether the spatial scale of the food distribution affects food selection by fallow deer and whether the foraging behaviour gives rise to associational effects in plant defences. In a population of captured wild fallow deer we simulated a natural situation where two separate plant patches are exposed to intense herbivory pressure. We presented different spatial arrangements of low- and high-tannin food to the deer, varying the frequency of the feeder types within and between patches. We found that the deer consumed palatable food among the unpalatable food on average as much as they consumed palatable food among other palatable feeders. However, when unpalatable food occurred among the palatable food it was more consumed than among other unpalatable feeders. Hence, we did not find support for associational defence, but our results supported associational susceptibility. At the between patch level a patch of mainly high-tannin feeders was consumed less when presented near to a patch of mainly low-tannin feeders, suggesting that for well-defended plants having palatable neighbours in a nearby patch might accentuate the effectiveness of their defence.

  6. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  7. A NOS1 variant implicated in cognitive performance influences evoked neural responses during a high density EEG study of early visual perception.

    LENUS (Irish Health Repository)

    O'Donoghue, Therese

    2012-05-01

    The nitric oxide synthasase-1 gene (NOS1) has been implicated in mental disorders including schizophrenia and variation in cognition. The NOS1 variant rs6490121 identified in a genome wide association study of schizophrenia has recently been associated with variation in general intelligence and working memory in both patients and healthy participants. Whether this variant is also associated with variation in early sensory processing remains unclear.

  8. Arsenic toxicity to cladocerans isolated and associated with iron: implications for aquatic environments

    Directory of Open Access Journals (Sweden)

    SUELLEN C.M. SALES

    2016-01-01

    Full Text Available ABSTRACT Arsenic is an ametal ubiquitous in nature and known by its high toxicity. Many studies have tried to elucidate the arsenic metabolism in the cell and its impact to plants, animals and human health. In aqueous phase, inorganic arsenic is more common and its oxidation state (As III and As V depends on physical and chemical environmental conditions. The aim of this study was to evaluate toxicity of arsenic to Daphnia similis and Ceriodaphnia silvestrii, isolated and associated with iron. The results showed differences in toxicity of As III and As V to both species. Effective concentration (EC50 mean values were 0.45 mg L-1 (As III and 0.54 mg L-1 (As V for D. similis, and 0.44 mg L-1 (As III and 0.69 mg L-1 (As V for C. silvestrii. However, As V IC25 mean value was 0.59 mg L-1, indicating that C. silvestrii has mechanisms to reduce arsenic toxicity. On the other hand, when associated with iron at 0.02 and 2.00 mg L-1, EC50 values decreased for D. similis (0.34 and 0.38 mg L-1 as well as C. silvestrii (0.37 and 0.37 mg L-1, showing synergistic effect of these substances.

  9. SYSTEMIC INFLAMMATION IMPAIRS ATTENTION AND COGNITIVE FLEXIBILITY BUT NOT ASSOCIATIVE LEARNING IN AGED RATS: Possible Implications for Delirium

    Directory of Open Access Journals (Sweden)

    Deborah J Culley

    2014-06-01

    Full Text Available Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 ug/kg or saline and were tested on the attentional shifting task (AST, an index of integrity of the prefrontal cortex, on days 1-3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24-48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly 3-fold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.

  10. A Contrastive Study of Reiteration between Chinese and English and its Implications on Translation Practice

    Institute of Scientific and Technical Information of China (English)

    杨星

    2009-01-01

    Through conducting comparisons in the occurrence and frequency of reiteration between Chinese and English, this paper tries to find out the laws underlying the discrepancies and thus provides implications for translation practice. Contrastive study of reiteration between Chinese and English provides us with insightful implications for translation practice. With the abundant analysis and research in this essay, I hope that the study of Reiteration can be emphasized.

  11. Joint linkage and association analysis with exome sequence data implicates SLC25A40 in hypertriglyceridemia.

    Science.gov (United States)

    Rosenthal, Elisabeth A; Ranchalis, Jane; Crosslin, David R; Burt, Amber; Brunzell, John D; Motulsky, Arno G; Nickerson, Deborah A; Wijsman, Ellen M; Jarvik, Gail P

    2013-12-01

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ~35 known single-nucleotide variants (SNVs) that explain only ~10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants.

  12. KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease.

    Science.gov (United States)

    Levinson, Ralph D; Yung, Madeline; Meguro, Akira; Ashouri, Elham; Yu, Fei; Mizuki, Nobuhisa; Ohno, Shigeaki; Rajalingam, Raja

    2016-01-01

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher's exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral

  13. KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease

    Science.gov (United States)

    Levinson, Ralph D.; Yung, Madeline; Meguro, Akira; Ashouri, Elham; Yu, Fei; Mizuki, Nobuhisa; Ohno, Shigeaki

    2016-01-01

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher’s exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral

  14. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  15. Age-associated decreases in human DNA repair capacity: Implications for the skin

    OpenAIRE

    Hadshiew, Ina M.; Eller, Mark S; Gilchrest, Barbara A.

    1999-01-01

    Multiple pathways are involved in accurate synthesis and distribution of DNA during replication, repair and maintenance of genomic integrity. An increased error rate, abovethe spontaneous mutation baseline, has been implicated in carcinogenesis and aging. Moreover, cytogenetic abnormalities are increased in Down’s, Edwards’, Patau’s, and Klinefelter’s syndromes with increasing maternal age, and in Marfan’s and Apert’s syndromes with paternal age. In response to DNA damage, multiple overlappin...

  16. Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions

    OpenAIRE

    Hassan, Waseem; Silva, Carlos Eduardo Barroso; Mohammadzai, Imdad Ullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J.

    2014-01-01

    Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe] and copper [Cu]), is an underlying cause of various neurodegenerative diseases. These reactive species are an inevitable by-product of cellular respiration or other metabolic processes that may cause the oxidation of lipids, nucleic acids, and proteins. Oxidative stress has recently been implicated in depression and anxiety-related di...

  17. A cross-sectional study of factors associated with adolescent sexual activity

    OpenAIRE

    Shashikumar, R.; R C Das; Prabhu, H. R. A.; K Srivastava; Bhat, P.S.; Prakash, J.; Seema, P.

    2012-01-01

    Context: Adolescents constitute about 20% of our population and increasingly more of them are initiating sexual activity at an early age. Several behaviors associated with adolescence like masturbation, expression of masculinity/femininity, lifestyle habits like attending late night parties, and consumption of alcohol have been variously implicated in initiating sexual activities. Sexual abuse can also lead to premature sexualization. In view of few worthwhile studies from India that have dea...

  18. Prevalence and associated factors of Schistosomiasis among children in Yemen: implications for an effective control programme.

    Directory of Open Access Journals (Sweden)

    Hany Sady

    Full Text Available BACKGROUND: Schistosomiasis, one of the most prevalent neglected tropical diseases, is a life-threatening public health problem in Yemen especially in rural communities. This cross-sectional study aims to determine the prevalence and associated risk factors of schistosomiasis among children in rural Yemen. METHODS/FINDINGS: Urine and faecal samples were collected from 400 children. Urine samples were examined using filtration technique for the presence of Schistosoma haematobium eggs while faecal samples were examined using formalin-ether concentration and Kato Katz techniques for the presence of S. mansoni. Demographic, socioeconomic and environmental information were collected via a validated questionnaire. Overall, 31.8% of the participants were found to be positive for schistosomiasis; 23.8% were infected with S. haematobium and 9.3% were infected with S. mansoni. Moreover, 39.5% of the participants were anaemic whereas 9.5% had hepatosplenomegaly. The prevalence of schistosomiasis was significantly higher among children aged >10 years compared to those aged ≤ 10 years (P<0.05. Multivariate analysis confirmed that presence of other infected family member (P<0.001, low household monthly income (P = 0.003, using unsafe sources for drinking water (P = 0.003, living nearby stream/spring (P = 0.006 and living nearby pool/pond (P = 0.002 were the key factors significantly associated with schistosomiasis among these children. CONCLUSIONS/SIGNIFICANCE: This study reveals that schistosomiasis is still highly prevalent in Yemen. These findings support an urgent need to start an integrated, targeted and effective schistosomiasis control programme with a mission to move towards the elimination phase. Besides periodic drug distribution, health education and community mobilisation, provision of clean and safe drinking water, introduction of proper sanitation are imperative among these communities in order to curtail the transmission and morbidity caused

  19. Entrepreneurship Education at Tertiary Education Level: Implication to Historical Studies

    Directory of Open Access Journals (Sweden)

    Salahu Mohammed Lawal

    2012-07-01

    Full Text Available Nigeria is richly endowed with both human and material resources that when well utilized can make her one of the richest and developed nation in the world.  But poor utilization of the resources, corruption and dwindling fortune in her education system made her among the first twenty five poorest nations in the world.  Similarly, report shows that 26% of the employable population remained unemployed.  This called for the need for entrepreneurship education most especially at tertiary level where high level manpower is supposed to be trained.  It is on this premise that the paper attempts to examine entrepreneurship education and its implication to history students and graduates.

  20. Rift Valley fever virus-infected mosquito ova and associated pathology: possible implications for endemic maintenance

    Directory of Open Access Journals (Sweden)

    Romoser WS

    2011-09-01

    Full Text Available William S Romoser1, Marco Neira Oviedo1, Kriangkrai Lerdthusnee2, Lisa A Patrican3, Michael J Turell4, David J Dohm4, Kenneth J Linthicum5, Charles L Bailey61Department of Biomedical Sciences, College of Osteopathic Medicine, Tropical Disease Institute, Ohio University, Athens, Ohio, USA; 2Department of Entomology, Faculty of Agriculture, Kasetsart University, Bangkok, Thailand; 3Infectious Disease Division, National Center for Medical Intelligence, Fort Detrick, Frederick, Maryland, USA; 4Department of Vector Assessment, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA; 5Center for Medical, Agricultural, and Veterinary Entomology, United States Department of Agriculture – Agricultural Research Service, Gainesville, Florida, USA; 6National Center for Biodefense and Infectious Disease, School of Systems Biology, College of Science, George Mason University, Manassas, Virginia, USABackground: Endemic/enzootic maintenance mechanisms like vertical transmission (pathogen passage from infected adults to their offspring are central in the epidemiology of zoonotic pathogens. In Kenya, Rift Valley fever virus (RVFV may be maintained by vertical transmission in ground-pool mosquitoes such as Aedes mcintoshi. RVFV can cause serious morbidity and mortality in humans and livestock. Past epidemics/epizootics have occurred in sub-Saharan Africa but, since the late 1970s, RVFV has also appeared in North Africa and the Middle East. Preliminary results revealed RVFV-infected eggs in Ae. mcintoshi after virus injection into the hemocoel after the first of two blood meals, justifying further study.Methods: Mosquitoes were collected from an artificially flooded water-catching depression along a stream in Kenya, shipped live to the USA, and studied using an immunocytochemical method for RVFV-antigen localization in mosquito sections.Results and conclusion: After virus injection into the

  1. Contrasting movements and connectivity of reef-associated sharks using acoustic telemetry: implications for management.

    Science.gov (United States)

    Espinoza, Mario; Lédée, Elodie J I; Simpfendorfer, Colin A; Tobin, Andrew J; Heupel, Michelle R

    2015-12-01

    Understanding the efficacy of marine protected areas (MPAs) for wide-ranging predators is essential to designing effective management and conservation approaches. The use of acoustic monitoring and network analysis can improve our understanding of the spatial ecology and functional connectivity of reef-associated species, providing a useful approach for reef-based conservation planning. This study compared and contrasted the movement and connectivity of sharks with different degrees of reef association. We examined the residency, dispersal, degree of reef connectivity, and MPA use of grey reef (Carcharhinus amblyrhynchos), silvertip (C. albimarginatus), and bull (C. leucas) sharks monitored in the central Great Barrier Reef (GBR). An array of 56 acoustic receivers was used to monitor shark movements on 17 semi-isolated reefs. Carcharhinus amblyrhynchos and C. albimarginatus were detected most days at or near their tagging reef. However, while C. amblyrhynchos spent 80% of monitoring days in the array, C. albimarginatus was only detected 50% of the time. Despite both species moving similar distances (long-range migrations to other arrays in the GBR. Networks derived for C. leucas were larger and more complex than those for C. amblyrhynchos and C. albimarginatus. Our findings suggest that protecting specific reefs based on prior knowledge (e.g., healthier reefs with high fish biomass) and increasing the level of protection to include nearby, closely spaced reef habitats (ranging sharks like C. leucas, a combination of spatial planning and other alternative measures is critical. Our findings demonstrate that acoustic monitoring can serve as a useful platform for designing more effective MPA networks for reef predators displaying a range of movement patterns. PMID:26910942

  2. Contrasting movements and connectivity of reef-associated sharks using acoustic telemetry: implications for management.

    Science.gov (United States)

    Espinoza, Mario; Lédée, Elodie J I; Simpfendorfer, Colin A; Tobin, Andrew J; Heupel, Michelle R

    2015-12-01

    Understanding the efficacy of marine protected areas (MPAs) for wide-ranging predators is essential to designing effective management and conservation approaches. The use of acoustic monitoring and network analysis can improve our understanding of the spatial ecology and functional connectivity of reef-associated species, providing a useful approach for reef-based conservation planning. This study compared and contrasted the movement and connectivity of sharks with different degrees of reef association. We examined the residency, dispersal, degree of reef connectivity, and MPA use of grey reef (Carcharhinus amblyrhynchos), silvertip (C. albimarginatus), and bull (C. leucas) sharks monitored in the central Great Barrier Reef (GBR). An array of 56 acoustic receivers was used to monitor shark movements on 17 semi-isolated reefs. Carcharhinus amblyrhynchos and C. albimarginatus were detected most days at or near their tagging reef. However, while C. amblyrhynchos spent 80% of monitoring days in the array, C. albimarginatus was only detected 50% of the time. Despite both species moving similar distances (reefs and moved more frequently between reefs and management zones than C. amblyrhynchos. Carcharhinus leucas was detected less than 20% of the time within the tagging array, and 42% of the population undertook long-range migrations to other arrays in the GBR. Networks derived for C. leucas were larger and more complex than those for C. amblyrhynchos and C. albimarginatus. Our findings suggest that protecting specific reefs based on prior knowledge (e.g., healthier reefs with high fish biomass) and increasing the level of protection to include nearby, closely spaced reef habitats (reef predators displaying a range of movement patterns.

  3. A study of military recruitment strategies for dentists: possible implications for academia.

    Science.gov (United States)

    Hsu, Ronald H; Roberts, Michael W; Tulloch, J F Camilla; Trotman, Carroll-Ann

    2007-04-01

    Results of the annual American Dental Education Association surveys of dental school seniors show approximately 10 percent of graduates enter federal government services while less than 1 percent enter dental academia. To examine this difference, this study sought the perceptions of senior dental students and junior military dental officers regarding their choice of a military career in order to determine how military recruitment strategies influenced their career decisions. Official documents explaining military recruitment efforts were requested from the military services and summarized. In-depth telephone interviews were conducted to gather perception data from the students and dental officers on successful strategies. By employing several strategies, the military was able to inform potential recruits about the benefits of being a dentist in the military. The opportunity to have the military finance a student's dental education was a successful military recruitment tool. Other enticing factors included guaranteed employment upon graduation, prestige associated with serving in the military, access to postgraduate training, minimal practice management responsibilities, and opportunities to continue learning and improve clinical skills without significant financial implications. It was concluded that dental education can use the same strategies to highlight the benefits of an academic career and offer many similar incentives that may encourage students to consider a career path in dental education. PMID:17468311

  4. Clinicians’ perspectives of health related quality of life (HRQoL) implications of amblyopia: a qualitative study

    Science.gov (United States)

    2011-01-01

    Aims or Purpose The health related quality of life (HRQoL) implications of amblyopia and/or its treatment have been reported. However the clinician’s perspective has not previously been explored. The purpose of this study was to explore the HRQoL implications of amblyopia and/or its treatment from a clinicians’ perspective. Methods Three focus group sessions were conducted with practising orthoptists. Thematic content analysis was undertaken, to identify HRQoL themes associated with amblyopia and/or its treatment. Results Nine HRQoL themes associated with amblyopia and/or its treatment were identified. These included adult quality of life issues; hospital appointments; appearance; glasses-wear; patching treatment; atropine treatment; limited activities; relationships within the family; and treatment compliance. Conclusions The HRQoL implications of amblyopia and/or its treatment was similar to those identified in the literature. Participants acknowledged a change in societal attitudes towards glasses and patching; with glasses becoming more socially acceptable. Further research is needed to explore the exact impact of amblyopia and/or its treatment from both the child and the parental perspective. PMID:22022338

  5. Examining the association between childhood asthma and parent and grandparent asthma status: Implications for Practice

    OpenAIRE

    Valerio, Melissa A.; Andreski, Patricia M.; Schoeni, Robert F.; McGonagle, Katherine A.

    2010-01-01

    Examination of intergenerational asthma beyond maternal asthma has been limited. The association between childhood asthma and intergenerational asthma status among a national cohort of children was examined.

  6. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  7. Prognostic implications of left ventricular mass and geometry following myocardial infarction: the VALIANT (VALsartan In Acute myocardial iNfarcTion) Echocardiographic Study

    DEFF Research Database (Denmark)

    Verma, Anil; Meris, Alessandra; Skali, Hicham;

    2008-01-01

    OBJECTIVES: This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction. BACKGROUND: The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse ca...

  8. Interpretation of illness in patients with chronic diseases from Shanghai and their associations with life satisfaction, escape from illness, and ability to reflect the implications of illness

    Institute of Scientific and Technical Information of China (English)

    Arndt Bssing; Ariane von Bergh; Xiao-feng Zhai; Chang-quan Ling

    2014-01-01

    OBJECTIVE:The aim of this study is to analyze how patients with chronic diseases from Shanghai interpret their disease, and how these interpretations inlfuence patients’ life satisfaction, intention to escape from their illness and their ability to relfect on the implications of their illness. METHODS:A cross-sectional study enrolling 142 patients (mean age (50 ± 16) years;63%men, 37%women) with chronic diseases (60%cancer) was recruited in the Changhai Hospital of Traditional Chinese Medicine, Shanghai, China and surveyed using standardized questionnaires. RESULTS: Patients with chronic diseases from Shanghai interpreted their illness mostly as an Adverse Interruption of Life (55%), as a Threat/Enemy (50%), but also as a Challenge (49%), and only rarely as a Call for Help (18%) or as a Punishment (13%). Particularly fatalistic negative (i.e., Threat/Enemy, Adverse Interruption of Life) and strategy-associated disease interpretations (i.e., Relieving Break, Call for Help) were moderately associated with patients’ intention to escape from illness. In contrast, positive interpretations (i.e., something of Value, Challenge) and also the guilt-associated negative interpretation Failure were moderately related with patients’ ability to relfect on their illness. However, life satisfaction was weakly associated only with the view that il ness might be a Chal enge. Interestingly, 58%of those who would see their il ness as an Adverse Interruption (AI+) could see it also as a Challenge (Ch+). Detailed analyses showed that AI+Ch+patients differ from their AI+Ch- counterparts signiifcantly with respect to their ability to relfect life and implications of illness (F=9.1;P=0.004). CONCLUSION: The observed interpretations of illness, particularly the negative perceptions, could be used as indicators that patients require further psychological assistance to cope with their burden. Helping AI+patients see their illness also as a Challenge, and thus develop a higher

  9. The Danish Association for Science and Technology Studies

    DEFF Research Database (Denmark)

    A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments.......A presentation of the Danish Association for Science and Technology Studies (DASTS). Organization, experiences, challenges and future developments....

  10. Health implications associated with exposure to farmed and wild sea turtles.

    Science.gov (United States)

    Warwick, Clifford; Arena, Phillip C; Steedman, Catrina

    2013-01-01

    Exposure to sea turtles may be increasing with expanding tourism, although reports of problems arising from interaction with free-living animals appear of negligible human health and safety concern. Exposure both to wild-caught and captive-housed sea turtles, including consumption of turtle products, raises several health concerns for the public, including: microbiological (bacteria, viruses, parasites and fungi), macrobiological (macroparasites), and organic and inorganic toxic contaminants (biotoxins, organochlorines and heavy metals). We conducted a review of sea turtle associated human disease and its causative agents as well as a case study of the commercial sea turtle facility known as the Cayman Turtle Farm (which receives approximately 240,000 visitors annually) including the use of water sampling and laboratory microbial analysis which identified Pseudomonas aeruginosa, Aeromonas spp., Vibrio spp. and Salmonella spp. Our assessment is that pathogens and toxic contaminants may be loosely categorized to represent the following levels of potential risk: viruses and fungi = very low; protozoan parasites = very low to low; metazoan parasites, bacteria and environmental toxic contaminants = low or moderate to high; and biotoxin contaminant = moderate to very high. Farmed turtles and their consumable products may constitute a significant reservoir of potential human pathogen and toxin contamination. Greater awareness among health-care professionals regarding both potential pathogens and toxic contaminants from sea turtles, as well as key signs and symptoms of sea turtle-related human disease, is important for the prevention and control of salient disease.

  11. Factors associated with job satisfaction among commune health workers: implications for human resource policies

    Directory of Open Access Journals (Sweden)

    Bach Xuan Tran

    2013-01-01

    Full Text Available Background: Job satisfaction among health workers is an important indicator in assessing the performance and efficiency of health services. Objective: This study measured job satisfaction and determined associated factors among health workers in 38 commune health stations in an urban district and a rural district of Hanoi, Vietnam. A total of 252 health workers (36 medical doctors and 216 nurses and technicians; 74% female were interviewed. A job satisfaction measure was developed using factor analysis, from which four dimensions emerged, namely ‘benefits and prospects,’ ‘facility and equipment,’ ‘performance,’ and ‘professionals.’ Results: The results demonstrate that respondents were least satisfied with the following categories: salary and incentives (24.0%, benefit packages (25.1%, equipment (35.7%, and environment (41.8%. The average satisfaction score was moderate across four domains; it was the highest for ‘performance’ (66.6/100 and lowest for ‘facility and equipment’ (50.4/100. Tobit-censored regression models, constructed using stepwise selection, determined significant predictors of job satisfaction including age, areas of work and expertise, professional education, urban versus rural setting, and sufficient number of staff. Conclusion: The findings highlight the need to implement health policies that focus on incentives, working conditions, workloads, and personnel management at grassroots level.

  12. Restoring Wisconsin Art Therapy Association in Art Therapy History: Implications for Professional Definition and Inclusivity

    Science.gov (United States)

    Potash, Jordan; Burnie, Michele; Pearson, Rosemary; Ramirez, Wayne

    2016-01-01

    The Wisconsin Art Therapy Association (WATA), formally established in 1969, was the first incorporated organization of art therapists in the United States. Under the leadership of Wayne Ramirez, WATA lobbied the national association for an inclusive definition of art therapy that aimed to foster respect for psychiatric, educational, and community…

  13. Sea-ice hazards, associated risks and implications for human activities in the Arctic

    Science.gov (United States)

    Eicken, Hajo; Mahoney, Andrew; Jones, Joshua

    2014-05-01

    Polar sea ice serves important functions in the Earth system, including as climate regulator, habitat for diverse biological communities, or substrate and platform for a range of human activities. Subsumed under the concept of sea-ice services, polar ice covers are associated with benefits and risks of harm to ecosystems and people. Recent changes in Arctic ice extent, thickness and mobility have transformed services derived from sea ice. We summarize how these changes have diminished some benefits derived from the ice cover, while increasing others. More important, growing maritime activities in the North and a changing ice cover drive a need for better understanding of sea-ice hazards and the risk they represent in the context of human activities in the Arctic. Three major aspects of this problem are: (1) Broader risks associated with a rapid reduction in summer ice extent, such as geographic shifts in marine ecosystems and warming of submarine permafrost and adjacent land; (2) hazards resulting from changes in sea ice extent and dynamics such as increased coastal erosion and threats to infrastructure; and (3) risks derived from the combination of sea-ice hazards and human activities such as shipping or offshore resource development. Problem (1) is typically seen as a slow-onset hazard that requires a response in the form of mitigation and adaptation. At the same time, the importance of linkages between summer sea-ice reduction to processes outside of the Arctic has only recently emerged (such as atmospheric circulation patterns and extreme weather events) and remains difficult to quantify. Hazards and risks subsumed under (2) and (3) are more localized but with potentially major ecological and socio-economic consequences beyond the Arctic. Drawing on examples from our research in Alaska, we review and illustrate key aspects of sea-ice hazards in terms of risks to ecosystems, people and infrastructure in the coastal zone and Arctic shelf seas. In the Pacific

  14. Recent advances in the study of HPV-associated carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Liyan; Jin; Zhi-Xiang; Xu

    2015-01-01

    Human papillomaviruses(HPVs) cause virtually all cervical cancers, the second leading cause of death by cancer among women, as well as other anogenital cancers and a subset of head and neck cancers. Approximately half of women, who develop cervical cancer die from it. Despite the optimism that has accompanied the introduction of prophylactic vaccines to prevent some HPV infections, the relatively modest uptake of the vaccine, especially in the developing world, and the very high fraction of men and women who are already infected, means that HPV-associated disease will remain as a significant public health problem for decades. In this review, we summarize some recent findings on HPV-associated carcinogenesis, such as mi RNAs in HPV-associated cancers, implication of stem cells in the biology and therapy of HPV-positive cancers, HPV vaccines, targeted therapy of cervical cancer, and drug treatment for HPV-induced intraepithelial neoplasias.

  15. Certified Health Education Specialists' Participation in Professional Associations: Implications for Marketing and Membership

    Science.gov (United States)

    Thackeray, Rosemary; Neiger, Brad L.; Roe, Kathleen M.

    2005-01-01

    A number of health education professional associations exist to advance the profession through research, practice, and professional development. Benefits of individual membership may include continuing education, networking, leadership, professional recognition, advocacy, professional mobility, access to research findings, advances in the…

  16. Epigenome-Wide Association Studies for common human diseases

    OpenAIRE

    Rakyan, Vardhman K; Down, Thomas A; Balding, David J.; Beck, Stephan

    2011-01-01

    Despite the success of genome-wide association studies (GWAS) in identifying loci associated with common diseases, a significant proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation (DNAm). Such Epigenome-Wide Association Studies (EWAS) present novel opportunities but also create new challenges that are not...

  17. Incorporating Unstructured Socializing Into the Study of Secondary Exposure to Community Violence: Etiological and Empirical Implications.

    Science.gov (United States)

    Zimmerman, Gregory M; Messner, Steven F; Rees, Carter

    2014-07-01

    Secondary exposure to community violence, defined as witnessing or hearing violence in the community, has the potential to profoundly impact long-term development, health, happiness, and security. While research has explored pathways to community violence exposure at the individual, family, and neighborhood levels, prior work has largely neglected situational factors conducive to secondary violence exposure. The present study evaluates "unstructured socializing with peers in the absence of authority figures" as a situational process that has implications for secondary exposure to violence. Results indicate that a measure of unstructured socializing was significantly associated with exposure to violence, net of an array of theoretically relevant covariates of violence exposure. Moreover, the relationships between exposure to violence and three of the most well-established correlates of violence exposure in the literature-age, male, and prior violence-were mediated to varying degrees by unstructured socializing. The results suggest a more nuanced approach to the study of secondary violence exposure that expands the focus of attention beyond individual and neighborhood background factors to include situational opportunities presented by patterns of everyday activities. PMID:24366963

  18. Community College Study Abroad: Implications for Student Success

    Science.gov (United States)

    Raby, Rosalind Latiner; Rhodes, Gary M.; Biscarra, Albert

    2014-01-01

    The aim of this research is to explore whether participation in study abroad by community college students impacts levels of engagement and if there is a connection between studying abroad and academic achievement. While university-level studies have a history in exploring these questions, the same is not true for community colleges. The…

  19. Risk factors associated with pulmonary arterial hypertension in patients with systemic sclerosis and implications for screening

    Directory of Open Access Journals (Sweden)

    C.P. Denton

    2011-12-01

    Full Text Available Pulmonary arterial hypertension (PAH is a relatively common complication of systemic sclerosis (SSc affecting 5–12% of patients, and its development is associated with significant morbidity and a particularly poor prognosis. Deaths associated with other complications of SSc, such as renal crisis, have fallen significantly in recent years in line with improvements in their treatment and management. However, mortality due to PAH in this population, although improved, has shown a less dramatic decline. The early diagnosis of PAH in SSc would allow for earlier treatment, before functional and haemodynamic impairment becomes severe; this may further improve outcome, and evidence suggests that screening of SSc patients for PAH is associated with improved survival. In addition, patients with PAH associated with SSc are not a homogeneous population and they differ in terms of disease haemodynamic severity, functional capacity and rate of disease progression. Likewise, management strategies may differ, and the ability to stratify patients may help optimise screening and treatment. A number of patient-, clinical- and disease-specific risk factors associated with the development and prognosis of PAH in SSc have been identified, but their optimal use, alone or in combination, in screening and stratification of patients remains to be established.

  20. Coaches' implicit associations between size and giftedness: implications for the relative age effect.

    Science.gov (United States)

    Furley, Philip; Memmert, Daniel

    2016-01-01

    The relative age effect (RAE) is a well-established phenomenon in education and sports. Coaches have been assumed to be important social agents of RAE via biased selection decisions in favour of children with maturation advantages. In the present research, we used the Implicit Association Test to investigate automatic associations between body size and a player's domain-specific giftedness amongst youth baseball (N = 18) and youth soccer coaches (N = 34). We found medium to strong automatic associations between body size and player giftedness (baseball: MD = 0.62; soccer: MD = 0.51). Specifically, taller players were associated with positive performance-related attributes, whereas smaller players were associated with negative attributes. The results are in line with theories of grounded cognition by showing that the abstract concept of "sport giftedness" is partly grounded in the perception of physical height amongst youth sports coaches. We argue that this grounded cognition has the potential to influence coaches' selection decisions and in turn account for RAE as coaches are biased towards physically more matured players, even when no apparent performance advantage is evident.

  1. Studies of Beliefs about EFL Teaching and Learning and Its Significance and Implications

    Institute of Scientific and Technical Information of China (English)

    周小惠; 徐汝舟

    2013-01-01

    This paper gives a brief review of teacher and learner beliefs, so as to highlight the important roles these beliefs play in EFL teaching and learning. Based on it, the paper goes deeper into the significance of the studies of beliefs for EFL teaching, learning, teacher education, etc. Furthermore, some implications emerging from the studies are discussed.

  2. Implications of Queer Theory for the Study of Religion and Gender: Entering the Third Decade

    Directory of Open Access Journals (Sweden)

    Claudia Schippert

    2011-08-01

    Full Text Available This essay explores the conceptual and contextual shifts in queer theoretical work as it is entering into its third decade of articulation. The essay reviews important recent themes in, and examines implications of, queer theoretical scholarship for the study of religion and gender. I suggest that among the implications are a (more undisciplined study of religion (and secularism that takes seriously shifts resulting from transnational and diasporic queer scholarship, shifts in conceptions of agency and resistance resulting from analyses  and critique of homonormative positions, and can critically intervene in homonationalism and Islamophobia.

  3. Terrestrial case studies of ilmenite exploration and lunar implications

    Science.gov (United States)

    Feldman, S. C.; Franklin, H. A.

    1993-01-01

    The Space Exploration Initiative (SEI) includes space resource utilization as one of the four architectures to achieve U.S. goals in space. Space resource utilization will make use of lunar resources to support long term activities on the lunar surface. Lunar ilmenite and regolith are two of the materials that can be mined and processed for lunar oxygen production. During this investigation, several sources were reviewed to assess terrestrial exploration methods used for locating ilmenite resources. These sources included published reports on terrestrial ilmenite exploration methods, analytical methods, case histories, chemical and physical properties, and associations with other minerals. Using a terrestrial analog and considering the differences between terrestrial and lunar environmental conditions, rocks, and minerals, exploration methods and analytical instruments can be recommended for a lunar orbiter and lander for assessing lunar resources. Twelve terrestrial case histories were reviewed to gain insight into ilmenite exploration on the Moon. All exploration case histories follow the same pattern. They begin with a model, use remote geophysical techniques, define regional sampling sites from the model and geophysics, narrow down the area of exploration based on the preceding work, collect more samples and cores, and perform laboratory analyses of samples. An important part of this process is the collection of samples to determine the correctness of the model. Surface and core samples are collected in areas expected to contain both high and low concentration of the commodity to test the model. After samples are analyzed and the area of mineralization is defined, reserves are calculated to determine the cost/benefit ratio, the necessary capacity of the processing plant, and the life of the mine. The exploration methods used for locating terrestrial ilmenite resources are reviewed with respect to the petrology, chemistry, and mineral associations of the

  4. Oncostatin M promotes excitotoxicity by inhibiting glutamate uptake in astrocytes : implications in HIV-associated neurotoxicity

    NARCIS (Netherlands)

    Moidunny, Shamsudheen; Matos, Marco; Wesseling, Evelyn; Banerjee, Santanu; Volsky, David J; Cunha, Rodrigo A; Agostinho, Paula; Boddeke, Hendrikus W; Roy, Sabita

    2016-01-01

    BACKGROUND: Elevated levels of oncostatin M (OSM), an interleukin-6 cytokine family member, have been observed in HIV-1-associated neurocognitive disorders (HAND) and Alzheimer's disease. However, the function of OSM in these disease conditions is unclear. Since deficient glutamate uptake by astrocy

  5. Genome-wide association study of multiplex schizophrenia pedigrees

    DEFF Research Database (Denmark)

    Levinson, Douglas F; Shi, Jianxin; Wang, Kai;

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  6. American Bar Association Supplementary Guidelines for the Mitigation Function of Defense Teams in Death Penalty Cases: implications for social work.

    Science.gov (United States)

    Andrews, Arlene Bowers

    2012-04-01

    When a client faces a penalty of death, defense attorneys may call on social workers in many capacities: mitigation specialist, expert witness, consulting specialist, direct witness, or defense-initiated victim outreach worker. The American Bar Association set forth standards for capital defense attorneys, which led an interdisciplinary team to produce the "Supplementary Guidelines for the Mitigation Function of Defense Teams in Death Penalty Cases" to promote the exceptional competence and diligence required when the consequence is life or death. This article summarizes the "Supplementary Guidelines," with implications for social work practice--that is, professional responsibility, competence, interviewing skill, knowledge of behavioral and mental impairment, records review, life history compilation, data interpretation, witness support, law-related knowledge, and testimony. The social work, which is scrutinized in a court of law, requires cultural competence, diverse oral and written communication skills, diligence, and the highest ethical standards.

  7. Genome-wide association study identifies novel loci association with fasting insulin and insulin resistance in African Americans.

    Science.gov (United States)

    Chen, Guanjie; Bentley, Amy; Adeyemo, Adebowale; Shriner, Daniel; Zhou, Jie; Doumatey, Ayo; Huang, Hanxia; Ramos, Edward; Erdos, Michael; Gerry, Norman; Herbert, Alan; Christman, Michael; Rotimi, Charles

    2012-10-15

    Insulin resistance (IR) is a key determinant of type 2 diabetes (T2D) and other metabolic disorders. This genome-wide association study (GWAS) was designed to shed light on the genetic basis of fasting insulin (FI) and IR in 927 non-diabetic African Americans. 5 396 838 single-nucleotide polymorphisms (SNPs) were tested for associations with FI or IR with adjustments for age, sex, body mass index, hypertension status and first two principal components. Genotyped SNPs (n = 12) with P KLF14 and PPARG) which exert their action via IR. In summary, variants in/near SC4MOL, and TCERG1L were associated with FI and IR in this cohort of African Americans and were replicated in West Africans. SC4MOL is under-expressed in an animal model of T2D and plays a key role in lipid biosynthesis, with implications for the regulation of energy metabolism, obesity and dyslipidemia. TCERG1L is associated with plasma adiponectin, a key modulator of obesity, inflammation, IR and diabetes. PMID:22791750

  8. Association between depression and development of coronary artery disease: pathophysiologic and diagnostic implications

    Directory of Open Access Journals (Sweden)

    Sakamoto

    2011-03-01

    Full Text Available Carlos V Serrano Jr1, Karina Tiemi Setani2, Erica Sakamoto2, Anna Maria Andrei3, Renério Fraguas41Heart Institute (InCor, 2Medical School, University of São Paulo, Brazil; 3Albert Einstein Hospital, São Paulo, Brazil; 4Department and Institute of Psychiatry, Medical School, University of São Paulo, BrazilAbstract: Depression and coronary artery disease (CAD are both extremely prevalent diseases. In addition, compromised quality of life and life expectancy are characteristics of both situations. There are several conditions that aggravate depression and facilitate the development of CAD, as well as provoke a worse prognosis in patients with already established CAD: inferior adherence to medical orientations (medications and life style modifications, greater platelet activation and aggregation, endothelial dysfunction, and impaired autonomic dysfunction (lowered heart rate variability. Recent literature has shown that depression alone is becoming an independent risk factor for cardiac events both in primary and secondary prevention. As the diagnosis of depression in patients with heart disease is difficult, due to similarities of symptoms, the health professional should perform a careful evaluation to differentiate the clinical signs of depression from those related with general heart diseases. After a myocardial infarction, depression is an independent risk factor for mortality. Successful therapy of depression has been shown to improve patients’ quality of life and cardiovascular outcome. However, multicentric clinical trials are needed to support this inference. A practical liaison between qualified professionals is necessary for the better management of depressed patients with excess risk in developing CAD. Accordingly, pathophysiological and clinical implications between depression and CAD are discussed in this article.Keywords: depression, coronary artery disease, behavioral disorders, prognosis

  9. Detection of noroviruses in foods: a study on virus extraction procedures in foods implicated in outbreaks of human gastroenteritis.

    Science.gov (United States)

    Rutjes, Saskia A; Lodder-Verschoor, Froukje; van der Poel, Wim H M; van Duijnhoven, Yvonne T H P; de Roda Husman, Ana Maria

    2006-08-01

    Disease outbreaks in which foods are epidemiologically implicated as the common source are frequently reported. Noroviruses and enteric hepatitis A viruses are among the most prevalent causative agents of foodborne diseases. However, the detection of these viruses in foods other than shellfish is often time-consuming and unsuccessful. In this study, three virus concentration methods were compared: polyethylene glycol (PEG) plus NaCl, ultracentrifugation, and ultrafiltration. Two RNA extraction methods, TRIzol and RNeasy Mini Kit (Qiagen), were compared for detection of viruses in whipped cream and lettuce (as representatives of the dairy and vegetable-fruit food groups, respectively). A seeding experiment with canine calicivirus was conducted to determine the efficiency of each virus extraction procedure. The PEG-NaCl-TRIzol method was most efficient for the detection of viruses in whipped cream and the ultracentrifugation-RNeasy-Mini Kit procedure was best for detection on lettuce. Based on the seeding experiments, food items implicated in norovirus-associated gastroenteritis outbreaks were subjected to the optimal procedure for a specific composition and matrix. No noroviruses were detected in the implicated food items, possibly because the concentration of virus on the food item was too low or because of the presence of inhibitory factors. For each food group, a specific procedure is optimal. Inhibitory factors should be controlled in these procedures because they influence virus detection in food.

  10. Associated disease risk from the introduced generalist pathogen Sphaerothecum destruens: management and policy implications.

    Science.gov (United States)

    Andreou, Demetra; Gozlan, Rodolphe Elie

    2016-08-01

    The rosette agent Sphaerothecum destruens is a novel pathogen, which is currently believed to have been introduced into Europe along with the introduction of the invasive fish topmouth gudgeon Pseudorasbora parva (Temminck & Schlegel, 1846). Its close association with P. parva and its wide host species range and associated host mortalities, highlight this parasite as a potential source of disease emergence in European fish species. Here, using a meta-analysis of the reported S. destruens prevalence across all reported susceptible hosts species; we calculated host-specificity providing support that S. destruens is a true generalist. We have applied all the available information on S. destruens and host-range to an established framework for risk-assessing non-native parasites to evaluate the risks posed by S. destruens and discuss the next steps to manage and prevent disease emergence of this generalist parasite. PMID:27216376

  11. The Association of Cryptosporidium parvum With Suspended Sediments: Implications for Transport in Surface Waters

    Science.gov (United States)

    Searcy, K. E.; Packman, A. I.; Atwill, E. R.; Harter, T.

    2003-12-01

    Understanding the transport and fate of microorganisms in surface waters is of vital concern in protecting the integrity and safety of municipal water supply systems. The human pathogen Cryptosporidium parvum is a particular public health interest, as it is ubiquitous in the surface waters of the United States, it can persist for long periods in the environment, and it is difficult to disinfect in water treatment plants. Due to its small size (5 um), low specific gravity (1.05 g/cm3), and negative surface charge, C. parvum oocysts are generally considered to move through watersheds from their source to drinking water reservoirs with little attenuation. However, the transport of the oocysts in surface waters may be mediated by interactions with suspended sediments. Batch experiments were conducted to determine the extent of C. parvum oocyst attachment to several inorganic and organic sediments under varying water chemical conditions, and settling column experiments were performed to demonstrate how these associations influence the effective settling velocity of C. parvum oocysts. Results from these experiments showed that C. parvum oocysts do associate with inorganic and organic sediments and often settle at the rate of the suspended sediment. The size and surface charge of the host suspended sediment influenced the extent of oocyst attachment as oocysts preferentially associated with particles greater than 3 um, and fewer oocysts associated with particles having a highly negative surface charge. Background water chemical conditions including ionic strength, ion composition, and pH did not have a significant effect on oocyst attachment to suspended sediments.

  12. Exploring membrane-associated NAC transcription factors in Arabidopsis: implications for membrane biology in genome regulation

    OpenAIRE

    Kim, Sun-Young; Kim, Sang-Gyu; Kim, Youn-Sung; Seo, Pil Joon; Bae, Mikyoung; Yoon, Hye-Kyung; Park, Chung-Mo

    2006-01-01

    Controlled proteolytic cleavage of membrane-associated transcription factors (MTFs) is an intriguing activation strategy that ensures rapid transcriptional responses to incoming stimuli. Several MTFs are known to regulate diverse cellular functions in prokaryotes, yeast, and animals. In Arabidopsis, a few NAC MTFs mediate either cytokinin signaling during cell division or endoplasmic reticulum (ER) stress responses. Through genome-wide analysis, it was found that at least 13 members of the NA...

  13. HIV-associated obstructive lung diseases: insights and implications for the clinician

    OpenAIRE

    Drummond, M Bradley; Kirk, Gregory D

    2014-01-01

    The effectiveness of antiretroviral therapy to control HIV infection has led to the emergence of an older HIV population who are at risk of chronic diseases. Through a comprehensive search of major databases, this Review summarises information about the associations between chronic obstructive pulmonary disease (COPD), asthma, and HIV infection. Asthma and COPD are more prevalent in HIV-infected populations; 16–20% of individuals with HIV infection have asthma or COPD, and poorly controlled H...

  14. Factors associated with female genital mutilation in Burkina Faso and its policy implications

    OpenAIRE

    Karmaker, Bue; Kandala, Ngianga-Bakwin; Chung, Donna; Clarke, Aileen

    2011-01-01

    Background Female genital mutilation (FGM) usually undertaken between the ages of 1-9 years and is widely practised in some part of Africa and by migrants from African countries in other parts of the world. Laws prohibit FGM in almost every country. FGM can cause immediate complications (pain, bleeding and infection) and delayed complications (sexual, obstetric, psychological problems). Several factors have been associated with an increased likelihood of FGM. In Burkina Faso, the prevalence o...

  15. Factors associated with female genital mutilation in Burkina Faso and its policy implications

    OpenAIRE

    Chung Donna; Kandala Ngianga-Bakwin; Karmaker Bue; Clarke Aileen

    2011-01-01

    Abstract Background Female genital mutilation (FGM) usually undertaken between the ages of 1-9 years and is widely practised in some part of Africa and by migrants from African countries in other parts of the world. Laws prohibit FGM in almost every country. FGM can cause immediate complications (pain, bleeding and infection) and delayed complications (sexual, obstetric, psychological problems). Several factors have been associated with an increased likelihood of FGM. In Burkina Faso, the pre...

  16. Gendered Risk Perceptions Associated with Human-Wildlife Conflict: Implications for Participatory Conservation

    OpenAIRE

    Gore, Meredith L.; Kahler, Jessica S.

    2012-01-01

    This research aims to foster discourse about the extent to which gender is important to consider within the context of participatory approaches for biological conservation. Our objectives are to: (1) gender-disaggregate data about stakeholders' risk perceptions associated with human-wildlife conflict (HWC) in a participatory conservation context, and (2) highlight insights from characterizing gendered similarities and differences in the way people think about HWC-related risks. Two communal c...

  17. Associations between ectomycorrhizal fungi and bacterial needle endophytes in Pinus radiata: implications for biotic selection of microbial communities

    OpenAIRE

    Megan Arlene Rúa; Emily Catherine Wilson; Sarah eSteele; Munters, Arielle R.; Hoeksema, Jason D.; Carolin eFrank

    2016-01-01

    Studies of the ecological and evolutionary relationships between plants and their associated microbes have long been focused on single microbes, or single microbial guilds, but in reality, plants associate with a diverse array of microbes from a varied set of guilds. As such, multitrophic interactions among plant-associated microbes from multiple guilds represent an area of developing research, and can reveal how complex microbial communities are structured around plants. Interactions between...

  18. Genome-wide association study of autistic-like traits in a general population study of young adults

    Directory of Open Access Journals (Sweden)

    Rachel Maree Jones

    2013-10-01

    Full Text Available Research has proposed that autistic-like traits in the general population lie on a continuum, with clinical Autism Spectrum Disorder (ASD representing the extreme end of this distribution. Inherent in this proposal is that biological mechanisms associated with clinical ASD may also underpin variation in autistic-like traits within the general population. A genome-wide association study using 2,462,046 single nucleotide polymorphisms (SNPs was undertaken for ASD in 965 individuals from the Western Australian Pregnancy Cohort (Raine Study. No SNP associations reached genome-wide significance (p < 5.0 x 10-8. However, investigations into nominal observed SNP associations (p < 1.0 x 10-5 add support to two positional candidate genes previously implicated in ASD aetiology, PRKCB1 and CBLN1.The rs198198 SNP (p = 9.587 x 10-6, is located within an intron of the protein kinase C, beta 1 (PRKCB1 gene on chromosome 16p11. The PRKCB1 gene has been previously reported in linkage and association studies for ASD, and its mRNA expression has been shown to be significantly down regulated in ASD cases compared with controls. The rs16946931 SNP (p = 1.78 x 10-6 is located in a region flanking the Cerebellin 1 (CBLN1 gene on chromosome 16q12.1. The CBLN1 gene is involved with synaptogenesis and is part of a gene family previously implicated in ASD. This GWA study is only the second to examine SNPs associated with autistic-like traits in the general population, and provides evidence to support roles for the PRKCB1 and CBLN1 genes in risk of clinical ASD.

  19. The Implications of Service-Learning for Technology Studies.

    Science.gov (United States)

    Folkestad, James E.; Senior, Bolivar A.; DeMirana, Michael A.

    2002-01-01

    A "toys for tots" service-learning experience integrated into an industrial technology management course required development and planning using a process planning and costing model and work with a variety of stakeholders including an Even-Start learning center. Challenges include the lack of service-learning precedent in technology studies and…

  20. Implications of Programmed Instruction for a World Study of Music.

    Science.gov (United States)

    Carlsen, James C.

    Programed instruction can be applied fruitfully in teaching about music within and outside Western culture. The content of such study could include cognitive material, such as the social role of music in various cultures, the history of music, the visual identification of instruments, and perhaps notational skills; performance skills, dealing with…

  1. Savant Syndrome: Case Studies, Hypotheses, and Implications for Special Education.

    Science.gov (United States)

    Cheatham, Susan Klug; And Others

    1995-01-01

    The concept of savant syndrome, encompassing those individuals historically known as "idiot savants," is reviewed. Case studies demonstrating special abilities in the areas of calendar calculating, musical ability, artistic talent, memorization, mathematical skills, mechanical achievement, and fine sensory discrimination are discussed, as well as…

  2. Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

    International Nuclear Information System (INIS)

    Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 ± 1.7) were studied with [18F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

  3. The role of associative and non-associative learning in the training of horses and implications for the welfare (a review

    Directory of Open Access Journals (Sweden)

    Paolo Baragli

    2015-03-01

    Full Text Available Horses were domesticated 6000 years ago and since then different types of approaches have been developed to enhance the horse's wellbeing and the human-horse relationship. Even though horse training is an increasingly important research area and many articles have been published on the subject, equitation is still the sport with the highest rate of human injuries, and a significant percentage of horses are sold or slaughtered due to behavioral problems. One explanation for this data is that the human-horse relationship is complex and the communication between humans and horses has not yet been accurately developed. Thus, this review addresses correct horse training based on scientific knowledge in animal learning and psychology. Specifically, it starts from the basic communication between humans and horses and then focuses on associative and non-associative learning, with many practical outcomes in horse management from the ground and under saddle. Finally, it highlights the common mistakes in the use of negative reinforcement, as well as all the implications that improper training could have on horse welfare. Increased levels of competence in horse training could be useful for equine technicians, owners, breeders, veterinarians, and scientists, in order to safeguard horse welfare, and also to reduce the number of human injuries and economic loss for civil society and the public health system.

  4. Implications of recent multimodel attribution studies for climate sensitivity

    Science.gov (United States)

    Lewis, Nicholas

    2016-03-01

    Equilibrium climate sensitivity (ECS) is inferred from estimates of instrumental-period warming attributable solely to greenhouse gases (AW), as derived in two recent multi-model detection and attribution (D&A) studies that apply optimal fingerprint methods with high spatial resolution to 3D global climate model simulations. This approach minimises the key uncertainty regarding aerosol forcing without relying on low-dimensional models. The "observed" AW distributions from the D&A studies together with an observationally-based estimate of effective planetary heat capacity (EHC) are applied as observational constraints in (AW, EHC) space. By varying two key parameters—ECS and effective ocean diffusivity—in an energy balance model forced solely by greenhouse gases, an invertible map from the bivariate model parameter space to (AW, EHC) space is generated. Inversion of the constrained (AW, EHC) space through a transformation of variables allows unique recovery of the observationally-constrained joint distribution for the two model parameters, from which the marginal distribution of ECS can readily be derived. The method is extended to provide estimated distributions for transient climate response (TCR). The AW distributions from the two D&A studies produce almost identical results. Combining the two sets of results provides best estimates (5-95 % ranges) of 1.66 (0.7-3.2) K for ECS and 1.37 (0.65-2.2) K for TCR, in line with those from several recent studies based on observed warming from all causes but with tighter uncertainty ranges than for some of those studies. Almost identical results are obtained from application of an alternative profile likelihood statistical methodology.

  5. Association between arterial stiffness and atherosclerosis: the Rotterdam Study

    NARCIS (Netherlands)

    N.M-L. van Popele (Nicole); D.E. Grobbee (Diederick); M.L. Bots (Michiel); R. Asmar (Roland); J. Topouchian; R.S. Reneman; A.P.G. Hoeks; D.A. van der Kuip (Deirdre); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2001-01-01

    textabstractBACKGROUND AND PURPOSE: Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis. METHODS: This study was conducted w

  6. Arab Teens Lifestyle Study (ATLS): objectives, design, methodology and implications

    OpenAIRE

    Al-Hazzaa, Hazzaa; Musiager, Abdulrahman

    2011-01-01

    Hazzaa M Al-Hazzaa1,2, Abdulrahman O Musaiger3, ATLS Research Group1Exercise Physiology Laboratory, Department of Physical Education and Movement Sciences, College of Education, King Saud University, 2Scientific Board, Obesity Research Chair, King Saud University, Riyadh, Saudi Arabia; 3Arab Center for Nutrition, Manama, Bahrain, and Nutrition and Health Studies Unit, Deanship of Scientific Research, University of Bahrain, BahrainBackground: There is a lack of comparable data on physical acti...

  7. Social constructivism and its implications for critical media studies

    OpenAIRE

    Wilhelm Kempf

    2006-01-01

    While media critics maintain that war coverage has a strong bias toward promoting conflict escalation, their opponents claim that the concept of distorted reality cannot be upheld. What seems to be a media-political dispute results from an epistemological issue that tangles the very roots of cultural studies in general: the question of whether the social construction of reality implies the arbitrariness of opinions. The present paper discusses this proposition from a constructivist point o...

  8. Reelin-Related Disturbances in Depression: Implications for Translational Studies

    OpenAIRE

    Caruncho, Hector J.; Brymer, Kyle; Romay-Tallón, Raquel; Mitchell, Milann A.; Rivera-Baltanás, Tania; Botterill, Justin; Jose M. Olivares; Kalynchuk, Lisa E.

    2016-01-01

    The finding that reelin expression is significantly decreased in mood and psychotic disorders, together with evidence that reelin can regulate key aspects of hippocampal plasticity in the adult brain, brought our research group and others to study the possible role of reelin in the pathogenesis of depression. This review describes recent progress on this topic using an animal model of depression that makes use of repeated corticosterone (CORT) injections. This methodology produces depression-...

  9. REELIN-RELATED DISTURBANCES IN DEPRESSION: IMPLICATIONS FOR TRANSLATIONAL STUDIES

    OpenAIRE

    Hector J eCaruncho; Kyle eBrymer; Raquel eRoman-Tallon; Milann A eMitchell; Tania eRivera-Baltanas; Justin eBotterill; Jose M eOlivares; Lisa E eKalynchuk

    2016-01-01

    The finding that reelin expression is significantly decreased in mood and psychotic disorders, together with evidence that reelin can regulate key aspects of hippocampal plasticity in the adult brain, brought our research group and others to study the possible role of reelin in the pathogenesis of depression. This review describes recent progress on this topic using an animal model of depression that makes use of repeated corticosterone injections. This methodology produces depression-like sy...

  10. Generic information can retrieve known biological associations: implications for biomedical knowledge discovery.

    Directory of Open Access Journals (Sweden)

    Herman H H B M van Haagen

    Full Text Available MOTIVATION: Weighted semantic networks built from text-mined literature can be used to retrieve known protein-protein or gene-disease associations, and have been shown to anticipate associations years before they are explicitly stated in the literature. Our text-mining system recognizes over 640,000 biomedical concepts: some are specific (i.e., names of genes or proteins others generic (e.g., 'Homo sapiens'. Generic concepts may play important roles in automated information retrieval, extraction, and inference but may also result in concept overload and confound retrieval and reasoning with low-relevance or even spurious links. Here, we attempted to optimize the retrieval performance for protein-protein interactions (PPI by filtering generic concepts (node filtering or links to generic concepts (edge filtering from a weighted semantic network. First, we defined metrics based on network properties that quantify the specificity of concepts. Then using these metrics, we systematically filtered generic information from the network while monitoring retrieval performance of known protein-protein interactions. We also systematically filtered specific information from the network (inverse filtering, and assessed the retrieval performance of networks composed of generic information alone. RESULTS: Filtering generic or specific information induced a two-phase response in retrieval performance: initially the effects of filtering were minimal but beyond a critical threshold network performance suddenly drops. Contrary to expectations, networks composed exclusively of generic information demonstrated retrieval performance comparable to unfiltered networks that also contain specific concepts. Furthermore, an analysis using individual generic concepts demonstrated that they can effectively support the retrieval of known protein-protein interactions. For instance the concept "binding" is indicative for PPI retrieval and the concept "mutation abnormality" is

  11. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications.

    Science.gov (United States)

    Vgontzas, A N; Bixler, E O; Lin, H M; Prolo, P; Mastorakos, G; Vela-Bueno, A; Kales, A; Chrousos, G P

    2001-08-01

    Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medical significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, there is a paucity of data regarding the activity of the hypothalamic-pituitary-adrenal axis in insomniacs. We hypothesized that chronic insomnia is associated with increased plasma levels of ACTH and cortisol. Eleven young insomniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) without sleep disturbances, matched for age and body mass index, were monitored in the sleep laboratory for 4 consecutive nights, whereas serial 24-h plasma measures of ACTH and cortisol were obtained during the fourth day. Insomniacs, compared with controls, slept poorly (significantly higher sleep latency and wake during baseline nights). The 24-h ACTH and cortisol secretions were significantly higher in insomniacs, compared with normal controls (4.2 +/- 0.3 vs. 3.3 +/- 0.3 pM, P = 0.04; and 218.0 +/- 11.0 vs. 190.4 +/- 8.3 nM, P = 0.07). Within the 24-h period, the greatest elevations were observed in the evening and first half of the night. Also, insomniacs with a high degree of objective sleep disturbance (% sleep time insomnia is associated with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a disorder of central nervous system hyperarousal rather than one of sleep loss, which is usually associated with no change or decrease in cortisol secretion or a circadian disturbance. Chronic activation of the hypothalamic-pituitary-adrenal axis in insomnia suggests that insomniacs are at risk not only for mental disorders, i.e. chronic anxiety and depression, but also for significant medical morbidity associated with such activation. The therapeutic goal in insomnia should be to decrease the

  12. CCNA Cisco Certified Network Associate Study Guide

    CERN Document Server

    Lammle, Todd

    2011-01-01

    Learn from the Best - Cisco Networking Authority Todd LammleWritten by Cisco networking authority Todd Lammle, this comprehensive guide has been completely updated to reflect the latest CCNA 640-802 exam. Todd's straightforward style provides lively examples, hands on and written labs, easy-to-understand analogies, and real-world scenarios that will not only help you prepare for the exam, but also give you a solid foundation as a Cisco networking professional.This Study Guide teaches you how toDescribe how a network worksConfigure, verify and troubleshoot a switch with VLANs and interswitch co

  13. Impact of the 2001 Foot-and-Mouth Disease Outbreak in Britain: Implications for Rural Studies

    Science.gov (United States)

    Scott, Alister; Christie, Michael; Midmore, Peter

    2004-01-01

    This paper assesses the impact of the 2001 foot-and-mouth disease outbreak in terms of its implications for the discipline of rural studies. In particular, it focuses on the position of agriculture in rural economy and society, the standing of the government after its management of the outbreak, and the performance of the new devolved regional…

  14. A Retrospective Study of Phonetic Inventory Complexity in Acquisition of Spanish: Implications for Phonological Universals

    Science.gov (United States)

    Catano, Lorena; Barlow, Jessica A.; Moyna, Maria Irene

    2009-01-01

    This study evaluates 39 different phonetic inventories of 16 Spanish-speaking children (ages 0;11 to 5;1) in terms of hierarchical complexity. Phonetic featural differences are considered in order to evaluate the proposed implicational hierarchy of Dinnsen et al.'s phonetic inventory typology for English. The children's phonetic inventories are…

  15. Comparative Study of University and Polytechnic Graduates in Finland: Implications of Higher Education on Earnings

    Science.gov (United States)

    Xia, Belle Selene; Liitiainen, Elia; Rekola, Mika

    2012-01-01

    This study explores the implications of higher education on earnings in Finland. The challenges as well as opportunities of obtaining a university degree as compared to graduating from polytechnics are evaluated using the REFLEX (The Flexible Professional in the Knowledge Society) data. As a Nordic country, Finland is known for its educated…

  16. Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Haluska, F.G.; Russo, G.; Croce, C.M. (Fels Institute for Cancer Research and Molecular Biology, Philadelphia, PA (USA)); Kant, J. (Univ. of Pennsylvania School of Medicine, Philadelphia (USA)); Andreef, M. (Memorial Sloan Kettering Institute, New York, NY (USA))

    1989-11-01

    Non-Hodgkin lymphoma is a common feature of AIDS. Approximately 30-40% of these tumors exhibit clinical features suggestive of endemic Burkitt lymphoma: they are aggressive malignancies that occur in association with Epstein-Barr virus infection, they arise in the setting of immunosuppression, and they carry t(8;14) translocations without detectable rearrangement of the MYC oncogene. To understand the molecular basis of these parallels, the authors analyzed a case of Epstein-Barr-positive AIDS-associated undifferentiated lymphoma. Southern blots show that the tumor exhibits immunoglobulin joining segment rearrangement but no rearrangement of the MYC oncogene. Cloning of the rearranged joining segment allowed the isolation of recombinant clones encompassing the translocation breakpoint, and sequencing of the translocation junction disclosed that the breakpoint is situated 7 base pairs from the chromosome 14 site involved in a previously described endemic Burkitt lymphoma translocation. Furthermore, the breakpoint is situated far from MYC on chromosome 8, a constant finding in endemic Burkitt lymphomas. That the molecular architecture of the translocation in this case is strikingly similar to previously analyzed translocations from endemic Burkitt lymphomas strongly suggests that common molecular mechanisms must be operative in the pathogenesis of these tumors.

  17. Size distribution of particle-associated polybrominated diphenyl ethers (PBDEs) and their implications for health

    Science.gov (United States)

    Lyu, Yan; Xu, Tingting; Li, Xiang; Cheng, Tiantao; Yang, Xin; Sun, Xiaomin; Chen, Jianmin

    2016-03-01

    In order to better understand the size distribution of particle-associated PBDEs and their deposition pattern in the human respiratory tract, we carried out a 1-year campaign during 2012-2013 for the measurement of size-resolved particles at the urban site of Shanghai. The results showed that particulate PBDEs exhibited a bimodal distribution with a mode peak in the accumulation particle size range and the second mode peak in the coarse particle size ranges. As the number of bromine atoms in the molecule increases, accumulation-mode peak intensity increased while coarse-mode peak intensity decreased. This change was consistent with the variation of PBDEs' subcooled vapor pressure. Absorption and adsorption processes dominated the distribution of PBDEs among the different size particles. The evaluated deposition flux of Σ13 PBDEs was 26.8 pg h-1, in which coarse particles contributed most PBDEs in head and tracheobronchial regions, while fine-mode particles contributed major PBDEs in the alveoli region. In association with the fact that fine particles can penetrate deeper into the respiratory system, fine-particle-bound highly brominated PBDEs can be inhaled more deeply into human lungs and cause a greater risk to human health.

  18. Ferritin Diversity: Mechanistic Studies, Disease Implications, and Materials Chemistry

    Science.gov (United States)

    Hilton, Robert J.

    2011-07-01

    The study of ferritin includes a rich history of discoveries and scientific progress. Initially, the composition of ferritin was determined. Soon, it was shown that ferritin is a spherical, hollow protein. Eventually, over several decades of research, the structure and some function of this interesting protein was elucidated. However, the ferritin field was not completely satisfied. Today, for example, researchers are interested in refining the details of ferritin function, in discovering the role of ferritin in a variety of diseases, and in using ferritin for materials chemistry applications. The work presented in this dissertation highlights the progress that we have made in each of these three areas: (1) Mechanistic studies: The buffer used during horse spleen ferritin iron loading significantly influences the mineralization process and the quantity of iron deposited in ferritin. The ferrihydrite core of ferritin is crystalline and ordered when iron is loaded into ferritin in the presence of imidazole buffer. On the other hand, when iron is loaded into ferritin in the presence of MOPS buffer, the ferrihydrite core is less crystalline and less ordered, and a smaller amount of total iron is loaded in ferritin. We also show that iron can be released from the ferritin core in a non-reductive manner. The rate of Fe3+ release from horse spleen ferritin was measured using the Fe3+-specific chelator desferoxamine. We show that iron release occurs by three kinetic events. (2) Disease studies: In order to better understand iron disruption during disease states, we performed in vitro assays that mimicked chronic kidney disease. We tested the hypothesis that elevated levels of serum phosphate interrupted normal iron binding by transferrin and ferritin. Results show that phosphate competes for iron, forming an iron(III)-phosphate complex that is inaccessible to either transferrin or ferritin. Ferritin samples separated from the iron(III)-phosphate complex shows that as the

  19. The study of fear extinction: implications for anxiety disorders.

    Science.gov (United States)

    Graham, Bronwyn M; Milad, Mohammed R

    2011-12-01

    In this review, the authors propose that the fear extinction model can be used as an experimental tool to cut across symptom dimensions of multiple anxiety disorders to enhance our understanding of the psychopathology of these disorders and potentially facilitate the detection of biomarkers for them. The authors evaluate evidence for this proposition from studies examining the neurocircuitry underlying fear extinction in rodents, healthy humans, and clinical populations. The authors also assess the potential use of the fear extinction model to predict vulnerability for anxiety and treatment response and to improve existing treatments or develop novel ones. Finally, the authors suggest potential directions for future research that will help to further validate extinction as a biomarker for anxiety across diagnostic categories and to bridge the gap between basic neuroscience and clinical practice. PMID:21865528

  20. Social constructivism and its implications for critical media studies

    Directory of Open Access Journals (Sweden)

    Wilhelm Kempf

    2006-04-01

    Full Text Available While media critics maintain that war coverage has a strong bias toward promoting conflict escalation, their opponents claim that the concept of distorted reality cannot be upheld. What seems to be a media-political dispute results from an epistemological issue that tangles the very roots of cultural studies in general: the question of whether the social construction of reality implies the arbitrariness of opinions. The present paper discusses this proposition from a constructivist point of view and shows that it is based on an inadequate and logically incorrect understanding of truth and reality, and on a lack of differentiation between facts and meanings, between truth and beliefs and between objective and subjective realities. Defining a third path between cultural imperialism and a naïve understanding of cultural relativism, the paper finally discusses the methodological basis on which media criticism can build.

  1. Surface roughness of minerals and implications for dissolution studies

    Science.gov (United States)

    Anbeek, Chris

    1992-04-01

    Large, naturally weathered mineral fragments are often ground and sieved to obtain samples for dissolution studies. If the fragments are ground to much smaller dimensions, the samples are normally assumed to contain one type of (fresh) surface only. A model has been developed to test the validity of this assumption. The model describes the surface roughness factor of ground mineral material as a function of grain size and can be used to: (1) estimate the roughness factors of the freshly created and the naturally weathered surfaces; (2) estimate the ratio of fresh to total surface area for the ground samples, both for geometric and for actual surfaces; and (3) check the internal consistency of surface area measurements. Literature data were evaluated for intensively ground size fractions of nine different naturally weathered feldspars. Roughness factors of freshly created surfaces ranged from 2.5-11. Roughness factors of naturally weathered surfaces ranged from 130-2600, which is much higher than is generally recognized for feldspars. Comparison with surface roughness estimates from Scanning Electron Microscopy strongly suggests that etch pit formation plays a minor role in the increase in actual surface area during natural weathering. Instead, virtually all increase in surface area must be attributed to the formation of internal surface structures like micropores. The model also showed that for these ground samples, the assumption of one type of (fresh) surface is approximately correct for the geometric surfaces. For the actual (BET) surfaces, ratios of fresh to total surface area varied over almost the entire range from 0 to 1. This demonstrates that, even after intensive grinding, samples from large, naturally weathered mineral fragments can still contain substantial proportions of weathered BET surface area. Thus, previous dissolution studies in terms of fresh BET surface only may have been misinterpreted.

  2. Geo hazard studies and their policy implications in Nicaragua

    Science.gov (United States)

    Strauch, W.

    2007-05-01

    Nicaragua, situated at the Central American Subduction zone and placed in the trajectory of tropical storms and hurricanes, is a frequent showplace of natural disasters which have multiplied the negative effects of a long term socioeconomic crisis leaving Nicaragua currently as the second poorest country of the Americas. In the last years, multiple efforts were undertaken to prevent or mitigate the affectation of the natural phenomena to the country. National and local authorities have become more involved in disaster prevention policy and international cooperation boosted funding for disaster prevention and mitigation measures in the country. The National Geosciences Institution (INETER) in cooperation with foreign partners developed a national monitoring and early warning system on geological and hydro-meteorological phenomena. Geological and risk mapping projects were conducted by INETER and international partners. Universities, NGO´s, International Technical Assistance, and foreign scientific groups cooperated to capacitate Nicaraguan geoscientists and to improve higher education on disaster prevention up to the master degree. Funded by a World Bank loan, coordinated by the National System for Disaster Prevention, Mitigation and Attention (SINAPRED) and scientifically supervised by INETER, multidisciplinary hazard and vulnerability studies were carried out between 2003 and 2005 with emphasis on seismic hazard. These GIS based works provided proposals for land use policies on a local level in 30 municipalities and seismic vulnerability and risk information for each single building in Managua, Capital of Nicaragua. Another large multidisciplinary project produced high resolution air photos, elaborated 1:50,000 vectorized topographic maps, and a digital elevation model for Western Nicaragua. These data, integrated in GIS, were used to assess: 1) Seismic Hazard for Metropolitan Managua; 2) Tsunami hazard for the Pacific coast; 3) Volcano hazard for Telica

  3. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna

    2011-06-28

    The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen.

  4. Habitat fragmentation is associated to gut microbiota diversity of an endangered primate: implications for conservation.

    Science.gov (United States)

    Barelli, Claudia; Albanese, Davide; Donati, Claudio; Pindo, Massimo; Dallago, Chiara; Rovero, Francesco; Cavalieri, Duccio; Tuohy, Kieran Michael; Hauffe, Heidi Christine; De Filippo, Carlotta

    2015-01-01

    The expansion of agriculture is shrinking pristine forest areas worldwide, jeopardizing the persistence of their wild inhabitants. The Udzungwa red colobus monkey (Procolobus gordonorum) is among the most threatened primate species in Africa. Primarily arboreal and highly sensitive to hunting and habitat destruction, they provide a critical model to understanding whether anthropogenic disturbance impacts gut microbiota diversity. We sampled seven social groups inhabiting two forests (disturbed vs. undisturbed) in the Udzungwa Mountains of Tanzania. While Ruminococcaceae and Lachnospiraceae dominated in all individuals, reflecting their role in extracting energy from folivorous diets, analysis of genus composition showed a marked diversification across habitats, with gut microbiota α-diversity significantly higher in the undisturbed forest. Functional analysis suggests that such variation may be associated with food plant diversity in natural versus human-modified habitats, requiring metabolic pathways to digest xenobiotics. Thus, the effects of changes in gut microbiota should not be ignored to conserve endangered populations. PMID:26445280

  5. Habitat fragmentation is associated to gut microbiota diversity of an endangered primate: implications for conservation.

    Science.gov (United States)

    Barelli, Claudia; Albanese, Davide; Donati, Claudio; Pindo, Massimo; Dallago, Chiara; Rovero, Francesco; Cavalieri, Duccio; Tuohy, Kieran Michael; Hauffe, Heidi Christine; De Filippo, Carlotta

    2015-10-07

    The expansion of agriculture is shrinking pristine forest areas worldwide, jeopardizing the persistence of their wild inhabitants. The Udzungwa red colobus monkey (Procolobus gordonorum) is among the most threatened primate species in Africa. Primarily arboreal and highly sensitive to hunting and habitat destruction, they provide a critical model to understanding whether anthropogenic disturbance impacts gut microbiota diversity. We sampled seven social groups inhabiting two forests (disturbed vs. undisturbed) in the Udzungwa Mountains of Tanzania. While Ruminococcaceae and Lachnospiraceae dominated in all individuals, reflecting their role in extracting energy from folivorous diets, analysis of genus composition showed a marked diversification across habitats, with gut microbiota α-diversity significantly higher in the undisturbed forest. Functional analysis suggests that such variation may be associated with food plant diversity in natural versus human-modified habitats, requiring metabolic pathways to digest xenobiotics. Thus, the effects of changes in gut microbiota should not be ignored to conserve endangered populations.

  6. Macrofauna associated with an introduced oyster, Pinctada radiata: Spatial scale implications of community differences

    Science.gov (United States)

    Tlig-Zouari, Sabiha; Rabaoui, Lotfi; Cosentino, Andrea; Irathni, Ikram; Ghrairi, Hafedh; Hassine, Oum Kalthoum Ben

    2011-01-01

    The macrozoobenthos associated with the introduced pearl oyster Pinctada radiata has been sampled at two different spatial scales of three sectors (order of hundreds of kilometres) and of eight localities (order of tens of kilometres). Moreover, the NW sector was selected to compare three localities with the presence of P. radiata (low density) and one locality where it was totally absent. The first design was hierarchical, with random localities nested within sectors; the second one was an asymmetrical factorial design, in which the presence/absence of Pinctada and hydrodynamism were considered. Similarity relationships were investigated by means of multivariate clustering, similarity percentage analysis and nm-MDS ordination; the two experimental designs have been tested by permutational MANOVA and analysis of dispersion (PERMDISP). Most of the variability of the associated zoobenthic community appeared to be mainly captured by local environmental factors; the meso-scale variability was more discriminating than differences at larger spatial scale. Large scale NW-SE biogeographic gradient may also have some effects in the assemblage composition. Although the whole arrangement of samples in the MDS plane showed a clear Bray-Curtis distance between the locality without Pinctada and all the remaining sites, pair-wise contrasts were not all significant. The factor "presence/absence" was not significant in this design, whereas the exposure was more indicative of differences in the local assemblage composition. These results may not confirm that the community structure variability is due to the impact of Pincata invasion because the potential and subtle community shift may be masked by the overwhelming influence of just the local environmental gradients. In spite of this, the introduced oyster may play the role of an engineer species at high densities, contributing to the complexity of the benthic habitat and influencing the trophic pattern of its fauna.

  7. Soil metal concentrations and toxicity: Associations with distances to industrial facilities and implications for human health

    Energy Technology Data Exchange (ETDEWEB)

    Aelion, C. Marjorie [Department of Environmental Health Sciences, University of South Carolina, 921 Assembly Street, Columbia, SC 29208 (United States); Department of Public Health, University of Massachusetts, 715 North Pleasant Street, Amherst, MA 01003 (United States)], E-mail: maelion@schoolph.umass.edu; Davis, Harley T. [Department of Environmental Health Sciences, University of South Carolina, 921 Assembly Street, Columbia, SC 29208 (United States); McDermott, Suzanne [Department of Family and Preventive Medicine, University of South Carolina, 3209 Colonial Drive, Columbia, SC 29203 (United States); Lawson, Andrew B. [Department of Biostatistics, Bioinformatics, and Epidemiology, Medical University of South Carolina, 135 Cannon Street, Charleston, SC 29425 (United States)

    2009-03-15

    Urban and rural areas may have different levels of environmental contamination and different potential sources of exposure. Many metals, i.e., arsenic (As), lead (Pb), and mercury (Hg), have well-documented negative neurological effects, and the developing fetus and young children are particularly at risk. Using a database of mother and child pairs, three areas were identified: a rural area with no increased prevalence of mental retardation and developmental delay (MR/DD) (Area A), and a rural area (Area B) and an urban area (Area C) with significantly higher prevalence of MR/DD in children as compared to the state-wide average. Areas were mapped and surface soil samples were collected from nodes of a uniform grid. Samples were analyzed for As, barium (Ba), beryllium (Be), chromium (Cr), copper (Cu), Pb, manganese (Mn), nickel (Ni), and Hg concentrations and for soil toxicity, and correlated to identify potential common sources. ArcGIS was used to determine distances between sample locations and industrial facilities, which were correlated with both metal concentrations and soil toxicity. Results indicated that all metal concentrations (except Be and Hg) in Area C were significantly greater than those in Areas A and B (p {<=} 0.0001) and that Area C had fewer correlations between metals suggesting more varied sources of metals than in rural areas. Area C also had a large number of facilities whose distances were significantly correlated with metals, particularly Cr (maximum r = 0.33; p = 0.0002), and with soil toxicity (maximum r = 0.25; p = 0.007) over a large spatial scale. Arsenic was not associated with distance to any facility and may have a different anthropogenic, or natural source. In contrast to Area C, both rural areas had lower concentrations of metals, lower soil toxicity, and a small number of facilities with significant associations between distance and soil metals.

  8. Taphonomy for taxonomists: Implications of predation in small mammal studies

    Science.gov (United States)

    Fernández-Jalvo, Yolanda; Andrews, Peter; Denys, Christiane; Sesé, Carmen; Stoetzel, Emmanuelle; Marin-Monfort, Dolores; Pesquero, Dolores

    2016-05-01

    Predation is one of the most recurrent sources of bone accumulations. The influence of predation is widely studied for large mammal sites where humans, acting as predators, produce bone accumulations similar to carnivore accumulations. Similarly, small mammal fossil sites are mainly occupation levels of predators (nests or dens). In both cases, investigations of past events can be compared with present day equivalents or proxies. Chewing marks are sometimes present on large mammal predator accumulations, but digestion traits are the most direct indication of predation, and evidence for this is always present in small mammal (prey) fossil assemblages. Digestion grades and frequency indicates predator type and this is well established since the publication of Andrews (1990). The identification of the predator provides invaluable information for accurate interpretation of the palaeoenvironment. Traditionally, palaeoenvironmental interpretations are obtained from the taxonomic species identified in the site, but rather than providing direct interpretations of the surrounding palaeoenvironment, this procedure actually describes the dietary preferences of the predators and the type of occupation (nests, marking territory, dens, etc). This paper reviews the identification of traits produced by predators on arvicolins, murins and soricids using a method that may be used equally by taxonomists and taphonomists. It aims to provide the "tools" for taxonomists to identify the predator based on their methodology, which is examining the occlusal surfaces of teeth rather than their lateral aspects. This will greatly benefit both the work of taphonomists and taxonomists to recognize signs of predation and the improvement of subsequent palaeoecological interpretations of past organisms and sites by identifying both the prey and the predator.

  9. REELIN-RELATED DISTURBANCES IN DEPRESSION: IMPLICATIONS FOR TRANSLATIONAL STUDIES

    Directory of Open Access Journals (Sweden)

    Hector J eCaruncho

    2016-02-01

    Full Text Available The finding that reelin expression is significantly decreased in mood and psychotic disorders, together with evidence that reelin can regulate key aspects of hippocampal plasticity in the adult brain, brought our research group and others to study the possible role of reelin in the pathogenesis of depression. This review describes recent progress on this topic using an animal model of depression that makes use of repeated corticosterone injections. This methodology produces depression-like symptoms in both rats and mice that are reversed by antidepressant treatment. We have reported that corticosterone causes a decrease in the number of reelin-immunopositive cells in the dentate gyrus subgranular zone, where adult hippocampal neurogenesis takes place; that down-regulation of the number of reelin-positive cells closely parallels the development of a depression-like phenotype during repeated corticosterone treatment; that reelin downregulation alters the co-expression of reelin with neuronal nitric oxide synthase; that deficits in reelin might also create imbalances in glutamatergic and GABAergic circuits within the hippocampus and other limbic structures; and that co-treatment with antidepressant drugs prevents both reelin deficits and the development of a depression-like phenotype. We also observed alterations in the pattern of membrane protein clustering in peripheral lymphocytes in animals with low levels of reelin. Importantly, we found parallel changes in membrane protein clustering in depression patients, which differentiated two subpopulations of naïve depression patients that showed a different therapeutic response to antidepressant treatment. Here we review these findings and develop the hypothesis that restoring reelin-related function could represent a novel approach for antidepressant therapies.

  10. Reelin-Related Disturbances in Depression: Implications for Translational Studies.

    Science.gov (United States)

    Caruncho, Hector J; Brymer, Kyle; Romay-Tallón, Raquel; Mitchell, Milann A; Rivera-Baltanás, Tania; Botterill, Justin; Olivares, Jose M; Kalynchuk, Lisa E

    2016-01-01

    The finding that reelin expression is significantly decreased in mood and psychotic disorders, together with evidence that reelin can regulate key aspects of hippocampal plasticity in the adult brain, brought our research group and others to study the possible role of reelin in the pathogenesis of depression. This review describes recent progress on this topic using an animal model of depression that makes use of repeated corticosterone (CORT) injections. This methodology produces depression-like symptoms in both rats and mice that are reversed by antidepressant treatment. We have reported that CORT causes a decrease in the number of reelin-immunopositive cells in the dentate gyrus subgranular zone (SGZ), where adult hippocampal neurogenesis takes place; that down-regulation of the number of reelin-positive cells closely parallels the development of a depression-like phenotype during repeated CORT treatment; that reelin downregulation alters the co-expression of reelin with neuronal nitric oxide synthase (nNOS); that deficits in reelin might also create imbalances in glutamatergic and GABAergic circuits within the hippocampus and other limbic structures; and that co-treatment with antidepressant drugs prevents both reelin deficits and the development of a depression-like phenotype. We also observed alterations in the pattern of membrane protein clustering in peripheral lymphocytes in animals with low levels of reelin. Importantly, we found parallel changes in membrane protein clustering in depression patients, which differentiated two subpopulations of naïve depression patients that showed a different therapeutic response to antidepressant treatment. Here, we review these findings and develop the hypothesis that restoring reelin-related function could represent a novel approach for antidepressant therapies. PMID:26941609

  11. Cancer genetic association studies in the genome-wide age

    OpenAIRE

    Savage, Sharon A

    2008-01-01

    Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case–control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-sca...

  12. Optimal use of video for teaching the practical implications of studying business information systems

    DEFF Research Database (Denmark)

    Fog, Benedikte; Ulfkjær, Jacob Kanneworff Stigsen; Schlichter, Bjarne Rerup

    The study of business information systems has become increasingly important in the Digital Economy. However, it has been found that students have difficulties understanding the practical implications thereof and this leads to a motivational decreases. This study aims to investigate how to optimize...... the use of video to increase comprehension of the practical implications of studying business information systems. This qualitative study is based on observations and focus group interviews with first semester business students. The findings suggest that the video examined in the case study did not...... sufficiently reflect the theoretical recommendations of using video optimally in a management education. It did not comply with the video learning sequence as introduced by Marx and Frost (1998). However, it questions if the level of cognitive orientation activities can become too extensive. It finds that...

  13. Implications of the road traffic and aircraft noise exposure and children's cognition and health (RANCH) study results for classroom acoustics

    Science.gov (United States)

    Stansfeld, Stephen A.; Clark, Charlotte

    2005-04-01

    Studies in West London have found associations between aircraft noise exposure and childrens' cognitive performance. This has culminated in the RANCH Study examining exposure-effect associations between aircraft and road traffic noise exposure and cognitive performance and health. The RANCH project, the largest cross-sectional study of noise and childrens health, examined 2844 children, 9-10 years old, from 89 schools around three major airports: in the Netherlands, Spain and the United Kingdom. Children were selected by external aircraft and road traffic noise exposure at school predicted from noise contour maps, modeling and on-site measurements. A substudy indicated high internal levels of noise within classrooms. Schools were matched for socioeconomic position within countries. Cognitive and health outcomes were measured by standardized tests and questionnaires administered in the classroom. A parental questionnaire collected information on socioeconomic position, parental education and ethnicity. Linear exposure-effect associations were found between chronic aircraft noise exposure and impairment of reading comprehension and recognition memory, maintained after adjustment for mothers education, socioeconomic factors, longstanding illness and classroom insulation. Road traffic noise exposure was linearly associated with episodic memory. The implications of these results for childrens' learning environments will be discussed. [Work supported by European Community (QLRT-2000-00197) Vth framework program.

  14. Factors associated with knowledge of hypertension among adolescents: implications for preventive education programs in primary care

    OpenAIRE

    Grad, Iga; Mastalerz-Migas, Agnieszka; Kiliś-Pstrusińska, Katarzyna

    2015-01-01

    Background Hypertension (HT) amongst adolescents remains a vital issue of both a medical and social nature. There is a lack of data regarding the factors influencing the awareness of the disease among the youth. The aim of this study was to evaluate the knowledge about HT among adolescents and its level corresponding to the selected demographic, environmental and medical factors. Methods The study was carried out among 250 adolescents of secondary schools. The authors’ questionnaire poll and ...

  15. Implications of the Implicit Association Test D-Transformation for Psychological Assessment.

    Science.gov (United States)

    Blanton, Hart; Jaccard, James; Burrows, Christopher N

    2015-08-01

    Psychometricians strive to eliminate random error from their psychological inventories. When random error affecting tests is diminished, tests more accurately characterize people on the psychological dimension of interest. We document an unusual property of the scoring algorithm for a measure used to assess a wide range of psychological states. The "D-score" algorithm for coding the Implicit Association Test (IAT) requires the presence of random noise in order to obtain variability. Without consequential degrees of random noise, all individuals receive extreme scores. We present results from an algebraic proof, a computer simulation, and an online survey of implicit racial attitudes to show how trial error can bias IAT assessments. We argue as a result that the D-score algorithm should not be used for formal assessment purposes, and we offer an alternative to this approach based on multiple regression. Our critique focuses primarily on the IAT designed to measure unconscious racial attitudes, but it applies to any IAT developed to provide psychological assessments within clinical, organizational, and developmental branches of psychology-and in any other field where the IAT might be used. PMID:25296761

  16. Implication of the association between GBM transient 150914 and LIGO Gravitational Wave event GW150914

    CERN Document Server

    Li, Xiang; Yuan, Qiang; Jin, Zhi-Ping; Fan, Yi-Zhong; Liu, Si-Ming; Wei, Da-Ming

    2016-01-01

    On September 14, 2015 the two detectors of LIGO simultaneously detected a transient gravitational-wave signal GW150914 and the Fermi GBM observations found a weak short gamma-ray burst (SGRB)-like transient (i.e., the GBM transient 150914). The time and location coincidences favor the association between GW150904 and GBM transient 150914. We compared GBM transient 150914 with other SGRBs and found that such an event is indeed a distinct outlier in the $E_{\\rm p,rest}-E_{\\rm iso}$ and $E_{\\rm p,rest}-L_{\\gamma}$ diagrams ($E_{\\rm iso}$ is the isotropic-equivalent energy, $L_\\gamma$ is the luminosity and $E_{\\rm p,rest}$ is the rest frame peak energy of the prompt emission), possibly due to its specific binary-black-hole merger origin. However, the presence of a "new" group of SGRBs with "low" $L_\\gamma$ and $E_{\\rm iso}$ but high $E_{\\rm p,rest}$ is also possible. If the outflow of GBM transient 150914 was launched by the accretion onto the nascent black hole, we estimate the accretion disk mass to be $\\sim 10...

  17. An Empirical Bayes Mixture Model for Effect Size Distributions in Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Thompson, Wesley K.; Wang, Yunpeng; Schork, Andrew J.;

    2015-01-01

    for discovery, and polygenic risk prediction. To this end, previous work has used effect-size models based on various distributions, including the normal and normal mixture distributions, among others. In this paper we propose a scale mixture of two normals model for effect size distributions of genome......-wide association study (GWAS) test statistics. Test statistics corresponding to null associations are modeled as random draws from a normal distribution with zero mean; test statistics corresponding to non-null associations are also modeled as normal with zero mean, but with larger variance. The model is fit via...... minimizing discrepancies between the parametric mixture model and resampling-based nonparametric estimates of replication effect sizes and variances. We describe in detail the implications of this model for estimation of the non-null proportion, the probability of replication in de novo samples, the local...

  18. Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia

    DEFF Research Database (Denmark)

    Carrera, Noa; Arrojo, Manuel; Sanjuán, Julio;

    2012-01-01

    Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem......, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs)....

  19. Implications of liver activity associated with 133Xe ventilation lung scans

    International Nuclear Information System (INIS)

    A series of 35 xenon-133 (133Xe) ventilation studies yielded nine cases demonstrating accumulation of activity in the liver. Maximum intrahepatic deposition of radioxenon occurred during the washout phase of the study. In addition to those clinical instances which make this phenomenon possible, i.e., obesity, alcoholic-induced liver steatosis and diabetes mellitus, we found that hyperlipidemia and coronary artery disease also favor xenon-133 localization into the hepatic parenchyma. It is concluded that the lipid avidity of 133Xe facilitates its liver accumulation hyperlipidemic patients and in patients with coronary artery disease, and that this action may be explored to further understand deranged metabolic pathways in the liver of these patients. Hepatic accumulation of 133Xe during ventilation studies must be considered when assessing regional ventilation/perfusion relationships

  20. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha;

    2013-01-01

    Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this ...

  1. Modification of trout sperm membranes associated with activation and cryopreservation. Implications for fertilizing potential.

    Science.gov (United States)

    Purdy, P H; Barbosa, E A; Praamsma, C J; Schisler, G J

    2016-08-01

    We investigated the effects of two trout sperm activation solutions on sperm physiology and membrane organization prior to and following cryopreservation using flow cytometry and investigated their impact on in vitro fertility. Overall, frozen-thawed samples had greater phospholipid disorder when compared with fresh samples (high plasma membrane fluidity; P < 0.0001) and sperm activated with water also had high plasma membrane fluidity when compared to sperm activated with Lahnsteiner solution (LAS; P < 0.0001). Following cryopreservation water activated samples had membranes with greater membrane protein disorganization compared with LAS but the membrane protein organization of LAS samples was similar to samples prior to freezing (P < 0.0001). Post-thaw water activation resulted in significant increases in intracellular calcium compared to LAS (P < 0.002). In vitro fertility trials with frozen-thawed milt and LAS activation resulted in greater fertility (45%) compared to water activated samples (10%; P < 0.0001). Higher fertility rates correlated with lower intracellular calcium with water (R(2) = -0.9; P = 0.01) and LAS (R(2) = -0.85; P = 0.03) activation. Greater plasma membrane phospholipid (R(2) = -0.89; P = 0.02) and protein (R(2) = -0.84; P = 0.04) disorder correlated with lower water activation fertility rates. These membrane organization characteristics only approached significance with LAS activation in vitro fertility (P = 0.09, P = 0.06, respectively). Potentially the understanding of sperm membrane reorganizations and the physiology associated with activation following cryopreservation may enable users in a repository or hatchery setting to estimate the fertilizing potential of a sample and determine its value. PMID:27234987

  2. Associations among Nonword Repetition and Phonemic and Vocabulary Awareness: Implications for Intervention

    Science.gov (United States)

    Tattersall, Patricia J.; Nelson, Nickola Wolf; Tyler, Ann A.

    2015-01-01

    Prior research has shown possible relations among nonword repetition (NWR), vocabulary, and phonological processing skills in children with and without language impairment. This study was designed to investigate whether relationships would differ for students with primary language impairment (PLI) and typical language (TL) and whether they would…

  3. Preschool Children's Views on Emotion Regulation: Functional Associations and Implications for Social-Emotional Adjustment

    Science.gov (United States)

    Dennis, Tracy A.; Kelemen, Deborah A.

    2009-01-01

    Previous studies show that preschool children view negative emotions as susceptible to intentional control. However, the extent of this understanding and links with child social-emotional adjustment are poorly understood. To examine this, 62 3- and 4-year-olds were presented with puppet scenarios in which characters experienced anger, sadness, and…

  4. A study of association between dental health status and pregnancy

    OpenAIRE

    Bhavana Gupta; Attiuddin Siddique

    2013-01-01

    Background: To study the association between dental health status and pregnancy in rural India. Methods: The cohort study was carried out in the department of Obstetrics and Gynecology at Integral Institute of Medical Sciences and Research, Lucknow from March 2012 to April 2013, for the period of 1year. The dental health statuses of 600 antenatal cases were studied. The prevalence of gingivitis, dental caries and periodontal disease were studied. The association between poor oral hygiene, ...

  5. Digital mammography in a screening programme and its implications for pathology: a comparative study.

    LENUS (Irish Health Repository)

    Feeley, Linda

    2011-03-01

    Most studies comparing full-field digital mammography (FFDM) with conventional screen-film mammography (SFM) have been radiology-based. The pathological implications of FFDM have received little attention in the literature, especially in the context of screening programmes. The primary objective of this retrospective study is to compare FFDM with SFM in a population-based screening programme with regard to a number of pathological parameters.

  6. Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function.

    Science.gov (United States)

    Jing, Jiaojiao; Pattaro, Cristian; Hoppmann, Anselm; Okada, Yukinori; Fox, Caroline S; Köttgen, Anna

    2016-10-01

    Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR-associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to-creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis. PMID:27263491

  7. Endocrine disruptors and dental materials: health implications associated with their use in Brazil

    Directory of Open Access Journals (Sweden)

    Coelho Antonio Jorge Molinário

    2002-01-01

    Full Text Available This study analyzes international historical trends in the use of different types of materials in dental practice. The author describes the chemical properties of their ingredients and the potential and observed adverse effects in patients and dental technicians resulting from clinical or occupational exposure to various metals like beryllium, used to produce metal alloys. The growing use of various products (resin cements, ionomer cements, aesthetic restorative materials, resins, endodontal cements, and others based on the compound bisphenol-A, whose chemical structure is similar to that of estrogen. Considering the demographic and contemporary work force characteristics of those involved in dental practice in the Brazil, the study highlights the possible effect of the use of these materials in both male and female patients and all age strata, as well as in health professionals with occupational exposure to products containing bisphenol-A.

  8. The EU-Eastern Partnership Countries: Association Agreements and Transdisciplinarity in Studies, Training and Research

    Directory of Open Access Journals (Sweden)

    Muravska Tatyana

    2014-10-01

    Full Text Available The European Union (EU signed Association Agreements on 27 June 2014 with Georgia, the Republic of Moldova, and Ukraine. The Association Agreement (AA is the EU’s main instrument to bring the countries in the Eastern Partnership (EaP closer to EU standards and norms. For the citizens of the EaP countries to benefit from these agreements, a more in-depth knowledge of the EU and the EU Member States is required to be reflected in a comparative approach to European Union studies. We examine these implications on the need to expand and adapt, the content and approach to research and teaching European Union studies, with the transdisciplinary approach becoming increasingly dominant, becoming a modern tool for research in social sciences. This contribution aims to offer insight into the implementation of transdisciplinarity in the methodology of education and research as it is determined by current increasing global challenges. This approach should serve as a means of integrating a number of main goals as part of learning, teaching and research processes: strengthening employability of young people and preparing them for citizenship. We discuss the need for modernizing European studies in the EU Member States that could serve as an example for the EU Eastern Partnership countries. We conclude that the theoretical approach to European and related studies of other disciplines and their practical implications should always be transdisciplinary in nature and benefit from direct in-situ exposure and should be fully integrated in university curricula

  9. Indoor to outdoor air quality associations with self-pollution implications inside passenger car cabins

    Science.gov (United States)

    Abi-Esber, L.; El-Fadel, M.

    2013-12-01

    In this study, in-vehicle and out-vehicle concentrations of fine particulate matter (PM2.5) and carbon monoxide (CO) are measured to assess commuter's exposure in a commercial residential area and on a highway, under three popular ventilation modes namely, one window half opened, air conditioning on fresh air intake, and air conditioning on recirculation and examine its relationship to scarcely studied parameters including self pollution, out-vehicle sample intake location and meteorological gradients. Self pollution is the intrusion of a vehicle's own engine fumes into the passenger's compartment. For this purpose, six car makes with different ages were instrumented to concomitantly monitor in- and out-vehicle PM2.5 and CO concentrations as well as meteorological parameters. Air pollution levels were unexpectedly higher in new cars compared to old cars, with in-cabin air quality most correlated to that of out-vehicle air near the front windshield. Self-pollution was observed at variable rates in three of the six tested cars. Significant correlations were identified between indoor to outdoor pressure difference and PM2.5 and CO In/Out (IO) ratios under air recirculation and window half opened ventilation modes whereas temperature and humidity difference affected CO IO ratios only under the air recirculation ventilation mode.

  10. Genetic association studies in drug-induced liver injury.

    Science.gov (United States)

    Daly, Ann K; Day, Chris P

    2009-11-01

    Genetic studies on drug-induced liver injury (DILI) have proved challenging, both because of their rarity and their difficulty in replicating observed effects. However, significant progress has now been achieved by both candidate-gene and genome-wide association studies. These two approaches are considered in detail, together with examples of DILI due to specific drugs where consistent associations have been reported. Particular consideration is given to associations between antituberculosis drug-related liver injury and the "slow acetylator" genotype for N-acetyltransferase 2, amoxicillin/clavulanate-related liver injury, and the human leukocyte antigen (HLA) class II DRB1*1501 allele and flucloxacillin-related injury and the HLA class I B*5701 allele. Although these associations are drug-specific, the possibility that additional, more general susceptibility genes for DILI exist requires further investigation, ideally by genome-wide association studies involving international collaboration. The possibility of interethnic variation in susceptibility to DILI also requires further study.

  11. Naturalising Ethics: The Implications of Darwinism for the Study of Moral Philosophy

    Science.gov (United States)

    Cartwright, John

    2010-05-01

    The nature of moral values has occupied philosophers and educationalists for centuries and a variety of claims have been made about their origin and status. One tradition suggests they may be thoughts in the mind of God; another that they are eternal truths to be reached by rational reflection (much like the truths of mathematics) or alternatively through intuition; another that they are social conventions; and another (from the logical positivists) that they are not verifiable facts but simply the expression of emotional likes and dislikes. Standard introductory texts (e.g., Bowie 2004; Vardy and Grosch 1999) on the subject of ethics rarely mention Darwin or Darwinism (Mepham 2005 is a useful exception) possibly mindful of the fact that the relationship of evolutionary biology to moral questions has had a troublesome history. The effect of this has been that whole generations of moral philosophers have given the biological sciences a wide berth and consequently often remain poorly informed about recent advances in evolutionary thought and the neurosciences. On the other hand, scientists have developed interesting models of the evolution of the moral sentiments and are using new imaging techniques to explore the centres of the brain associated with emotion and motivation, but many have been fearful of committing the naturalistic fallacy and so have steered clear of extrapolating their findings to ethical questions. No one after all wants to be seen to be committing an elementary logical blunder. But in the last 20 years, evolutionary biologists have regained the confidence to explore the implications of evolution for the study of ethics (de Waal 1996; Wilson 1998; Wright 1994; Greene 2003). This paper is designed to encourage those entrusted with the teaching of ethics to be open to the potential of Darwinism as a source of ideas on the origins and status of ethical thought and behaviour. It is also hoped that it will illustrate for science educators the enormous

  12. Characteristics and prognostic implications of high-risk HPV-associated hypopharyngeal cancers.

    Directory of Open Access Journals (Sweden)

    Young-Hoon Joo

    Full Text Available BACKGROUND: High-risk human papillomavirus (HPV is an oncogenic virus that causes oropharyngeal cancers, and it has a favorable outcome after the treatment. Unlike in oropharyngeal cancer, the prevalence and role of high-risk HPV in the etiology of hypopharyngeal squamous cell carcinoma (HPSCC is uncertain. OBJECTIVE: The aim of the present study was to evaluate the effect and prognostic significance of high-risk HPV in patients with HPSCC. METHODS: The study included 64 subjects with HPSCC who underwent radical surgery with or without radiation-based adjuvant therapy. Primary tumor sites were the pyriform sinus in 42 patients, posterior pharyngeal wall in 19 patients, and postcricoid area in 3 patients. High-risk HPV in situ hybridization was performed to detect HPV infection. RESULTS: The positive rate of high-risk HPV in situ hybridization was 10.9% (7/64. There was a significant difference in the fraction of positive high-risk HPV among pyriform sinus cancer (16.7%, posterior pharyngeal wall cancer (0%, and postcricoid area cancer (0% (p = 0.042. The laryngoscopic examination revealed a granulomatous and exophytic appearance in 85.7% (6/7 of patients with high-risk HPV-positive pyriform sinus cancer, but in only 31.4% (11/35 of patients with high-risk HPV-negative pyriform sinus cancer (p = 0.012. Significant correlations were found between positive high-risk HPV and younger age (p = 0.050 and non-smoking status (p = 0.017. HPV-positive patients had a significantly better disease-free survival (p = 0.026 and disease-specific survival (p = 0.047 than HPV-negative patients. CONCLUSIONS: High-risk HPV infection is significantly related to pyriform sinus cancer in patients with HPSCC.

  13. Factors Associated With General and Sexual Alcohol-Related Consequences: An Examination of College Students Studying Abroad

    OpenAIRE

    Hummer, Justin F.; Pedersen, Eric R.; Mirza, Tehniat; LaBrie, Joseph W.

    2010-01-01

    This study contributes to the scarce research on U.S. college students studying abroad by documenting general and sexual negative alcohol-related risks and factors associated with such risk. The manner of drinking (quantity vs. frequency), predeparture expectations surrounding alcohol use while abroad, culture-related social anxiety, and perceived disparity between home and host cultures differentially predicted consequences abroad. The findings include important implications for student affa...

  14. Recurrent Glioblastomas Reveal Molecular Subtypes Associated with Mechanistic Implications of Drug-Resistance.

    Directory of Open Access Journals (Sweden)

    So Mee Kwon

    Full Text Available Previously, transcriptomic profiling studies have shown distinct molecular subtypes of glioblastomas. It has also been suggested that the recurrence of glioblastomas could be achieved by transcriptomic reprograming of tumors, however, their characteristics are not yet fully understood. Here, to gain the mechanistic insights on the molecular phenotypes of recurrent glioblastomas, gene expression profiling was performed on the 43 cases of glioblastomas including 15 paired primary and recurrent cases. Unsupervised clustering analyses revealed two subtypes of G1 and G2, which were characterized by proliferation and neuron-like gene expression traits, respectively. While the primary tumors were classified as G1 subtype, the recurrent glioblastomas showed two distinct expression types. Compared to paired primary tumors, the recurrent tumors in G1 subtype did not show expression alteration. By contrast, the recurrent tumors in G2 subtype showed expression changes from proliferation type to neuron-like one. We also observed the expression of stemness-related genes in G1 recurrent tumors and the altered expression of DNA-repair genes (i.e., AURK, HOX, MGMT, and MSH6 in the G2 recurrent tumors, which might be responsible for the acquisition of drug resistance mechanism during tumor recurrence in a subtype-specific manner. We suggest that recurrent glioblastomas may choose two different strategies for transcriptomic reprograming to escape the chemotherapeutic treatment during tumor recurrence. Our results might be helpful to determine personalized therapeutic strategy against heterogeneous glioma recurrence.

  15. Monsoonal influence on variation of hydrochemistry and isotopic signatures: Implications for associated arsenic release in groundwater

    Science.gov (United States)

    Majumder, Santanu; Datta, Saugata; Nath, Bibhash; Neidhardt, Harald; Sarkar, Simita; Roman-Ross, Gabriela; Berner, Zsolt; Hidalgo, Manuela; Chatterjee, Debankur; Chatterjee, Debashis

    2016-04-01

    The present study examines the groundwater and surface water geochemistry of two different geomorphic domains within the Chakdaha block, West Bengal, in an attempt to decipher potential influences of groundwater abstraction on the hydrochemical evolution of the aquifer, the effect of different water inputs (monsoon rain, irrigation and downward percolation from surface water impoundments) to the groundwater system and concomitant As release. A low-land flood plain and a natural levee have been selected for this purpose. Although the stable isotopic signatures of oxygen (δ18O) and hydrogen (δ2H) are largely controlled by local precipitation, the isotopic composition falls sub-parallel to the Global Meteoric Water Line (GMWL). The Cl/Br molar ratio indicates vertical recharge into the wells within the flood plain area, especially during the post-monsoon season, while influences of both evaporation and vertical mixing are visible within the natural levee wells. Increase in mean DOC concentrations (from 1.33 to 6.29 mg/L), from pre- to post-monsoon season, indicates possible inflow of organic carbon to the aquifer during the monsoonal recharge. Concomitant increase in AsT, Fe(II) and HCO3- highlights a possible initial episode of reductive dissolution of As-rich Fe-oxyhydroxides. The subsequent sharp increase in the mean As(III) proportions (by 223%), particularly in the flood plain samples during the post-monsoon season, which is accompanied by a slight increase in mean AsT (7%) may refer to anaerobic microbial degradation of DOC coupled with the reduction of As(V) to As(III) without triggering additional As release from the aquifer sediments.

  16. Habitat association and conservation implications of endangered Francois' langur (Trachypithecus francoisi.

    Directory of Open Access Journals (Sweden)

    Yajie Zeng

    Full Text Available Francois' langur (Trachypithecus francoisi is an endangered primate and endemic to the limestone forests of the tropical and subtropical zone of northern Vietnam and South-west China with a population of about 2,000 individuals. Conservation efforts are hampered by limited knowledge of habitat preference in its main distribution area. We surveyed the distribution of Francois' langur and modeled the relationship between the probability of use and habitat features in Mayanghe National Nature Reserve, Guizhou, China. The main objectives of this study were to provide quantitative information on habitat preference, estimating the availability of suitable habitat, and providing management guidelines for the effective conservation of this species. By comparing 92 used locations with habitat available in the reserve, we found that Francois' langur was mainly distributed along valleys and proportionally, used bamboo forests and mixed conifer-broadleaf forests more than their availability, whereas they tended to avoid shrubby areas and coniferous forests. The langur tended to occur at sites with lower elevation, steeper slope, higher tree canopy density, and a close distance to roads and water. The habitat occupancy probability was best modeled by vegetation type, vegetation coverage, elevation, slope degree, distances to nearest water, paved road, and farmland edge. The suitable habitat in this reserve concentrated in valleys and accounted for about 25% of the total reserve area. Our results showed that Francois' langur was not only restricted at the landscapes level at the regions with karst topography, limestone cliffs, and caves, but it also showed habitat preference at the local scale. Therefore, the protection and restoration of the langur preferred habitats such as mixed conifer-broadleaf forests are important and urgent for the conservation of this declining species.

  17. Exhalites Associated with Pb-Zn Mineralization in Devonian System and Their Prospecting Implications,Qinling,China

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    The exhalation origin of the ankerite-siliceous rocks associated with Pb-Zn mineralizations in the Devonian system of Qinling is discussed in the light of geologic setting,sedimentary-tectonic environment,lithological and chemical characteristics.On this basis,criteria for distinguishing them and their potential role as an indicator in prospecting are described.Ankerite-siliceous rocks are developed in the strata-bound Pb-Zn polymetallic belt in the Devonian system of Qinling.They are microcrystalline,dark grey and compact in appearance and are commonly carbonaceous,As a persistent ore-bearing horizon in the region,their genetic relation to the Pb-Zn deposits in generally accepted.However,a consensus has yet to be reached among geologists concerning their origein as a product of hydrothermal metasomtism at the late stage of sedimentation or as exhalite resulting from submarine exhalation.Accumulating evidence from direct observations on modern submarine hydrothermal systems strongly indicates that seafloor exhalation is a much more common geologic process than previously thought nd its metallogenic implications have long been overlooked.Characteristics of the ankerite-siliceous rocks as a product of exhalation and their significance as a guide in prospecting are described on the basis or geological setting,lithology,lithochemistry,REE,and isotopic and trace element features.

  18. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

    Science.gov (United States)

    Hayes, M Geoffrey; Urbanek, Margrit; Ehrmann, David A; Armstrong, Loren L; Lee, Ji Young; Sisk, Ryan; Karaderi, Tugce; Barber, Thomas M; McCarthy, Mark I; Franks, Stephen; Lindgren, Cecilia M; Welt, Corrine K; Diamanti-Kandarakis, Evanthia; Panidis, Dimitrios; Goodarzi, Mark O; Azziz, Ricardo; Zhang, Yi; James, Roland G; Olivier, Michael; Kissebah, Ahmed H; Stener-Victorin, Elisabet; Legro, Richard S; Dunaif, Andrea

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case-control meta-analysis, two novel loci mapping to chr 8p23.1 [Corrected] and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis. PMID:26284813

  19. Proactive interference and concurrent inhibitory processes do not differentially affect item and associative recognition: Implication for the age-related associative memory deficit.

    Science.gov (United States)

    Guez, Jonathan; Naveh-Benjamin, Moshe

    2016-09-01

    Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. ( 2000 ). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170-1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes.

  20. Genome-wide association study of shared components of reading disability and language impairment.

    Science.gov (United States)

    Eicher, J D; Powers, N R; Miller, L L; Akshoomoff, N; Amaral, D G; Bloss, C S; Libiger, O; Schork, N J; Darst, B F; Casey, B J; Chang, L; Ernst, T; Frazier, J; Kaufmann, W E; Keating, B; Kenet, T; Kennedy, D; Mostofsky, S; Murray, S S; Sowell, E R; Bartsch, H; Kuperman, J M; Brown, T T; Hagler, D J; Dale, A M; Jernigan, T L; St Pourcain, B; Davey Smith, G; Ring, S M; Gruen, J R

    2013-11-01

    Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language. PMID:24024963

  1. UGT2B4 previously implicated in the risk of breast cancer is associated with menarche timing in Ukrainian females.

    Science.gov (United States)

    Yermachenko, Anna; Dvornyk, Volodymyr

    2016-09-15

    Age at menarche (AAM) is a multifactorial trait that is regulated by dozens environmental and genetic factors. Recent meta-analysis of GWAS showed significant association of 106 loci with AAM. These polymorphisms need replicating in different ethnic populations in order to confirm their association with menarche timing. This study was aimed to replicate 53 polymorphisms that were previously associated with AAM. DNA samples were collected from 416 Ukrainian young females for further genotyping. After data quality control 47 polymorphisms remained for the association analysis using the linear regression model. SNP rs13111134 located in UGT2B4 showed the most significant association with AAM (0.431years per allele A, padj=0.044 after the Bonferroni correction). Polymorphisms rs7589318 in POMC, rs11724758 in FABP2, rs7753051 in IGF2R, rs2288696 in FGFR1 and rs12444979 in GPRC5B may also contribute to menarche timing. However, none of these associations remained significant after the Bonferroni correction for multiple testing. The obtained results provide evidence that UGT2B4, which was previously associated with predisposition to breast cancer, may play a role in the onset of menarche. PMID:27282283

  2. Australian and South Pacific External Studies Association: Odlaa's Regional Predecessor

    Science.gov (United States)

    Bewley, Donald

    2008-01-01

    The Australian and South Pacific External Studies Association (ASPESA)-- the predecessor of the Open and Distance Learning Association of Australia, Inc. (ODLAA)--was founded in 1973. From the outset, ASPESA adopted a broader-than-Australia focus for open and distance learning that included New Zealand, Papua New Guinea, and the member countries…

  3. Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2012-03-01

    interacts with risk allele count, such that PTSD is increased in those with higher risk allele counts and higher trauma exposures. Since the single nucleotide polymorphisms studied encompass stress circuitry and addiction biology, these findings may have implications for neuropsychiatric research and treatment.Keywords: posttraumatic stress disorder, genetic association study, single nucleotide polymorphism, risk alleles, trauma exposure, neuroticism, childhood adversity

  4. Prognostic Implication of M2 Macrophages Are Determined by the Proportional Balance of Tumor Associated Macrophages and Tumor Infiltrating Lymphocytes in Microsatellite-Unstable Gastric Carcinoma.

    Directory of Open Access Journals (Sweden)

    Kyung-Ju Kim

    Full Text Available Tumor associated macrophages are major inflammatory cells that play an important role in the tumor microenvironment. In this study, we investigated the prognostic significance of tumor associated macrophages (TAMs in MSI-high gastric cancers using immunohistochemistry. CD68 and CD163 were used as markers for total infiltrating macrophages and M2-polarized macrophages, respectively. The density of CD68+ or CD163+ TAMs in four different areas (epithelial and stromal compartments of both the tumor center and invasive front were analyzed in 143 cases of MSI-high advanced gastric cancers using a computerized image analysis system. Gastric cancers were scored as "0" or "1" in each area when the density of CD68+ and CD163+ TAMs was below or above the median value. Low density of CD68+ or CD163+ macrophages in four combined areas was closely associated with more frequent low-grade histology and the intestinal type tumor of the Lauren classification. In survival analysis, the low density of CD163+ TAMs was significantly associated with poor disease-free survival. In multivariate survival analysis, CD163+ TAMs in four combined areas, stromal and epithelial compartments of both tumor center and invasive front were independent prognostic indicator in MSI-high gastric cancers. In addition, the density of CD163+ TAMs correlated with tumor infiltrating lymphocytes (TILs. Our results indicate that the high density of CD163+ TAMs is an independent prognostic marker heralding prolonged disease-free survival and that the prognostic implication of CD163+ TAMs might be determined by the proportional balance of TAMs and TILs in MSI-high gastric cancers.

  5. A Cross-sectional Study of Prevalence and Implications of Depression and Anxiety in Psoriasis

    OpenAIRE

    Sreelatha Lakshmy; Sivaprakash Balasundaram; Sukanto Sarkar; Moutusi Audhya; Eswaran Subramaniam

    2015-01-01

    Background: Physical and mental comorbidity is common and has significant implications for overall health outcomes. Psoriasis, a psychocutaneous disorder, is a classic example of mental-physical comorbidity. Aims: In view of the impact of socio-cultural influences on mind-body interactions and the paucity of Indian research pertaining to psychiatric morbidity in psoriatic patients, this study was undertaken to measure the prevalence of anxiety and depression in patients with psoriasis, and to...

  6. Associations of postural knowledge and basic motor skill with dyspraxia in autism: implication for abnormalities in distributed connectivity and motor learning.

    Science.gov (United States)

    Dowell, Lauren R; Mahone, E Mark; Mostofsky, Stewart H

    2009-09-01

    Children with autism often have difficulty performing skilled movements. Praxis performance requires basic motor skill, knowledge of representations of the movement (mediated by parietal regions), and transcoding of these representations into movement plans (mediated by premotor circuits). The goals of this study were (a) to determine whether dyspraxia in autism is associated with impaired representational ("postural") knowledge and (b) to examine the contributions of postural knowledge and basic motor skill to dyspraxia in autism. Thirty-seven children with autism spectrum disorder (ASD) and 50 typically developing (TD) children, ages 8-13, completed (a) an examination of basic motor skills, (b) a postural knowledge test assessing praxis discrimination, and (c) a praxis examination. Children with ASD showed worse basic motor skill and postural knowledge than did controls. The ASD group continued to show significantly poorer praxis than did controls after accounting for age, IQ, basic motor skill, and postural knowledge. Dyspraxia in autism appears to be associated with impaired formation of spatial representations, as well as transcoding and execution. Distributed abnormality across parietal, premotor, and motor circuitry, as well as anomalous connectivity, may be implicated. PMID:19702410

  7. Geochemical mapping using stream sediments in west-central Nigeria: Implications for environmental studies and mineral exploration in West Africa

    International Nuclear Information System (INIS)

    This paper provides an overview of regional geochemical mapping using stream sediments from central and south-western Nigeria. A total of 1569 stream sediment samples were collected and 54 major and trace elements determined by ICP-MS and Au, Pd and Pt by fire assay. Multivariate statistical techniques (e.g., correlation analysis and principal factor analysis) were used to explore the data, following appropriate data transformation, to understand the data structure, investigate underlying processes controlling spatial geochemical variability and identify element associations. Major geochemical variations are controlled by source geology and provenance, as well as chemical weathering and winnowing processes, more subtle variations are a result of land use and contamination from anthropogenic activity. This work has identified placer deposits of potential economic importance for Au, REE, Ta, Nb, U and Pt, as well as other primary metal deposits. Areas of higher As and Cr (>2 mg/kg and >70 mg/kg respectively) are associated with Mesozoic and younger coastal sediments in SW Nigeria. High stream sediment Zr concentrations (mean >0.2%), from proximal zircons derived from weathering of basement rocks, have important implications for sample preparation and subsequent analysis due to interferences. Associated heavy minerals enriched in high field strength elements, and notably rare earths, may also have important implications for understanding magmatic processes within the basement terrain of West Africa. This study provides important new background/baseline geochemical values for common geological domains in Nigeria (which extend across other parts of West Africa) for assessment of contamination from urban/industrial land use changes and mining activities. Regional stream sediment mapping is also able to provide important new information with applications across a number of sectors including agriculture, health, land use and planning.

  8. Genome-wide association study of clinical dimensions of schizophrenia

    DEFF Research Database (Denmark)

    Fanous, Ayman H; Zhou, Baiyu; Aggen, Steven H;

    2012-01-01

    Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia....

  9. Current approaches of genome-wide association studies

    Institute of Scientific and Technical Information of China (English)

    Jianfeng Xu

    2008-01-01

    @@ With rapid advances in high-throughput genotyping technology and the great increase in information available on SNPs throughout the genuine, genuine-wide association(GWA) studies have now become feasible.

  10. Genome-wide association study identifies three novel genetic markers associated with elite endurance performance

    DEFF Research Database (Denmark)

    Ahmetov, Ii; Kulemin, Na; Popov, Dv;

    2015-01-01

    To investigate the association between multiple single-nucleotide polymorphisms (SNPs), aerobic performance and elite endurance athlete status in Russians. By using GWAS approach, we examined the association between 1,140,419 SNPs and relative maximal oxygen consumption rate ([Formula: see text]O2...... Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six 'endurance alleles' were identified showing discrete associations with [Formula: see text]O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs......7144481, RBFOX1 rs7191721) associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of [Formula: see text]O2max (males: P = 0.0051; females: P = 0.0005). Furthermore, the frequency of the rs1572312 C allele was significantly higher...

  11. A Genomewide Association Study of DSM-IV Cannabis Dependence

    OpenAIRE

    Agrawal, Arpana; Lynskey, Michael T.; Hinrichs, Anthony; Grucza, Richard; Saccone, Scott F; Krueger, Robert; Neuman, Rosalind; Howells, William; Fisher, Sherri; Fox, Louis; Cloninger, Robert,; Dick, Danielle M; Doheny, Kimberly F.; Edenberg, Howard J.; Goate, Alison M.

    2010-01-01

    Despite twin studies showing that 50–70% of variation in DSM-IV cannabis dependence is attributable to heritable influences, little is known of specific genotypes that influence vulnerability to cannabis dependence. We conducted a genomewide association study of DSM-IV cannabis dependence. Association analyses of 708 DSM-IV cannabis dependent cases with 2,346 cannabis exposed nondependent controls was conducted using logistic regression in PLINK. None of the 948,142 SNPs met genomewide signif...

  12. Families or Unrelated: The Evolving Debate in Genetic Association Studies

    OpenAIRE

    Fardo, David W.; Charnigo, Richard; Epstein, Michael P.

    2012-01-01

    To help uncover the genetic determinants of complex disease, a scientist often designs an association study using either unrelated subjects or family members within pedigrees. But which of these two subject recruitment paradigms is preferable? This editorial addresses the debate over the relative merits of family- and population-based genetic association studies. We begin by briefly recounting the evolution of genetic epidemiology and the rich crossroads of statistics and genetics. We then de...

  13. Implications of Ocean Acidification for Marine Microorganisms from the Free-Living to the Host-Associated

    Directory of Open Access Journals (Sweden)

    Paul A O'Brien

    2016-04-01

    Full Text Available Anthropogenic CO2 emissions are causing oceans to become more acidic, with consequences for all marine life including microorganisms. Studies reveal that from the microbes that occupy the open ocean to those intimately associated with their invertebrate hosts, changing ocean chemistry will alter the critical functions of these important organisms. Our current understanding indicates that bacterial communities associated with their host will shift as pH drops by another 0.2-0.4 units over the next 100 years. It is unclear what impacts this will have for host health, however increased vulnerability to disease seems likely for those associated with reef corals. Natural CO2 seeps have provided a unique setting for the study of microbial communities under OA in situ, where shifts in the bacterial communities associated with corals at the seep are correlated with a decline in abundance of the associated coral species. Changes to global biogeochemical cycles also appear likely as photosynthesis and nitrogen fixation by pelagic microbes becomes enhanced under low pH conditions. However, recent long-term studies have shown that pelagic microbes are also capable of evolutionary adaptation, with some physiological responses to a decline in pH restored after hundreds of generations at high pCO2 levels. The impacts of ocean acidification (OA also will not work in isolation, thus synergistic interactions with other potential stressors, such as rising seawater temperatures, will likely exacerbate the microbial response to OA. This review discusses our existing understanding of the impacts of OA on both pelagic and host-associated marine microbial communities, whilst highlighting the importance of controlled laboratory studies and in situ experiments, to fill the current gaps in our knowledge.

  14. A genome wide association study identifies common variants associated with lipid levels in the Chinese population.

    Directory of Open Access Journals (Sweden)

    Li Zhou

    Full Text Available Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC, triglycerides (TG, low-density lipoprotein cholesterol (LDL and high-density lipoprotein cholesterol (HDL in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16, 1.38 × 10(-6 and 5.59 × 10(-9, respectively. These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

  15. Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese

    Directory of Open Access Journals (Sweden)

    Li Sheng-Bin

    2011-10-01

    Full Text Available Abstract Background Monoamine oxidases (MAOs catalyze the metabolism of dopaminergic neurotransmitters. Polymorphisms of isoforms MAOA and MAOB have been implicated in the etiology of mental disorders such as schizophrenia. Association studies detected these polymorphisms in several populations, however the data have not been conclusive to date. Here, we investigated the association of MAOA and MAOB polymorphisms with schizophrenia in a Han Chinese population. Methods Two functional single nucleotide polymorphisms (SNPs, rs6323 of MAOA and rs1799836 of MAOB, were selected for association analysis in 537 unrelated schizophrenia patients and 536 healthy controls. Single-locus and Haplotype associations were calculated. Results No differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as a risk factor in the development of schizophrenia (P = 0.00001. The risk haplotype rs6323T-rs1799836G was associated with schizophrenia in female patients (P = 0.0002, but the frequency difference was not significant among male groups. Conclusions Our results suggest that MAOB is a susceptibility gene for schizophrenia. In contrast, no significant associations were observed for the MAOA functional polymorphism with schizophrenia in Han Chinese. These data support further investigation of the role of MAO genes in schizophrenia.

  16. Genome-wide association studies and contribution to cardiovascular physiology.

    Science.gov (United States)

    Munroe, Patricia B; Tinker, Andrew

    2015-09-01

    The study of family pedigrees with rare monogenic cardiovascular disorders has revealed new molecular players in physiological processes. Genome-wide association studies of complex traits with a heritable component may afford a similar and potentially intellectually richer opportunity. In this review we focus on the interpretation of genetic associations and the issue of causality in relation to known and potentially new physiology. We mainly discuss cardiometabolic traits as it reflects our personal interests, but the issues pertain broadly in many other disciplines. We also describe some of the resources that are now available that may expedite follow up of genetic association signals into observations on causal mechanisms and pathophysiology.

  17. Contribution of phytoliths to total biogenic silica volumes in the tropical rivers of Malaysia and associated implications for the marine biogeochemical cycle

    Science.gov (United States)

    Zang, Jiaye; Liu, Sen; Liu, Yanguang; Ma, Yongxing; Ran, Xiangbin

    2016-09-01

    The contribution of phytoliths to total biogenic silica (BSi) volumes in rivers worldwide, and the associated implications for the biogeochemical cycle, require in-depth study. Based on samples from rivers in Peninsular Malaysia, this project investigated the source and characteristics of BSi found in Asian tropical rivers, as well as the process of reverse weathering taking place in these fluvial systems. Results indicated that BSi samples collected in sediments consisted of phytolith, diatom and sponge spicules. Phytoliths, predominantly of the elongate form, comprised 92.8%-98.3% of BSi in the Pahang River. Diatom BSi in this river consisted mainly of pennatae diatoms, but represented a relatively small proportion of the total BSi volume. However, diatom BSi (predominantly of the Centricae form) was more prevalent in the Pontian and Endau Rivers with shares of 68.8% and 79.3% of the total BSi volumes, respectively, than Pahang River. Carbon contents of the BSi particulates ranged from 1.85% to 10.8% with an average of 4.79%. These values are higher than those recorded in other studies to date, and indicate that BSi plays a major role in controlling permanent carbon burial. This study suggests that phytoliths from terrestrial plants are the primary constituents of BSi in the rivers of Peninsular Malaysia, and therefore represent a significant proportion of the coastal silica budget.

  18. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

    Science.gov (United States)

    Lanktree, Matthew B.; Guo, Yiran; Murtaza, Muhammed; Glessner, Joseph T.; Bailey, Swneke D.; Onland-Moret, N. Charlotte; Lettre, Guillaume; Ongen, Halit; Rajagopalan, Ramakrishnan; Johnson, Toby; Shen, Haiqing; Nelson, Christopher P.; Klopp, Norman; Baumert, Jens; Padmanabhan, Sandosh; Pankratz, Nathan; Pankow, James S.; Shah, Sonia; Taylor, Kira; Barnard, John; Peters, Bas J.; M. Maloney, Cliona; Lobmeyer, Maximilian T.; Stanton, Alice; Zafarmand, M. Hadi; Romaine, Simon P.R.; Mehta, Amar; van Iperen, Erik P.A.; Gong, Yan; Price, Tom S.; Smith, Erin N.; Kim, Cecilia E.; Li, Yun R.; Asselbergs, Folkert W.; Atwood, Larry D.; Bailey, Kristian M.; Bhatt, Deepak; Bauer, Florianne; Behr, Elijah R.; Bhangale, Tushar; Boer, Jolanda M.A.; Boehm, Bernhard O.; Bradfield, Jonathan P.; Brown, Morris; Braund, Peter S.; Burton, Paul R.; Carty, Cara; Chandrupatla, Hareesh R.; Chen, Wei; Connell, John; Dalgeorgou, Chrysoula; Boer, Anthonius de; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goel, Anuj; Grobbee, Diederik E.; Hastie, Claire; Howard, Philip J.; Huang, Guan-Hua; Johnson, W. Craig; Li, Qing; Kleber, Marcus E.; Klein, Barbara E.K.; Klein, Ronald; Kooperberg, Charles; Ky, Bonnie; LaCroix, Andrea; Lanken, Paul; Lathrop, Mark; Li, Mingyao; Marshall, Vanessa; Melander, Olle; Mentch, Frank D.; J. Meyer, Nuala; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondahl, Dave; Onipinla, Abiodun; Rafelt, Suzanne; Newhouse, Stephen J.; Otieno, F. George; Patel, Sanjey R.; Putt, Mary E.; Rodriguez, Santiago; Safa, Radwan N.; Sawyer, Douglas B.; Schreiner, Pamela J.; Simpson, Claire; Sivapalaratnam, Suthesh; Srinivasan, Sathanur R.; Suver, Christine; Swergold, Gary; Sweitzer, Nancy K.; Thomas, Kelly A.; Thorand, Barbara; Timpson, Nicholas J.; Tischfield, Sam; Tobin, Martin; Tomaszweski, Maciej; Verschuren, W.M. Monique; Wallace, Chris; Winkelmann, Bernhard; Zhang, Haitao; Zheng, Dongling; Zhang, Li; Zmuda, Joseph M.; Clarke, Robert; Balmforth, Anthony J.; Danesh, John; Day, Ian N.; Schork, Nicholas J.; de Bakker, Paul I.W.; Delles, Christian; Duggan, David; Hingorani, Aroon D.; Hirschhorn, Joel N.; Hofker, Marten H.; Humphries, Steve E.; Kivimaki, Mika; Lawlor, Debbie A.; Kottke-Marchant, Kandice; Mega, Jessica L.; Mitchell, Braxton D.; Morrow, David A.; Palmen, Jutta; Redline, Susan; Shields, Denis C.; Shuldiner, Alan R.; Sleiman, Patrick M.; Smith, George Davey; Farrall, Martin; Jamshidi, Yalda; Christiani, David C.; Casas, Juan P.; Hall, Alistair S.; Doevendans, Pieter A.; D. Christie, Jason; Berenson, Gerald S.; Murray, Sarah S.; Illig, Thomas; Dorn, Gerald W.; Cappola, Thomas P.; Boerwinkle, Eric; Sever, Peter; Rader, Daniel J.; Reilly, Muredach P.; Caulfield, Mark; Talmud, Philippa J.; Topol, Eric; Engert, James C.; Wang, Kai; Dominiczak, Anna; Hamsten, Anders; Curtis, Sean P.; Silverstein, Roy L.; Lange, Leslie A.; Sabatine, Marc S.; Trip, Mieke; Saleheen, Danish; Peden, John F.; Cruickshanks, Karen J.; März, Winfried; O'Connell, Jeffrey R.; Klungel, Olaf H.; Wijmenga, Cisca; Maitland-van der Zee, Anke Hilse; Schadt, Eric E.; Johnson, Julie A.; Jarvik, Gail P.; Papanicolaou, George J.; Grant, Struan F.A.; Munroe, Patricia B.; North, Kari E.; Samani, Nilesh J.; Koenig, Wolfgang; Gaunt, Tom R.; Anand, Sonia S.; van der Schouw, Yvonne T.; Soranzo, Nicole; FitzGerald, Garret A.; Reiner, Alex; Hegele, Robert A.; Hakonarson, Hakon; Keating, Brendan J.

    2011-01-01

    Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10−6), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10−8). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10−11). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait. PMID:21194676

  19. Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

    Science.gov (United States)

    Gottlieb, D J; Hek, K; Chen, T-H; Watson, N F; Eiriksdottir, G; Byrne, E M; Cornelis, M; Warby, S C; Bandinelli, S; Cherkas, L; Evans, D S; Grabe, H J; Lahti, J; Li, M; Lehtimäki, T; Lumley, T; Marciante, K D; Pérusse, L; Psaty, B M; Robbins, J; Tranah, G J; Vink, J M; Wilk, J B; Stafford, J M; Bellis, C; Biffar, R; Bouchard, C; Cade, B; Curhan, G C; Eriksson, J G; Ewert, R; Ferrucci, L; Fülöp, T; Gehrman, P R; Goodloe, R; Harris, T B; Heath, A C; Hernandez, D; Hofman, A; Hottenga, J-J; Hunter, D J; Jensen, M K; Johnson, A D; Kähönen, M; Kao, L; Kraft, P; Larkin, E K; Lauderdale, D S; Luik, A I; Medici, M; Montgomery, G W; Palotie, A; Patel, S R; Pistis, G; Porcu, E; Quaye, L; Raitakari, O; Redline, S; Rimm, E B; Rotter, J I; Smith, A V; Spector, T D; Teumer, A; Uitterlinden, A G; Vohl, M-C; Widen, E; Willemsen, G; Young, T; Zhang, X; Liu, Y; Blangero, J; Boomsma, D I; Gudnason, V; Hu, F; Mangino, M; Martin, N G; O'Connor, G T; Stone, K L; Tanaka, T; Viikari, J; Gharib, S A; Punjabi, N M; Räikkönen, K; Völzke, H; Mignot, E; Tiemeier, H

    2015-10-01

    Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease. PMID:25469926

  20. Ambivalent implications of health care information systems: a study in the Brazilian public health care system

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    João Porto de Albuquerque

    2011-01-01

    Full Text Available This article evaluates social implications of the "SIGA" Health Care Information System (HIS in a public health care organization in the city of São Paulo. The evaluation was performed by means of an in-depth case study with patients and staff of a public health care organization, using qualitative and quantitative data. On the one hand, the system had consequences perceived as positive such as improved convenience and democratization of specialized treatment for patients and improvements in work organization. On the other hand, negative outcomes were reported, like difficulties faced by employees due to little familiarity with IT and an increase in the time needed to schedule appointments. Results show the ambiguity of the implications of HIS in developing countries, emphasizing the need for a more nuanced view of the evaluation of failures and successes and the importance of social contextual factors.

  1. Reference group theory with implications for information studies: a theoretical essay

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    E. Murell Dawson

    2001-01-01

    Full Text Available This article explores the role and implications of reference group theory in relation to the field of library and information science. Reference group theory is based upon the principle that people take the standards of significant others as a basis for making self-appraisals, comparisons, and choices regarding need and use of information. Research that applies concepts of reference group theory to various sectors of library and information studies can provide data useful in enhancing areas such as information-seeking research, special populations, and uses of information. Implications are promising that knowledge gained from like research can be beneficial in helping information professionals better understand the role theory plays in examining ways in which people manage their information and social worlds.

  2. Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.

    Science.gov (United States)

    Wheeler, Heather E; Metter, E Jeffrey; Tanaka, Toshiko; Absher, Devin; Higgins, John; Zahn, Jacob M; Wilhelmy, Julie; Davis, Ronald W; Singleton, Andrew; Myers, Richard M; Ferrucci, Luigi; Kim, Stuart K

    2009-10-01

    Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6 x 10(-5), empirical p = 0.01) that explains 1%-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans.

  3. Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.

    Directory of Open Access Journals (Sweden)

    Heather E Wheeler

    2009-10-01

    Full Text Available Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR using combined data from the Baltimore Longitudinal Study of Aging (BLSA and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20 with kidney aging (uncorrected p = 3.6 x 10(-5, empirical p = 0.01 that explains 1%-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans.

  4. Genetic association studies in lumbar disc degeneration: a systematic review.

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    Pasi J Eskola

    Full Text Available OBJECTIVE: Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI in humans. METHODS: A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. RESULTS: Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat, COL11A1 (rs1676486, GDF5 (rs143383, SKT (rs16924573, THBS2 (rs9406328 and MMP9 (rs17576. CONCLUSIONS: Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

  5. Genome-wide association study of pancreatic cancer in Japanese population.

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    Siew-Kee Low

    Full Text Available Pancreatic cancer shows very poor prognosis and is the fifth leading cause of cancer death in Japan. Previous studies indicated some genetic factors contributing to the development and progression of pancreatic cancer; however, there are limited reports for common genetic variants to be associated with this disease, especially in the Asian population. We have conducted a genome-wide association study (GWAS using 991 invasive pancreatic ductal adenocarcinoma cases and 5,209 controls, and identified three loci showing significant association (P-value<5x10(-7 with susceptibility to pancreatic cancer. The SNPs that showed significant association carried estimated odds ratios of 1.29, 1.32, and 3.73 with 95% confidence intervals of 1.17-1.43, 1.19-1.47, and 2.24-6.21; P-value of 3.30x10(-7, 3.30x10(-7, and 4.41x10(-7; located on chromosomes 6p25.3, 12p11.21 and 7q36.2, respectively. These associated SNPs are located within linkage disequilibrium blocks containing genes that have been implicated some roles in the oncogenesis of pancreatic cancer.

  6. A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

    OpenAIRE

    Zhou, Li; He, Meian; Mo, Zengnan; Wu, Chen; Handong YANG; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue

    2013-01-01

    Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome w...

  7. Worrying affects associative fear learning: a startle fear conditioning study.

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    Femke J Gazendam

    Full Text Available A valuable experimental model for the pathogenesis of anxiety disorders is that they originate from a learned association between an intrinsically non-aversive event (Conditioned Stimulus, CS and an anticipated disaster (Unconditioned Stimulus, UCS. Most anxiety disorders, however, do not evolve from a traumatic experience. Insights from neuroscience show that memory can be modified post-learning, which may elucidate how pathological fear can develop after relatively mild aversive events. Worrying--a process frequently observed in anxiety disorders--is a potential candidate to strengthen the formation of fear memory after learning. Here we tested in a discriminative fear conditioning procedure whether worry strengthens associative fear memory. Participants were randomly assigned to either a Worry (n = 23 or Control condition (n = 25. After fear acquisition, the participants in the Worry condition processed six worrisome questions regarding the personal aversive consequences of an electric stimulus (UCS, whereas the Control condition received difficult but neutral questions. Subsequently, extinction, reinstatement and re-extinction of fear were tested. Conditioned responding was measured by fear-potentiated startle (FPS, skin conductance (SCR and UCS expectancy ratings. Our main results demonstrate that worrying resulted in increased fear responses (FPS to both the feared stimulus (CS(+ and the originally safe stimulus (CS(-, whereas FPS remained unchanged in the Control condition. In addition, worrying impaired both extinction and re-extinction learning of UCS expectancy. The implication of our findings is that they show how worry may contribute to the development of anxiety disorders by affecting associative fear learning.

  8. A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass

    Institute of Scientific and Technical Information of China (English)

    Shawn; LEVY

    2010-01-01

    Osteoporosis is a highly heritable common bone disease leading to fractures that severely impair the life quality of patients.Wrist fractures caused by osteoporosis are largely due to the scarcity of wrist bone mass.Here we report the results of a genome-wide association study (GWAS) of wrist bone mineral density (BMD).We examined ~500000 SNP markers in 1000 unrelated homogeneous Caucasian subjects and found a novel allelic association with wrist BMD at rs11023787 in the SOX6 (SRY (sex determining region Y)-box 6) gene (P=9.00×10-5).Subjects carrying the C allele of rs11023787 in SOX6 had significantly higher mean wrist BMD values than those with the T allele (0.485:0.462 g cm-2 for C allele vs.T allele carriers).For validation,we performed SOX6 association for BMD in an independent Chinese sample and found that SNP rs11023787 was significantly associated with wrist BMD in the Chinese sample (P=6.41×10-3).Meta-analyses of the GWAS scan and the replication studies yielded P-values of 5.20×10-6 for rs11023787.Results of this study,together with the functional relevance of SOX6 in cartilage formation,support the SOX6 gene as an important gene for BMD variation.

  9. The inflammasome and danger associated molecular patterns (DAMPs) are implicated in cytokine and chemokine responses following stressor exposure.

    Science.gov (United States)

    Maslanik, Thomas; Mahaffey, Lucas; Tannura, Kate; Beninson, Lida; Greenwood, Benjamin N; Fleshner, Monika

    2013-02-01

    Exposure to stressors or trauma in the absence of pathogenic challenge can stimulate a systemic sterile inflammatory response characterized by high concentrations of blood and tissue cytokines, chemokines, and danger associated molecular patterns (DAMPs) such as heat shock protein-72 (Hsp72), and uric acid. The signaling pathways responsible for these responses remain unclear, however, the inflammasome may play a role. In vitro, DAMPs are known to stimulate the inflammasome in the presence of LPS to activate caspase-1 which cleaves immature precursors of interleukin (IL)-1β and IL-18 into their mature releasable forms. Furthermore, in vivo neutralization of the LPS selectively attenuates the stress-induced increase in the inflammasome-dependent cytokines IL-1β and IL-18. Thus, the current experiments tested the hypothesis that inflammasome-mediated processes are necessary for a systemic stress-induced inflammatory response to an acute stressor. The data presented (1) establish that male F344 rats exposed to an acute severe stressor (100 tail shocks) have elevated plasma concentrations of inflammatory proteins (IL-1β, IL-18, IL-6, IL-10, and monocyte chemotactic protein (MCP)-1), and DAMPs (uric acid and Hsp72); (2) demonstrate that inhibiting caspase-1 in vivo, using the caspase-1 inhibitor ac-YVAD-cmk, attenuates stress-induced production of IL-1β, IL-18, and IL-6 in both the circulation and peripheral tissues; and (3) implicates the DAMPs uric acid and Hsp72 as important signals contributing to inflammasome-dependent inflammatory responses using a stepwise multiple regression. The results increase our mechanistic understanding of systemic sterile inflammatory responses, and provide novel evidence that the inflammasome may be an important pharmacological target for treatment of these conditions. PMID:23103443

  10. Assessing exposure risk for dust storm events-associated lung function decrement in asthmatics and implications for control

    Science.gov (United States)

    Hsieh, Nan-Hung; Liao, Chung-Min

    2013-04-01

    Asian dust storms (ADS) events are seasonally-based meteorological phenomena that exacerbate chronic respiratory diseases. The purpose of this study was to assess human health risk from airborne dust exposure during ADS events in Taiwan. A probabilistic risk assessment framework was developed based on exposure and experimental data to quantify ADS events induced lung function decrement. The study reanalyzed experimental data from aerosol challenge in asthmatic individuals to construct the dose-response relationship between inhaled dust aerosol dose and decreasing percentage of forced expiratory volume in 1 s (%FEV1). An empirical lung deposition model was used to predict deposition fraction for size specific dust aerosols in pulmonary regions. The toxicokinetic and toxicodynamic models were used to simulate dust aerosols binding kinetics in lung airway in that %FEV1 change was also predicted. The mask respirators were applied to control the inhaled dose under dust aerosols exposure. Our results found that only 2% probability the mild ADS events were likely to cause %FEV1 decrement higher than 5%. There were 50% probability of decreasing %FEV1 exceeding 16.9, 18.9, and 7.1% in north, center, and south Taiwan under severe ADS events, respectively. Our result implicates that the use of activated carbon of mask respirators has the best efficacy for reducing inhaled dust aerosol dose, by which the %FEV1 decrement can be reduced up to less than 1%.

  11. Prediction of disease and phenotype associations from genome-wide association studies.

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    Stephanie N Lewis

    Full Text Available BACKGROUND: Genome wide association studies (GWAS have proven useful as a method for identifying genetic variations associated with diseases. In this study, we analyzed GWAS data for 61 diseases and phenotypes to elucidate common associations based on single nucleotide polymorphisms (SNP. The study was an expansion on a previous study on identifying disease associations via data from a single GWAS on seven diseases. METHODOLOGY/PRINCIPAL FINDINGS: Adjustments to the originally reported study included expansion of the SNP dataset using Linkage Disequilibrium (LD and refinement of the four levels of analysis to encompass SNP, SNP block, gene, and pathway level comparisons. A pair-wise comparison between diseases and phenotypes was performed at each level and the Jaccard similarity index was used to measure the degree of association between two diseases/phenotypes. Disease relatedness networks (DRNs were used to visualize our results. We saw predominant relatedness between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis for the first three levels of analysis. Expected relatedness was also seen between lipid- and blood-related traits. CONCLUSIONS/SIGNIFICANCE: The predominant associations between Multiple Sclerosis, type 1 diabetes, and rheumatoid arthritis can be validated by clinical studies. The diseases have been proposed to share a systemic inflammation phenotype that can result in progression of additional diseases in patients with one of these three diseases. We also noticed unexpected relationships between metabolic and neurological diseases at the pathway comparison level. The less significant relationships found between diseases require a more detailed literature review to determine validity of the predictions. The results from this study serve as a first step towards a better understanding of seemingly unrelated diseases and phenotypes with similar symptoms or modes of treatment.

  12. An Association Study of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Amphetamine Response

    OpenAIRE

    Brody A Flanagin; Cook, Edwin H.; de Wit, Harriet

    2006-01-01

    Although genetic factors are known to be important in addiction, no candidate genes have yet been consistently linked to drug use or abuse. Brain-derived neurotrophic factor (BDNF), which has been implicated in the behavioral response to psychomotor stimulants and potentiates neurotransmitters that are strongly linked to addiction, is a logical candidate gene to study. Using a drug challenge approach, we tested for association between BDNF G196A (val66met) genotype and subjective responses to...

  13. Allelic association studies of genome wide association data can reveal errors in marker position assignments

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    Curtis David

    2007-06-01

    Full Text Available Abstract Background Genome wide association (GWA studies provide the opportunity to develop new kinds of analysis. Analysing pairs of markers from separate regions might lead to the detection of allelic association which might indicate an interaction between nearby genes. Methods 396,591 markers typed in 541 subjects were studied. 7.8*1010 pairs of markers were screened and those showing initial evidence for allelic association were subjected to more thorough investigation along with 10 flanking markers on either side. Results No evidence was detected for interaction. However 6 markers appeared to have an incorrect map position according to NCBI Build 35. One of these was corrected in Build 36 and 2 were dropped. The remaining 3 were left with map positions inconsistent with their allelic association relationships. Discussion Although no interaction effects were detected the method was successful in identifying markers with probably incorrect map positions. Conclusion The study of allelic association can supplement other methods for assigning markers to particular map positions. Analyses of this type may usefully be applied to data from future GWA studies.

  14. An epidemiological study of respiratory syncytial virus associated hospitalizations in Denmark

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    Stensballe Lone

    2002-06-01

    Full Text Available Abstract Respiratory syncytial virus (RSV is the most common viral pathogen that causes lower respiratory tract infections in infants. Studies have implicated severe RSV infections early in life as a risk factor for subsequent development of reactive airway disease. We are conducting a study to validate RSV-associated diagnoses in the Danish National Patient Registry, to assess whether the incidence of severe RSV infection is increasing in Denmark, to identify predisposing and protective factors for RSV-associated hospitalization in Denmark, and to examine the association of severe RSV infection with reactive airway disease. The influence of various biological, social and environmental factors on hospitalization for RSV infection will be studied through several population-based registers, including the Danish National Birth Cohort: 'Better health for mothers and children'. The RSV hospitalization cases will be compared with control individuals selected within the same population groups on a case–control or a cohort basis in order to produce estimates of age-adjusted and sex-adjusted relative risks (odds ratio and relative risk for hospitalization associated with various risk factors. Using register linkage and unique registration of exposures collected through interviews and blood samples from the Danish National Birth Cohort, we will be able to resolve the issues referred to above in a very large sample of Danish children.

  15. Sialolithiasis is associated with nephrolithiasis: a case-control study.

    Science.gov (United States)

    Wu, Chuan-Chang; Hung, Shih-Han; Lin, Herng-Ching; Lee, Cha-Ze; Lee, Hsin-Chien; Chung, Shiu-Dong

    2016-05-01

    Conclusions This study demonstrates an association between sialolithiasis and nephrolithiasis. The results call for more awareness of this association among physicians and patients with nephrolithiasis. Objective Very few empirical studies have been conducted to explore the potential association between sialolithiasis and nephrolithiasis. As such, the association between sialolithiasis and nephrolithiasis still remains unclear. This study aimed to explore the possible association between sialolithiasis and nephrolithiasis using a population-based dataset. Methods Using data from the Taiwan Longitudinal Health Insurance Database 2005, this case-control study identified 966 patients with sialolithiasis as cases and 2898 sex- and age-matched subjects without sialolithiasis as controls. Conditional logistic regressions were conducted to examine the association of sialolithiasis with previously diagnosed nephrolithiasis. Results Out of 3864 sampled patients, 165 (4.27%) had prior nephrolithiasis. Using Chi-square test, it was found that there was a significant difference in the prevalence of prior nephrolithiasis between the cases and controls (10.25% vs 2.28%, p nephrolithiasis for cases was 4.74 (95% CI = 3.41-6.58, p < 0.001) when compared to controls after adjusting for monthly income, geographic location, urbanization level of residence, diabetes, hypertension, heart failure, chronic renal disease, and tobacco use. PMID:26808906

  16. Joint Analysis of Multiple Traits in Rare Variant Association Studies.

    Science.gov (United States)

    Wang, Zhenchuan; Wang, Xuexia; Sha, Qiuying; Zhang, Shuanglin

    2016-05-01

    The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, the majority of existing methods for the joint analysis of multiple traits test association between one common variant and multiple traits. However, the variant-by-variant methods for common variant association studies may not be optimal for rare variant association studies due to the allelic heterogeneity as well as the extreme rarity of individual variants. Current statistical methods for rare variant association studies are for one single trait only. In this paper, we propose an adaptive weighting reverse regression (AWRR) method to test association between multiple traits and rare variants in a genomic region. AWRR is robust to the directions of effects of causal variants and is also robust to the directions of association of traits. Using extensive simulation studies, we compare the performance of AWRR with canonical correlation analysis (CCA), Single-TOW, and the weighted sum reverse regression (WSRR). Our results show that, in all of the simulation scenarios, AWRR is consistently more powerful than CCA. In most scenarios, AWRR is more powerful than Single-TOW and WSRR. PMID:26990300

  17. Associations between Ectomycorrhizal Fungi and Bacterial Needle Endophytes in Pinus radiata: Implications for Biotic Selection of Microbial Communities

    Science.gov (United States)

    Rúa, Megan A.; Wilson, Emily C.; Steele, Sarah; Munters, Arielle R.; Hoeksema, Jason D.; Frank, Anna C.

    2016-01-01

    Studies of the ecological and evolutionary relationships between plants and their associated microbes have long been focused on single microbes, or single microbial guilds, but in reality, plants associate with a diverse array of microbes from a varied set of guilds. As such, multitrophic interactions among plant-associated microbes from multiple guilds represent an area of developing research, and can reveal how complex microbial communities are structured around plants. Interactions between coniferous plants and their associated microbes provide a good model system for such studies, as conifers host a suite of microorganisms including mutualistic ectomycorrhizal (ECM) fungi and foliar bacterial endophytes. To investigate the potential role ECM fungi play in structuring foliar bacterial endophyte communities, we sampled three isolated, native populations of Monterey pine (Pinus radiata), and used constrained analysis of principal coordinates to relate the community matrices of the ECM fungi and bacterial endophytes. Our results suggest that ECM fungi may be important factors for explaining variation in bacterial endophyte communities but this effect is influenced by population and environmental characteristics, emphasizing the potential importance of other factors — biotic or abiotic — in determining the composition of bacterial communities. We also classified ECM fungi into categories based on known fungal traits associated with substrate exploration and nutrient mobilization strategies since variation in these traits allows the fungi to acquire nutrients across a wide range of abiotic conditions and may influence the outcome of multi-species interactions. Across populations and environmental factors, none of the traits associated with fungal foraging strategy types significantly structured bacterial assemblages, suggesting these ECM fungal traits are not important for understanding endophyte-ECM interactions. Overall, our results suggest that both biotic

  18. Associations between ectomycorrhizal fungi and bacterial needle endophytes in Pinus radiata: implications for biotic selection of microbial communities

    Directory of Open Access Journals (Sweden)

    Megan Arlene Rúa

    2016-03-01

    Full Text Available Studies of the ecological and evolutionary relationships between plants and their associated microbes have long been focused on single microbes, or single microbial guilds, but in reality, plants associate with a diverse array of microbes from a varied set of guilds. As such, multitrophic interactions among plant-associated microbes from multiple guilds represent an area of developing research, and can reveal how complex microbial communities are structured around plants. Interactions between coniferous plants and their associated microbes provide a good model system for such studies, as conifers host a suite of microorganisms including mutualistic ectomycorrhizal (ECM fungi and foliar bacterial endophytes. To investigate the potential role ECM fungi play in structuring foliar bacterial endophyte communities, we sampled three isolated, native populations of Monterey pine (Pinus radiata, and used constrained analysis of principal coordinates to relate the community matrices of the ECM fungi and bacterial endophytes. Our results suggest that ECM fungi may be important factors for explaining variation in bacterial endophyte communities but this effect is influenced by population and environmental characteristics, emphasizing the potential importance of other factors — biotic or abiotic — in determining the composition of bacterial communities. We also classified ECM fungi into categories based on known fungal traits associated with substrate exploration and nutrient mobilization strategies since variation in these traits allows the fungi to acquire nutrients across a wide range of abiotic conditions and may influence the outcome of multi-species interactions. Across populations and environmental factors, none of the traits associated with fungal foraging strategy types significantly structured bacterial assemblages, suggesting these ECM fungal traits are not important for understanding endophyte-ECM interactions. Overall, our results suggest

  19. Associations between Ectomycorrhizal Fungi and Bacterial Needle Endophytes in Pinus radiata: Implications for Biotic Selection of Microbial Communities.

    Science.gov (United States)

    Rúa, Megan A; Wilson, Emily C; Steele, Sarah; Munters, Arielle R; Hoeksema, Jason D; Frank, Anna C

    2016-01-01

    Studies of the ecological and evolutionary relationships between plants and their associated microbes have long been focused on single microbes, or single microbial guilds, but in reality, plants associate with a diverse array of microbes from a varied set of guilds. As such, multitrophic interactions among plant-associated microbes from multiple guilds represent an area of developing research, and can reveal how complex microbial communities are structured around plants. Interactions between coniferous plants and their associated microbes provide a good model system for such studies, as conifers host a suite of microorganisms including mutualistic ectomycorrhizal (ECM) fungi and foliar bacterial endophytes. To investigate the potential role ECM fungi play in structuring foliar bacterial endophyte communities, we sampled three isolated, native populations of Monterey pine (Pinus radiata), and used constrained analysis of principal coordinates to relate the community matrices of the ECM fungi and bacterial endophytes. Our results suggest that ECM fungi may be important factors for explaining variation in bacterial endophyte communities but this effect is influenced by population and environmental characteristics, emphasizing the potential importance of other factors - biotic or abiotic - in determining the composition of bacterial communities. We also classified ECM fungi into categories based on known fungal traits associated with substrate exploration and nutrient mobilization strategies since variation in these traits allows the fungi to acquire nutrients across a wide range of abiotic conditions and may influence the outcome of multi-species interactions. Across populations and environmental factors, none of the traits associated with fungal foraging strategy types significantly structured bacterial assemblages, suggesting these ECM fungal traits are not important for understanding endophyte-ECM interactions. Overall, our results suggest that both biotic species

  20. Free Associations Mirroring Self- and World-Related Concepts: Implications for Personal Construct Theory, Psycholinguistics and Philosophical Psychology.

    Science.gov (United States)

    Kuška, Martin; Trnka, Radek; Kuběna, Aleš A; Růžička, Jiří

    2016-01-01

    People construe reality by using words as basic units of meaningful categorization. The present theory-driven study applied the method of a free association task to explore how people express the concepts of the world and the self in words. The respondents were asked to recall any five words relating with the word world. Afterward they were asked to recall any five words relating with the word self. The method of free association provided the respondents with absolute freedom to choose any words they wanted. Such free recall task is suggested as being a relatively direct approach to the respondents' self- and world-related conceptual categories, without enormous rational processing. The results provide us, first, with associative ranges for constructs of the world and the self, where some associative dimensions are defined by semantic polarities in the meanings of peripheral categories (e.g., Nature vs. Culture). Second, our analysis showed that some groups of verbal categories that were associated with the words world and self are central, while others are peripheral with respect to the central position. Third, the analysis of category networks revealed that some categories play the role of a transmitter, mediating the pathway between other categories in the network.

  1. Delayed gastric emptying is associated with pylorus-preserving but not classical Whipple pancreaticoduodenectomy: A review of the literature and critical reappraisal of the implicated pathomechanism

    Institute of Scientific and Technical Information of China (English)

    Kosmas I Paraskevas; Costas Avgerinos; Costas Manes; Dimitris Lytras; Christos Dervenis

    2006-01-01

    Pylorus-preserving pancreaticoduodenectomy (PPPD)is nowadays considered the treatment of choice for periampullary tumors, namely carcinoma of the head,neck, or uncinate process of the pancreas, the ampulla of Vater, distal common bile duct or carcinoma of the peri-Vaterian duodenum. Delayed gastric emptying (DGE)comprises one of the most troublesome complications of this procedure. A search of the literature using Pubmed/Medline was performed to identify clinical trials examining the incidence rate of DGE following standard Whipple pancreaticoduodenectomy (PD) vs PPPD. Additionally we performed a thorough in-depth analysis of the implicated pathomechanism underlying the occurrence of DGE after PPPD. In contrast to early studies, the majority of recently performed clinical trials demonstrated no significant association between the occurrence of DGE with either PD or PPPD. PD and PPPD procedures are equally effective operations regarding the postoperative occurrence of DGE. Further randomized trials are required to investigate the efficacy of a recently reported (but not yet tested in largescale studies) modification, that is, PPPD with antecolic duodenojejunostomy.(C) 2006 The WJG Press. All rights reserved.

  2. Generalization of Rare Variant Association Tests for Longitudinal Family Studies.

    Science.gov (United States)

    Chien, Li-Chu; Hsu, Fang-Chi; Bowden, Donald W; Chiu, Yen-Feng

    2016-02-01

    Given the functional relevance of many rare variants, their identification is frequently critical for dissecting disease etiology. Functional variants are likely to be aggregated in family studies enriched with affected members, and this aggregation increases the statistical power to detect rare variants associated with a trait of interest. Longitudinal family studies provide additional information for identifying genetic and environmental factors associated with disease over time. However, methods to analyze rare variants in longitudinal family data remain fairly limited. These methods should be capable of accounting for different sources of correlations and handling large amounts of sequencing data efficiently. To identify rare variants associated with a phenotype in longitudinal family studies, we extended pedigree-based burden (BT) and kernel (KS) association tests to genetic longitudinal studies. Generalized estimating equation (GEE) approaches were used to generalize the pedigree-based BT and KS to multiple correlated phenotypes under the generalized linear model framework, adjusting for fixed effects of confounding factors. These tests accounted for complex correlations between repeated measures of the same phenotype (serial correlations) and between individuals in the same family (familial correlations). We conducted comprehensive simulation studies to compare the proposed tests with mixed-effects models and marginal models, using GEEs under various configurations. When the proposed tests were applied to data from the Diabetes Heart Study, we found exome variants of POMGNT1 and JAK1 genes were associated with type 2 diabetes.

  3. Elevated Serum Ferritin Level Is Associated with the Incident Type 2 Diabetes in Healthy Korean Men: A 4 Year Longitudinal Study

    OpenAIRE

    Chang Hee Jung; Min Jung Lee; Jenie Yoonoo Hwang; Jung Eun Jang; Jaechan Leem; Joong-Yeol Park; JungBok Lee; Hong-Kyu Kim; Woo Je Lee

    2013-01-01

    BACKGROUND: Elevated ferritin concentration has been implicated in the etiology of type 2 diabetes. Accumulating evidence, mostly from studies conducted on western populations, has demonstrated a strong association between the elevated ferritin concentrations and incident type 2 diabetes. In Asian populations, however, the longitudinal studies investigating the association of elevated serum ferritin levels and type 2 diabetes are lacking. In present study, we aimed to determine whether elevat...

  4. Genome-wide association study of metabolic traits reveals novel gene-metabolite-disease links.

    Directory of Open Access Journals (Sweden)

    Rico Rueedi

    2014-02-01

    Full Text Available Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8 and independent associations between single nucleotide polymorphisms (SNP and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44 and lysine (rs8101881, P = 1.2×10(-33, respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.

  5. Associations of heart failure with sleep quality: The rotterdam study

    NARCIS (Netherlands)

    L.A. Zuurbier (Lisette); A.I. Luik (Annemarie); M.J.G. Leening (Maarten); A. Hofman (Albert); R. Freak-Poli (Rosanne); O.H. Franco (Oscar); B.H. Stricker; H.W. Tiemeier (Henning)

    2015-01-01

    textabstractStudy Objectives: The prevalence of sleep disturbances and heart failure increases with age. We aimed to evaluate the associations of incident heart failure and cardiac dysfunction with changes in sleep quality. Methods: This prospective population-based study was conducted in the Rotter

  6. A genome-wide association study of anorexia nervosa

    NARCIS (Netherlands)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, Annemarie; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countri

  7. Potential association of hyperhomocysteinemia with the progression of IgA nephropathy: a retrospective study

    Institute of Scientific and Technical Information of China (English)

    Duan Shuwei; Liu Shuwen; Sun Xuefeng; Zheng Ying; Liu Linchang; Yao Feixiang; Wu Jie

    2014-01-01

    Background The high blood homocysteine (Hcy) levels found in patients with hyperhomocysteinemia (HHcy) have been implicated in an increased risk of cardiovascular disease morbidity and mortality in end-stage renal disease (ESRD).This study investigated the association of HHcy with progression of IgA nephropathy.Methods We analyzed 108 participants newly diagnosed with IgA nephropathy between August 2005 and August 2007 in the Department of Nephrology,Chinese People's Liberation Army General Hospital.The association between clinicopathological factors and the Hcy levels were analyzed by Logistic regression and those with ESRD risk were analyzed by Cox regression.Results Patients were aged (35.71±10.73) years and included 45.71% women and 12.04% patients with HHcy.In multivariate Logistic regression analysis,HHcy was associated with arterial lesions (OR 2.60; 95% CI 1.55-4.34; P<0.001) even when age,body mass index,estimated glomerular filtration rate,mean arterial pressure,and initial proteinuria were taken into account.Mean follow-up was (67.37±16.21) months.HHcy was also associated with worse ESRD-free survival (HR 4.71; 95% CI 1.45 to 15.31; P=0.010).Conclusion HHcy is associated with the risk of intrarenal arterial lesions and may be useful for estimating the prognosis of IgA nephropathy.

  8. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  9. Genome-Wide Association Studies of the Human Gut Microbiota.

    Science.gov (United States)

    Davenport, Emily R; Cusanovich, Darren A; Michelini, Katelyn; Barreiro, Luis B; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  10. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma.

    Science.gov (United States)

    Chahal, Harvind S; Wu, Wenting; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A; Li, Wen-Qing; Kraft, Peter; Hinds, David A; Tang, Jean Y; Han, Jiali; Sarin, Kavita Y

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  11. Genome-wide Association Study of Biochemical Traits in Korčula Island, Croatia

    Science.gov (United States)

    Zemunik, Tatijana; Boban, Mladen; Lauc, Gordan; Janković, Stipan; Rotim, Krešimir; Vatavuk, Zoran; Benčić, Goran; Đogaš, Zoran; Boraska, Vesna; Torlak, Vesela; Sušac, Jelena; Zobić, Ivana; Rudan, Diana; Pulanić, Dražen; Modun, Darko; Mudnić, Ivana; Gunjača, Grgo; Budimir, Danijela; Hayward, Caroline; Vitart, Veronique; Wright, Alan F.; Campbell, Harry; Rudan, Igor

    2009-01-01

    Aim To identify genetic variants underlying biochemical traits – total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, uric acid, albumin, and fibrinogen, in a genome-wide association study in an isolated population where rare variants of larger effect may be more easily identified. Methods The study included 944 adult inhabitants of the island of Korčula, as a part of a larger DNA-based genetic epidemiological study in 2007. Biochemical measurements were performed in a single laboratory with stringent internal and external quality control procedures. Examinees were genotyped using Human Hap370CNV chip by Illumina, with a genome-wide scan containing 346 027 single nucleotide polymorphisms (SNP). Results A total of 31 SNPs were associated with 7 investigated traits at the level of P < 1.00 × 10−5. Nine of SNPs implicated the role of SLC2A9 in uric acid regulation (P = 4.10 × 10−6-2.58 × 10−12), as previously found in other populations. All 22 remaining associations fell into the P = 1.00 × 10−5-1.00 × 10−6 significance range. One of them replicated the association between cholesteryl ester transfer protein (CETP) and HDL, and 7 associations were more than 100 kilobases away from the closest known gene. Nearby SNPs, rs4767631 and rs10444502, in gene kinase suppressor of ras 2 (KSR2) on chromosome 12 were associated with LDL cholesterol levels, and rs10444502 in the same gene with total cholesterol levels. Similarly, rs2839619 in gene PBX/knotted 1 homeobox 1 (PKNOX1) on chromosome 21 was associated with total and LDL cholesterol levels. The remaining 9 findings implied possible associations between phosphatidylethanolamine N-methyltransferase (PEMT) gene and total cholesterol; USP46, RAP1GDS1, and ZCCHC16 genes and triglycerides; BCAT1 and SLC14A2 genes and albumin; and NR3C2, GRIK2, and PCSK2 genes and fibrinogen. Conclusion Although this study was

  12. Statistical trends in the Journal of the American Medical Association and implications for training across the continuum of medical education.

    Directory of Open Access Journals (Sweden)

    Lauren D Arnold

    Full Text Available BACKGROUND: Statistical training across the continuum of medical education may not have advanced at the pace of statistical reporting in the medical literature, yet a comprehensive understanding of statistical concepts most commonly presented in current research is critical to the effective practice of Evidence Based Medicine. The objective of this content analysis was to describe statistical techniques used in a leading medical journal, JAMA, across a 20-year period, with a focus on implications for medical education. METHODS AND FINDINGS: Two issues of JAMA published each month in 1990, 2000, and 2010 were randomly selected; from these, 361 articles were reviewed. Primary focus, study design, and statistical components were abstracted and examined by year of publication. The number of published RCTs and cohort studies differed significantly across years of interest, with an increasing trend of publication. The most commonly reported statistics over the 20-year period of interest included measures of morbidity and mortality, descriptive statistics, and epidemiologic outcomes. However, between 1990 and 2010, there was an increase in reporting of more advanced methods, such as multivariable regression, multilevel modeling, survival analysis, and sensitivity analysis. While this study is limited by a focus on one specific journal, a strength is that the journal examined is widely read by a range of clinical specialties and is considered a leading journal in the medical field, setting standards for published research. CONCLUSIONS: The increases in frequency and complexity of statistical reporting in the literature over the past two decades may suggest that moving beyond basic statistical concepts to a more comprehensive understanding of statistical methods is an important component of clinicians' ability to effectively read and use the medical research. These findings provide information to consider as medical schools and graduate medical education

  13. Genome-wide association implicates numerous genes and pleiotropy underlying ecological trait variation in natural populations of Populus trichocarpa

    Energy Technology Data Exchange (ETDEWEB)

    McKown, Athena [University of British Columbia, Vancouver; Klapste, Jaroslav [University of British Columbia, Vancouver; Guy, Robert [University of British Columbia, Vancouver; Geraldes, Armando [University of British Columbia, Vancouver; Porth, Ilga [University of British Columbia, Vancouver; Hannemann, Jan [University of Victoria, Canada; Friedmann, Michael [University of British Columbia, Vancouver; Muchero, Wellington [ORNL; Tuskan, Gerald A [ORNL; Ehlting, Juergen [University of Victoria, Canada; Cronk, Quentin [University of British Columbia, Vancouver; El-Kassaby, Yousry [University of British Columbia, Vancouver; Mansfield, Shawn [University of British Columbia, Vancouver; Douglas, Carl [University of British Columbia, Vancouver

    2014-01-01

    To uncover the genetic basis of phenotypic trait variation, we used 448 unrelated wild accessions of black cottonwood (Populus trichocarpa Torr. & Gray) from natural populations throughout western North America. Extensive information from large-scale trait phenotyping (with spatial and temporal replications within a common garden) and genotyping (with a 34K Populus SNP array) of all accessions were used for gene discovery in a genome-wide association study (GWAS).

  14. Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

    Science.gov (United States)

    Huang, Minjun; Graham, Britney E; Zhang, Ge; Harder, Reed; Kodaman, Nuri; Moore, Jason H; Muglia, Louis; Williams, Scott M

    2016-01-01

    Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with

  15. Long-Term Association Between Developmental Assets and Health Behaviors: An Exploratory Study.

    Science.gov (United States)

    Bleck, Jennifer; DeBate, Rita

    2016-10-01

    Introduction Based on internal and external assets, the positive youth development approach aims to increase the capacity among adolescents to overcome challenges as they transition to adulthood. Developmental assets have been found to be positively associated with academic achievement, a variety of health promoting behaviors, and improved physical and mental health. The purpose of this exploratory study was to assess the long-term association between positive youth developmental assets with health risk and promoting behaviors. Method A continuous scale of developmental assets was created using 30 items from Wave I of the National Longitudinal Study of Adolescent to Adult Health, when participants were in 7th to 12th grades. Health behavior outcomes including cigarette use, substance use, fast food consumption, and physical activity were measured at both Wave III (age 18-26) and Wave IV (age 24-32). Path analysis was employed to assess the relationship between these observed measures. Results The well-fitted path model revealed associations between developmental assets with each health behavior at Wave III. Developmental assets indirectly influenced each health behavior and direct associations were observed between assets with substance use and physical activity at Wave IV. Conclusion Findings provide additional support for the developmental assets approach to adolescent health. Implications include Healthy People 2020 objectives related to tobacco and alcohol use and nutrition and physical activity. PMID:26462541

  16. Genetics of Myasthenia Gravis: A Case-Control Association Study in the Hellenic Population

    Directory of Open Access Journals (Sweden)

    Zoi Zagoriti

    2012-01-01

    Full Text Available Myasthenia gravis (MG is an heterogeneous autoimmune disease characterized by the production of autoantibodies against proteins of the postsynaptic membrane, in the neuromuscular junction. The contribution of genetic factors to MG susceptibility has been evaluated through family and twin studies however, the precise genetic background of the disease remains elusive. We conducted a case-control association study in 101 unrelated MG patients of Hellenic origin and 101 healthy volunteers in order to assess the involvement of common genetic variants in susceptibility to MG. We focused on three candidate genes which have been clearly associated with several autoimmune diseases, aiming to investigate their potential implication in MG pathogenesis. These are interferon regulatory factor 5 (IRF-5, TNFα-induced protein 3 (TNFAIP3, also known as A20, and interleukin-10 (IL-10, key molecules in the regulation of immune function. A statistical trend of association (P=0.068 between IL-10 promoter single nucleotide polymorphisms (SNPs and the subgroups of early and late-onset MG patients was revealed. No statistically significant differences were observed in the rest of the variants examined. As far as we are aware, this is the first worldwide attempt to address the possible association between IRF-5 and TNFAIP3 common genetic variants and the genetic basis of MG.

  17. MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer.

    Science.gov (United States)

    Torruella-Loran, Ignasi; Laayouni, Hafid; Dobon, Begoña; Gallego, Alicia; Balcells, Ingrid; Garcia-Ramallo, Eva; Espinosa-Parrilla, Yolanda

    2016-10-01

    Nucleotide variants in microRNA regions have been associated with disease; nevertheless, few studies still have addressed the allele-dependent effect of these changes. We studied microRNA genetic variation in human populations and found that while low-frequency variants accumulate indistinctly in microRNA regions, the mature and seed regions tend to be depleted of high-frequency variants, probably as a result of purifying selection. Comparison of pairwise population fixation indexes among regions showed that the seed had higher population fixation indexes than the other regions, suggesting the existence of local adaptation in the seed region. We further performed functional studies of three microRNA variants associated with cancer (rs2910164:C > G in MIR146A, rs11614913:C > T in MIR196A2, and rs3746444:A > G in both MIR499A and MIR499B). We found differences in the expression between alleles and in the regulation of several genes involved in cancer, such as TP53, KIT, CDH1, CLH, and TERT, which may result in changes in regulatory networks related to tumorigenesis. Furthermore, luciferase-based assays showed that MIR499A could be regulating the cadherin CDH1 and the cell adhesion molecule CLH1 in an allele-dependent fashion. A better understanding of the effect of microRNA variants associated with disease could be key in our way to a more personalized medicine.

  18. Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to the Patient.

    Science.gov (United States)

    Zondervan, Krina T; Rahmioglu, Nilufer; Morris, Andrew P; Nyholt, Dale R; Montgomery, Grant W; Becker, Christian M; Missmer, Stacey A

    2016-07-01

    Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remains unknown. Genome-wide association studies (GWAS) to date have identified 12 single nucleotide polymorphisms at 10 independent genetic loci associated with endometriosis. Most of these were more strongly associated with revised American Fertility Society stage III/IV, rather than stage I/II. The loci are almost all located in intergenic regions that are known to play a role in the regulation of expression of target genes yet to be identified. To identify the target genes and pathways perturbed by the implicated variants, studies are required involving functional genomic annotation of the surrounding chromosomal regions, in terms of transcription factor binding, epigenetic modification (e.g., DNA methylation and histone modification) sites, as well as their correlation with RNA transcription. These studies need to be conducted in tissue types relevant to endometriosis-in particular, endometrium. In addition, to allow biologically and clinically relevant interpretation of molecular profiling data, they need to be combined and correlated with detailed, systematically collected phenotypic information (surgical and clinical). The WERF Endometriosis Phenome and Biobanking Harmonisation Project is a global standardization initiative that has produced consensus data and sample collection protocols for endometriosis research. These now pave the way for collaborative studies integrating phenomic with genomic data, to identify informative subtypes of endometriosis that will enhance understanding of the pathogenic mechanisms of the disease and discovery of novel, targeted treatments. PMID:27513026

  19. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and it

  20. Genome-wide association study reveals regions associated with gestation length in two pig populations

    NARCIS (Netherlands)

    Hidalgo, A.M.; Lopes, M.S.; Harlizius, B.; Bastiaansen, J.W.M.

    2016-01-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available

  1. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

    NARCIS (Netherlands)

    D.J. Gottlieb (Daniel J); K. Hek (Karin); T.-H. Chen; N.F. Watson; G. Eiriksdottir (Gudny); E.M. Byrne; M. Cornelis (Marilyn); S.C. Warby; S. Bandinelli; L. Cherkas (Lynn); D.S. Evans (Daniel); H.J. Grabe (Hans Jörgen); J. Lahti (Jari); M. Li (Man); T. Lehtimäki (Terho); T. Lumley (Thomas); K. Marciante (Kristin); L. Perusse (Louis); B.M. Psaty (Bruce); J. Robbins; G.J. Tranah (Gregory); J.M. Vink; J.B. Wilk; J.M. Stafford; C. Bellis (Claire); R. Biffar; C. Bouchard (Claude); B. Cade; G.C. Curhan (Gary); J. Eriksson; R. Ewert; L. Ferrucci (Luigi); T. Fülöp; P.R. Gehrman (Philip); R. Goodloe (Robert); T.B. Harris (Tamara B.); A.C. Heath (Andrew C.); D.G. Hernandez (Dena); A. Hofman (Albert); J.J. Hottenga (Jouke Jan); D. Hunter (David); M.K. Jensen (Majken K.); A.D. Johnson (Andrew); M. Kähönen (Mika); W.H.L. Kao (Wen); P. Kraft (Peter); E.K. Larkin; D.S. Lauderdale; A.I. Luik (Annemarie I); M. Medici; G.W. Montgomery (Grant W.); A. Palotie; S.R. Patel (Sanjay); G. Pistis (Giorgio); E. Porcu; L. Quaye (Lydia); O. Raitakari (Olli); S. Redline (Susan); E.B. Rimm (Eric B.); J.I. Rotter; A.V. Smith; T.D. Spector (Timothy); A. Teumer (Alexander); A.G. Uitterlinden (André); M.-C. Vohl (Marie-Claude); E. Widen; G.A.H.M. Willemsen (Gonneke); T.L. Young (Terri L.); X. Zhang; Y. Liu; J. Blangero (John); D.I. Boomsma (Dorret); V. Gudnason (Vilmundur); F. Hu; M. Mangino; N.G. Martin (Nicholas); G.T. O'Connor (George); K.L. Stone (Katie L); T. Tanaka; J. Viikari (Jorma); S.A. Gharib (Sina); N.M. Punjabi (Naresh); K. Räikkönen (Katri); H. Völzke (Henry); E. Mignot; H.W. Tiemeier (Henning)

    2015-01-01

    textabstractUsual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 popula

  2. Genome-wide association study identifies 74 loci associated with educational attainment

    NARCIS (Netherlands)

    Okbay, Aysu; Beauchamp, Jonathan P.; Fontana, Mark Alan; Lee, James J.; Pers, Tune H.; Rietveld, Cornelius A.; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S. Fleur W.; Oskarsson, Sven; Pickrell, Joseph K.; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S.; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H.; Concas, Maria Pina; Derringer, Jaime; Furlotte, Nicholas A.; Galesloot, Tessel E.; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M.; Harris, Sarah E.; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E.; Kaasik, Kadri; Kalafati, Ioanna P.; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J.; de Leeuw, Christiaan; Lind, Penelope A.; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B.; van der Most, Peter J.; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J.; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Brge; Schraut, Katharina E.; Shi, Jianxin; Smith, Albert V.; Poot, Raymond A.; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z.; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E.; Biino, Ginevra; Bonnelykke, Klaus; Boyle, Patricia A.; Campbell, Harry; Cappuccio, Francesco P.; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M.; Faul, Jessica D.; Feitosa, Mary F.; Forstner, Andreas J.; Gandin, Ilaria; Gunnarsson, Bjarni; Halldorsson, Bjarni V.; Harris, Tamara B.; Heath, Andrew C.; Hocking, Lynne J.; Holliday, Elizabeth G.; Homuth, Georg; Horan, Michael A.; Hottenga, Jouke-Jan; de Jager, Philip L.; Joshi, Peter K.; Jugessur, Astanand; Kaakinen, Marika A.; Kahonen, Mika; Kanoni, Stavroula; Keltigangas-Jarvinen, Liisa; Kiemeney, Lambertus A. L. M.; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T.; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J.; Lebreton, Mael P.; Levinson, Douglas F.; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C. M.; Loukola, Anu; Madden, Pamela A.; Magi, Reedik; Maki-Opas, Tomi; Marioni, Riccardo E.; Marques-Vidal, Pedro; Meddens, Gerardus A.; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W.; Myhre, Ronny; Nelson, Christopher P.; Nyholt, Dale R.; Ollier, William E. R.; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L.; Petrovic, Katja E.; Porteous, David J.; Raikkonen, Katri; Ring, Susan M.; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R.; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J.; Smith, Blair H.; Smith, Jennifer A.; Staessen, Jan A.; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D.; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J. A.; Venturini, Cristina; Vinkhuyzen, Anna A. E.; Volker, Uwe; Volzke, Henry; Vonk, Judith M.; Waage, Johannes; Ware, Erin B.; Willemsen, Gonneke; Attia, John R.; Bennett, David A.; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I.; Borecki, Ingrid B.; Bultmann, Ute; Chabris, Christopher F.; Cucca, Francesco; Cusi, Daniele; Deary, Ian J.; Dedoussis, George V.; van Duijn, Cornelia M.; Eriksson, Johan G.; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V.; Gieger, Christian; Grabe, Hans-Jorgen; Gratten, Jacob; Groenen, Patrick J. F.; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A.; Hoffmann, Wolfgang; Hyppnen, Elina; Iacono, William G.; Jacobsson, Bo; Jarvelin, Marjo-Riitta; Jockel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L. R.; Lehtimaki, Terho; Lehrer, Steven F.; Magnusson, Patrik K. E.; Martin, Nicholas G.; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W. J. H.; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A.; Samani, Nilesh J.; Schlessinger, David; Schmidt, Reinhold; Sorensen, Thorkild I. A.; Spector, Tim D.; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tiemeier, Henning; Tung, Joyce Y.; Uitterlinden, Andre G.; Vitart, Veronique; Vollenweider, Peter; Weir, David R.; Wilson, James F.; Wright, Alan F.; Conley, Dalton C.; Krueger, Robert F.; Smith, George Davey; Hofman, Albert; Laibson, David I.; Medland, Sarah E.; Meyer, Michelle N.; Yang, Jian; Johannesson, Magnus; Visscher, Peter M.; Esko, Tonu; Koellinger, Philipp D.; Cesarini, David; Benjamin, Daniel J.

    2016-01-01

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends

  3. Metagenome-wide association studies: fine-mining the microbiome.

    Science.gov (United States)

    Wang, Jun; Jia, Huijue

    2016-08-01

    Metagenome-wide association studies (MWAS) have enabled the high-resolution investigation of associations between the human microbiome and several complex diseases, including type 2 diabetes, obesity, liver cirrhosis, colorectal cancer and rheumatoid arthritis. The associations that can be identified by MWAS are not limited to the identification of taxa that are more or less abundant, as is the case with taxonomic approaches, but additionally include the identification of microbial functions that are enriched or depleted. In this Review, we summarize recent findings from MWAS and discuss how these findings might inform the prevention, diagnosis and treatment of human disease in the future. Furthermore, we highlight the need to better characterize the biology of many of the bacteria that are found in the human microbiota as an essential step in understanding how bacterial strains that have been identified by MWAS are associated with disease. PMID:27396567

  4. Genome-wide association analysis of tolerance to methylmercury toxicity in Drosophila implicates myogenic and neuromuscular developmental pathways.

    Directory of Open Access Journals (Sweden)

    Sara L Montgomery

    Full Text Available Methylmercury (MeHg is a persistent environmental toxin present in seafood that can compromise the developing nervous system in humans. The effects of MeHg toxicity varies among individuals, despite similar levels of exposure, indicating that genetic differences contribute to MeHg susceptibility. To examine how genetic variation impacts MeHg tolerance, we assessed developmental tolerance to MeHg using the sequenced, inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP. We found significant genetic variation in the effects of MeHg on development, measured by eclosion rate, giving a broad sense heritability of 0.86. To investigate the influence of dietary factors, we measured MeHg toxicity with caffeine supplementation in the DGRP lines. We found that caffeine counteracts the deleterious effects of MeHg in the majority of lines, and there is significant genetic variance in the magnitude of this effect, with a broad sense heritability of 0.80. We performed genome-wide association (GWA analysis for both traits, and identified candidate genes that fall into several gene ontology categories, with enrichment for genes involved in muscle and neuromuscular development. Overexpression of glutamate-cysteine ligase, a MeHg protective enzyme, in a muscle-specific manner leads to a robust rescue of eclosion of flies reared on MeHg food. Conversely, mutations in kirre, a pivotal myogenic gene identified in our GWA analyses, modulate tolerance to MeHg during development in accordance with kirre expression levels. Finally, we observe disruptions of indirect flight muscle morphogenesis in MeHg-exposed pupae. Since the pathways for muscle development are evolutionarily conserved, it is likely that the effects of MeHg observed in Drosophila can be generalized across phyla, implicating muscle as an additional hitherto unrecognized target for MeHg toxicity. Furthermore, our observations that caffeine can ameliorate the toxic effects of MeHg show

  5. Diverse Pseudotachylites Associated with the Whipple Detachment Fault: Implications for Seismogenesis on Low-Angle Normal Faults

    Science.gov (United States)

    Gentry, E.; Behr, W. M.; Wafforn, S.

    2014-12-01

    The Whipple detachment fault in E. California is a classic example of a large-displacement (~40 km), low-angle normal fault formed during Miocene Basin and Range extension. The footwall of this fault exhibits a range of mid-crustal rocks deformed near the brittle-ductile transition, including mylonites, cataclasites, and pseudotachylites, which provide insight into mid-crustal rheology from steady-state to seismic strain rates. Here we focus on a diverse array of pseudotachylites discovered in the Whipple footwall that have not been previously described. We examine the structural contexts, morphologies, and compositions of the pseudotachylites and discuss their implications for seismogenesis on continental low-angle normal faults. Veins that we interpret to be pseudotachylites occur as planar, anastomosing, and reservoir-like injections found along the margins of dikes, along mini-detachments kinematically linked to the Whipple fault, and within a few tens of centimeters below the silicified, erosionally resistant "microbreccia ledge" of the main detachment. The orientations of the vein generation surfaces are dominantly shallowly E-dipping, subparallel to the detachment fault itself; some occur on higher angle normal faults that sole into low angle shear zones. Veins were not found cutting the microbreccia ledge itself, suggesting that comminution and silicification post-dates pseudotachylite formation. In thin section, the veins exhibit a range in composition and degree of preservation. Some contain lath-shaped spherulites, others contain opaque, microcrystalline matrices with relict flow banding and embayed, primarily quartz clasts. Some pseudotachylite veins grade into cataclasites at their margins, suggesting cataclasis was precursory to vein formation, whereas others cut pristine mylonites with no evidence of earlier brittle deformation. Those that cut pristine mylonites contain clasts with dynamically recrystallized quartz grains with diameters of 5-7

  6. Genome-wide association study reveals regions associated with gestation length in two pig populations.

    Science.gov (United States)

    Hidalgo, A M; Lopes, M S; Harlizius, B; Bastiaansen, J W M

    2016-04-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available for 2081 Dutch Landrace-based (DL) and 2301 Large White-based (LW) pigs. We identified two QTL regions for GLE, one in each population. For DL, three associated SNPs were detected in one QTL region spanning 0.52 Mbp on Sus scrofa chromosome (SSC) 2. For LW, four associated SNPs were detected in one region of 0.14 Mbp on SSC5. The region on SSC2 contains the heparin-binding EGF-like growth factor (HBEGF) gene, which promotes embryo implantation and has been described to be involved in embryo survival throughout gestation. The associated SNP can be used for marker-assisted selection in the studied populations, and further studies of the HBEGF gene are warranted to investigate its role in GLE.

  7. Susceptibility to Chronic Mucus Hypersecretion, a Genome Wide Association Study

    Science.gov (United States)

    Dijkstra, Akkelies E.; Smolonska, Joanna; van den Berge, Maarten; Wijmenga, Ciska; Zanen, Pieter; Luinge, Marjan A.; Platteel, Mathieu; Lammers, Jan-Willem; Dahlback, Magnus; Tosh, Kerrie; Hiemstra, Pieter S.; Sterk, Peter J.; Spira, Avi; Vestbo, Jorgen; Nordestgaard, Borge G.; Benn, Marianne; Nielsen, Sune F.; Dahl, Morten; Verschuren, W. Monique; Picavet, H. Susan J.; Smit, Henriette A.; Owsijewitsch, Michael; Kauczor, Hans U.; de Koning, Harry J.; Nizankowska-Mogilnicka, Eva; Mejza, Filip; Nastalek, Pawel; van Diemen, Cleo C.; Cho, Michael H.; Silverman, Edwin K.; Crapo, James D.; Beaty, Terri H.; Lomas, David A.; Bakke, Per; Gulsvik, Amund; Bossé, Yohan; Obeidat, M. A.; Loth, Daan W.; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Andre; Stricker, Bruno H.; Brusselle, Guy G.; van Duijn, Cornelia M.; Brouwer, Uilke; Koppelman, Gerard H.; Vonk, Judith M.; Nawijn, Martijn C.; Groen, Harry J. M.; Timens, Wim; Boezen, H. Marike; Postma, Dirkje S.

    2014-01-01

    Background Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations. Methods GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP). Results A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10−6, OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3×10−9) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. Conclusions Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH. PMID:24714607

  8. Susceptibility to chronic mucus hypersecretion, a genome wide association study.

    Directory of Open Access Journals (Sweden)

    Akkelies E Dijkstra

    Full Text Available BACKGROUND: Chronic mucus hypersecretion (CMH is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA study of CMH in Caucasian populations. METHODS: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and meta-analysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (≥20 pack-years. Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP. RESULTS: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25×10(-6, OR = 1.17, located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1 on chromosome 3. The risk allele (G was associated with higher mRNA expression of SATB1 (4.3×10(-9 in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture. CONCLUSIONS: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.

  9. From Mental Game to Cultural Praxis: A Cultural Studies Model's Implications for the Future of Sport Psychology

    Science.gov (United States)

    Ryba, Tatiana V.; Wright, Handel Kashope

    2005-01-01

    This paper explores the implications of a cultural studies as praxis heuristic "model: for transforming sport psychology". It provides a brief introduction to both cultural studies and sport psychology and discusses a cultural studies intersection with sport studies and sport psychology. Cultural studies, it asserts, provides one of several…

  10. Optimal use of video for teaching the practical implications of studying business information systems:- a case study among of first semester business students

    OpenAIRE

    Fog, Benedikte; Ulfkjær, Jacob Kanneworff Stigsen; Schlichter, Bjarne Rerup

    2013-01-01

    The study of business information systems has become increasingly important in the Digital Economy. However, it has been found that students have difficulties understanding the practical implications thereof and this leads to a motivational decreases. This study aims to investigate how to optimize the use of video to increase comprehension of the practical implications of studying business information systems. This qualitative study is based on observations and focus group interviews with fir...

  11. Genome-wide association studies and resting heart rate

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas

    2016-01-01

    Genome-wide association studies (GWASs) have revolutionized the search for genetic variants regulating resting heart rate. In the last 10 years, GWASs have led to the identification of at least 21 novel heart rate loci. These discoveries have provided valuable insights into the mechanisms...... and pathways that regulate heart rate and link heart rate to cardiovascular morbidity and mortality. GWASs capture majority of genetic variation in a population sample by utilizing high-throughput genotyping chips measuring genotypes for up to several millions of SNPs across the genome in thousands...... of individuals. This allows the identification of the strongest heart rate associated signals at genome-wide level. While GWASs provide robust statistical evidence of the association of a given genetic locus with heart rate, they are only the starting point for detailed follow-up studies to locate the causal...

  12. Association between Helicobacter pylori seropositivity and mild to moderate COPD: clinical implications in an Asian country with a high prevalence of H. pylori

    Science.gov (United States)

    Lee, Ha Youn; Kim, Ji Won; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Keom

    2016-01-01

    Background Helicobacter pylori infection is a major cause of gastric diseases. The clinical implications of H. pylori infection in various diseases outside the gastrointestinal system have also been reported, including in some respiratory disorders. In this study, we investigated the seroprevalence of H. pylori in patients with mild to moderate COPD in an Asian country with a high prevalence of H. pylori infection. Also, we aimed to elucidate the association between the seroprevalence of H. pylori and the decline of lung function in patients with COPD. Methods Participants who underwent a medical checkup for H. pylori at a referral hospital in Korea were recruited for this study. All participants were tested for H. pylori infection using an immunoassay of the H. pylori-specific immunoglobulin G (IgG) concentration and a rapid urease test at the time of endoscopy with a gastric mucosal specimen. We assessed the decline in lung function using the spirometric data of those who underwent spirometry more than three times. Results In total, 603 participants (201 patients with COPD and 402 controls) were analyzed. The seroprevalence of H. pylori IgG in the patients and controls was 45.8% and 52.2%, respectively (P=0.134). The H. pylori IgG level in patients with COPD was not significantly different from that of the controls (114.8 and 109.6 units/mL, respectively; P=0.549). In addition, there were no significant differences in the annual forced expiratory volume in 1 second or forced vital capacity between the participants with H. pylori seropositivity and seronegativity. Conclusion This study showed no relationship between H. pylori infection and COPD in a country with a high burden of H. pylori infection. Furthermore, H. pylori infection did not affect the rate of lung function decline in this study population.

  13. The association of aggressive and chronic periodontitis with systemic manifestations and dental anomalies in a jordanian population: a case control study

    OpenAIRE

    Karasneh Jumana A; Abbadi Muna S; Taha Anas H; Ababneh Khansa T; Khader Yousef S

    2010-01-01

    Abstract Background The relationship between dental anomalies and periodontitis has not been documented by earlier studies. Although psychological factors have been implicated in the etiopathogenesis of periodontitis, very little information has so far been published about the association of anxiety and depression with aggressive periodontitis. The aim of this study was to investigate the association of chronic periodontitis and aggressive periodontitis with certain systemic manifestations an...

  14. Genome-wide association studies in nephrology: using known associations for data checks.

    Science.gov (United States)

    Wuttke, Matthias; Schaefer, Franz; Wong, Craig S; Köttgen, Anna

    2015-02-01

    Prior to conducting genome-wide association studies (GWAS) of renal traits and diseases, systematic checks to ensure data integrity and analytical work flow should be conducted. Using positive controls (ie, known associations between a single-nucleotide polymorphism [SNP] and a corresponding trait) allows for identifying errors that are not apparent solely from global evaluation of summary statistics. Strong genetic control associations of chronic kidney disease (CKD), as derived from GWAS, are lacking in the non-African ancestry CKD population; thus, in this perspective, we provide examples of and considerations for using positive controls among patients with CKD. Using data from individuals with CKD who participated in the CRIC (Chronic Renal Insufficiency Cohort) Study or PediGFR (Pediatric Investigation for Genetic Factors Linked to Renal Progression) Consortium, we evaluated 2 kinds of positive control traits: traits unrelated to kidney function (bilirubin level and body height) and those related to kidney function (cystatin C and urate levels). For the former, the proportion of variance in the control trait that is explained by the control SNP is the main determinant of the strength of the observable association, irrespective of adjustment for kidney function. For the latter, adjustment for kidney function can be effective in uncovering known associations among patients with CKD. For instance, in 1,092 participants in the PediGFR Consortium, the P value for the association of cystatin C concentrations and rs911119 in the CST3 gene decreased from 2.7×10(-3) to 2.4×10(-8) upon adjustment for serum creatinine-based estimated glomerular filtration rate. In this perspective, we give recommendations for the appropriate selection of control traits and SNPs that can be used for data checks prior to conducting GWAS among patients with CKD.

  15. Genome-wide association study of relative telomere length.

    Science.gov (United States)

    Prescott, Jennifer; Kraft, Peter; Chasman, Daniel I; Savage, Sharon A; Mirabello, Lisa; Berndt, Sonja I; Weissfeld, Joel L; Han, Jiali; Hayes, Richard B; Chanock, Stephen J; Hunter, David J; De Vivo, Immaculata

    2011-05-10

    Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.

  16. Genome-wide association study of relative telomere length.

    Directory of Open Access Journals (Sweden)

    Jennifer Prescott

    Full Text Available Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003 identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.

  17. Genes in the ureteric budding pathway: association study on vesico-ureteral reflux patients.

    Directory of Open Access Journals (Sweden)

    Albertien M van Eerde

    Full Text Available Vesico-ureteral reflux (VUR is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureteric budding is implicated in the pathogenesis. VUR is part of the spectrum of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT. We performed an extensive association study for primary VUR using a two-stage, case-control design, investigating 44 candidate genes in the ureteric budding pathway in 409 Dutch VUR patients. The 44 genes were selected from the literature and a set of 567 single nucleotide polymorphisms (SNPs capturing their genetic variation was genotyped in 207 cases and 554 controls. The 14 SNPs with p<0.005 were included in a follow-up study in 202 cases and 892 controls. Of the total cohort, ~50% showed a clear-cut primary VUR phenotype and ~25% had both a duplex collecting system and VUR. We also looked for association in these two extreme phenotype groups. None of the SNPs reached a significant p-value. Common genetic variants in four genes (GREM1, EYA1, ROBO2 and UPK3A show a trend towards association with the development of primary VUR (GREM1, EYA1, ROBO2 or duplex collecting system (EYA1 and UPK3A. SNPs in three genes (TGFB1, GNB3 and VEGFA have been shown to be associated with VUR in other populations. Only the result of rs1800469 in TGFB1 hinted at association in our study. This is the first extensive study of common variants in the genes of the ureteric budding pathway and the genetic susceptibility to primary VUR.

  18. SNPTrack™ : an integrated bioinformatics system for genetic association studies.

    Science.gov (United States)

    Xu, Joshua; Kelly, Reagan; Zhou, Guangxu; Turner, Steven A; Ding, Don; Harris, Stephen C; Hong, Huixiao; Fang, Hong; Tong, Weida

    2012-01-01

    A genetic association study is a complicated process that involves collecting phenotypic data, generating genotypic data, analyzing associations between genotypic and phenotypic data, and interpreting genetic biomarkers identified. SNPTrack is an integrated bioinformatics system developed by the US Food and Drug Administration (FDA) to support the review and analysis of pharmacogenetics data resulting from FDA research or submitted by sponsors. The system integrates data management, analysis, and interpretation in a single platform for genetic association studies. Specifically, it stores genotyping data and single-nucleotide polymorphism (SNP) annotations along with study design data in an Oracle database. It also integrates popular genetic analysis tools, such as PLINK and Haploview. SNPTrack provides genetic analysis capabilities and captures analysis results in its database as SNP lists that can be cross-linked for biological interpretation to gene/protein annotations, Gene Ontology, and pathway analysis data. With SNPTrack, users can do the entire stream of bioinformatics jobs for genetic association studies. SNPTrack is freely available to the public at http://www.fda.gov/ScienceResearch/BioinformaticsTools/SNPTrack/default.htm. PMID:23245293

  19. Academic Over- and Underachievement and Residence Patterns: An Associative Study.

    Science.gov (United States)

    Weislogel, Louis F.

    The purpose of this study was to examine the impact of various types of living accommodations on the academic performance of college freshmen at West Chester State College (Pennsylvania). Three types of housing were defined: single-sex dormitories, coeducational dormitories, and commuter living accommodations. The association of housing…

  20. Genome-wide association study identifies five new schizophrenia loci

    DEFF Research Database (Denmark)

    Ripke, Stephan; Sanders, Alan R; Kendler, Kenneth S;

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis...

  1. Genome-wide association study identifies five new schizophrenia loci

    NARCIS (Netherlands)

    Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan-Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; Clair, David St.; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H. R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; De Hert, Marc; Jonsson, Erik G.; Bitter, Istvan; Pietilainen, Olli P. H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E.; Black, Donald W.; Borglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A.; Datta, Susmita; De Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthoj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Hultman, Christina M.; Ingason, Andres; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Juergens, Gesche; Kahn, Renes; Keller, Matthew C.; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K.; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F. Bernard; Liang, Kung-Yee; Lichtenstein, Paul; Lieberman, Jeffrey A.; Linszen, Don H.; Lonnqvist, Jouko; Loughland, Carmel M.; Maclean, Alan W.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A.; McGrath, John J.; McIntosh, Andrew; McLean, Duncan E.; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T.; Milanova, Vihra; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Noethen, Markus M.; O'Dushlaine, Colm T.; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Orntoft, Torben F.; Owen, Michael J.; Pantelis, Christos; Papadimitriou, George; Pato, Michele T.; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Quinn, Emma M.; Rasmussen, Henrik B.; Rethelyi, Janos M.; Ribble, Robert; Rietschel, Marcella; Riley, Brien P.; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scott, Rodney J.; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M.; Spencer, Chris C. A.; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H.; Timm, Sally; Toncheva, Draga; van den Oord, Edwin; van Os, Jim; van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G.; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F.; O'Donovan, Michael C.; Daly, Mark J.; Gejman, Pablo V.

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded

  2. Genome-wide association study identifies five new schizophrenia loci

    DEFF Research Database (Denmark)

    Ripke, Stephan; Sanders, Alan R; Kendler, Kenneth S;

    2011-01-01

    We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yiel...

  3. Genome-Wide Association Study of Serum Selenium Concentrations

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    2013-05-01

    Full Text Available Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening and the Women’s Health Initiative (WHI. We tested association between 2,474,333 single nucleotide polymorphisms (SNPs and serum selenium concentrations using linear regression models. In the first stage (PLCO 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003 in the second stage (WHI. Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11 and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI. Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

  4. Association between Carotid Artery Stenosis and Cognitive Impairment in Stroke Patients: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Wei Yue

    Full Text Available To investigate potential associations between carotid artery stenosis and cognitive impairment among patients with acute ischemic stroke and to provide important clinical implications. We measured the degree of carotid artery stenosis and recorded the Mini-Mental State Examination score (MMSE at admission in 3116 acute ischemic stroke patients. The association between carotid stenosis and cognitive impairment assessed by MMSE was tested using multivariate regression analysis. Other clinical variables of interest were also studied. After adjusting for age, gender, education level, marriage, alcohol use, tobacco use, physical activity, hypertension, diabetes, hypercholesterolemia, atrial fibrillation, myocardial infarction and NIHSS (National Institutes of Health Stroke Scale score, we found that participants with high-grade stenosis of the carotid artery had a higher likelihood of cognitive impairment compared to those without carotid artery stenosis (OR = 1.49, 95%CI: 1.05-2.11, p<0.001. Left common carotid artery stenosis was associated with cognitive impairment in the univariate analysis, although this effect did not persist after adjustment for the NIHSS score. Cognitive impairment was associated with high-grade stenosis of the right carotid artery.

  5. Organizational and market factors associated with leadership development programs in hospitals: a national study.

    Science.gov (United States)

    Kim, Tae Hyun; Thompson, Jon M

    2012-01-01

    Effective leadership in hospitals is widely recognized as the key to organizational performance. Clinical, financial, and operational performance is increasingly being linked to the leadership practices of hospital managers. Moreover, effective leadership has been described as a means to achieve competitive advantage. Recent environmental forces, including reimbursement changes and increased competition, have prompted many hospitals to focus on building leadership competencies to successfully address these challenges. Using the resource dependence theory as our conceptual framework, we present results from a national study of hospitals examining the association of organizational and market factors with the provision of leadership development program activities, including the presence of a leadership development program, a diversity plan, a program for succession planning, and career development resources. The data are taken from the American Hospital Association's (AHA) 2008 Survey of Hospitals, the Area Resource File, and the Centers for Medicare & Medicaid Services. The results of multilevel logistic regressions of each leadership development program activity on organizational and market factors indicate that hospital size, system and network affiliation, and accreditation are significantly and positively associated with all leadership development program activities. The market factors significantly associated with all leadership development activities include a positive odds ratio for metropolitan statistical area location and a negative odds ratio for the percentage of the hospital's service area population that is female and minority. For-profit hospitals are less likely to provide leadership development program activities. Additional findings are presented, and the implications for hospital management are discussed. PMID:22530292

  6. Increased mortality associated with HTLV-II infection in blood donors: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Smith James W

    2004-03-01

    Full Text Available Abstract Background HTLV-I is associated with adult T-cell leukemia, and both HTLV-I and -II are associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Several published reports suggest that HTLV-I may lead to decreased survival, but HTLV-II has not previously been associated with mortality. Results We examined deaths among 138 HTLV-I, 358 HTLV-II, and 759 uninfected controls enrolled in a prospective cohort study of U.S. blood donors followed biannually since 1992. Proportional hazards models yielded hazard ratios (HRs for the association between mortality and HTLV infection, controlling for sex, race/ethnicity, age, income, educational level, blood center, smoking, injection drug use history, alcohol intake, hepatitis C status and autologous donation. After a median follow-up of 8.6 years, there were 45 confirmed subject deaths. HTLV-I infection did not convey a statistically significant excess risk of mortality (unadjusted HR 1.9, 95%CI 0.8–4.4; adjusted HR 1.9, 95%CI 0.8–4.6. HTLV-II was associated with death in both the unadjusted model (HR 2.8, 95%CI 1.5–5.5 and in the adjusted model (HR 2.3, 95%CI 1.1–4.9. No single cause of death appeared responsible for the HTLV-II effect. Conclusions After adjusting for known and potential confounders, HTLV-II infection is associated with increased mortality among healthy blood donors. If replicated in other cohorts, this finding has implications for both HTLV pathogenesis and counseling of infected persons.

  7. Genome-wide association study identifies 74 loci associated with educational attainment.

    Science.gov (United States)

    Okbay, Aysu; Beauchamp, Jonathan P; Fontana, Mark Alan; Lee, James J; Pers, Tune H; Rietveld, Cornelius A; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S Fleur W; Oskarsson, Sven; Pickrell, Joseph K; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H; Pina Concas, Maria; Derringer, Jaime; Furlotte, Nicholas A; Galesloot, Tessel E; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M; Harris, Sarah E; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E; Kaasik, Kadri; Kalafati, Ioanna P; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J; deLeeuw, Christiaan; Lind, Penelope A; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B; van der Most, Peter J; Oldmeadow, Christopher; Payton, Antony; Pervjakova, Natalia; Peyrot, Wouter J; Qian, Yong; Raitakari, Olli; Rueedi, Rico; Salvi, Erika; Schmidt, Börge; Schraut, Katharina E; Shi, Jianxin; Smith, Albert V; Poot, Raymond A; St Pourcain, Beate; Teumer, Alexander; Thorleifsson, Gudmar; Verweij, Niek; Vuckovic, Dragana; Wellmann, Juergen; Westra, Harm-Jan; Yang, Jingyun; Zhao, Wei; Zhu, Zhihong; Alizadeh, Behrooz Z; Amin, Najaf; Bakshi, Andrew; Baumeister, Sebastian E; Biino, Ginevra; Bønnelykke, Klaus; Boyle, Patricia A; Campbell, Harry; Cappuccio, Francesco P; Davies, Gail; De Neve, Jan-Emmanuel; Deloukas, Panos; Demuth, Ilja; Ding, Jun; Eibich, Peter; Eisele, Lewin; Eklund, Niina; Evans, David M; Faul, Jessica D; Feitosa, Mary F; Forstner, Andreas J; Gandin, Ilaria; Gunnarsson, Bjarni; Halldórsson, Bjarni V; Harris, Tamara B; Heath, Andrew C; Hocking, Lynne J; Holliday, Elizabeth G; Homuth, Georg; Horan, Michael A; Hottenga, Jouke-Jan; de Jager, Philip L; Joshi, Peter K; Jugessur, Astanand; Kaakinen, Marika A; Kähönen, Mika; Kanoni, Stavroula; Keltigangas-Järvinen, Liisa; Kiemeney, Lambertus A L M; Kolcic, Ivana; Koskinen, Seppo; Kraja, Aldi T; Kroh, Martin; Kutalik, Zoltan; Latvala, Antti; Launer, Lenore J; Lebreton, Maël P; Levinson, Douglas F; Lichtenstein, Paul; Lichtner, Peter; Liewald, David C M; Loukola, Anu; Madden, Pamela A; Mägi, Reedik; Mäki-Opas, Tomi; Marioni, Riccardo E; Marques-Vidal, Pedro; Meddens, Gerardus A; McMahon, George; Meisinger, Christa; Meitinger, Thomas; Milaneschi, Yusplitri; Milani, Lili; Montgomery, Grant W; Myhre, Ronny; Nelson, Christopher P; Nyholt, Dale R; Ollier, William E R; Palotie, Aarno; Paternoster, Lavinia; Pedersen, Nancy L; Petrovic, Katja E; Porteous, David J; Räikkönen, Katri; Ring, Susan M; Robino, Antonietta; Rostapshova, Olga; Rudan, Igor; Rustichini, Aldo; Salomaa, Veikko; Sanders, Alan R; Sarin, Antti-Pekka; Schmidt, Helena; Scott, Rodney J; Smith, Blair H; Smith, Jennifer A; Staessen, Jan A; Steinhagen-Thiessen, Elisabeth; Strauch, Konstantin; Terracciano, Antonio; Tobin, Martin D; Ulivi, Sheila; Vaccargiu, Simona; Quaye, Lydia; van Rooij, Frank J A; Venturini, Cristina; Vinkhuyzen, Anna A E; Völker, Uwe; Völzke, Henry; Vonk, Judith M; Vozzi, Diego; Waage, Johannes; Ware, Erin B; Willemsen, Gonneke; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Bisgaard, Hans; Boomsma, Dorret I; Borecki, Ingrid B; Bültmann, Ute; Chabris, Christopher F; Cucca, Francesco; Cusi, Daniele; Deary, Ian J; Dedoussis, George V; van Duijn, Cornelia M; Eriksson, Johan G; Franke, Barbara; Franke, Lude; Gasparini, Paolo; Gejman, Pablo V; Gieger, Christian; Grabe, Hans-Jörgen; Gratten, Jacob; Groenen, Patrick J F; Gudnason, Vilmundur; van der Harst, Pim; Hayward, Caroline; Hinds, David A; Hoffmann, Wolfgang; Hyppönen, Elina; Iacono, William G; Jacobsson, Bo; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Lehtimäki, Terho; Lehrer, Steven F; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Pendleton, Neil; Penninx, Brenda W J H; Perola, Markus; Pirastu, Nicola; Pirastu, Mario; Polasek, Ozren; Posthuma, Danielle; Power, Christine; Province, Michael A; Samani, Nilesh J; Schlessinger, David; Schmidt, Reinhold; Sørensen, Thorkild I A; Spector, Tim D; Stefansson, Kari; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Tung, Joyce Y; Uitterlinden, André G; Vitart, Veronique; Vollenweider, Peter; Weir, David R; Wilson, James F; Wright, Alan F; Conley, Dalton C; Krueger, Robert F; Davey Smith, George; Hofman, Albert; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Yang, Jian; Johannesson, Magnus; Visscher, Peter M; Esko, Tõnu; Koellinger, Philipp D; Cesarini, David; Benjamin, Daniel J

    2016-05-26

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases. PMID:27225129

  8. Logistic regression protects against population structure in genetic association studies

    OpenAIRE

    Setakis, Efrosini; Stirnadel, Heide; Balding, David J.

    2006-01-01

    We conduct an extensive simulation study to compare the merits of several methods for using null (unlinked) markers to protect against false positives due to cryptic substructure in population-based genetic association studies. The more sophisticated “structured association” methods perform well but are computationally demanding and rely on estimating the correct number of subpopulations. The simple and fast “genomic control” approach can lose power in certain scenarios. We find that procedur...

  9. Population Structure and Cryptic Relatedness in Genetic Association Studies

    OpenAIRE

    Astle, William; Balding, David J.

    2010-01-01

    We review the problem of confounding in genetic association studies, which arises principally because of population structure and cryptic relatedness. Many treatments of the problem consider only a simple ``island'' model of population structure. We take a broader approach, which views population structure and cryptic relatedness as different aspects of a single confounder: the unobserved pedigree defining the (often distant) relationships among the study subjects. Kinship is therefore a cent...

  10. A Retrospective Study of Congenital Cardiac Abnormality Associated with Scoliosis

    OpenAIRE

    Bozcali, Evin; Ucpunar, Hanifi; Sevencan, Ahmet; Balioglu, Mehmet Bulent; Albayrak, Akif; Polat, Veli

    2016-01-01

    Study Design Retrospective study. Purpose To identify the incidence of congenital cardiac abnormalities in patients who had scoliosis and underwent surgical treatment for scoliosis. Overview of Literature Congenital and idiopathic scoliosis (IS) are associated with cardiac abnormalities. We sought to establish and compare the incidence of congenital cardiac abnormalities in patients with idiopathic and congenital scoliosis (CS) who underwent surgical treatment for scoliosis. Methods Ninety co...

  11. Automated quality control for genome wide association studies

    Science.gov (United States)

    Ellingson, Sally R.; Fardo, David W.

    2016-01-01

    This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process.

  12. A STUDY ON CO MORBIDITIES ASSOCIATED WITH PSORIASIS

    OpenAIRE

    Remya Reghu; Roshni PR; Meenu Vijayan; Emmanuel James

    2013-01-01

    Psoriasis is a chronic, disfiguring inflammatory and proliferative condition of the skin. The present study focused on the comorbidities associated with psoriasis patients and also the medications used for the treatment of the same. It was a Non experimental (Observational) prospective and cross sectional study and done in the department of dermatology, Amrita Institute of Medical Sciences, (a tertiary care referral and teaching hospital, in Kochi). A total of 100 cases of psoriasis were iden...

  13. Genome-wide association study of circulating retinol levels

    OpenAIRE

    Mondul, Alison M.; Yu, Kai; Wheeler, William; Zhang, Hong; Weinstein, Stephanie J.; Major, Jacqueline M.; Cornelis, Marilyn C; Männistö, Satu; Hazra, Aditi; Hsing, Ann W.; Jacobs, Kevin B.; Eliassen, Heather; Tanaka, Toshiko; Reding, Douglas J.; Hendrickson, Sara

    2011-01-01

    Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucl...

  14. Heterogeneity of environments associated with transmission of visceral leishmaniasis in South-Eastern France and implication for control strategies.

    Directory of Open Access Journals (Sweden)

    Benoit Faucher

    Full Text Available BACKGROUND: Visceral leishmaniasis due to Leishmania infantum is currently spreading into new foci across Europe. Leishmania infantum transmission in the Old World was reported to be strongly associated with a few specific environments. Environmental changes due to global warming or human activity were therefore incriminated in the spread of the disease. However, comprehensive studies were lacking to reliably identify all the environments at risk and thereby optimize monitoring and control strategy. METHODOLOGY/FINDINGS: We exhaustively collected 328 cases of autochthonous visceral leishmaniasis from 1993 to 2009 in South-Eastern France. Leishmaniasis incidence decreased from 31 yearly cases between 1993 and 1997 to 12 yearly cases between 2005 and 2009 mostly because Leishmania/HIV coinfection were less frequent. No spread of human visceral leishmaniasis was observed in the studied region. Two major foci were identified, associated with opposite environments: whereas one involved semi-rural hillside environments partly made of mixed forests, the other involved urban and peri-urban areas in and around the region main town, Marseille. The two neighboring foci were related to differing environments despite similar vectors (P. perniciosus, canine reservoir, parasite (L. infantum zymodeme MON-1, and human host. CONCLUSIONS/SIGNIFICANCE: This unprecedented collection of cases highlighted the occurrence of protracted urban transmission of L. infantum in France, a worrisome finding as the disease is currently spreading in other areas around the Mediterranean. These results complete previous studies about more widespread canine leishmaniasis or human asymptomatic carriage. This first application of systematic geostatistical methods to European human visceral leishmaniasis demonstrated an unsuspected heterogeneity of environments associated with the transmission of the disease. These findings modify the current view of leishmaniasis epidemiology. They

  15. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes.

    Science.gov (United States)

    Arendt, Maja; Fall, Tove; Lindblad-Toh, Kerstin; Axelsson, Erik

    2014-10-01

    High amylase activity in dogs is associated with a drastic increase in copy numbers of the gene coding for pancreatic amylase, AMY2B, that likely allowed dogs to thrive on a relatively starch-rich diet during early dog domestication. Although most dogs thus probably digest starch more efficiently than do wolves, AMY2B copy numbers vary widely within the dog population, and it is not clear how this variation affects the individual ability to handle starch nor how it affects dog health. In humans, copy numbers of the gene coding for salivary amylase, AMY1, correlate with both salivary amylase levels and enzyme activity, and high amylase activity is related to improved glycemic homeostasis and lower frequencies of metabolic syndrome. Here, we investigate the relationship between AMY2B copy numbers and serum amylase activity in dogs and show that amylase activity correlates with AMY2B copy numbers. We then describe how AMY2B copy numbers vary in individuals from 20 dog breeds and find strong breed-dependent patterns, indicating that the ability to digest starch varies both at the breed and individual level. Finally, to test whether AMY2B copy number is strongly associated with the risk of developing diabetes mellitus, we compare copy numbers in cases and controls as well as in breeds with varying diabetes susceptibility. Although we see no such association here, future studies using larger cohorts are needed before excluding a possible link between AMY2B and diabetes mellitus.

  16. Ulcerated yellow spot syndrome: implications of aquaculture-related pathogens associated with soft coral Sarcophyton ehrenbergi tissue lesions.

    Science.gov (United States)

    Cervino, James M; Hauff, Briana; Haslun, Joshua A; Winiarski-Cervino, Kathryn; Cavazos, Michael; Lawther, Pamela; Wier, Andrew M; Hughen, Konrad; Strychar, Kevin B

    2012-12-27

    We introduce a new marine syndrome called ulcerated yellow spot, affecting the soft coral Sarcophyton ehrenbergi. To identify bacteria associated with tissue lesions, tissue and mucus samples were taken during a 2009 Indo-Pacific research expedition near the Wakatobi Island chain, Indonesia. Polymerase chain reaction targeting the 16S rDNA gene indicated associations with the known fish-disease-causing bacterium Photobacterium damselae, as well as multiple Vibrio species. Results indicate a shift toward decreasing diversity of bacteria in lesioned samples. Photobacterium damselae ssp. piscicida, formerly known as Pasteurella piscicida, is known as the causative agent of fish pasteurellosis and in this study, was isolated solely in lesioned tissues. Globally, fish pasteurellosis is one of the most damaging fish diseases in marine aquaculture. Vibrio alginolyticus, a putative pathogen associated with yellow band disease in scleractinian coral, was also isolated from lesioned tissues. Lesions appear to be inflicting damage on symbiotic zooxanthellae (Symbiodinium sp.), measurable by decreases in mitotic index, cell density and photosynthetic efficiency. Mitotic index of zooxanthellae within infected tissue samples was decreased by ~80%, while zooxanthellae densities were decreased by ~40% in lesioned tissue samples compared with healthy coral. These results provide evidence for the presence of known aquaculture pathogens in lesioned soft coral and may be a concern with respect to cross-species epizootics in the tropics. PMID:23269388

  17. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes.

    Science.gov (United States)

    Arendt, Maja; Fall, Tove; Lindblad-Toh, Kerstin; Axelsson, Erik

    2014-10-01

    High amylase activity in dogs is associated with a drastic increase in copy numbers of the gene coding for pancreatic amylase, AMY2B, that likely allowed dogs to thrive on a relatively starch-rich diet during early dog domestication. Although most dogs thus probably digest starch more efficiently than do wolves, AMY2B copy numbers vary widely within the dog population, and it is not clear how this variation affects the individual ability to handle starch nor how it affects dog health. In humans, copy numbers of the gene coding for salivary amylase, AMY1, correlate with both salivary amylase levels and enzyme activity, and high amylase activity is related to improved glycemic homeostasis and lower frequencies of metabolic syndrome. Here, we investigate the relationship between AMY2B copy numbers and serum amylase activity in dogs and show that amylase activity correlates with AMY2B copy numbers. We then describe how AMY2B copy numbers vary in individuals from 20 dog breeds and find strong breed-dependent patterns, indicating that the ability to digest starch varies both at the breed and individual level. Finally, to test whether AMY2B copy number is strongly associated with the risk of developing diabetes mellitus, we compare copy numbers in cases and controls as well as in breeds with varying diabetes susceptibility. Although we see no such association here, future studies using larger cohorts are needed before excluding a possible link between AMY2B and diabetes mellitus. PMID:24975239

  18. On the analysis of genome-wide association studies in family-based designs: a universal, robust analysis approach and an application to four genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Sungho Won

    2009-11-01

    Full Text Available For genome-wide association studies in family-based designs, we propose a new, universally applicable approach. The new test statistic exploits all available information about the association, while, by virtue of its design, it maintains the same robustness against population admixture as traditional family-based approaches that are based exclusively on the within-family information. The approach is suitable for the analysis of almost any trait type, e.g. binary, continuous, time-to-onset, multivariate, etc., and combinations of those. We use simulation studies to verify all theoretically derived properties of the approach, estimate its power, and compare it with other standard approaches. We illustrate the practical implications of the new analysis method by an application to a lung-function phenotype, forced expiratory volume in one second (FEV1 in 4 genome-wide association studies.

  19. Genetics, Genome-Wide Association Studies, and Menarche.

    Science.gov (United States)

    Witchel, Selma Feldman

    2016-07-01

    Puberty is characterized by maturation of the hypothalamic-pituitary-gonadal axis, development of secondary sexual features, increased linear growth velocity, maturation of the epiphyses limiting additional growth, and achievement of menarche. The age at menarche appears to have a significant genetic component. With the advent of genome-wide association studies (GWASs), the genome has been interrogated to find associations between specific loci and age at menarche. It is apparent that multiple genetic loci, epigenetic mechanisms, and environmental factors modulate this biological event crucial for reproductive competence. PMID:27513021

  20. Genotypic and phenotypic properties of cattle-associated Campylobacter and their implications to public health in the USA.

    Directory of Open Access Journals (Sweden)

    Yasser M Sanad

    Full Text Available Since cattle are a major source of food and the cattle industry engages people from farms to processing plants and meat markets, it is conceivable that beef-products contaminated with Campylobacter spp. would pose a significant public health concern. To better understand the epidemiology of cattle-associated Campylobacter spp. in the USA, we characterized the prevalence, genotypic and phenotypic properties of these pathogens. Campylobacter were detected in 181 (19.2% out of 944 fecal samples. Specifically, 71 C. jejuni, 132 C. coli, and 10 other Campylobacter spp. were identified. The prevalence of Campylobacter varied regionally and was significantly (P<0.05 higher in fecal samples collected from the South (32.8% as compared to those from the North (14.8%, Midwest (15.83%, and East (12%. Pulsed Field Gel Electrophoresis (PFGE analysis showed that C. jejuni and C. coli isolates were genotypically diverse and certain genotypes were shared across two or more of the geographic locations. In addition, 13 new C. jejuni and two C. coli sequence types (STs were detected by Multi Locus Sequence Typing (MLST. C. jejuni associated with clinically human health important sequence type, ST-61 which was not previously reported in the USA, was identified in the present study. Most frequently observed clonal complexes (CC were CC ST-21, CC ST-42, and CC ST-61, which are also common in humans. Further, the cattle associated C. jejuni strains showed varying invasion and intracellular survival capacity; however, C. coli strains showed a lower invasion and intracellular survival potential compared to C. jejuni strains. Furthermore, many cattle associated Campylobacter isolates showed resistance to several antimicrobials including ciprofloxacin, erythromycin, and gentamicin. Taken together, our results highlight the importance of cattle as a potential reservoir for clinically important Campylobacter.

  1. SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

    International Nuclear Information System (INIS)

    Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients. A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs. Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy

  2. Risk Management and Insurance Implications Associated with the Americans with Disabilities Act: Accessibility to Places of Public Accommodation

    OpenAIRE

    Robert J. Aalberts; Donald W. Hardigree

    1992-01-01

    The authors provided an analysis of Title Ill of the Americans with Disabilities Act and its impact on risk managers. They explained the issue of accessibility to public accommodations, along with the requirements for conforming with the Title III requirements of the Act. Potential insurance and risk management implications are addressed, with an analysis of possible loss control actions or remedies and insurance coverages.

  3. Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy

    OpenAIRE

    Pillas, D.; Hoggart, C. J.; Evans, D. M.; O'Reilly, P. F.; Sipila, K.; Lahdesmaki, R.; Millwood, I. Y.; Kaakinen, M; Netuveli, G.; Blane, D; Charoen, P.; Sovio, U; Pouta, A.; Freimer, N; Hartikainen, A. L.

    2010-01-01

    Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,...

  4. Genetic Variants Associated with Increased Risk of Malignant Pleural Mesothelioma: A Genome-Wide Association Study

    OpenAIRE

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; De Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara

    2013-01-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5–17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complet...

  5. An Epigenome-Wide Association Study of Total Serum Immunoglobulin E Concentration

    Science.gov (United States)

    Liang, Liming; Wong, Kenny C.C.; Davies, Gwyneth A.; Hudson, Thomas J.; Binia, Aristea; Hopkin, Julian M.; Yang, Ivana V.; Grundberg, Elin; Busche, Stephan; Hudson, Marie; Rönnblom, Lars; Pastinen, Tomi M.; Schwartz, David A.; Lathrop, G. Mark; Moffatt, Miriam F.; Cookson, William O.C.M.

    2014-01-01

    Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE benefit hay fever1 and allergic asthma1,2. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation3-6. We therefore surveyed epigenetic association between serum IgE concentrations and methylation at loci concentrated in CpG islands (CGI) genome-wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes (PBL). We validated positive results in additional families and in subjects from the general population. We show here replicated associations with a meta-analysis false discovery rate <10−4 between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors, and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining 10 fold higher variance than that derived from large SNP GWAS3,4. The study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases. PMID:25707804

  6. Genome-wide association studies in pediatric chronic kidney disease.

    Science.gov (United States)

    Gupta, Jayanta; Kanetsky, Peter A; Wuttke, Matthias; Köttgen, Anna; Schaefer, Franz; Wong, Craig S

    2016-08-01

    The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression.

  7. Study on multimers and their structures in molecular association mixture

    Institute of Scientific and Technical Information of China (English)

    NI Yi; DOU XiaoMing; ZHAO HaiYing; YIN GuangZhong; YAMAGUCHI Yoshinori; OZAKI Yukihiro

    2007-01-01

    Self-association system of (R)-1,3-butanediol in dilute carbon tetrachloride (CCl4) solution is studied as a model of molecular association mixture. Analysis methods including FSMWEFA (fixed-size moving window evolving factor analysis) combined with PCA (principal component analysis), SIMPLISMA (simple-to-use interactive self-modeling mixture analysis), and ITTFA (iterative target transformation factor analysis) are adopted to resolve infrared spectra of (R)-1,3-butanediol solution. Association number and equilibrium constant are computed. (R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium system. Theoretical investigation of trimer structures is carried out with DFT (density functional theory), and structural factors are analyzed.

  8. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Qiong Yang

    2012-01-01

    Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

  9. Study on multimers and their structures in molecular association mixture

    Institute of Scientific and Technical Information of China (English)

    YAMAGUCHI; Yoshinori; OZAKI; Yukihiro

    2007-01-01

    Self-association system of(R)-1,3-butanediol in dilute carbon tetrachloride(CCl4)solution is studied as a model of molecular association mixture.Analysis methods including FSMWEFA(fixed-size moving window evolving factor analysis)combined with PCA(principal component analysis),SIMPLISMA (simple-to-use interactive self-modeling mixture analysis),and ITTFA(iterative target transformation factor analysis)are adopted to resolve infrared spectra of(R)-1,3-butanediol solution.Association number and equilibrium constant are computed.(R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium system.Theoretical investigation of trimer structures is carried out with DFT(density functional theory),and structural factors are analyzed.

  10. Genome-wide association studies in pharmacogenetics research debate

    Science.gov (United States)

    Bailey, Kent R; Cheng, Cheng

    2016-01-01

    Will genome-wide association studies (GWAS) ‘work’ for pharmacogenetics research? This question was the topic of a staged debate, with pro and con sides, aimed to bring out the strengths and weaknesses of GWAS for pharmacogenetics studies. After a full day of seminars at the Fifth Statistical Analysis Workshop of the Pharmacogenetics Research Network, the lively debate was held – appropriately – at Goonies Comedy Club in Rochester (MN, USA). The pro side emphasized that the many GWAS successes for identifying genetic variants associated with disease risk show that it works; that the current genotyping platforms are efficient, with good imputation methods to fill in missing data; that its global assessment is always a success even if no significant associations are detected; and that genetic effects are likely to be large because humans have not evolved in a drug-therapy environment. By contrast, the con side emphasized that we have limited knowledge of the complexity of the genome; limited clinical phenotypes compromise studies; the likely multifactorial nature of drug response clouding the small genetic effects; and limitations of sample size and replication studies in pharmacogenetic studies. Lively and insightful discussions emphasized further research efforts that might benefit GWAS in pharmacogenetics. PMID:20235786

  11. Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS.

    LENUS (Irish Health Repository)

    Wilcz-Villega, E

    2013-11-29

    Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms.

  12. Kamin blocking is associated with reduced medial-frontal gyrus activation: implications for prediction error abnormality in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Paula M Moran

    Full Text Available The following study used 3-T functional magnetic resonance imaging (fMRI to investigate the neural signature of Kamin blocking. Kamin blocking is an associative learning phenomenon seen where prior association of a stimulus (A with an outcome blocks subsequent learning to an added stimulus (B when both stimuli are later presented together (AB with the same outcome. While there are a number of theoretical explanations of Kamin blocking, it is widely considered to exemplify the use of prediction error in learning, where learning occurs in proportion to the difference between expectation and outcome. In Kamin blocking as stimulus A fully predicts the outcome no prediction error is generated by the addition of stimulus B to form the compound stimulus AB, hence learning about it is "blocked". Kamin blocking is disrupted in people with schizophrenia, their relatives and healthy individuals with high psychometrically-defined schizotypy. This disruption supports suggestions that abnormal prediction error is a core deficit that can help to explain the symptoms of schizophrenia. The present study tested 9 healthy volunteers on an f-MRI adaptation of Oades' "mouse in the house task", the only task measuring Kamin blocking that shows disruption in schizophrenia patients that has been independently replicated. Participant's Kamin blocking scores were found to inversely correlate with Kamin-blocking-related activation within the prefrontal cortex, specifically the medial frontal gyrus. The medial frontal gyrus has been associated with the psychological construct of uncertainty, which we suggest is consistent with disrupted Kamin blocking and demonstrated in people with schizophrenia. These data suggest that the medial frontal gyrus merits further investigation as a potential locus of reduced Kamin blocking and abnormal prediction error in schizophrenia.

  13. Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

    Science.gov (United States)

    Sung, Yun Ju; Pérusse, Louis; Sarzynski, Mark A.; Fornage, Myriam; Sidney, Steve; Sternfeld, Barbara; Rice, Treva; Terry, Gregg; Jacobs, David R.; Katzmarzyk, Peter; Curran, Joanne E; Carr, John Jeffrey; Blangero, John; Ghosh, Sujoy; Després, Jean-Pierre; Rankinen, Tuomo; Rao, D.C.; Bouchard, Claude

    2015-01-01

    Background To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR). Subjects and Methods Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for BMI, and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2,513 subjects of European descent were available for the discovery phase. For replication, 2,171 European Americans and 772 African Americans were available. Results A total of 52 SNPs encompassing 7 loci showed suggestive evidence of association (p < 1.0 × 10−6) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; p= 1.10 × 10−7), an association that was replicated (p = 0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; p= 2.42 × 10−7). Our sex-specific analyses identified one genome-wide significant (p < 5.0 × 10−8) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (p = 3.97 × 10−8 to 1.13 × 10−8). The THNSL2 gene previously associated with VAT in women was also replicated (p= 0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively. Conclusions Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2

  14. Liposomes- and ethosomes-associated distamycins: a comparative study.

    Science.gov (United States)

    Cortesi, Rita; Romagnoli, Romeo; Drechsler, Markus; Menegatti, Enea; Zaid, Abdel N; Ravani, Laura; Esposito, Elisabetta

    2010-12-01

    The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration.

  15. Liposomes- and ethosomes-associated distamycins: a comparative study.

    Science.gov (United States)

    Cortesi, Rita; Romagnoli, Romeo; Drechsler, Markus; Menegatti, Enea; Zaid, Abdel N; Ravani, Laura; Esposito, Elisabetta

    2010-12-01

    The present article describes a comparative study of the performances of liposomes and ethosomes as specialized delivery systems for distamycin A (DA) and two of its derivatives. Liposomes and ethosomes were prepared by classical methods, extruded through polycarbonate filters, and characterized in terms of dimensions, morphology, and encapsulation efficiency. It was found that DA was associated with vesicles (either liposomes or ethosomes) by around 16.0%, while both derivatives of DA showed a percentage of association around 80% in the case of liposomes and around 50% in the case of ethosomes. In vitro antiproliferative activity experiments performed on cultured human and mouse leukemic cells demonstrated that vesicles were able to increase the activity of both derivatives of DA. In addition, it was demonstrated that the aging of both liposomes- and ethosomes-associated distamycin suspensions did not heavily influence the vesicle size, while all samples showed a relevant drug leakage with time. Moreover, according to the different physicochemical characteristics of DA and its derivatives (i.e., log P), vesicle-associated DA showed the highest loss of drug with respect to both its derivatives. In conclusion, the enhancement of drug activity expressed by these specialized delivery systems-associated DD could be interesting to obtain an efficient therapeutic effect aimed at reducing or minimizing toxic effects occurring with distamycins administration. PMID:19961302

  16. Multiple Comparisons in Genetic Association Studies: A Hierarchical Modeling Approach

    Science.gov (United States)

    Yi, Nengjun; Xu, Shizhong; Lou, Xiang-Yang; Mallick, Himel

    2016-01-01

    Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically ‘significant’ effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/). PMID:24259248

  17. A study of associated congenital anomalies with biliary atresia

    Directory of Open Access Journals (Sweden)

    Lucky Gupta

    2016-01-01

    Full Text Available Background/Purpose: This study aims to analyze the incidence and type of various associated anomalies among infants with extrahepatic biliary atresia (EHBA, compare their frequency with those quoted in the existing literature and assess their role in the overall management. Materials and Methods: A retrospective study was performed on 137 infants who underwent the Kasai procedure for EHBA during the past 12 years. The medical records were reviewed for the incidence and type of associated anomalies in addition to the details of the management of the EHBA. Results: Of the137 infants, 40 (29.2% were diagnosed as having 58 anomalies. The majority of patients had presented in the 3 rd month of life; mean age was 81 ± 33 days (range = 20-150 days. There were 32 males and 8 females; boys with EHBA had a higher incidence of associated anomalies. Of these 40 patients, 22 (37.9% had vascular anomalies, 13 patients (22.4% had hernias (umbilical-10, inguinal-3, 7 patients (12.1% had intestinal malrotation, 4 patients (6.8% had choledochal cyst, 1 patient (1.7% had Meckel′s diverticulum, 3 patients (5% had undergone prior treatment for jejunoileal atresias (jejunal-2, ileal-1, 2 patients (3.4% had undergone prior treatment for esophageal atresia and tracheoesophageal fistula, 2 patients (3.4% had spleniculi, and 2 patients (3.4% were diagnosed as having situs inversus. Conclusions: The most common associated anomalies in our study were related to the vascular variation at the porta hepatis and the digestive system. The existence of anomalies in distantly developing anatomic regions in patients with EHBA supports the possibility of a "generalized" insult during embryogenesis rather than a "localized" defect. In addition, male infants were observed to have significantly more associated anomalies as compared with the female infants in contrast to earlier reports.

  18. A whole-genome association study for pig reproductive traits.

    Science.gov (United States)

    Onteru, S K; Fan, B; Du, Z-Q; Garrick, D J; Stalder, K J; Rothschild, M F

    2012-02-01

    A whole-genome association study was performed for reproductive traits in commercial sows using the PorcineSNP60 BeadChip and Bayesian statistical methods. The traits included total number born (TNB), number born alive (NBA), number of stillborn (SB), number of mummified foetuses at birth (MUM) and gestation length (GL) in each of the first three parities. We report the associations of informative QTL and the genes within the QTL for each reproductive trait in different parities. These results provide evidence of gene effects having temporal impacts on reproductive traits in different parities. Many QTL identified in this study are new for pig reproductive traits. Around 48% of total genes located in the identified QTL regions were predicted to be involved in placental functions. The genomic regions containing genes important for foetal developmental (e.g. MEF2C) and uterine functions (e.g. PLSCR4) were associated with TNB and NBA in the first two parities. Similarly, QTL in other foetal developmental (e.g. HNRNPD and AHR) and placental (e.g. RELL1 and CD96) genes were associated with SB and MUM in different parities. The QTL with genes related to utero-placental blood flow (e.g. VEGFA) and hematopoiesis (e.g. MAFB) were associated with GL differences among sows in this population. Pathway analyses using genes within QTL identified some modest underlying biological pathways, which are interesting candidates (e.g. the nucleotide metabolism pathway for SB) for pig reproductive traits in different parities. Further validation studies on large populations are warranted to improve our understanding of the complex genetic architecture for pig reproductive traits.

  19. Association studies in common endocrine diseases (review article

    Directory of Open Access Journals (Sweden)

    Akrami SM

    2007-05-01

    Full Text Available Our understanding of the pathogenesis of endocrine disorders increase rapidly by genetic studies at the molecular level. Common endocrine disorders such as diabetes mellitus, obesity, osteoporosis, dyslipidemia and cancer follow the multifactorial model in the genetic aspect. This review tries to clarify the approach in molecular studies of such diseases for clinicians in different specialties. How to evaluate a possible association between a single nucleotide polymorphism and an endocrinopathy or its complication is the main concern of this review. Two approaches for gene mapping will be discussed as well as main challenges regarding each approach. All such genetic studies ideally include some test of the association between genome sequence variation and the phenotype of interest such as the trait itself, the presence of a given complication, or measures of some endocrinopathy-related intermediate trait. Despite different advances in this analysis, there are major concerns regarding the overall performance and robustness of genetic association studies. By using powerful new high-throughput methods, further insights to molecular basis of such endocrine disorders can be expected. Close correlation between geneticists and clinicians can effectively bridge between basic sciences and clinical investigations.

  20. A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

    Directory of Open Access Journals (Sweden)

    Jason P Wendler

    Full Text Available BACKGROUND: Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs. METHODS AND PRINCIPAL FINDINGS: Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set. CONCLUSIONS/SIGNIFICANCE: Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.

  1. Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women.

    Science.gov (United States)

    Polimanti, Renato; Kranzler, Henry R; Gelernter, Joel

    2016-10-01

    To identify novel traits associated with alleles known to predispose to alcohol and nicotine use, we conducted a phenome-wide association study (PheWAS) in a large multi-population cohort. We investigated 7688 African-Americans, 1133 Asian-Americans, 14 081 European-Americans, and 3492 Hispanic-Americans from the Women's Health Initiative, analyzing alleles at the CHRNA3-CHRNA5 locus, ADH1B, and ALDH2 with respect to phenotypic traits related to anthropometric characteristics, dietary habits, social status, psychological traits, reproductive history, health conditions, and nicotine/alcohol use. In ADH1B trans-population meta-analysis and population-specific analysis, we replicated prior associations with drinking behaviors and identified multiple novel phenome-wide significant and suggestive findings related to psychological traits, socioeconomic status, vascular/metabolic conditions, and reproductive health. We then applied Bayesian network learning algorithms to provide insight into the causative relationships of the novel ADH1B associations: ADH1B appears to affect phenotypic traits via both alcohol-mediated and alcohol-independent effects. In an independent sample of 2379 subjects, we also replicated the novel ADH1B associations related to socioeconomic status (household gross income and highest grade finished in school). For CHRNA3-CHRNA5 risk alleles, we replicated association with smoking behaviors, lung cancer, and asthma. There were also novel suggestive CHRNA3-CHRNA5 findings with respect to high-cholesterol-medication use and distrustful attitude. In conclusion, the genetics of alcohol and tobacco use potentially has broader implications on physical and mental health than is currently recognized. In particular, ADH1B may be a gene relevant for the human phenome via both alcohol metabolism-related mechanisms and other alcohol metabolism-independent mechanisms. PMID:27187070

  2. Whole-genome association study of fatty acid composition in a diverse range of beef cattle breeds.

    Science.gov (United States)

    Kelly, M J; Tume, R K; Fortes, M; Thompson, J M

    2014-05-01

    Fatty acid composition of adipose tissue associated with meat is an important factor for the beef industry because of its implications for human health, processing, meat quality, and palatability. Individual fatty acid composition is a trait under genetic control, so improvement via selective breeding of cattle is possible. The objective of this study was to investigate the genetic architecture of fatty acid composition and identify genes associated with this trait in 3 breed types: Bos indicus (Brahman), Bos taurus (4 breeds), and tropically adapted composites (2 breeds). Using high-density data, regions on chromosomes 1, 9, 14, 16, 19, 23, 26, 29, and X were associated with fat composition and quantity traits. Known candidate genes, such as fatty acid synthase (FASN; chromosome 19) and stearoyl-CoA desaturase (SCD; chromosome 26), were confirmed in our results. Other candidate genes and regions represent novel association results, requiring further validation. PMID:24782392

  3. Common Variants Confer Susceptibility to Barrett's Esophagus: Insights from the First Genome-Wide Association Studies.

    Science.gov (United States)

    Palles, Claire; Findlay, John M; Tomlinson, Ian

    2016-01-01

    Eight loci have been identified by the two genome-wide association studies of Barrett's esophagus that have been conducted to date. Esophageal adenocarcinoma cases were included in the second study following evidence that predisposing genetic variants for this cancer overlap with those for Barrett's esophagus. Genes with roles in embryonic development of the foregut are adjacent to 6 of the loci identified (FOXF1, BARX1, FOXP1, GDF7, TBX5, and ALDH1A2). An additional locus maps to a gene with known oncogenic potential (CREB-regulated transcription coactivator 1), but expression quantitative trait data implicates yet another gene involved in esophageal development (PBX4). These results strongly support a model whereby dysregulation of genes involved in esophageal and thoracic development increases susceptibility to Barrett's esophagus and esophageal adenocarcinoma, probably by reducing anatomical antireflux mechanisms. An additional signal at 6p21 in the major histocompatibility complex also reinforces evidence that immune and inflammatory response to reflux is involved in the development of both diseases. All of the variants identified are intronic or intergenic rather than coding and are presumed to be or to mark regulatory variants. As with genome-wide association studies of other diseases, the functional variants at each locus are yet to be identified and the genes affected need confirming. In this chapter as well as discussing the biology behind each genome-wide association signal, we review the requirements for successfully conducting genome-wide association studies and discuss how progress in understanding the genetic variants that contribute to Barrett's esophagus/esophageal adenocarcinoma susceptibility compares to other cancers. PMID:27573776

  4. The Tuskegee Syphilis Study, 1932 to 1972: Implications for HIV Education and AIDS Risk Education Programs in the Black Community.

    Science.gov (United States)

    Thomas, Stephen B.; Quinn, Sandra Crouse

    1991-01-01

    The Tuskegee study of untreated syphilis in black males caused distrust by blacks of the public health system that has implications for Acquired Immune Deficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) studies. AIDS prevention among blacks may require openness about the Tuskegee study to allay fears of repetition. (SLD)

  5. Genetic association- and linkage studies in colorectal cancer

    OpenAIRE

    Holst, Susanna von

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer type in the Western world. Over one million patients are diagnosed worldwide yearly. A family history of CRC is a major risk factor for CRC. The total genetic contribution to disease development is estimated to be 35%. High-risk syndromes caused by known genes such as familial adenomatous polyposis (FAP) and Lynch Syndrome (LS) explain less than 5% of that number. Recently, several genome-wide association studies (GWAS) ha...

  6. Genome-Wide Association Study of Proneness to Anger

    OpenAIRE

    Mick, Eric; Mcgough, James,; Deutsch, Curtis K.; Jean A. Frazier; Kennedy, David; Goldberg, Robert J.

    2014-01-01

    Background Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. Methods With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger S...

  7. Facial dermatosis associated with Demodex: a case-control study*

    OpenAIRE

    Zhao, Ya-e; Peng, Yan; Wang, Xiang-lan; Wu, Li-ping; Wang, Mei; Yan, Hu-ling; XIAO, SHENG-XIANG

    2011-01-01

    Demodex has been considered to be related with multiple skin disorders, but controversy persists. In this case-control study, a survey was conducted with 860 dermatosis patients aged 12 to 84 years in Xi’an, China to identify the association between facial dermatosis and Demodex. Amongst the patients, 539 suffered from facial dermatosis and 321 suffered from non-facial dermatosis. Demodex mites were sampled and examined using the skin pressurization method. Multivariate regression analysis wa...

  8. Associative learning on imbalanced environments: An empirical study

    OpenAIRE

    Cleofas Sánchez, Laura; Sánchez Garreta, José Salvador; García, V.; Valdovinos, R.M.

    2015-01-01

    Associative memories have emerged as a powerful computational neural network model for several pattern classification problems. Like most traditional classifiers, these models assume that the classes share similar prior probabilities. However, in many real-life applications the ratios of prior probabilities between classes are extremely skewed. Although the literature has provided numerous studies that examine the performance degradation of renowned classifiers on different imbalanced scenari...

  9. Inhibitions and implications associated with celebrity participation in social marketing programs focusing on HIV prevention: an exploratory research

    OpenAIRE

    Beatriz Casais; Proença, João F.

    2010-01-01

    This paper discusses celebrity participation in social marketing programs focusing on public health, especially on HIV programs. The research identifies the inhibitions of celebrity people and implications that this involvement may have upon their lives. The paper analysis data from in-depth interviews made to twenty-seven Portuguese celebrities from arts, show business and sports. The results show absence of prejudice against HIV. Famous people feel motivated to join public health and HIV ca...

  10. Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Luca Valenti; Paola Dongiovanni; Silvia Fargion

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD),defined by excessive liver fat deposition related to the metabolic syndrome,is a leading cause of progressive liver disease,for which accurate non-invasive staging systems and effective treatments are still lacking.Evidence has shown that increased ferritin levels are associated with the metabolic insulin resistance syndrome,and higher hepatic iron and fat content.Hyperferritinemia and iron stores have been associated with the severity of liver damage in NAFLD,and iron depletion reduced insulin resistance and liver enzymes.Recently,Kowdley et al demonstrated in a multicenter study in 628 adult patients with NAFLD from the NAFLD-clinical research network database with central re-evaluation of liver histology and iron staining that the increased serum ferritin level is an independent predictor of liver damage in patients with NAFLD,and is useful to identify NAFLD patients at risk of non-alcoholic steatohepatitis and advanced fibrosis.These data indicate that incorporation of serum ferritin level may improve the performance of noninvasive scoring of liver damage in patients with NAFLD,and that iron depletion still represents an attractive therapeutic target to prevent the progression of liver damage in these patients.

  11. Genome-Wide Association Study of Antiphospholipid Antibodies

    Directory of Open Access Journals (Sweden)

    M. Ilyas Kamboh

    2013-01-01

    Full Text Available Background. The persistent presence of antiphospholipid antibodies (APA may lead to the development of primary or secondary antiphospholipid syndrome. Although the genetic basis of APA has been suggested, the identity of the underlying genes is largely unknown. In this study, we have performed a genome-wide association study (GWAS in an effort to identify susceptibility loci/genes for three main APA: anticardiolipin antibodies (ACL, lupus anticoagulant (LAC, and anti-β2 glycoprotein I antibodies (anti-β2GPI. Methods. DNA samples were genotyped using the Affymetrix 6.0 array containing 906,600 single-nucleotide polymorphisms (SNPs. Association of SNPs with the antibody status (positive/negative was tested using logistic regression under the additive model. Results. We have identified a number of suggestive novel loci with Passociations of HLA genes and APOH with APA but these were not the top loci. Conclusions. We have identified a number of suggestive novel loci for APA that will stimulate follow-up studies in independent and larger samples to replicate our findings.

  12. A Western dietary pattern is associated with overweight and obesity in a national sample of Lebanese adolescents (13–19 years): a cross-sectional study

    OpenAIRE

    Naja, Farah; Hwalla, Nahla; Itani, Leila; Karam, Sabine; Mehio Sibai, Abla; Nasreddine, Lara

    2015-01-01

    Adolescent obesity is associated with both immediate and longer-term health implications. This study aims to identify dietary patterns among a nationally representative sample of Lebanese adolescents aged between 13 and 19 years (n 446) and to assess the association of these patterns with overweight and obesity. Through face-to-face interviews, socio-demographic, lifestyle and anthropometric variables were collected. Dietary intake was assessed using a sixty-one-item FFQ. Dietary patterns wer...

  13. Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility

    Science.gov (United States)

    Cook, James P; Morris, Andrew P

    2016-01-01

    Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases. We identified a novel locus for T2D susceptibility at genome-wide significance (P<5 × 10−8) that maps to TOMM40-APOE, a region previously implicated in lipid metabolism and Alzheimer's disease. We have also confirmed previous reports that single-nucleotide polymorphisms at the TCF7L2 locus demonstrate the greatest extent of heterogeneity in allelic effects between ethnic groups, with the lowest risk observed in populations of East Asian ancestry. PMID:27189021

  14. Studying the role of dystrophin-associated proteins in influencing Becker muscular dystrophy disease severity.

    Science.gov (United States)

    van den Bergen, J C; Wokke, B H A; Hulsker, M A; Verschuuren, J J G M; Aartsma-Rus, A M

    2015-03-01

    Becker muscular dystrophy is characterized by a variable disease course. Many factors have been implicated to contribute to this diversity, among which the expression of several components of the dystrophin associated glycoprotein complex. Together with dystrophin, most of these proteins anchor the muscle fiber cytoskeleton to the extracellular matrix, thus protecting the muscle from contraction induced injury, while nNOS is primarily involved in inducing vasodilation during muscle contraction, enabling adequate muscle oxygenation. In the current study, we investigated the role of three components of the dystrophin associated glycoprotein complex (beta-dystroglycan, gamma-sarcoglycan and nNOS) and the dystrophin homologue utrophin on disease severity in Becker patients. Strength measurements, data about disease course and fresh muscle biopsies of the anterior tibial muscle were obtained from 24 Becker patients aged 19 to 66. The designation of Becker muscular dystrophy in this study was based on the mutation and not on the clinical severity. Contrary to previous studies, we were unable to find a relationship between expression of nNOS, beta-dystroglycan and gamma-sarcoglycan at the sarcolemma and disease severity, as measured by muscle strength in five muscle groups and age at reaching several disease milestones. Unexpectedly, we found an inverse correlation between utrophin expression at the sarcolemma and age at reaching disease milestones.

  15. Genome-wide association study of aggressive behaviour in chicken

    Science.gov (United States)

    Li, Zhenhui; Zheng, Ming; Abdalla, Bahareldin Ali; Zhang, Zhe; Xu, Zhenqiang; Ye, Qiao; Xu, Haiping; Luo, Wei; Nie, Qinghua; Zhang, Xiquan

    2016-01-01

    In the poultry industry, aggressive behaviour is a large animal welfare issue all over the world. To date, little is known about the underlying genetics of the aggressive behaviour. Here, we performed a genome-wide association study (GWAS) to explore the genetic mechanism associated with aggressive behaviour in chickens. The GWAS results showed that a total of 33 SNPs were associated with aggressive behaviour traits (P < 4.6E-6). rs312463697 on chromosome 4 was significantly associated with aggression (P = 2.10905E-07), and it was in the intron region of the sortilin-related VPS10 domain containing receptor 2 (SORCS2) gene. In addition, biological function analysis of the nearest 26 genes around the significant SNPs was performed with Ingenuity Pathway Analysis. An interaction network contained 17 genes was obtained and SORCS2 was involved in this network, interacted with nerve growth factor (NGF), nerve growth factor receptor (NGFR), dopa decarboxylase (L-dopa) and dopamine. After knockdown of SORCS2, the mRNA levels of NGF, L-dopa and dopamine receptor genes DRD1, DRD2, DRD3 and DRD4 were significantly decreased (P < 0.05). In summary, our data indicated that SORCS2 might play an important role in chicken aggressive behaviour through the regulation of dopaminergic pathways and NGF. PMID:27485826

  16. [Association study of telomere length with idiopathic male infertility].

    Science.gov (United States)

    Shuyuan, Liu; Changjun, Zhang; Haiying, Peng; Xiaoqin, Huang; Hao, Sun; Keqin, Lin; Kai, Huang; Jiayou, Chu; Zhaoqing, Yang

    2015-11-01

    Telomeres are evolutionary conserved, multifunctional DNA-protein complexes located at the ends of eukaryotic chromosomes. Telomeres maintain chromosome stability and genome integrity and also play an important role in meiosis which aid in synapsis, homologous recombination, and segregation. Sperm telomere has been reported to play an important role in fertilization and embryo development. Nowadays, the association between telomere and reproduction is one of the major areas of interest, however whether sperm telomere associated with male infertility is not clear. In this study, in order to find out the association between Chinese idiopathic infertility and sperm telomere length, we analyzed the difference of sperm telomere length between idiopathic infertile men and normal fertile men, as well as the correlations between sperm telomere length and human semen characteristics. We analyzed 126 Chinese idiopathic infertile men and 138 normal fertile men for sperm telomere length by using quantitative PCR. We found that the relative sperm mean telomere length of infertile men was significantly shorter than that of fertile men (2.894 ± 0.115 vs. 4.016 ± 0.603, P=5.097 x 10⁻⁵). Both sperm count and semen progressive motility are related with telomere length. Our results suggest that sperm telomere length is associated with idiopathic male infertility of China and we proposed the possibility that shorter telomeres in sperm chromosome will reduce spermatogenesis and sperm functions, which finally affected the fertility of male.

  17. Adult Learning Open University Determinants (ALOUD) study: Psychological factors associated with study success

    NARCIS (Netherlands)

    Neroni, Joyce; De Groot, Renate; Kirschner, Paul A.

    2013-01-01

    Neroni, J., De Groot, R. H. M., & Kirschner, P. A. (2012, 7 November). Adult Learning Open University Determinants (ALOUD) study: Psychological factors associated with study success. Poster presentation at the International ICO Fall School, Girona, Spain.

  18. Adult Learning Open University Determinants study (ALOUD): Biological lifestyle factors associated with study success

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2012-01-01

    Gijselaers, H. J. M., De Groot, R. H. M., & Kirschner, P. A. (2012, 7 November). Adult Learning Open University Determinants study (ALOUD): Biological lifestyle factors associated with study success. Poster presentation at the International ICO Fall School, Girona, Spain.

  19. Carbon sinks and biomass energy. A study of linkages, options and implications

    International Nuclear Information System (INIS)

    This study illustrates the important potential role of bioenergy in meeting carbon abatement requirements, in particular in relation to the Kyoto Protocol's first commitment period (2008-2012), based on carbon substitution and associated carbon sinks. Bioenergy-associated carbon sinks could strongly contribute to the acceptability of carbon sinks as a viable means for carbon abatement. Kyoto Protocol agreements and mechanisms, in particular the Bonn agreement, could prove of great value in stimulating sustainable modern bioenergy schemes. (author)

  20. Automated quality control for genome wide association studies.

    Science.gov (United States)

    Ellingson, Sally R; Fardo, David W

    2016-01-01

    This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process. PMID:27635224

  1. [Genome-wide association study for adolescent idiopathic scoliosis].

    Science.gov (United States)

    Ogura, Yoji; Kou, Ikuyo; Scoliosis, Japan; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2016-04-01

    Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1. After the discovery, we have extended our study by increasing the numbers of subjects and SNPs. In total, our Japanese GWAS has identified four susceptibility genes. GWASs for AIS have also been performed in the USA and China, which identified one and three susceptibility genes, respectively. Here we review GWASs in Japan and abroad and functional analysis to clarify the pathomechanism of AIS. PMID:27013625

  2. [Genome-wide association study for adolescent idiopathic scoliosis].

    Science.gov (United States)

    Ogura, Yoji; Kou, Ikuyo; Scoliosis, Japan; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2016-04-01

    Adolescent idiopathic scoliosis(AIS)is a polygenic disease. Genome-wide association studies(GWASs)have been performed for a lot of polygenic diseases. For AIS, we conducted GWAS and identified the first AIS locus near LBX1. After the discovery, we have extended our study by increasing the numbers of subjects and SNPs. In total, our Japanese GWAS has identified four susceptibility genes. GWASs for AIS have also been performed in the USA and China, which identified one and three susceptibility genes, respectively. Here we review GWASs in Japan and abroad and functional analysis to clarify the pathomechanism of AIS.

  3. High-frequency sea level variations and implications for coastal flooding: A case study of the Solent, UK

    Science.gov (United States)

    Ozsoy, Ozgun; Haigh, Ivan D.; Wadey, Matthew P.; Nicholls, Robert J.; Wells, Neil C.

    2016-07-01

    This study examines the occurrence and characteristics of high-frequency (meteorological activity, namely a marked reduction in air pressure and onset of strong southwesterly-southeasterly winds. Sea level observations from tide gauges around the Solent and the wider English Channel region (23 in total) were used to assess the spatial characteristics of these events. Analysis of time series and phase information indicates the occurrence of standing waves oscillating across the English Channel between southern England and northern France. This study provides a unique example of standing waves generated by extra-tropical cyclones over a large basin (the English Channel) with implications for flood inundation. The event of 28th October 2013 - the highest-amplitude (1.16 m) event in the record - was associated with minor coastal flooding at Yarmouth, Isle of Wight. This flood occurred during a neap tide, when such events are widely thought to be impossible. Hence, our findings emphasize the relevance of high-frequency sea level variability for regional sea level forecasting and flood risk management.

  4. Genome-wide association study of antisocial personality disorder

    Science.gov (United States)

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-01-01

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53–3.14), P=1.9 × 10-5). Two polymorphisms at 6p21.2 LINC00951–LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37–1.85), P=1.6 × 10−9) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder. PMID:27598967

  5. Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

    Science.gov (United States)

    Matullo, Giuseppe; Guarrera, Simonetta; Betti, Marta; Fiorito, Giovanni; Ferrante, Daniela; Voglino, Floriana; Cadby, Gemma; Di Gaetano, Cornelia; Rosa, Fabio; Russo, Alessia; Hirvonen, Ari; Casalone, Elisabetta; Tunesi, Sara; Padoan, Marina; Giordano, Mara; Aspesi, Anna; Casadio, Caterina; Ardissone, Francesco; Ruffini, Enrico; Betta, Pier Giacomo; Libener, Roberta; Guaschino, Roberto; Piccolini, Ezio; Neri, Monica; Musk, Arthur W B; de Klerk, Nicholas H; Hui, Jennie; Beilby, John; James, Alan L; Creaney, Jenette; Robinson, Bruce W; Mukherjee, Sutapa; Palmer, Lyle J; Mirabelli, Dario; Ugolini, Donatella; Bonassi, Stefano; Magnani, Corrado; Dianzani, Irma

    2013-01-01

    Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos. PMID:23626673

  6. Genetic variants associated with increased risk of malignant pleural mesothelioma: a genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Giuseppe Matullo

    Full Text Available Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM, a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes, causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14. Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28. These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

  7. A neurocognitive model of the ethical decision-making process: implications for study and practice.

    Science.gov (United States)

    Reynolds, Scott J

    2006-07-01

    The field of business ethics is entrenched in a cognitive approach that portrays the ethical decision-making process as a completely deliberate and reasoned exercise. In light of growing concerns about the veracity of this approach, I build upon current knowledge of how the brain functions to present a neurocognitive model of ethical decision making. The model suggests that ethical decision making involves 2 interrelated yet functionally distinct cycles, a reflexive pattern matching cycle and a higher order conscious reasoning cycle, and thereby describes not only reasoned analysis, but also the intuitive and retrospective aspects of ethical decision making. The model sparks research in new areas, holds significant implications for the study of ethical decision making, and provides suggestions for improving ethical behavior in organizations.

  8. Sediment-associated pesticides in an urban stream in Guangzhou, China: implication of a shift in pesticide use patterns.

    Science.gov (United States)

    Li, Huizhen; Sun, Baoquan; Lydy, Michael J; You, Jing

    2013-04-01

    Pesticide use patterns in China have changed in recent years; however, the study of the environmental fate of current-use pesticides (CUPs) and their ecotoxicological significance in aquatic ecosystems is limited. In the present study, sediments were collected from an urban stream in the Chinese city of Guangzhou. Sediment-associated legacy organochlorine pesticides and CUPs-including organophosphates, pyrethroids, fipronil, and abamectin-were analyzed. Additionally, the relative toxicity of the sediments was evaluated with 10-d bioassays using Chironomus dilutus. Fifteen of 16 sediments collected from the stream were acutely toxic to C. dilutus, with 81% of the samples causing 100% mortality. Abamectin, fipronil, and pyrethroids (mainly cypermethrin) were identified as the principal contributors to the noted toxicity in the midges, with median predicted toxic units of 1.63, 1.63, and 1.03, respectively. Sediments taken from downstream sites, where residential and industrial regions were located, had elevated CUP concentrations and sediment toxicity compared with upstream sites. The present study is the first of its kind to link sediment CUPs, fipronil, and abamectin concentrations with toxicity in urban streams in China with a focus on shifting pesticide usage patterns. PMID:23377859

  9. Genome-wide association study and premature ovarian failure.

    Science.gov (United States)

    Christin-Maitre, S; Tachdjian, G

    2010-05-01

    Premature ovarian failure (POF) is defined as an amenorrhea for more than 4months, associated with elevated gonadotropins, usually higher than 20mIU/ml, occurring in a woman before the age of 40. Some candidate genes have been identified in the past 15years, such as FOXL2, FSHR, BMP15, GDF9, Xfra premutation. However, POF etiology remains unknown in more than 90% of cases. The first strategy to identify candidate gene, apart from studying genes involved in ovarian failure in animal models, relies on the study of X chromosome deletions and X;autosome translocations in patients. The second strategy is based on linkage analysis, the third one on Comparative Genomic Hybridization (CGH) array. The latest strategy relies on Genome-Wide Association Studies (GWAS). This technique consists in screening single nucleotide polymorphisms (SNPs) in patients and controls. So far, three studies have been performed and have identified different loci potentially linked to POF, such as PTHB1 and ADAMTS19. However, replications in independent cohorts need to be performed. GWAS studies on large cohorts of women with POF should find new candidate genes in the near future.

  10. The Western dietary pattern is associated with increased serum concentrations of free estradiol in postmenopausal women: implications for breast cancer prevention.

    Science.gov (United States)

    Sánchez-Zamorano, Luisa María; Flores-Luna, Lourdes; Angeles-Llerenas, Angélica; Ortega-Olvera, Carolina; Lazcano-Ponce, Eduardo; Romieu, Isabelle; Mainero-Ratchelous, Fernando; Torres-Mejía, Gabriela

    2016-08-01

    Little is known about the possible influence of food consumption on the serum concentrations of endogenous sex hormones in postmenopausal women. We evaluated the relationships of the Western dietary pattern with serum concentrations of free estradiol and testosterone of postmenopausal women to test the hypothesis that a highly Western dietary pattern is associated with high serum concentrations of these hormones. We used data from a representative subsample of 305 women from the control group of a population-based case-control study conducted in Mexico from 2004 to 2007. A Western dietary pattern index value was compared with log natural serum concentrations of testosterone and estradiol using multiple linear regression models. The median values of serum concentrations of free estradiol and testosterone were 0.26 pg/mL (interquartile range, 0.14-0.43) and 0.40 pg/mL (interquartile range, 0.30-0.70), respectively. A multiple linear regression model showed that for each unit increase in the Western dietary pattern index, there was a 16.2% increase in the serum concentrations of free estradiol (β=0.15; 95% confidence interval [CI], 0.01-0.29); for each additional serving per week of chicken eggs, the increase was 31.0% (β=0.27; 95% CI, 0.106-0.441); for each additional serving per week of red meat, the increase was 64.9% (β=0.50; 95% CI, 0.01-1.01). There was no relationship found between dietary patterns and serum concentrations of free testosterone. The present findings suggest that intake of a Western diet, particularly of chicken eggs and meat, increases serum concentrations of free estradiol; these results have implications for breast cancer prevention. PMID:27440539

  11. Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

    Directory of Open Access Journals (Sweden)

    Sandosh Padmanabhan

    2010-10-01

    Full Text Available Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹. The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91], reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027. In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003. In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

  12. Multiple Sclerosis Associated Risk Factors: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Jalal POOROLAJAL

    2015-11-01

    Full Text Available Background: Hamadan Province is one of the high-risk regions in Iran for Multiple sclerosis (MS. A majority of the epidemiological studies conducted in Iran addressing MS are descriptive. This study was conducted to assess MS and its associated risk factors in Hamadan Province, the west of Iran.Methods: This case-control study compared 100 patients with MS (case group and 100 patients with acute infectious diseases (control group from September 2013 to March 2014. A checklist was used to assess the demographic, medical, and family history of the patients. The Friedman-Rosenman questionnaire was also used to assess personality type. Statistical analysis was performed using logistic regression model with Stata 11 software program.Results: The adjusted odds ratio (OR estimate of MS was 4.37 (95% CI: 2.33, 8.20 for females compared to males; 0.15 (95% CI: 0.06, 0.43 for people aged above 50 years compared to aged 14 to 29 years; 0.44 (95% CI: 0.21, 0.91 for overweight or obese people compared to normal weights. Crude OR indicated a significant association between the occurrence of MS and exclusive breast feeding, season of birth, and smoking. However, the association was not statistically significant after adjustment for other covariates.Conclusion: The risk of MS is significantly lower in male gender, obese/overweight, and old people. Furthermore, non-smoking, non-exclusive breast-feeding, and born in autumn may increase the risk of MS but need further investigation. However, long-term large prospective cohort studies are needed to investigate the true effect of the potential risk factors on MS. Keywords: Multiple sclerosis, Risk factors, Case-control study, Iran

  13. Characterization of the deleted in autism 1 protein family: implications for studying cognitive disorders.

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    Azhari Aziz

    Full Text Available Autism spectrum disorders (ASDs are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1 and cXorf36 or Deleted in Autism-1 Related (DIA1R are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L, lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental

  14. A genome-wide association study in multiple system atrophy

    Science.gov (United States)

    Sailer, Anna; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R.; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A.; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B.

    2016-01-01

    Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. PMID:27629089

  15. An efficient empirical Bayes method for genomewide association studies.

    Science.gov (United States)

    Wang, Q; Wei, J; Pan, Y; Xu, S

    2016-08-01

    Linear mixed model (LMM) is one of the most popular methods for genomewide association studies (GWAS). Numerous forms of LMM have been developed; however, there are two major issues in GWAS that have not been fully addressed before. The two issues are (i) the genomic background noise and (ii) low statistical power after Bonferroni correction. We proposed an empirical Bayes (EB) method by assigning each marker effect a normal prior distribution, resulting in shrinkage estimates of marker effects. We found that such a shrinkage approach can selectively shrink marker effects and reduce the noise level to zero for majority of non-associated markers. In the meantime, the EB method allows us to use an 'effective number of tests' to perform Bonferroni correction for multiple tests. Simulation studies for both human and pig data showed that EB method can significantly increase statistical power compared with the widely used exact GWAS methods, such as GEMMA and FaST-LMM-Select. Real data analyses in human breast cancer identified improved detection signals for markers previously known to be associated with breast cancer. We therefore believe that EB method is a valuable tool for identifying the genetic basis of complex traits. PMID:26582716

  16. Study on acute burn injury survivors and the associated issues

    Institute of Scientific and Technical Information of China (English)

    Jonathan Bayuo; Pius Agbenorku; Richcane Amankwa

    2016-01-01

    Objective: To explore the phenomenon of surviving burn injury and its associated issues and concerns. Methods: A cross sectional survey approach was utilized to obtain data from one hundred burn survivors who were purposely selected. Descriptive statistics and content analysis were used to analyze data. Results: Findings from the study indicate that burns from flames stood out as a major cause of burns. Physical discomfort/pain, anxiety, needing assistance in meeting self-care needs, financial and social limitations were identified as the major impact of the injury. Furthermore, participants perceived the existence of societal stigma. In addition, hope in God or a spiritual being as well as family support were the two key resources participants relied on to cope effectively. Conclusions: Surviving burn injury is associated with varied physical, social and psy-chological factors and survivors may need professional assistance to fully adjust after discharge.

  17. Feasibility study for banking loan using association rule mining classifier

    Directory of Open Access Journals (Sweden)

    Agus Sasmito Aribowo

    2015-03-01

    Full Text Available The problem of bad loans in the koperasi can be reduced if the koperasi can detect whether member can complete the mortgage debt or decline. The method used for identify characteristic patterns of prospective lenders in this study, called Association Rule Mining Classifier. Pattern of credit member will be converted into knowledge and used to classify other creditors. Classification process would separate creditors into two groups: good credit and bad credit groups. Research using prototyping for implementing the design into an application using programming language and development tool. The process of association rule mining using Weighted Itemset Tidset (WIT–tree methods. The results shown that the method can predict the prospective customer credit. Training data set using 120 customers who already know their credit history. Data test used 61 customers who apply for credit. The results concluded that 42 customers will be paying off their loans and 19 clients are decline

  18. Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

    Science.gov (United States)

    Teumer, Alexander; Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C; Olden, Matthias; Hiraki, Linda T; Tayo, Bamidele O; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R; Smith, Albert V; Zappa, Allison M; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K; Paulweber, Bernhard; Mitchell, Braxton D; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Mateo Leach, I; Rudan, Igor; Hillege, Hans L; Beckmann, Jacques S; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C; Butterbach, Katja; Launer, Lenore J; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S; Gansevoort, Ron T; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J; Katz, Ronit; Loos, Ruth J F; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R; Parsa, Afshin; Heid, Iris M; Paterson, Andrew D; de Boer, Ian H; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J; Böger, Carsten A; Fox, Caroline S; Pattaro, Cristian; Köttgen, Anna

    2016-03-01

    Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10(-10)). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10(-7)) and 13% for RAB38/CTSC (P = 5.8 × 10(-7)). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PMID:26631737

  19. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

    Directory of Open Access Journals (Sweden)

    Jingwei Yuan

    Full Text Available Egg number (EN, egg laying rate (LR and age at first egg (AFE are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens.

  20. A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip

    DEFF Research Database (Denmark)

    Evangelou, Evangelos; Kerkhof, Hanneke J; Styrkarsdottir, Unnur;

    2014-01-01

    Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.......Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects....

  1. Polycyclic aromatic hydrocarbons associated with road deposited solid and their ecological risk: Implications for road stormwater reuse.

    Science.gov (United States)

    Liu, Liang; Liu, An; Li, Yang; Zhang, Lixun; Zhang, Guijuan; Guan, Yuntao

    2016-09-01

    Reusing stormwater is becoming popular worldwide. However, urban road stormwater commonly contains toxic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), which could undermine reuse safety. This study investigated pollution level of PAHs and their composition build-up on urban roads in a typical megacity in South China. The potential ecological risk posed by PAHs associated with road deposited solid (RDS) was also assessed. Results showed that ecological risk levels varied based on different land use types, which could be significantly influenced by the composition of PAHs and characteristics of RDS. A higher percentage of high-ring PAHs, such as more than four rings, could pose higher ecological risk and are more likely to undermine stormwater reuse safety. Additionally, the degree of traffic congestion rather than traffic volume was found to exert a more significant influence on the generation of high-ring PAH generation. Therefore, stormwater from more congested roads might need proper treatment (particularly for removing high-ring PAHs) before reuse or could be suitable for purposes requiring low-water-quality. The findings of this study are expected to contribute to adequate stormwater reuse strategy development and to enhance the safety of urban road stormwater reuse. PMID:27135582

  2. Polycyclic aromatic hydrocarbons associated with road deposited solid and their ecological risk: Implications for road stormwater reuse.

    Science.gov (United States)

    Liu, Liang; Liu, An; Li, Yang; Zhang, Lixun; Zhang, Guijuan; Guan, Yuntao

    2016-09-01

    Reusing stormwater is becoming popular worldwide. However, urban road stormwater commonly contains toxic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), which could undermine reuse safety. This study investigated pollution level of PAHs and their composition build-up on urban roads in a typical megacity in South China. The potential ecological risk posed by PAHs associated with road deposited solid (RDS) was also assessed. Results showed that ecological risk levels varied based on different land use types, which could be significantly influenced by the composition of PAHs and characteristics of RDS. A higher percentage of high-ring PAHs, such as more than four rings, could pose higher ecological risk and are more likely to undermine stormwater reuse safety. Additionally, the degree of traffic congestion rather than traffic volume was found to exert a more significant influence on the generation of high-ring PAH generation. Therefore, stormwater from more congested roads might need proper treatment (particularly for removing high-ring PAHs) before reuse or could be suitable for purposes requiring low-water-quality. The findings of this study are expected to contribute to adequate stormwater reuse strategy development and to enhance the safety of urban road stormwater reuse.

  3. Neuregulin-1 and schizophrenia in the genome-wide association study era.

    Science.gov (United States)

    Mostaid, Md Shaki; Lloyd, David; Liberg, Benny; Sundram, Suresh; Pereira, Avril; Pantelis, Christos; Karl, Tim; Weickert, Cynthia Shannon; Everall, Ian P; Bousman, Chad A

    2016-09-01

    Clinical and pre-clinical evidence has implicated neuregulin 1 (NRG1) as a critical component in the pathophysiology of schizophrenia. However, the arrival of the genome-wide association study (GWAS) era has yielded results that challenge the relevance of NRG1 in schizophrenia due to the absence of a genome-wide significant NRG1 variant associated with schizophrenia. To assess NRG1's relevance to schizophrenia in the GWAS era, we provide a targeted review of recent preclinical evidence on NRG1's role in regulating several aspects of excitatory/inhibitory neurotransmission and in turn schizophrenia risk. We also present a systematic review of the last decade of clinical research examining NRG1 in the context of schizophrenia. We include concise summaries of genotypic variation, gene-expression, protein expression, structural and functional neuroimaging as well as cognitive studies conducted during this time period. We conclude with recommendations for future clinical and preclinical work that we hope will help prioritize a strategy forward to further advance our understanding of the relationship between NRG1 and schizophrenia. PMID:27283360

  4. Genome-wide association study identified a narrow chromosome 1 region associated with chicken growth traits.

    Directory of Open Access Journals (Sweden)

    Liang Xie

    Full Text Available Chicken growth traits are important economic traits in broilers. A large number of studies are available on finding genetic factors affecting chicken growth. However, most of these studies identified chromosome regions containing putative quantitative trait loci and finding causal mutations is still a challenge. In this genome-wide association study (GWAS, we identified a narrow 1.5 Mb region (173.5-175 Mb of chicken (Gallus gallus chromosome (GGA 1 to be strongly associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth traits included aggregate body weight (BW at 0-90 d of age measured weekly, biweekly average daily gains (ADG derived from weekly body weight, and breast muscle weight (BMW, leg muscle weight (LMW and wing weight (WW at 90 d of age. Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant effects for all growth traits in this study, including a SNP at 8.9 Kb upstream of FOXO1A for BW at 22-48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29-42 d, a SNP in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3-FOXO1A region contained two microRNA genes that could bind to messenger ribonucleic acid (mRNA of IGF1, FOXO1A and KPNA3. It was further indicated that the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22-42 d.

  5. A candidate gene association study on muscat flavor in grapevine (Vitis vinifera L.

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    Boursiquot Jean-Michel

    2010-11-01

    Full Text Available Abstract Background The sweet, floral flavor typical of Muscat varieties (Muscats, due to high levels of monoterpenoids (geraniol, linalool and nerol, is highly distinct and has been greatly appreciated both in table grapes and in wine since ancient times. Muscat flavor determination in grape (Vitis vinifera L. has up to now been studied by evaluating monoterpenoid levels through QTL analysis. These studies have revealed co-localization of 1-deoxy-D-xylulose 5-phosphate synthase (VvDXS with the major QTL positioned on chromosome 5. Results We resequenced VvDXS in an ad hoc association population of 148 grape varieties, which included muscat-flavored, aromatic and neutral accessions as well as muscat-like aromatic mutants and non-aromatic offsprings of Muscats. Gene nucleotide diversity and intragenic linkage disequilibrium (LD were evaluated. Structured association analysis revealed three SNPs in moderate LD to be significantly associated with muscat-flavored varieties. We identified a putative causal SNP responsible for a predicted non-neutral substitution and we discuss its possible implications for flavor metabolism. Network analysis revealed a major star-shaped cluster of reconstructed haplotypes unique to muscat-flavored varieties. Moreover, muscat-like aromatic mutants displayed unique non-synonymous mutations near the mutated site of Muscat genotypes. Conclusions This study is a crucial step forward in understanding the genetic regulation of muscat flavor in grapevine and it also sheds light on the domestication history of Muscats. VvDXS appears to be a possible human-selected locus in grapevine domestication and post-domestication. The putative causal SNP identified in Muscat varieties as well as the unique mutations identifying the muscat-like aromatic mutants under study may be immediately applied in marker-assisted breeding programs aimed at enhancing fragrance and aroma complexity respectively in table grape and wine cultivars.

  6. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

    Directory of Open Access Journals (Sweden)

    James D McKay

    2011-03-01

    Full Text Available Genome-wide association studies (GWAS have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷. Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸ located near DNA repair related genes HEL308 and FAM175A (or Abraxas and a 12q24 variant (rs4767364, p =2 × 10⁻⁸ located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2 gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸; rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02. These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

  7. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

    LENUS (Irish Health Repository)

    McKay, James D

    2011-03-01

    Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

  8. Universal design of workplaces through the use of Poka-Yokes: Case study and implications

    Directory of Open Access Journals (Sweden)

    Cristóbal Miralles

    2011-10-01

    Full Text Available Purpose: Employment plays an important part in many people’s lives beyond merely providing income, since continued participation in work can have many therapeutic benefits for workers defined as disabled. However, disabled workers face a range of barriers to employment, despite legislation intended to improve workplace accessibility emphasizing adaptations to the workplace, which many employers often find difficult and expensive. The Poka-Yoke approach was developed in the manufacturing industry as a way of improving productivity by reducing errors using often very simple adaptations. This paper argues that, as Poka-Yokes are designed to make life easier and improve the performance of workers without impairments, they are closer to the philosophy of Universal Design than to Accessible Design, and offer an easy and inclusive way of making work more accessible for all kind of workers. Design/methodology/approach: This paper provides a case study demonstrating the use of the Poka-Yoke approach in a sheltered work centre for disabled; highlighting how they served to improve accessibility to work by fulfilling Universal Design principles. Findings: Our research allows us to demonstrate the great potential of Poka-yokes for gaining accessibility to the workplace. The real application of this approach, both in sheltered work centres and ordinary companies, can contribute to improve the high unemployment rates of disabled people. Research limitations/implications: The proposal is innovative and was applied in one specific company. Thus, a range of customized Poka-yokes would be desirable for different industrial sectors. Practical implications: Managers of sheltered work centres, and also of ordinary companies, can realize about the great potential of Poka-Yokes as an easy means of gaining flexibility and accessibility. Originality/value: There are very few papers relating lean manufacturing tools and disability. Our approach analyzes the benefits of

  9. Genome-wide association studies in pharmacogenomics of antidepressants.

    Science.gov (United States)

    Lin, Eugene; Lane, Hsien-Yuan

    2015-01-01

    Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Doctors must prescribe antidepressants based on educated guesses due to the fact that it is unmanageable to predict the effectiveness of any particular antidepressant in an individual patient. With the recent advent of scientific research, the genome-wide association study (GWAS) is extensively employed to analyze hundreds of thousands of single nucleotide polymorphisms by high-throughput genotyping technologies. In addition to the candidate-gene approach, the GWAS approach has recently been utilized to investigate the determinants of antidepressant response to therapy. In this study, we reviewed GWAS studies, their limitations and future directions with respect to the pharmacogenomics of antidepressants in MDD.

  10. Multicentric Genome-Wide Association Study for Primary Spontaneous Pneumothorax.

    Science.gov (United States)

    Sousa, Inês; Abrantes, Patrícia; Francisco, Vânia; Teixeira, Gilberto; Monteiro, Marta; Neves, João; Norte, Ana; Robalo Cordeiro, Carlos; Moura E Sá, João; Reis, Ernestina; Santos, Patrícia; Oliveira, Manuela; Sousa, Susana; Fradinho, Marta; Malheiro, Filipa; Negrão, Luís; Feijó, Salvato; Oliveira, Sofia A

    2016-01-01

    Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29-2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis. PMID:27203581

  11. Detecting rare variants in case-parents association studies.

    Directory of Open Access Journals (Sweden)

    Kuang-Fu Cheng

    Full Text Available Despite the success of genome-wide association studies (GWASs in detecting common variants (minor allele frequency ≥0.05 many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT, multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

  12. Modelling BMI trajectories in children for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington

    Full Text Available BACKGROUND: The timing of associations between common genetic variants and changes in growth patterns over childhood may provide insight into the development of obesity in later life. To address this question, it is important to define appropriate statistical models to allow for the detection of genetic effects influencing longitudinal childhood growth. METHODS AND RESULTS: Children from The Western Australian Pregnancy Cohort (Raine; n=1,506 Study were genotyped at 17 genetic loci shown to be associated with childhood obesity (FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, LYPLAL1, TFAP2B, MTCH2, BCDIN3D, NRXN3, SH2B1, MRSA and an obesity-risk-allele-score was calculated as the total number of 'risk alleles' possessed by each individual. To determine the statistical method that fits these data and has the ability to detect genetic differences in BMI growth profile, four methods were investigated: linear mixed effects model, linear mixed effects model with skew-t random errors, semi-parametric linear mixed models and a non-linear mixed effects model. Of the four methods, the semi-parametric linear mixed model method was the most efficient for modelling childhood growth to detect modest genetic effects in this cohort. Using this method, three of the 17 loci were significantly associated with BMI intercept or trajectory in females and four in males. Additionally, the obesity-risk-allele score was associated with increased average BMI (female: β=0.0049, P=0.0181; male: β=0.0071, P=0.0001 and rate of growth (female: β=0.0012, P=0.0006; male: β=0.0008, P=0.0068 throughout childhood. CONCLUSIONS: Using statistical models appropriate to detect genetic variants, variations in adult obesity genes were associated with childhood growth. There were also differences between males and females. This study provides evidence of genetic effects that may identify individuals early in life that are more likely to rapidly increase their BMI

  13. Implications of the IQ-CSRC Prospective Study: Time to Revise ICH E14.

    Science.gov (United States)

    Darpo, Borje; Garnett, Christine; Keirns, James; Stockbridge, Norman

    2015-09-01

    Exposure-response (ER) analysis has evolved as an important tool to evaluate the effect of a drug on cardiac repolarization, as reflected in the QTc interval. It has been suggested that careful electrocardiogram (ECG) evaluation in 'first-in-human' studies using ER analysis could replace or serve as an alternative to the E14 'thorough QT' study. This commentary shares and discusses the results of a recently conducted study with the objective to evaluate this approach. Six drugs with a well-characterized QT effect, five of which are known QT prolongers, were evaluated in a study design similar to a conventional single-ascending-dose study. Each drug was given to nine healthy subjects (six for placebo) in two dose levels, which for the positive drugs (ondansetron, quinine, dolasetron, moxifloxacin, and dofetilide) were chosen with the intent to cause 10-12 ms and 15-20 ms QTc prolongation. Replicate 12-lead ECGs were extracted from continuous recordings pre-dose and serially after dosing and paired with drug concentration determinations. The ER criteria for the identification of a QT effect, a statistically significant positive ER slope and an effect above 10 ms, were met with all five positive drugs, and an effect exceeding 10 ms could be excluded at the supratherapeutic dose of the negative drug, levocetirizine. The study results thereby provided evidence to support that careful QT assessment in early phase clinical studies can be used as an alternative to the thorough QT study. Clinical and regulatory implications, as well as limitations of this approach, are discussed in the commentary. PMID:26162419

  14. Gene ontology analysis of pairwise genetic associations in two genome-wide studies of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Kim Nora

    2012-07-01

    analysis of pairwise genetic associations in two GWAS of sporadic ALS revealed a set of genes involved in cellular component organization and actin cytoskeleton, more specifically, that were not reported by prior GWAS. However, prior biological studies have implicated actin cytoskeleton in ALS and other motor neuron diseases. This study supports the idea that pathway-level analysis of GWAS data may discover important associations not revealed using conventional one-SNP-at-a-time approaches.

  15. Association between androgenetic alopecia and hyperlipidemia: a comparative study

    Directory of Open Access Journals (Sweden)

    Ramin Taheri

    2013-12-01

    Full Text Available Background: Androgenetic alopecia (AGA is the most common type of progressive balding that appears with early loss of hair, chiefly from the vertex. There has been significant relationship between AGA with coronary artery disease and related risk factors, such as hypertension in some studies. The aim of this study is to investigate the association between androgenetic alopecia with hyperlipidemia.Methods: This cross-sectional study was performed on 112 patients with vertex type AGA (in male grade 3 or higher Hamilton- Norwood scale, and in female grade 2 or higher Ludwig scale (study group and 115 persons age and sex matched, with normal hair status (Normal group. None of participants had diabetes mellitus, hypothyroidism, liver disease, kidney disease and none of them had history of smoking and using drugs with effect on serum lipids. They were 20-35 years old and their body mass index were 20-30. Blood samples were obtained following 12 hours fasting status and serum levels of triglyceride (TG, cholesterol, high-density lipoprotein (HDL and low-density lipoprotein (LDL were determined using standard laboratory methods. Total cholesterol greater than 240 or TG greater than 200 or LDL greater than 160 or HDL less than 40 in men or HDL less than 50 in women were considered hyperlipidemia.Results: In androgenetic alopecia group 46.4% and 47% of normal group were female. Mean (±SE of total cholesterol (172.4±3.1, 148.8±3.1, P 0.05.Conclusion: The findings showed that there is no relationship between AGA and hyperlipidemia. Regarding to high levels of total cholesterol, LDL and triglyceride in AGA patients, it seems that, AGA increases risk of coronary heart disease. To determine a definite association between AGA and hyperlipidemia more studies are recommended.

  16. QCD prediction of jet structure in 2D trigger-associated momentum correlations and implications for multiple parton interactions

    CERN Document Server

    Trainor, Thomas A

    2014-01-01

    The expression "multiple parton interactions" (MPI) denotes a conjectured QCD mechanism representing contributions from secondary (semi)hard parton scattering to the transverse azimuth region (TR) of jet-triggered p-p collisions. MPI is an object of underlying-event (UE) studies that consider variation of TR $n_{ch}$ or $p_t$ yields relative to a trigger condition (leading hadron or jet $p_t$). An alternative approach is 2D trigger-associated (TA) correlations on hadron transverse momentum $p_t$ or rapidity $y_t$ in which all hadrons from all p-p events are included. Based on a two-component (soft+hard) model (TCM) of TA correlations a jet-related TA hard component is isolated. Contributions to the hard component from the triggered dijet and from secondary dijets (MPI) can be distinguished, including their azimuth dependence relative to the trigger direction. Measured $e^+$-$e^-$ and p-\\=p fragmentation functions and a minimum-bias jet spectrum from 200 GeV p-\\=p collisions are convoluted to predict the 2D ha...

  17. Suprarenal solitary fibrous tumor associated with a NF1 gene mutation mimicking a kidney neoplasm: implications for surgical management.

    Science.gov (United States)

    Conzo, Giovanni; Tartaglia, Ernesto; Gambardella, Claudio; Mauriello, Claudio; Esposito, Daniela; Mascolo, Massimo; Russo, Daniela; Stornaiuolo, Gianfranca; Gaeta, Giovan Battista; Santini, Luigi

    2014-01-01

    Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm, usually occurring in the pleura. Pararenal SFT, mimicking an adrenal gland or renal tumor, as here described, is extremely rare. We report a case of a right suprarenal SFT, incidentally discovered by abdominal ultrasound in a 54-year-old woman carrying a point neurofibromatosis 1 (NF1) gene mutation. Preoperative diagnostic work-up was ineffective in evaluating its origin, and an open radical right nephrectomy was therefore undertaken. Immunohistochemical assay showed a positivity for CD34, CD99 and Bcl-2, so suggesting a diagnosis of SFT. According to our knowledge, the association between this type of tumor and NF1 gene mutation has never been described. In cases of pararenal tumors, a more detailed preoperative diagnosis could be useful to better plan the extension of resection, allowing, in selected cases, nephron-sparing surgery. More studies are needed to better analyze the relationship between NF1 gene mutation and SFT. PMID:24708790

  18. A genome-wide association study identifies five loci influencing facial morphology in Europeans.

    Directory of Open Access Journals (Sweden)

    Fan Liu

    2012-09-01

    Full Text Available Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.

  19. Counseling a Student Presenting Borderline Personality Disorder in the Small College Context: Case Study and Implications

    Science.gov (United States)

    Draper, Matthew R.; Faulkner, Ginger E.

    2009-01-01

    This case study examines the dynamics and challenges associated with counseling a client experiencing borderline personality disorder in the small college institutional context. The work of counseling centers at small private institutions has been relatively unexplored in the extant college counseling literature. To help fill this gap, the current…

  20. A synthesis of studies searching for school factors : implications for theory and research

    NARCIS (Netherlands)

    Kyriakides, Leonidas; Creemers, Bert; Antoniou, Panayiotis; Demetriou, Demetris

    2010-01-01

    This paper reports the results of a meta-analysis in which the dynamic model of educational effectiveness is used as a framework to search for school factors associated with student achievement. The methods and results of a synthesis of 67 studies are presented. Findings reveal that effective school

  1. A genome-wide association study of anorexia nervosa.

    Science.gov (United States)

    Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

    2014-10-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

  2. A genome-wide association study of anorexia nervosa

    Science.gov (United States)

    Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

    2015-01-01

    Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

  3. Acute telogen effluvium onset event is associated with the presence of female androgenetic alopecia: potential therapeutic implications.

    Science.gov (United States)

    Perez-Mora, Nicolas; Goren, Andy; Velasco, Carlos; Bermudez, Fernando

    2014-01-01

    Acute telogen effluvium (ATE) is often associated with female androgenetic alopecia (FAA), but predictive factors of ATE-FAA association and clinical factors or therapies that may influence the progression of ATE to chronic telogen effluvium (CTE) have not been reported. We have identified predictive factors of ATE-FAA association and retrospectively evaluated the impact of therapies on the progression to CTE. Conclusions are as follows: (i) Triggering cause is a significant independent factor that predicts association of ATE with FAA. (ii) Triggering causes with higher risk of concurrent FAA are severe diet, iron deficiency, and thyroid dysfunction. (iii) Patients suffering ATE may benefit from different therapeutic approaches (depending on which is the triggering cause) to prevent or treat the association with FAA. (iv) Minoxidil use shows a trend to lower the percentage of progression to CTE. (v) Apart from treating the precipitating cause, the different additional oral treatments used have not shown any correlation with progression to CTE. PMID:24850277

  4. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger;

    2009-01-01

    Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasiv...

  5. Bipolar disorder and the pseudoautosomal region: An association study

    Energy Technology Data Exchange (ETDEWEB)

    Parsian, A.; Todd, R.D. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-03-15

    From family, adoption, and twin studies it is clear that genetic factors play an important role in the etiology of bipolar disorder (McGuffin and Katz: The Biology of Depression, Gaskell, London, 1986). Recently Yoneda et al. reported an association between an allele (A4) of a VNTR marker (DXYS20) for the pseudoautosomal region and bipolar disorder in a Japanese population. In order to test for this association in a Caucasian population, we have typed a sample of 52 subjects with bipolar disorder and 61 normal controls. The bipolar subjects are probands of multiple incidence families. The normal controls are an epidemiologically ascertained sample of middle-aged, unrelated individuals. The two groups were matched for sex and ethnic background. There were no significant differences in the allele or genotype frequencies of DXYS20 between the two groups. In particular, there was no significant difference in the frequency of the A4 allele in normal controls and bipolar patients (0.377 vs. 0.317, respectively). The prevalence of the A4 allele in bipolar patients and normal controls was 0.567 and 0.622, respectively. We were not able to replicate the results of the 1992 Yoneda et al. study. 15 refs., 2 tabs.

  6. A genome-wide association study of aging.

    Science.gov (United States)

    Walter, Stefan; Atzmon, Gil; Demerath, Ellen W; Garcia, Melissa E; Kaplan, Robert C; Kumari, Meena; Lunetta, Kathryn L; Milaneschi, Yuri; Tanaka, Toshiko; Tranah, Gregory J; Völker, Uwe; Yu, Lei; Arnold, Alice; Benjamin, Emelia J; Biffar, Reiner; Buchman, Aron S; Boerwinkle, Eric; Couper, David; De Jager, Philip L; Evans, Denis A; Harris, Tamara B; Hoffmann, Wolfgang; Hofman, Albert; Karasik, David; Kiel, Douglas P; Kocher, Thomas; Kuningas, Maris; Launer, Lenore J; Lohman, Kurt K; Lutsey, Pamela L; Mackenbach, Johan; Marciante, Kristin; Psaty, Bruce M; Reiman, Eric M; Rotter, Jerome I; Seshadri, Sudha; Shardell, Michelle D; Smith, Albert V; van Duijn, Cornelia; Walston, Jeremy; Zillikens, M Carola; Bandinelli, Stefania; Baumeister, Sebastian E; Bennett, David A; Ferrucci, Luigi; Gudnason, Vilmundur; Kivimaki, Mika; Liu, Yongmei; Murabito, Joanne M; Newman, Anne B; Tiemeier, Henning; Franceschini, Nora

    2011-11-01

    Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.

  7. An evolutionary framework for association testing in resequencing studies.

    Directory of Open Access Journals (Sweden)

    C Ryan King

    2010-11-01

    Full Text Available Sequencing technologies are becoming cheap enough to apply to large numbers of study participants and promise to provide new insights into human phenotypes by bringing to light rare and previously unknown genetic variants. We develop a new framework for the analysis of sequence data that incorporates all of the major features of previously proposed approaches, including those focused on allele counts and allele burden, but is both more general and more powerful. We harness population genetic theory to provide prior information on effect sizes and to create a pooling strategy for information from rare variants. Our method, EMMPAT (Evolutionary Mixed Model for Pooled Association Testing, generates a single test per gene (substantially reducing multiple testing concerns, facilitates graphical summaries, and improves the interpretation of results by allowing calculation of attributable variance. Simulations show that, relative to previously used approaches, our method increases the power to detect genes that affect phenotype when natural selection has kept alleles with large effect sizes rare. We demonstrate our approach on a population-based re-sequencing study of association between serum triglycerides and variation in ANGPTL4.

  8. Colonial Hangovers: Social Studies Curriculum Dilemmas for Zimbabwe--Implications for Indiana Social Studies Teachers.

    Science.gov (United States)

    Nziramasanga, Caiphas T.

    This paper briefly examines the historical background to political independence in African nations, highlighting the control of the colonial masters on those nations. The "hangovers" describes how early colonial control has had serious influence on the development of social studies curriculum in Zimbabwe. The paper concludes by narrating the…

  9. Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

    Energy Technology Data Exchange (ETDEWEB)

    Yakushev, Igor; Mueller, Matthias J.; Schermuly, Ingrid; Fellgiebel, Andreas [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); Schreckenberger, Matthias [University Medical Center Mainz, Department of Nuclear Medicine, Mainz (Germany); Cumming, Paul [University of Munich, Department of Nuclear Medicine, Munich (Germany); Stoeter, Peter [University Medical Center Mainz, Institute of Neuroradiology, Mainz (Germany); Gerhard, Alex [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom)

    2011-12-15

    Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 {+-} 1.7) were studied with [{sup 18}F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

  10. Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

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    Brandon L Pierce

    Full Text Available Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10(-8 for percentages of both monomethylarsonic acid (MMA and dimethylarsinic acid (DMA near the AS3MT gene (arsenite methyltransferase; 10q24.32, with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity and 1,794 controls, we show that one of these five variants (rs9527 is also associated with skin lesion risk (P = 0.0005. Using a subset of individuals with prospectively measured arsenic (n = 769, we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01. Expression quantitative trait locus (eQTL analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10(-12 and neighboring gene C10orf32 (P = 10(-44, which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical

  11. A Case Study with an Identified Bully: Policy and Practice Implications

    Directory of Open Access Journals (Sweden)

    Huddleston, Lillie

    2011-07-01

    Full Text Available Objective: Bullying is a serious public health problem that may include verbal or physical injury as well as social isolation or exclusion. As a result, research is needed to establish a database for policies and interventions designed to prevent bullying and its negative effects. This paper presented a case study that contributed to the literature by describing an intervention for bullies that has implications for research, practice and related policies regarding bullying.Methods: An individualized intervention for an identified bully was implemented using the Participatory Culture-Specific Intervention Model (PCSIM; Nastasi, Moore, & Varjas, 2004 with a seventh-grade middle school student. Ecological and culture-specific perspectives were used to develop and implement the intervention that included psychoeducational sessions with the student and consultation with the parent and school personnel. A mixed methods intervention design was used with the following informants: the target student, the mother of the student, a teacher and the school counselor. Qualitative data included semi-structured interviews with the parent, teacher and student, narrative classroom observations and evaluation/feedback forms filled out by the student and interventionist. Quantitative data included the following quantitative surveys (i.e., Child Posttraumatic Stress Reaction Index [CPTS-RI] and the Behavior Assessment Scale for Children, 2nd Edition. Both qualitative and quantitative data were used to evaluate the acceptability, integrity and efficacy of this intervention.Results: The process of intervention design, implementation and evaluation are described through an illustrative case study. Qualitative and quantitative findings indicated a decrease in internalizing, externalizing and bullying behaviors as reported by the teacher and the mother, and a high degree of acceptability and treatment integrity as reported by multiple stakeholders.Conclusion: This case

  12. Low expression of leptin and its association with breast cancer: A transcriptomic study.

    Science.gov (United States)

    Karim, Sajjad; Merdad, Adnan; Schulten, Hans-Juergen; Jayapal, Manikandan; Dallol, Ashraf; Buhmeida, Abdelbaset; Al-Thubaity, Fatima; Mirza, Zeenat; Gari, Mamdooh A; Chaudhary, Adeel G; Abuzenadah, Adel M; Al-Qahtani, Mohammed H

    2016-07-01

    The incidence of breast cancer is alarmingly increasing worldwide and also among Saudi women. Obesity is linked with an increased cancer risk and studies have also revealed that leptin may be involved in breast tumorigenesis particularly among obese women. Numerous transcriptomic studies have been carried out worldwide; however, molecular studies among breast cancer patients of diverse ethnic groups from the Arabian Peninsula are scarce. In the present study, whole transcriptome analysis of 45 surgically resected breast tumors from Saudi Arabian female patients was carried out. Expression data were analyzed, and molecular networks and canonical pathways were identified. We identified 1,159 differentially expressed genes using p-value with a false discovery rate 2 as a cut-off. Using ingenuity pathway analysis tool, we identified many canonical pathways that were implicated in breast cancer for the first time. Notably, along with other lipid metabolism molecules, leptin (LEP)was one of the most downregulated genes (fold cut-off, -7.03) with significant differences between the breast cancer and the control groups (pcancer from a Saudi female population revealed downregulation of LEP. Molecular pathway analysis demonstrated the role of LEP and other associated molecules of the lipid metabolism pathway. Involvement of leptin and lipid metabolism in breast cancer was highlighted. The majority of cases presented were of late stage, stressing the need to educate individuals concerning early diagnostic testing and the life-style risk factors for breast cancer such as unhealthy diet and obesity. PMID:27177292

  13. Five known tagging DLL3 SNPs are not associated with congenital scoliosis: A case-control association study in a Chinese Han population.

    Science.gov (United States)

    Yang, Yong; Wang, Bing-Qiang; Wu, Zhi-Hong; Zhang, Hai-Yan; Qiu, Gui-Xing; Shen, Jian-Xiong; Zhang, Jian-Guo; Zhao, Yu; Wang, Yi-Peng; Fei, Qi

    2016-07-01

    Genetic etiology hypothesis is widely accepted in the development of congenital scoliosis (CS). The delta-like 3 (DLL3) gene, a member of the Notch signaling pathway, was implicated to contribute to human CS. In this study, a case-control association study was conducted to determine the association of single nucleotide polymorphism (SNP) in the DLL3 gene with CS in a Chinese Han Population. Five known tagging SNPs of the DLL3 gene were genotyped among 270 Chinese Han subjects (128 nonsyndromic CS patients and 142 matched controls). CS patients were divided into 3 types: type I-failure of formation (29 cases), type II-failure of segmentation (50 cases), and type III-mixed defects (49 cases). The 5 SNPs were analyzed by the allelic and genotypic association analysis, genotype-phenotype association analysis, and haplotype analysis. Allele frequencies of 5 tagging SNPs (SNP1: rs1110627, SNP2: rs3212276, SNP3: rs2304223, SNP4: rs2304222, and SNP5: rs2304214) in CS cases and controls were comparable and there were no available inheritance models. The SNPs were not associated with clinical phenotypes. Moreover, the 5 makers in the DLL3 gene were found to be in strong linkage disequilibrium (LD). Both global haplotype and individual haplotype analyses showed that the haplotypes of SNP1/SNP2/SNP3/SNP4/SNP5 did not correlate with the disease (P >0.05). Together, these data suggest that genetic variants of the DLL3 gene are not associated with CS in the Chinese Han population. PMID:27472720

  14. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

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    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  15. An association study between hypoxia inducible factor-1alpha (HIF-1α polymorphisms and osteonecrosis.

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    Georgia Chachami

    Full Text Available Bone hypoxia resulting from impaired blood flow is the final pathway for the development of osteonecrosis (ON. The aim of this study was to evaluate if HIF-1α, the major transcription factor triggered by hypoxia, is genetically implicated in susceptibility to ON. For this we analyzed frequencies of three known HIF-1α polymorphisms: one in exon 2 (C111A and two in exon 12 (C1772T and G1790A and their association with ON in a Greek population. Genotype analysis was performed using PCR-RFLP and rare alleles were further confirmed with sequencing. We found that genotype and allele frequency of C1772T and G1790A SNP of HIF-1α (SNPs found in our cohort were not significantly different in ON patients compared to control patients. Furthermore these SNPs could not be associated with the different subgroups of ON. At the protein level we observed that the corresponding mutations (P582S and A588T, respectively are not significant for protein function since the activity, expression and localization of the mutant proteins is practically indistinguishable from wt in HEK293 and Saos-2 cells. These results suggest that these missense mutations in the HIF-1α gene are not important for the risk of developing ON.

  16. Clinicians' perspectives of health related quality of life (HRQoL) implications of amblyopia: a qualitative study

    OpenAIRE

    Carlton, J.

    2010-01-01

    Aims or Purpose: The health related quality of life (HRQoL) implications of amblyopia and/or its treatment have been reported. However the clinician’s perspective has not previously been explored. The purpose of this study was to explore the HRQoL implications of amblyopia and/or its treatment from a clinician’s perspective. Methods: Three focus group sessions were conducted with practising orthoptists. The transcripts were analysed using “Framework” analysis to identify HRQoL ...

  17. Case-control association studies with matching and genomic controlling.

    Science.gov (United States)

    Lee, Wen-Chung

    2004-07-01

    Family-based association studies have gained in popularity for mapping disease-susceptibility gene(s) of complex diseases. However, recruiting family controls is often more difficult than recruiting unrelated controls. The author proposes a case-control study, where the possible biases due to population stratification are controlled by matching in the design stage and by genomic controlling in the data-analytic stage. The matching is based on a set of "stratum-delineating variables," such as, race, ethnicity, nationality, ancestry, and birthplace; and the genomic controlling is based on typing a number of null markers across the genome and applying the principle of multiplicative scaling of chi-square distribution. It pays to match carefully to have a higher proportion of correctly matched sets, as computer simulation showed that this would increase the power of the study. If matching is crude, one loses power but still has the correct type I error rate after genomic controlling. Power studies showed that the numbers of affected subjects required for the pair-matched study are comparable to those required by the case-parents design, if the study was conducted in a homogeneous population. As the (control-to-case) matching ratio increases, the number of affected subjects required decreases. With matching ratio tending toward infinity, the number required shrinks roughly by half. The case-control study with matching and genomic controlling frees us from family bondage, and the genetic problem as complicated as mapping genes can now be studied using simple epidemiologic methods. PMID:15185398

  18. Reorganization of the injured brain: Implications for studies of the neural substrate of cognition

    Directory of Open Access Journals (Sweden)

    Jesper eMogensen

    2011-01-01

    Full Text Available In the search for a neural substrate of cognitive processes, a frequently utilized method is the scrutiny of posttraumatic symptoms exhibited by individuals suffering focal injury to the brain. For instance, the presence or absence of conscious awareness within a particular domain may, combined with knowledge of which regions of the brain have been injured, provide important data in the search for neural correlates of consciousness. Like all studies addressing the consequences of brain injury, however, such research has to face the fact that in most cases, posttraumatic impairments are accompanied by a functional recovery during which symptoms are reduced or eliminated. The apparent contradiction between localization and recovery, respectively, of functions constitutes a problem to almost all aspects of cognitive neuroscience. Several lines of investigation indicate that although the brain remains highly plastic throughout life, the posttraumatic plasticity does not recreate a copy of the neural mechanisms lost to injury. Instead, the uninjured parts of the brain are functionally reorganized in a manner which – in spite of not recreating the basic information processing lost to injury – is able to allow a more or less complete return of the surface phenomena (including manifestations of consciousness originally impaired by the trauma. A novel model (the REF-model of these processes is presented – and some of its implications discussed relative to studies of the neural substrates of cognition and consciousness.

  19. The implications of embodiment for behavior and cognition: animal and robotic case studies

    CERN Document Server

    Hoffmann, Matej

    2012-01-01

    In this paper, we will argue that if we want to understand the function of the brain (or the control in the case of robots), we must understand how the brain is embedded into the physical system, and how the organism interacts with the real world. While embodiment has often been used in its trivial meaning, i.e. 'intelligence requires a body', the concept has deeper and more important implications, concerned with the relation between physical and information (neural, control) processes. A number of case studies are presented to illustrate the concept. These involve animals and robots and are concentrated around locomotion, grasping, and visual perception. A theoretical scheme that can be used to embed the diverse case studies will be presented. Finally, we will establish a link between the low-level sensory-motor processes and cognition. We will present an embodied view on categorization, and propose the concepts of 'body schema' and 'forward models' as a natural extension of the embodied approach toward firs...

  20. A study of starch gelatinisation behaviour in hydrothermally-processed plant food tissues and implications for in vitro digestibility

    OpenAIRE

    Edwards, Cathrina H; Warren, Frederick J; Campbell, Grant M.; Gaisford, Simon; Royall, Paul G.; Butterworth, Peter J; Ellis, Peter R

    2015-01-01

    The aim of this study was to investigate the role of the plant food matrix in influencing the extent of starch gelatinisation during hydrothermal processing, and its implications for starch digestibility. Differential scanning calorimetry (DSC) was used to provide a detailed examination of the gelatinisation behaviour of five distinct size fractions (diameters

  1. A musculoskeletal model of low grade connective tissue inflammation in patients with thyroid associated ophthalmopathy (TAO: the WOMED concept of lateral tension and its general implications in disease

    Directory of Open Access Journals (Sweden)

    Moncayo Helga

    2007-02-01

    Full Text Available Abstract Background Low level connective tissue inflammation has been proposed to play a role in thyroid associated ophthalmopathy (TAO. The aim of this study was to investigate this postulate by a musculoskeletal approach together with biochemical parameters. Methods 13 patients with TAO and 16 controls were examined. Erythrocyte levels of Zn, Cu, Ca2+, Mg, and Fe were determined. The musculoskeletal evaluation included observational data on body posture with emphasis on the orbit-head region. The angular foot position in the frontal plane was quantified following gait observation. The axial orientation of the legs and feet was evaluated in an unloaded supine position. Functional propioceptive tests based on stretch stimuli were done by using foot inversion and foot rotation. Results Alterations in the control group included neck tilt in 3 cases, asymmetrical foot angle during gait in 2, and a reaction to foot inversion in 5 cases. TAO patients presented facial asymmetry with displaced eye fissure inclination (mean 9.1° as well as tilted head-on-neck position (mean 5.7°. A further asymmetry feature was external rotation of the legs and feet (mean 27°. Both foot inversion as well as foot rotation induced a condition of neuromuscular deficit. This condition could be regulated by gentle acupressure either on the lateral abdomen or the lateral ankle at the acupuncture points gall bladder 26 or bladder 62, respectively. In 5 patients, foot rotation produced a phenomenon of moving toes in the contra lateral foot. In addition foot rotation was accompanied by an audible tendon snapping. Lower erythrocyte Zn levels and altered correlations between Ca2+, Mg, and Fe were found in TAO. Conclusion This whole body observational study has revealed axial deviations and body asymmetry as well as the phenomenon of moving toes in TAO. The most common finding was an arch-like displacement of the body, i.e. eccentric position, with foot inversion and head tilt

  2. Implications of Reverse Innovation for Socio-Economic Sustainability: A Case Study of Philips China

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    Juan Shan

    2016-06-01

    Full Text Available The idea of reverse innovation, local innovation happening in emerging markets for the global market, has gained much academic and managerial attention in recent years. The purpose of this study is to understand how reverse innovation has successfully diffused into the product and market development strategies at Philips Inc., a prominent multinational company (MNC of the modern era. Furthermore, the study presents the success achieved by these innovations at both the domestic and global levels, along with their implications regarding socio-economic sustainability in emerging markets. In order to investigate the research questions, a case study of Philips China was conducted involving three product innovations that were found to be suitable examples of reverse innovation. After the study of extant literature on the topic, drawing from research databases, newspaper articles, and company press releases, five semi-structuredinterviews were conducted with key managers and a market practitioner to gain sufficient understanding for this exploratory study. Subsequent case analysis concludes that these innovations are examples of reverse innovation representing a new paradigm change in innovation flow. This flow of innovation from emerging markets to developed markets as confirmed by Corsi’s framework could potentially disrupt developed markets as well as contribute to ensure healthy living conditions for the population living in developing countries. If so, this represents a sustainable socio-economic change in-line with the United Nations' Sustainable Development Goal (SDG of “ensuring healthy lives and promoting well-being for all at all ages.” This is relevant as Philips aspires to be a prominent private sector player in achieving the above-stated goal by defeating non-communicable disease and strengthening local healthcare systems.

  3. Susceptibility to Toxoplasmic Retinochoroiditis Is Associated with Hla Alleles Reported to Be Implicated with Rapid Progression to Aids

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    Ana Lúcia G. Demarco

    2012-01-01

    Full Text Available Background/aims: The frequency of HLA markers associated with rapid progression to AIDS was evaluated in Brazilian patients with AIDS exhibiting or not toxoplasmic retinochoroiditis (TRC.

  4. Comorbid Problems in ADHD : Degree of Association, Shared Endophenotypes, and Formation of Distinct Subtypes. Implications for a Future DSM

    NARCIS (Netherlands)

    Rommelse, Nanda N. J.; Altink, Marieke E.; Fliers, Ellen A.; Martin, Neilson C.; Buschgens, Cathelijne J. M.; Hartman, Catharina A.; Buitelaar, Jan K.; Faraone, Stephen V.; Sergeant, Joseph A.; Oosterlaan, Jaap

    2009-01-01

    We aimed to assess which comorbid problems (oppositional defiant behaviors, anxiety, autistic traits, motor coordination problems, and reading problems) were most associated with Attention-Deficit/Hyperactivity Disorder (ADHD); to determine whether these comorbid problems shared executive and motor

  5. The cannabinoid receptor 1 associates with NMDA receptors to produce glutamatergic hypofunction: implications in psychosis and schizophrenia.

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    Pilar eSánchez-Blázquez

    2014-01-01

    Full Text Available The endocannabinoid system is widespread throughout the central nervous system and its type 1 receptor (CB1 plays a crucial role in preventing the neurotoxicity caused by activation of glutamate N-methyl-D-aspartate receptors (NMDARs. Indeed, it is the activity of NMDARs themselves that provides the demands on the endogenous cannabinoids in order to control their calcium currents. Therefore, a physiological role of this system is to maintain NMDAR activity within safe limits, thereby protecting neural cells from excitotoxicity. Thus, cannabinoids may be able to control NMDAR overactivation-related neural dysfunctions; however the major obstacles to the therapeutic utilization of these compounds are their psychotropic effects and negative influence on cognitive performance. Studies in humans have indicated that abuse of smoked cannabis can promote psychosis and even circumstantially precipitate symptoms of schizophrenia, although the latter appears to require a prior vulnerability in the individual. It is possible that cannabinoids provoke psychosis/schizophrenia reflecting a mechanism common to neuroprotection the reduction of NMDAR activity. Cannabinoids are proposed to produce such effect by reducing the pre-synaptic release of glutamate or interfering with postsynaptic NMDAR-regulated signaling pathways. The efficacy of such control requires the endocannabinoid system to apply its negative influence in a manner that is proportional to the strength of NMDAR signaling. Thus, cannabinoids acting at the wrong time or exerting an inappropriate influence on their receptors may cause NMDAR hypofunction. The purpose of the present review is to draw the attention of the reader to the newly described functional and physical CB1-NMDAR association, which may elucidate the scenario required for the rapid and efficacious control of NMDAR activity. Whether alterations in these mechanisms may increase NMDAR hypofunction leading to vulnerability to

  6. Excess soluble CD40L contributes to blood brain barrier permeability in vivo: implications for HIV-associated neurocognitive disorders.

    Directory of Open Access Journals (Sweden)

    Donna C Davidson

    Full Text Available Despite the use of anti-retroviral therapies, a majority of HIV-infected individuals still develop HIV-Associated Neurocognitive Disorders (HAND, indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistently, we have previously shown that levels of the inflammatory mediator soluble CD40L (sCD40L are elevated in the circulation of HIV-infected, cognitively impaired individuals as compared to their infected, non-impaired counterparts. Recent studies from our group suggest a role for the CD40/CD40L dyad in blood brain barrier (BBB permeability and interestingly, sCD40L is thought to regulate BBB permeability in other inflammatory disorders of the CNS. Using complementary multiphoton microscopy and quantitative analyses in wild-type and CD40L deficient mice, we now reveal that the HIV transactivator of transcription (Tat can induce BBB permeability in a CD40L-dependent manner. This permeability of the BBB was found to be the result of aberrant platelet activation induced by Tat, since depletion of platelets prior to treatment reversed Tat-induced BBB permeability. Furthermore, Tat treatment led to an increase in granulocyte antigen 1 (Gr1 positive monocytes, indicating an expansion of the inflammatory subset of cells in these mice, which were found to adhere more readily to the brain microvasculature in Tat treated animals. Exploring the mechanisms by which the BBB becomes compromised during HIV infection has the potential to reveal novel therapeutic targets, thereby aiding in the development of adjunct therapies for the management of HAND, which are currently lacking.

  7. Excess soluble CD40L contributes to blood brain barrier permeability in vivo: implications for HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Davidson, Donna C; Hirschman, Michael P; Sun, Anita; Singh, Meera V; Kasischke, Karl; Maggirwar, Sanjay B

    2012-01-01

    Despite the use of anti-retroviral therapies, a majority of HIV-infected individuals still develop HIV-Associated Neurocognitive Disorders (HAND), indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistently, we have previously shown that levels of the inflammatory mediator soluble CD40L (sCD40L) are elevated in the circulation of HIV-infected, cognitively impaired individuals as compared to their infected, non-impaired counterparts. Recent studies from our group suggest a role for the CD40/CD40L dyad in blood brain barrier (BBB) permeability and interestingly, sCD40L is thought to regulate BBB permeability in other inflammatory disorders of the CNS. Using complementary multiphoton microscopy and quantitative analyses in wild-type and CD40L deficient mice, we now reveal that the HIV transactivator of transcription (Tat) can induce BBB permeability in a CD40L-dependent manner. This permeability of the BBB was found to be the result of aberrant platelet activation induced by Tat, since depletion of platelets prior to treatment reversed Tat-induced BBB permeability. Furthermore, Tat treatment led to an increase in granulocyte antigen 1 (Gr1) positive monocytes, indicating an expansion of the inflammatory subset of cells in these mice, which were found to adhere more readily to the brain microvasculature in Tat treated animals. Exploring the mechanisms by which the BBB becomes compromised during HIV infection has the potential to reveal novel therapeutic targets, thereby aiding in the development of adjunct therapies for the management of HAND, which are currently lacking.

  8. Interactive effects of cocaine on HIV infection: implication in HIV-associated neurocognitive disorder and neuroAIDS.

    Science.gov (United States)

    Dahal, Santosh; Chitti, Sai V P; Nair, Madhavan P N; Saxena, Shailendra K

    2015-01-01

    Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV), but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine (DA) in the brain, by blocking the dopamine transporters (DAT) which is critical for DA homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to DA, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs), which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND). HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the blood brain barrier (BBB) in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies against HIV-1 infection

  9. Interactive Effects of Cocaine on HIV Infection: Implication in HIV-Associated Neurocognitive Disorder and NeuroAIDS

    Directory of Open Access Journals (Sweden)

    Santosh eDahal

    2015-09-01

    Full Text Available Substantial epidemiological studies suggest that not only, being one of the reasons for the transmission of the human immunodeficiency virus (HIV, but drug abuse also serves its role in determining the disease progression and severity among the HIV infected population. This article focuses on the drug cocaine, and its role in facilitating entry of HIV into the CNS and mechanisms of development of neurologic complications in infected individuals. Cocaine is a powerfully addictive central nervous system stimulating drug, which increases the level of neurotransmitter dopamine in the brain, by blocking the dopamine transporters (DAT which is critical for dopamine homeostasis and neurocognitive function. Tat protein of HIV acts as an allosteric modulator of DAT, where as cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to dopamine, their number increases. These macrophages release inflammatory mediators and neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV infection enhances the production of platelet monocyte complexes (PMCs, which may cross transendothelial barrier, and result in HIV-associated neurocognitive disorder (HAND. HAND is characterized by neuroinflammation, including astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked to progressive virus infection and immune deterioration. Cocaine and viral proteins are capable of eliciting signaling transduction pathways in neurons, involving in mitochondrial membrane potential loss, oxidative stress, activation of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF-κB that leads to HAND. Tat-induced inflammation provokes permeability of the Blood Brain Barrier (BBB in the platelet dependent manner, which can potentially be the reason for progression to HAND during HIV infection. A better understanding on the role of cocaine in HIV infection can give a clue in developing novel therapeutic strategies

  10. The admixture structure and genetic variation of the archipelago of Cape Verde and its implications for admixture mapping studies.

    Directory of Open Access Journals (Sweden)

    Sandra Beleza

    implications for the design of association studies using this population.

  11. Fat-Free Body Mass but not Fat Mass is Associated with Reduced Gray Matter Volume of Cortical Brain Regions Implicated in Autonomic and Homeostatic Regulation

    Science.gov (United States)

    Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M; Chen, Kewei; Krakoff, Jonathan

    2014-01-01

    Obesity has been associated with alterations of both functional and structural aspects of the human central nervous system. In obese individuals both fat mass (FM; primarily consisting of adipose tissue) and fat-free mass (FFM; all non-adipose tissues) are increased and it remains unknown whether these compartments have separate effects on human brain morphology. We used voxel-based morphometry to investigate the relationships between measures of body composition and regional gray matter volume (GMV) in 76 healthy adults with a wide range of adiposity (24F/52M; age 32.1±8.8y; percentage of body fat [PFAT%] 25.5±10.9%; BMI 29.8±8.9). Faf-free mass index (FFMI kg*m-2) showed negative associations in bilateral temporal regions, the bilateral medial and caudolateral OFC, and the left insula. Fat mass index (FMI kg*m-2) showed similar, but less extensive negative associations within temporal cortical regions and the left caudolateral orbitofrontal cortex (OFC). In addition, negative associations were seen for FMI with GMV of the cerebellum. Associations of FFMI with temporal and medial orbitofrontal GMV appeared to be independent of adiposity. No associations were seen between measures of adiposity (i.e. FM and PFAT) and GMV when adjusted for FFM. The majority of regions that we find associated with FFM have been implicated in the regulation of eating behavior and show extensive projections to central autonomic and homeostatic core structures. These data indicate that not adipose tissue or relative adiposity itself, but obesity related increases in absolute tissue mass and particularly FFM may have a more predominant effect on the human brain. This might be explained by the high metabolic demand of FFM and related increases in total energy needs. PMID:22974975

  12. Mechanism study of goldenseal-associated DNA damage.

    Science.gov (United States)

    Chen, Si; Wan, Liqing; Couch, Letha; Lin, Haixia; Li, Yan; Dobrovolsky, Vasily N; Mei, Nan; Guo, Lei

    2013-07-31

    Goldenseal has been used for the treatment of a wide variety of ailments including gastrointestinal disturbances, urinary tract disorders, and inflammation. The five major alkaloid constituents in goldenseal are berberine, palmatine, hydrastine, hydrastinine, and canadine. When goldenseal was evaluated by the National Toxicology Program (NTP) in the standard 2-year bioassay, goldenseal induced an increase in liver tumors in rats and mice; however, the mechanism of goldenseal-associated liver carcinogenicity remains unknown. In this study, the toxicity of the five goldenseal alkaloid constituents was characterized, and their toxic potencies were compared. As measured by the Comet assay and the expression of γ-H2A.X, berberine, followed by palmatine, appeared to be the most potent DNA damage inducer in human hepatoma HepG2 cells. Berberine and palmatine suppressed the activities of both topoisomerase (Topo) I and II. In berberine-treated cells, DNA damage was shown to be directly associated with the inhibitory effect of Topo II, but not Topo I by silencing gene of Topo I or Topo II. In addition, DNA damage was also observed when cells were treated with commercially available goldenseal extracts and the extent of DNA damage was positively correlated to the berberine content. Our findings suggest that the Topo II inhibitory effect may contribute to berberine- and goldenseal-induced genotoxicity and tumorigenicity.

  13. Tomographic Study of Ionospheric Effects Associated with a Solar Eclipse

    Institute of Scientific and Technical Information of China (English)

    Wu Xiong-bin; Xu Ji-sheng; Ma Shu-ying; Tian Mao

    2003-01-01

    This paper studies the ionospheric effects associ-ated with the solar eclipse of October 24th, 1995 by means of Computerized Ionospheric Tomography (CIT). Since the re-constructed profiles from experimental CIT are sporadically located in time, a time domain interpolation method based onSingular Value Decomposition (SVD) technique is proposed and applied to extract the ionospheric effects. The effects canbe extracted by comparison analysis between the interpolated CIT profiles of the eclipse days and that of the reference day that are time-aligned. A series of figs have been obtained showing the attenuation of photonization effect at low alti-tudes and the weakening of plasma's transportation process athigh altitudes, etc. The photonization effect recovered to nor-mal level soon after the last contact. The maximum electron density diminishing is observed about 2 h after the eclipse maximum and the effects seem vanished in the hours fol-lowed. Analysis on vertical TEC's latitudinal temporal variation gives similar conclusions.

  14. Association studies in okra (Abelmoschus esculentus (L. Moench

    Directory of Open Access Journals (Sweden)

    Sateesh Adiger, G. Shanthkumar, P. I. Gangashetty* and P. M. Salimath

    2011-12-01

    Full Text Available The present study was undertaken on 163 genotypes including 43 parents and 120 crosses of okra to determine the geneticvariability, nature of association among different yield attributes and their direct and indirect contribution towards yield. Fromthe analysis of variance, it was observed that mean squares due to genotypes were significant for all the traits, indicating thepresence of genetic variability in the experimental material. The values of PCV were higher than that of GCV values for all theten characters indicating influence of environmental effects in the expression of these characters. The GCV, heritability andgenetic advance as percentage of mean were higher for plant height, fruit yield per plant, fruit weight and days to 50 per centflowering which might be attributed to additive gene action of inheritance. The Fruit yield has significantly positive correlationwith plant height, number of branches per plant, inter nodal length, fruit length, fruit weight and number of fruits per plant at bothgenotypic and phenotypic level, indicating mutual association of these traits. Path coefficient analysis revealed that fruit weighthad maximum direct contribution (0.884 towards fruit yield followed by number of fruits per plant (0.852, plant height (0.024and number of branches per plant (0.020. However, days to 50 per cent flowering exhibited highest negative direct effect (-0.013 followed by test weight (-0.009 and fruit diameter (-0.003. These important traits may be viewed in selection programmefor the further improvement of okra.

  15. Study of enteropathogens associated with paediatric gastroen-teritis

    Institute of Scientific and Technical Information of China (English)

    Maysaa El; Sayed Zaki

    2009-01-01

    Objective:To determine the etiology of acute diarrhea in children under 5 years of age and to improve knowl-edge of the etiology of gastrointestinal pathogens using traditional and molecular diagnostic techniques.Meth-ods:Various common enteropathogens (viral,bacterial and parasites)associated with diarrhea were investiga-ted by conventional and molecular techniques (PCR)for verotoxin present in Escherichia coli in 218 children less than 5 years of age admitted to Mansoura University Children hospital-Egypt.Results:The occurrence of enteropathogens identified was as follows:E.coli O157∶H7 38.8% followed by Salmonella Spp 29.4%,Aero-monas 20% and Shigella Spp 11.8%.Rotavirus was found in of samples 17.1%.Rotavirus was statistically significant in age <2 years old.The commonest parasites found were E.histolytica followed by Enterobius ver-micularis,Giardia lambia,Hymenolepis nana and Ascaries.Shigella and Salmonella isolates were tested for their susceptibility to common antimicrobial agents and most of the isolates were resistant to ampicillin and tri-methoprim /sulfamethoxazole.Conculsion:This study demonstrated that rotavirus,E.coli O157∶H7,Salmo-nella Spp,and Aeromonas were significant enteropathogens.Rotavirus was significantly associated with infan-tile gastroenteritis.The results highlight the value of using a combination of traditional and PCR techniques in the diagnosis of enteropathogens related to acute gastroenteritis in children.

  16. Associated factors to repeated consultations to the urgencies service for asthma in pediatric patient: Implications for an educational program

    International Nuclear Information System (INIS)

    Bronchial asthma is one of the most frequent respiratory diseases in childhood. Recurrent emergency department visits for asthma produce anxiety and high costs for the system of health and for the family. It is important to know the factors related to these recurrent emergency department visits to assist the targeting of appropriate future interventions aimed at reducing this avoidable presentation. The objective of the present study was to identify factors associated with recurrent emergency department visits for asthma in children liable to be modified by means of an education program. Data obtained from a survey of parents of 146 pediatric patients with asthma attending an asthma clinic and educational program were examined. Parents completed an asthma knowledge and attitudes questionnaire that also included other socio demographic and illness-related variables, including the number of consultations to emergency department by their children asthma in the previous 6 months. Of the 146 asthmatic patients enrolled, 41 (28.1%) consulted repeatedly to the emergency department for asthma. After controlling for age of the patient, educational level of the parents, and functional severity of the disease, we found that parents who reported that they attended to emergency room because asthma attacks of their children were severe enough to go elsewhere (OR, 4.57; CL95%, 1.76- 11.85; P = 0.002), parents who reported that asthma medications should be administered only in symptomatic moments (OR 278, CL 95%, 1.05 - 7.33, P = 0.038 and parents that did not recognize the fact that asthma attacks can be avoided if medications are administered when there are no symptoms (between asthma attacks) (OR 2.61; CL95%; 1.03 - 7.02; p = 0,045), had a greater probability to attend rapidly the emergency room because of asthma of their children. The fact that parents of asthmatic patients have thought that asthma medications should be administered only in symptomatic patients, that they hadn

  17. Interleukin-1 gene complex in schizophrenia: an association study.

    Science.gov (United States)

    Saiz, Pilar A; Garcia-Portilla, Maria P; Arango, Celso; Morales, Blanca; Martinez-Barrondo, Sara; Alvarez, Victoria; Coto, Eliecer; Fernandez, Juan; Bousono, Manuel; Bobes, Julio

    2006-09-01

    The aim of this study is to investigate the association between three polymorphisms of the interleukin-1 (IL-1) gene complex and schizophrenia. We genotyped 228 outpatients with schizophrenia (DSM-IV criteria) and 419 unrelated healthy controls. The following polymorphisms were analyzed: IL-1alpha -889 C/T, IL-1beta +3953 C/T, and IL-1RA (86 bp)n. No significant differences in genotype or in allelic distribution of the Il-1alpha, IL-1beta, and IL-1RA polymorphisms were found. Estimated haplotype frequencies were similar in both groups. Our data do not suggest that genetically determined changes in the IL-1 gene complex confer increased susceptibility for schizophrenia.

  18. Tomographic Study of Ionospheric Effects Associated with a Solar Eclipse

    Institute of Scientific and Technical Information of China (English)

    WuXiong-bin; XuJi-sheng; MaShu-ying; TianMao

    2003-01-01

    This paper studies the ionospheric effects associated with the solar eclipse of October 24th, 1995 by means of Computerized Ionospheric Tomography (CIT). Since the reconstructed profiles from experimental CIT are sporadically located in time, a time domain interpolation method based on Singular Value Decomposition (SVD) technique is proposed and applied to extract the ionospheric effects. The effects can be extracted by comparison analysis between the interpolated CIT profiles of the eclipse days and that of the reference day that are time-aligned. A series of figs have been obtained showing the attenuation of photonization effect at low altitudes and the weakening of plasma's transportation process at high altitudes, etc. The photonization effect recovered to normal level soon after the last contact. The maximum electron density diminishing is observed about 2 h after the eclipse maximum and the effects seem vanished in the hours followed. Analysis on vertical TEC's latitudinal-temporal variation gives similar conclusions.

  19. Sequence imputation of HPV16 genomes for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Benjamin Smith

    Full Text Available BACKGROUND: Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity. METHODS: A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica. RESULTS: HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution. CONCLUSIONS: Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable

  20. A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity

    International Nuclear Information System (INIS)

    Background and purpose: This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2 years after radiotherapy. Materials and methods: A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer. Results: Quantile–quantile plots show more associations at the P < 5 × 10−7 level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts. Conclusions: This largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable

  1. A strategy analysis for genetic association studies with known inbreeding

    Directory of Open Access Journals (Sweden)

    del Giacco Stefano

    2011-07-01

    Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is

  2. A genome-wide association study of pulmonary function measures in the Framingham Heart Study.

    Directory of Open Access Journals (Sweden)

    Jemma B Wilk

    2009-03-01

    Full Text Available The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1/FVC is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs associated with the FEV(1/FVC ratio, analyzed as a percent of the predicted value. Identified SNPs were examined in an independent set of 835 Family Heart Study participants enriched for airflow obstruction. Four SNPs in tight linkage disequilibrium on chromosome 4q31 were associated with the percent predicted FEV(1/FVC ratio with p-values of genome-wide significance in the Framingham sample (best p-value = 3.6e-09. One of the four chromosome 4q31 SNPs (rs13147758; p-value 2.3e-08 in Framingham was genotyped in the Family Heart Study and produced evidence of association with the same phenotype, percent predicted FEV(1/FVC (p-value = 2.0e-04. The effect estimates for association in the Framingham and Family Heart studies were in the same direction, with the minor allele (G associated with higher FEV(1/FVC ratio levels. Results from the Family Heart Study demonstrated that the association extended to FEV(1 and dichotomous airflow obstruction phenotypes, particularly among smokers. The SNP rs13147758 was associated with the percent predicted FEV(1/FVC ratio in independent samples from the Framingham and Family Heart Studies producing a combined p-value of 8.3e-11, and this region of chromosome 4 around 145.68 megabases was associated with COPD in three additional populations reported in the accompanying manuscript. The associated SNPs do not lie within a gene transcript but are near the hedgehog-interacting protein (HHIP gene and several expressed sequence tags cloned from fetal lung. Though it is unclear what gene or regulatory effect explains the association, the region warrants further investigation.

  3. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies

    DEFF Research Database (Denmark)

    Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L;

    2011-01-01

    Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.......Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors....

  4. STUDY ON BEIJING'S EMERGING MOBILE COMMUNICATION INDUSTRIAL CLUSTER AND ITS POLICY IMPLICATIONS

    Institute of Scientific and Technical Information of China (English)

    SUN Tie-shan; LI Guo-ping; LU Ming-hua

    2003-01-01

    This paper is a preliminary and illustrative case study of Beijing's emerging mobile communication industri-al (MCI) cluster, which helps understand the cluster by qualitative analysis and description. Beijing's MCI cluster is emerg-ing as far as the competence of the industry and its spatial concentration are concerned, although it is not the type of thecluster described by PORTER due to the low competence of indigenous firms. The formation of the cluster can be ex-plained by means of the factor and demand conditions of Beijing. However, it is mostly determined by the multinationalsthat promote the growth of the industry and the formation of the cluster, and by the government that also plays a key rolein many ways. As a matter of fact, the interaction between the multinationals and the local government is the key to under-standing the formation of the cluster. Allinall, Beijing's emerging MCI cluster is a value-chain, geographicallyconcentrat-ed but non-localized cluster, which is highly dominated by the multinationals and the local government. Its special character-istics bear some policy implications as to the change of the roles of the local government and the localization of multination-als, etc.

  5. Comparison of the observed and calculated clear sky greenhouse effect - Implications for climate studies

    Science.gov (United States)

    Kiehl, J. T.; Briegleb, B. P.

    1992-01-01

    The clear sky greenhouse effect is defined in terms of the outgoing longwave clear sky flux at the top of the atmosphere. Recently, interest in the magnitude of the clear sky greenhouse effect has increased due to the archiving of the clear sky flux quantity through the Earth Radiation Budget Experiment (ERBE). The present study investigates to what degree of accuracy this flux can be analyzed by using independent atmospheric and surface data in conjunction with a detailed longwave radiation model. The conclusion from this comparison is that for most regions over oceans the analyzed fluxes agree to within the accuracy of the ERBE-retrieved fluxes (+/- 5 W/sq m). However, in regions where deep convective activity occurs, the ERBE fluxes are significantly higher (10-15 W/sq m) than the calculated fluxes. This bias can arise from either cloud contamination problems or variability in water vapor amount. It is argued that the use of analyzed fluxes may provide a more consistent clear sky flux data set for general circulation modeling validation. Climate implications from the analyzed fluxes are explored. Finally, results for obtaining longwave surface fluxes over the oceans are presented.

  6. Rapid Urban Expansion and Its Implications on Geomorphology: A Remote Sensing and GIS Based Study

    Directory of Open Access Journals (Sweden)

    S. N. Mohapatra

    2014-01-01

    Full Text Available Topography, vegetation, climate, water table, and even the anthropogenic activities all are affected by urban growth through diverse mechanisms. The present study focuses on the implications of urban expansion on geomorphology in the historical city of Gwalior in central India. The expansion of urban area has been quantified by deriving data for four decades (1972–2013 from the Landsat images. The results show that the urban built-up area has increased by 08.48 sq. km during the first eighteen years (1972–1990 which has increased to 16.28 sq. km during the next sixteen years (1990–2006. The built-up area has gone up to 23.19 sq. km in the next seven years (2006–2013. Overall during the last 40 years the growth of the urban built-up is nearly three times of the built-up areas in 1972. The average decadal growth rate of population is 27.28 percent while that of built-up land is 36.29 percent. The construction activities have affected important geomorphic features such pediplain, buried pediplain, residual hills, and denudational hills. It was concluded that, instead of shortsighted urban development, proper measures should be taken in accordance with scientific planning for the urban expansion of the city in the future.

  7. Occurence and implications of radiation dose-rate effects for material aging studies

    Science.gov (United States)

    Gillen, Kenneth T.; Clough, Roger L.

    A number of commercial cable materials, including ethylene propylene rubber and crosslinked polyolefin insulations and chloroprene and chlorosulfonated polyethylene jackets have been radiation aged in air and nitrogen at radiation dose rates ranging from approximately 10 3 to 10 6{rad}/{hr}. Material degradation was followed using ultimate tensile properties (elongation and tensile strength), swelling measurements and infrared spectroscopy. The tensile results indicate that in air environments radiation dose rate effects are important for all four materials, with more mechanical damage occurring as the dose rate is lowered. These results are interpreted as coming from a competition between crosslinking and oxidative scission in which scission becomes more important as the dose rate is lowered. The swelling results offer direct evidence in support of this interpretation. In addition the infrared results show increased carbonyl content at lower dose rates, also indicative of increased oxidation. The conclusions of this study have important implications for the qualification of elastomeric materials for nuclear applications, since they clearly indicate that the mechanism of degradation is quite different (and the amount usually more severe) under low dose rate exposures compared to the mechanism occurring under the high dose rate exposures normally utilized for stimulating the natural aging.

  8. Students’ Understanding of the Concept of Democracy and Implications for Teacher Education in Social Studies

    Directory of Open Access Journals (Sweden)

    Nora Elise Hesby Mathé

    2016-04-01

    be actively encouraged and maintained also in successful democracies. Little is known, however, about how students understand and explain democracy as a subject-specific concept. Such knowledge may be valuable for social studies teachers and teacher educators to fulfil the purpose of the social studies curriculum. The present article investigates 16-year-old students’ understanding of the concept of democracy. In social studies, the concept of democracy is essential not only for disciplinary understanding and discourse, but also for students’ out-of-school democratic participation. To investigate students’ understanding of this concept, semi-structured group interviews were conducted with a total of 23 students at three different Norwegian upper secondary schools. A central finding is that students primarily expressed a liberal understanding of democracy focusing on voting in elections as the main political activity. Students also demonstrated more or less limited or elaborate understanding. In addition to presenting and discussing students’ understandings of the concept of democracy, this article considers implications for teacher education in social studies. One implication is that teacher educators need to engage actively in discussing and defining core concepts with their students. This is related to supporting student teachers’ professional development and in turn developing adolescents’ opportunities for democratic participation. Such a dual focus can provide a knowledge base to help student teachers in their professional development in their first years as practicing teachers.Keywords: democracy, concepts, understanding, teacher education, social studies, democratic theory

  9. Replication study implicates COMT val158met polymorphism as a modulator of probabilistic reward learning.

    Science.gov (United States)

    Lancaster, T M; Heerey, E A; Mantripragada, K; Linden, D E J

    2015-07-01

    Previous studies suggest that a single nucleotide polymorphism in the catechol-O-methyltransferase (COMT) gene (val158met) may modulate reward-guided decision making in healthy individuals. The polymorphism affects dopamine catabolism and thus modulates prefrontal dopamine levels, which may lead to variation in individual responses to risk and reward. We previously showed, using tasks that index reward responsiveness (measured by responses bias towards reinforced stimuli) and risk taking (measured by the Balloon Analogue Risk Task), that COMT met homozygotes had increased reward responsiveness and, thus, an increased propensity to seek reward. In this study, we sought to replicate these effects in a larger, independent cohort of Caucasian UK university students and staff with similar demographic characteristics (n = 101; 54 females, mean age: 22.2 years). Similarly to our previous study, we observed a significant trial × COMT genotype interaction (P = 0.047; η(2) = 0.052), which was driven by a significant effect of COMT on the incremental acquisition of response bias [response bias at block 3 - block 1 (met/met > val/val: P = 0.028) and block 3 - block 2 (met/met > val/val: P = 0.007)], suggesting that COMT met homozygotes demonstrated higher levels of reward responsiveness by the end of the task. However, we failed to see main effects of COMT genotype on overall response bias or risk-seeking behaviour. These results provide additional evidence that prefrontal dopaminergic variation may have a role in reward responsiveness, but not risk-seeking behaviour. Our findings may have implications for neuropsychiatric disorders characterized by clinical deficits in reward processing such as anhedonia. PMID:26096878

  10. A cross-sectional study of prevalence and implications of depression and anxiety in psoriasis

    Directory of Open Access Journals (Sweden)

    Sreelatha Lakshmy

    2015-01-01

    Full Text Available Background: Physical and mental comorbidity is common and has significant implications for overall health outcomes. Psoriasis, a psychocutaneous disorder, is a classic example of mental-physical comorbidity. Aims: In view of the impact of socio-cultural influences on mind-body interactions and the paucity of Indian research pertaining to psychiatric morbidity in psoriatic patients, this study was undertaken to measure the prevalence of anxiety and depression in patients with psoriasis, and to correlate these with severity of psoriasis and quality of life. Materials and Methods: This cross-sectional study was conducted on 90 consecutive patients of psoriasis, over a period of 12 months, in a tertiary care centre. The Psoriasis Area and Severity Index was used to assess severity of psoriasis. PHQ-9, GAD-7 and the Perceived Stress Scale were used to screen for depression, anxiety and perceived stress respectively. The WHOQOL-BREF was used to determine the quality of life. Statistics Analysis: All analysis was performed using Microsoft Excel software and Statistical Package for Social Sciences. Results: A total of 71 (78.9% subjects had depression and 69 (76.7% had anxiety. Fifty one patients had significant stress. A significant positive correlation was established between psoriasis variables (severity and duration of psoriasis and psychological variables (depression, anxiety and stress. Severity of psoriasis had a significant negative correlation with social relationships and environmental domains of WHOQOL. Quality of life was significantly worse in patients with psoriasis with comorbid anxiety/depression. Conclusion: Patients with psoriasis have a clinically significant prevalence of depression, anxiety and perceived stress. This study highlights the complex relationship between psoriasis, psychiatric comorbidity and quality of life and the need to simultaneously consider dermatological and psychological factors.

  11. Platelet-derived growth factor (PDGF-BB-mediated induction of monocyte chemoattractant protein 1 in human astrocytes: implications for HIV-associated neuroinflammation

    Directory of Open Access Journals (Sweden)

    Bethel-Brown Crystal

    2012-12-01

    Full Text Available Abstract Chemokine (C-C motif ligand 2, also known as monocyte chemoattractant protein 1 (MCP-1 is an important factor for the pathogenesis of HIV-associated neurocognitive disorders (HAND. The mechanisms of MCP-1-mediated neuropathogenesis, in part, revolve around its neuroinflammatory role and the recruitment of monocytes into the central nervous system (CNS via the disrupted blood-brain barrier (BBB. We have previously demonstrated that HIV-1/HIV-1 Tat upregulate platelet-derived growth factor (PDGF-BB, a known cerebrovascular permeant; subsequently, the present study was aimed at exploring the regulation of MCP-1 by PDGF-BB in astrocytes with implications in HAND. Specifically, the data herein demonstrate that exposure of human astrocytes to HIV-1 LAI elevated PDGF-B and MCP-1 levels. Furthermore, treating astrocytes with the human recombinant PDGF-BB protein significantly increased the production and release of MCP-1 at both the RNA and protein levels. MCP-1 induction was regulated by activation of extracellular-signal-regulated kinase (ERK1/2, c-Jun N-terminal kinase (JNK and p38 mitogen-activated protein (MAP kinases and phosphatidylinositol 3-kinase (PI3K/Akt pathways and the downstream transcription factor, nuclear factor κB (NFκB. Chromatin immunoprecipitation (ChIP assays demonstrated increased binding of NFκB to the human MCP-1 promoter following PDGF-BB exposure. Conditioned media from PDGF-BB-treated astrocytes increased monocyte transmigration through human brain microvascular endothelial cells (HBMECs, an effect that was blocked by STI-571, a tyrosine kinase inhibitor (PDGF receptor (PDGF-R blocker. PDGF-BB-mediated release of MCP-1 was critical for increased permeability in an in vitro BBB model as evidenced by blocking antibody assays. Since MCP-1 is linked to disease severity, understanding its modulation by PDGF-BB could aid in understanding the proinflammatory responses in HAND. These results suggest that astrocyte

  12. Genetic basis of interindividual susceptibility to cancer cachexia: selection of potential candidate gene polymorphisms for association studies

    Indian Academy of Sciences (India)

    N. Johns; B. H. Tan; M. Macmillan; T. S. Solheim; J. A. Ross; V. E. Baracos; S. Damaraju; K. C. H. Fearon

    2014-12-01

    Cancer cachexia is a complex and multifactorial disease. Evolving definitions highlight the fact that a diverse range of biological processes contribute to cancer cachexia. Part of the variation in who will and who will not develop cancer cachexia may be genetically determined. As new definitions, classifications and biological targets continue to evolve, there is a need for reappraisal of the literature for future candidate association studies. This review summarizes genes identified or implicated as well as putative candidate genes contributing to cachexia, identified through diverse technology platforms and model systems to further guide association studies. A systematic search covering 1986–2012 was performed for potential candidate genes / genetic polymorphisms relating to cancer cachexia. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Pathway analysis software was used to reveal possible network associations between genes. Functionality of SNPs/genes was explored based on published literature, algorithms for detecting putative deleterious SNPs and interrogating the database for expression of quantitative trait loci (eQTLs). A total of 154 genes associated with cancer cachexia were identified and explored for functional polymorphisms. Of these 154 genes, 119 had a combined total of 281 polymorphisms with functional and/or clinical significance in terms of cachexia associated with them. Of these, 80 polymorphisms (in 51 genes) were replicated in more than one study with 24 polymorphisms found to influence two or more hallmarks of cachexia (i.e., inflammation, loss of fat mass and/or lean mass and reduced survival). Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides a contemporary basis to select genes and/or polymorphisms for further association studies in cancer cachexia, and

  13. A study of Helicobacter pylori -associated gastritis patterns in Iraq and their association with strain virulence

    Directory of Open Access Journals (Sweden)

    Hussein Nawfal

    2009-01-01

    Full Text Available Background/Aim: Helicobacter pylori ( H. pylori infection causes peptic ulceration and gastric adenocarcinoma. In Iraq, gastric cancer is rare. We investigated whether infected adults had the antral-predominant pattern of H. pylori -associated gastritis, which does not predispose to cancer. Materials and Methods: We evaluated histopathological changes by the Sydney scoring system in gastric biopsies taken from 30 H. pylori -infected adults and studied the correlation of these changes with the virulence factors. The Mann-Whitney test was used for the comparison of histopathological data. The presence or absence of each pathological index was evaluated with respect to the possession of virulence factors by the infecting H. pylori strain using the χ2 test. Results: Gastric lymphocyte infiltration was more prominent in the antrum ( P = 0.01. Neutrophil infiltration was mild and gastric mucosal atrophy was rare. No relationship was found between virulence factors and histopathological changes. Conclusions: The mild pathology and antral-predominant gastritis help explain the low cancer rate in Iraq.

  14. Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsin-Chou Yang

    Full Text Available Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP quality, four SNPs from two SNP triplets with strong association signals (-log(10(p>7 and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10(p>8 were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.

  15. Genome-wide Association Study of Personality Traits in the Long Life Family Study

    Directory of Open Access Journals (Sweden)

    Harold T Bae

    2013-05-01

    Full Text Available Personality traits have been shown to be associated with longevity and healthy aging. In order to discover novel genetic modifiers associated with personality traits as related with longevity, we performed a genome-wide association study (GWAS on personality factors assessed by NEO-FFI in individuals enrolled in the Long Life Family Study (LLFS, a study of 583 families (N up to 4595 with clustering for longevity in the United States and Denmark. Three SNPs, in almost perfect LD, associated with agreeableness reached genome-wide significance (p<10-8 and replicated in an additional sample of 1279 LLFS subjects, although one (rs9650241 failed to replicate and the other two were not available in two independent replication cohorts, the Baltimore Longitudinal Study of Aging and the New England Centenarian Study. Based on 10,000,000 permutations, the empirical p-value of 2X10-7 was observed for the genome-wide significant SNPs. Seventeen SNPs that reached marginal statistical significance in the two previous GWASs (p-value < 10-4 and 10-5, were also marginally significantly associated in this study (p-value < 0.05, although none of the associations passed the Bonferroni correction. In addition, we tested age-by-SNP interactions and found some significant associations. Since scores of personality traits in LLFS subjects change in the oldest ages, and genetic factors outweigh environmental factors to achieve extreme ages, these age-by-SNP interactions could be a proxy for complex gene-gene interactions affecting personality traits and longevity.

  16. Dysregulated neutrophil-endothelial interaction in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides : Implications for pathogenesis and disease intervention

    NARCIS (Netherlands)

    Hu, Nan; Westra, Johanna; Kallenberg, Cees G. M.

    2011-01-01

    The interplay between neutrophils and endothelial cells allows ANCA to become pathogenic and results in uncontrolled inflammation in the vessel wall. This review presents an overall view on neutrophil-endothelial interaction during inflammation with a focus on ANCA-associated vasculitis, and summari

  17. Determinants of Mortality in a Combined Cohort of 501 Patients With HIV-Associated Cryptococcal Meningitis: Implications for Improving Outcomes

    Science.gov (United States)

    Jarvis, Joseph N.; Bicanic, Tihana; Loyse, Angela; Namarika, Daniel; Jackson, Arthur; Nussbaum, Jesse C.; Longley, Nicky; Muzoora, Conrad; Phulusa, Jacob; Taseera, Kabanda; Kanyembe, Creto; Wilson, Douglas; Hosseinipour, Mina C.; Brouwer, Annemarie E.; Limmathurotsakul, Direk; White, Nicholas; van der Horst, Charles; Wood, Robin; Meintjes, Graeme; Bradley, John; Jaffar, Shabbar; Harrison, Thomas

    2014-01-01

    Background. Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. Methods. Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. Results. Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0–1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4–11.1), high peripheral white blood cell count (>10 × 109 cells/L; OR, 8.7; 95% CI, 2.5–30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). Conclusions. CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes. PMID:24319084

  18. Adult Learning Open University Determinants study (ALOUD): physical activity associated with study success

    NARCIS (Netherlands)

    Gijselaers, Jérôme; De Groot, Renate; Kirschner, Paul A.

    2013-01-01

    Gijselaers, H. J. M., De Groot, R. H. M., & Kirschner, P. A. (2013, 23 May). Adult Learning Open University Determinants study (ALOUD): physical activity associated