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Sample records for association study implicates

  1. Human MHC architecture and evolution: implications for disease association studies

    PubMed Central

    Traherne, J A

    2008-01-01

    Major histocompatibility complex (MHC) variation is a key determinant of susceptibility and resistance to a large number of infectious, autoimmune and other diseases. Identification of the MHC variants conferring susceptibility to disease is problematic, due to high levels of variation and linkage disequilibrium. Recent cataloguing and analysis of variation over the complete MHC has facilitated localization of susceptibility loci for autoimmune diseases, and provided insight into the MHC's evolution. This review considers how the unusual genetic characteristics of the MHC impact on strategies to identify variants causing, or contributing to, disease phenotypes. It also considers the MHC in relation to novel mechanisms influencing gene function and regulation, such as epistasis, epigenetics and microRNAs. These developments, along with recent technological advances, shed light on genetic association in complex disease. PMID:18397301

  2. The estrogen hypothesis of Schizophrenia implicates glucose metabolism: Association study in three independent samples

    PubMed Central

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D; Djurovic, Srdjan; Melle, Ingrid; Agartz, Ingrid; Hall, Haakan; Ullum, Henrik; Timm, Sally; Wang, August G; Jönsson, Erik G; Andreassen, Ole A; Werge, Thomas

    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 networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia or at least with gender-associated aspects of the illness. Results We genotyped 185 SNPs in three independent case-control samples of Scandinavian origin (a total of 765 patients and 1274 control subjects). Variants of the mitogen-activated protein kinase 14 gene (MAPK14) and the phosphoenolpyruvate carboxykinase 1 (PCK1) and fructose-1,6-biphosphatase (FBP1) were nominal significantly associated with schizophrenia, and several haplotypes within enolase 2 gene (ENO2) consist of the same SNP allele having elevated risk of schizophrenia. Importantly, we find no evidence of stratification due to nationality or gender. Conclusion Several gene variants in the Glycolysis were associated with schizophrenia in three independent samples. However, the findings are weak and not

  3. Lessons and Implications from Genome-Wide Association Studies (GWAS) Findings of Blood Cell Phenotypes

    PubMed Central

    Chami, Nathalie; Lettre, Guillaume

    2014-01-01

    Genome-wide association studies (GWAS) have identified reproducible genetic associations with hundreds of human diseases and traits. The vast majority of these associated single nucleotide polymorphisms (SNPs) are non-coding, highlighting the challenge in moving from genetic findings to mechanistic and functional insights. Nevertheless, large-scale (epi)genomic studies and bioinformatic analyses strongly suggest that GWAS hits are not randomly distributed in the genome but rather pinpoint specific biological pathways important for disease development or phenotypic variation. In this review, we focus on GWAS discoveries for the three main blood cell types: red blood cells, white blood cells and platelets. We summarize the knowledge gained from GWAS of these phenotypes and discuss their possible clinical implications for common (e.g., anemia) and rare (e.g., myeloproliferative neoplasms) human blood-related diseases. Finally, we argue that blood phenotypes are ideal to study the genetics of complex human traits because they are fully amenable to experimental testing. PMID:24705286

  4. Discovery of Rare Variants via Sequencing: Implications for the Design of Complex Trait Association Studies

    PubMed Central

    Li, Bingshan; Leal, Suzanne M.

    2009-01-01

    There is strong evidence that rare variants are involved in complex disease etiology. The first step in implicating rare variants in disease etiology is their identification through sequencing in both randomly ascertained samples (e.g., the 1,000 Genomes Project) and samples ascertained according to disease status. We investigated to what extent rare variants will be observed across the genome and in candidate genes in randomly ascertained samples, the magnitude of variant enrichment in diseased individuals, and biases that can occur due to how variants are discovered. Although sequencing cases can enrich for casual variants, when a gene or genes are not involved in disease etiology, limiting variant discovery to cases can lead to association studies with dramatically inflated false positive rates. PMID:19436704

  5. Visitor behaviour and public health implications associated with exotic pet markets: an observational study

    PubMed Central

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

    2012-01-01

    Objectives To conduct on-site assessments of public health implications at key European pet markets. Design Observational study of visitor behaviour at stalls that displayed and sold animals, mainly amphibians and reptiles, to assess potential contamination risk from zoonotic pathogens. We noted initial modes of contact as ‘direct’ (handling animals) as well as ‘indirect’ (touching presumed contaminated animal-related sources) and observed whether these visitors subsequently touched their own head or mouth (H1), body (H2) or another person (H3). Setting Publicly accessible exotic animal markets in the UK, Germany and Spain. Participants Anonymous members of the public in a public place. Main outcome measures Occurrence and frequency of public contact (direct, indirect or no contact) with a presumed contaminated source. Results A total of 813 public visitors were observed as they attended vendors. Of these, 29 (3.6%) made direct contact with an animal and 222 (27.3%) made indirect contact with a presumed contaminated source, with subsequent modes of contact being H1 18.7%, H2 52.2% and H3 9.9%. Conclusions Our observations indicate that opportunities for direct and indirect contact at pet markets with presumed contaminated animals and inanimate items constitute a significant and major concern, and that public attendees are exposed to rapid contamination on their person, whether or not these contaminations become associated with any episode of disease involving themselves or others. These public health risks appear unresolvable given the format of the market environment. PMID:23323203

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

    PubMed Central

    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 over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. PMID:25599223

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

    PubMed

    2015-02-01

    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 over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. PMID:25599223

  8. Bipolar disorder with comorbid binge eating history: A genome-wide association study implicates APOB

    PubMed Central

    Winham, Stacey J.; Cuellar-Barboza, Alfredo B.; McElroy, Susan L.; Oliveros, Alfredo; Crow, Scott; Colby, Colin L.; Choi, Doo-Sup; Chauhan, Mohit; Frye, Mark A.; Biernacka, Joanna M.

    2014-01-01

    Background Bipolar disorder (BD) is a highly heritable disease. While genome-wide association (GWA) studies have identified several genetic risk factors for BD, few of these studies have investigated the genetic etiology of specific disease subtypes. In particular, BD is positively associated with eating dysregulation traits such as binge eating behavior (BE), yet the genetic risk factors underlying BD with comorbid BE have not been investigated. Methods Utilizing data from the Genetic Association Information Network study of BD, which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001 European American bipolar cases and 1034 controls, we performed GWA analyses of bipolar subtypes defined by the presence or absence of BE history, and performed a case-only analysis comparing BD subjects with and without BE history. Association signals were refined using imputation, and network analysis was performed with Ingenuity Pathway Analysis software. Based on these results, candidate SNPs were selected for replication in an independent sample of 855 cases and 857 controls. Results Top ranking SNPs in the discovery set included rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536. Rs10198175 in APOB also demonstrated evidence of association in the replication sample and a meta-analysis of the two samples. Limitations Without information of BE history in controls, it is not possible to determine whether the observed association with APOB reflects a risk factor for BE behavior in general or a risk factor for a subtype of BD with BE. Further longitudinal and functional studies are needed to determine the causal pathways underlying the observed associations. Conclusions This study identified new potential BD-susceptibility genes, highlighting the advantages of phenotypic sub-classification in genetic research and clinical practice. PMID:24882193

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

    SciTech Connect

    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.

  10. Glutamate Networks Implicate Cognitive Impairments in Schizophrenia: Genome-Wide Association Studies of 52 Cognitive Phenotypes

    PubMed Central

    Ohi, Kazutaka; Hashimoto, Ryota; Ikeda, Masashi; Yamamori, Hidenaga; Yasuda, Yuka; Fujimoto, Michiko; Umeda-Yano, Satomi; Fukunaga, Masaki; Fujino, Haruo; Watanabe, Yoshiyuki; Iwase, Masao; Kazui, Hiroaki; Iwata, Nakao; Weinberger, Daniel R.; Takeda, Masatoshi

    2015-01-01

    Cognitive impairments are a core feature in patients with schizophrenia. These deficits could serve as effective tools for understanding the genetic architecture of schizophrenia. This study investigated whether genetic variants associated with cognitive impairments aggregate in functional gene networks related to the pathogenesis of schizophrenia. Here, genome-wide association studies (GWAS) of a range of cognitive phenotypes relevant to schizophrenia were performed in 411 healthy subjects. We attempted to replicate the GWAS data using 257 patients with schizophrenia and performed a meta-analysis of the GWAS findings and the replicated results. Because gene networks, rather than a single gene or genetic variant, may be strongly associated with the susceptibility to schizophrenia and cognitive impairments, gene-network analysis for genes in close proximity to the replicated variants was performed. We observed nominal associations between 3054 variants and cognitive phenotypes at a threshold of P < 1.0 × 10− 4. Of the 3054 variants, the associations of 191 variants were replicated in the replication samples (P < .05). However, no variants achieved genome-wide significance in a meta-analysis (P > 5.0 × 10− 8). Additionally, 115 of 191 replicated single nucleotide polymorphisms (SNPs) have genes located within 10 kb of the SNPs (60.2%). These variants were moderately associated with cognitive phenotypes that ranged from P = 2.50 × 10− 5 to P = 9.40 × 10− 8. The genes located within 10 kb from the replicated SNPs were significantly grouped in terms of glutamate receptor activity (false discovery rate (FDR) q = 4.49 × 10− 17) and the immune system related to major histocompatibility complex class I (FDR q = 8.76 × 10− 11) networks. Our findings demonstrate that genetic variants related to cognitive trait impairment in schizophrenia are involved in the N-methyl-d-aspartate glutamate network. PMID:25537281

  11. Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

    PubMed Central

    Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

    2011-01-01

    Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

  12. A GENOME-WIDE ASSOCIATION STUDY OF BRONCHODILATOR RESPONSE IN LATINOS IMPLICATES RARE VARIANTS

    PubMed Central

    Drake, Katherine A.; Torgerson, Dara G.; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Oh, Sam S.; Yee, Sook Wah; Lin, Lawrence; Bustamante, Carlos D.; Moreno-Estrada, Andrés; Sandoval, Karla; Davis, Adam; Borrell, Luisa N.; Farber, Harold J.; Kumar, Rajesh; Avila, Pedro C.; Brigino-Buenaventura, Emerita; Chapela, Rocio; Ford, Jean G.; LeNoir, Michael A.; Lurmann, Fred; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodríguez-Cintrón, William; Sen, Saunak; Rodríguez-Santana, José R.; Hernandez, Ryan D.; Giacomini, Kathleen M.; Burchard, Esteban G.

    2013-01-01

    Rationale The primary rescue medication to treat acute asthma exacerbation is short-acting β2- adrenergic receptor (β2AR) agonists (SABAs), however there is variation in how well an individual responds to treatment. Although these differences may be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator drug response (BDR). Methods We performed a genome-wide association study (GWAS) for BDR in 1,782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified seven genetic variants associated with BDR at a genome-wide significant threshold (p<5×10−8), all of which had frequencies below 5%. Furthermore, we observed an excess of small p-values driven by rare variants (frequency < 5%), and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified five significant peaks; fine mapping within these peaks identified two rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. Conclusion Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in solute carrier genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multi-ethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR. PMID:23992748

  13. Genome-wide association studies in preterm birth: implications for the practicing obstetrician-gynaecologist.

    PubMed

    Dolan, Siobhan M; Christiaens, Inge

    2013-01-01

    Preterm birth has the highest mortality and morbidity of all pregnancy complications. The burden of preterm birth on public health worldwide is enormous, yet there are few effective means to prevent a preterm delivery. To date, much of its etiology is unexplained, but genetic predisposition is thought to play a major role. In the upcoming year, the international Preterm Birth Genome Project (PGP) consortium plans to publish a large genome wide association study in early preterm birth. Genome-wide association studies (GWAS) are designed to identify common genetic variants that influence health and disease. Despite the many challenges that are involved, GWAS can be an important discovery tool, revealing genetic variations that are associated with preterm birth. It is highly unlikely that findings of a GWAS can be directly translated into clinical practice in the short run. Nonetheless, it will help us to better understand the etiology of preterm birth and the GWAS results will generate new hypotheses for further research, thus enhancing our understanding of preterm birth and informing prevention efforts in the long run. PMID:23445776

  14. Electron-microprobe study of chromitites associated with alpine ultramafic complexes and some genetic implications

    USGS Publications Warehouse

    Bird, M.L.

    1978-01-01

    Electron-microprobe and petrographic studies of alpine chromite deposits from around the world demonstrate that they are bimodal with respect to the chromic oxide content of their chromite. The two modes occur at 54 ? 4 and 37 ? 3 weight per cent chromic oxide corresponding to chromite designated as high-chromium and high-aluminum chromite respectively. The high-chromium chromite occurs exclusively with highly magnesian olivine (Fo92-97) and some interstitial diopside. The high-aluminum chromite is associated with more ferrous olivine (Fo88-92), diopside, enstatite, and feldspar. The plot of the mole ratios Cr/(Cr+Al+Fe3+) vs. Mg/(Mg+Fe2+) usually presented for alpine chromite is shown to have a high-chromium, high-iron to low-chromium, low-iron trend contrary to that shown by stratiform chromite. This trend is characteristic of alpine type chromite and is termed the alpine trend. However, a trend similar to that for startiform chromite is discernable on the graph for the high-chromium chromite data. This latter trend is well-developed at Red Mountain, Seldovia, Alaska. Analysis of the iron-magnesium distribution coefficient, Kd=(Fe/Mg)ol/(Fe/Mg)ch, between olivine and chromite shows that Kd for the high-chromium chromite from all ultramafic complexes has essentially the same constant value of .05 while the distribution coefficient for the high-aluminum chromite varies with composition of the chromite. These distribution coefficients are also characteristic of alpine-type chromites. The constant value for Kd for the high-chromium chromite and associated high-magnesium olivine in all alpine complexes suggests that they all crystallized under similar physico-chemical conditions. The two types of massive chromite and their associations of silicate minerals suggest the possibility of two populations with different origins. Recrystallization textures associated with the high-aluminum chromite together with field relationships between the gabbro and the chromite pods

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

    PubMed

    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

  16. Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

    PubMed Central

    Liu, Lu; Yin, Xianyong; Wen, Leilei; Yang, Chao; Sheng, Yujun; Lin, Yan; Zhu, Zhengwei; Shen, Changbing; Shi, Yinjuan; Zheng, Yajie; Yang, Sen; Zhang, Xuejun; Cui, Yong

    2016-01-01

    We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6), CD14+ monocytes (P ≤ 2.74 × 10−4) and CD19+ B cells (P ≤ 2.00 × 10−6), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10−6). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE. PMID:27172182

  17. Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus.

    PubMed

    Liu, Lu; Yin, Xianyong; Wen, Leilei; Yang, Chao; Sheng, Yujun; Lin, Yan; Zhu, Zhengwei; Shen, Changbing; Shi, Yinjuan; Zheng, Yajie; Yang, Sen; Zhang, Xuejun; Cui, Yong

    2016-01-01

    We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells' findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10(-6)), CD14+ monocytes (P ≤ 2.74 × 10(-4)) and CD19+ B cells (P ≤ 2.00 × 10(-6)), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10(-6)). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10(-44)) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE. PMID:27172182

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

    PubMed Central

    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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  20. A Predictive Study of Advantages Associated with School-based School-Age Child Care: Implications for Program Policy Development.

    ERIC Educational Resources Information Center

    Coleman, Mick; Wallinga, Charlotte

    2000-01-01

    Examined institutional advantages of school-age child care (SACC) programming in schools. A study of 63 SACC programs in 2 southeastern states revealed that community support, number of extracurricular activities, and frequency of academic activities significantly contributed to predicting advantages associated with SAC programming. (Contains 23…

  1. A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies

    PubMed Central

    Huyghe, Jeroen R; Fransen, Erik; Hannula, Samuli; Van Laer, Lut; Van Eyken, Els; Mäki-Torkko, Elina; Aikio, Pekka; Sorri, Martti; Huentelman, Matthew J; Camp, Guy Van

    2011-01-01

    The understanding of patterns of genetic variation within and among human populations is a prerequisite for successful genetic association mapping studies of complex diseases and traits. Some populations are more favorable for association mapping studies than others. The Saami from northern Scandinavia and the Kola Peninsula represent a population isolate that, among European populations, has been less extensively sampled, despite some early interest for association mapping studies. In this paper, we report the results of a first genome-wide SNP-based study of genetic population structure in the Finnish Saami. Using data from the HapMap and the human genome diversity project (HGDP-CEPH) and recently developed statistical methods, we studied individual genetic ancestry. We quantified genetic differentiation between the Saami population and the HGDP-CEPH populations by calculating pair-wise FST statistics and by characterizing identity-by-state sharing for pair-wise population comparisons. This study affirms an east Asian contribution to the predominantly European-derived Saami gene pool. Using model-based individual ancestry analysis, the median estimated percentage of the genome with east Asian ancestry was 6% (first and third quartiles: 5 and 8%, respectively). We found that genetic similarity between population pairs roughly correlated with geographic distance. Among the European HGDP-CEPH populations, FST was smallest for the comparison with the Russians (FST=0.0098), and estimates for the other population comparisons ranged from 0.0129 to 0.0263. Our analysis also revealed fine-scale substructure within the Finnish Saami and warns against the confounding effects of both hidden population structure and undocumented relatedness in genetic association studies of isolated populations. PMID:21150888

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

    PubMed

    Hägg, Sara; Ganna, Andrea; Van Der Laan, Sander W; Esko, Tonu; Pers, Tune H; Locke, Adam E; Berndt, Sonja I; Justice, Anne E; Kahali, Bratati; Siemelink, Marten A; Pasterkamp, Gerard; Strachan, David P; Speliotes, Elizabeth K; North, Kari E; Loos, Ruth J F; Hirschhorn, Joel N; Pawitan, Yudi; Ingelsson, Erik

    2015-12-01

    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 of ANthropometric Traits (GIANT) consortium. Each cohort was tested for association between ∼2.4 million (Stage 1) or ∼200 000 (Stage 2) imputed or genotyped single variants and BMI, and summary statistics were subsequently meta-analyzed in 17 941 genes. We used the 'VErsatile Gene-based Association Study' (VEGAS) 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 were associated with BMI (P < 2.8 × 10(-6) for 17 941 gene tests). We confirmed all loci, and six of them were gene-wide significant in Stage 2 alone. We provide biological support for the loci by pathway, expression and methylation analyses. Our results indicate that gene-based meta-analysis of GWAS provides a useful strategy to find loci of interest that were not identified in standard single-marker analyses due to high allelic heterogeneity. PMID:26376864

  3. Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry

    PubMed Central

    Cheng, Wei; Palaniyappan, Lena; Li, Mingli; Kendrick, Keith M; Zhang, Jie; Luo, Qiang; Liu, Zening; Yu, Rongjun; Deng, Wei; Wang, Qiang; Ma, Xiaohong; Guo, Wanjun; Francis, Susan; Liddle, Peter; Mayer, Andrew R; Schumann, Gunter; Li, Tao; Feng, Jianfeng

    2015-01-01

    Background: Wernicke’s concept of ‘sejunction’ or aberrant associations among specialized brain regions is one of the earliest hypotheses attempting to explain the myriad of symptoms in psychotic disorders. Unbiased data mining of all possible brain-wide connections in large data sets is an essential first step in localizing these aberrant circuits. Methods: We analyzed functional connectivity using the largest resting-state neuroimaging data set reported to date in the schizophrenia literature (415 patients vs. 405 controls from UK, USA, Taiwan, and China). An exhaustive brain-wide association study at both regional and voxel-based levels enabled a continuous data-driven discovery of the key aberrant circuits in schizophrenia. Results: Results identify the thalamus as the key hub for altered functional networks in patients. Increased thalamus–primary somatosensory cortex connectivity was the most significant aberration in schizophrenia (P=10−18). Overall, a number of thalamic links with motor and sensory cortical regions showed increased connectivity in schizophrenia, whereas thalamo–frontal connectivity was weakened. Network changes were correlated with symptom severity and illness duration, and support vector machine analysis revealed discrimination accuracies of 73.53–80.92%. Conclusions: Widespread alterations in resting-state thalamocortical functional connectivity is likely to be a core feature of schizophrenia that contributes to the extensive sensory, motor, cognitive, and emotional impairments in this disorder. Changes in this schizophrenia-associated network could be a reliable mechanistic index to discriminate patients from healthy controls. PMID:27336032

  4. Genetic Variation and Population Substructure in Outbred CD-1 Mice: Implications for Genome-Wide Association Studies

    PubMed Central

    Aldinger, Kimberly A.; Sokoloff, Greta; Rosenberg, David M.; Palmer, Abraham A.; Millen, Kathleen J.

    2009-01-01

    Outbred laboratory mouse populations are widely used in biomedical research. Since little is known about the degree of genetic variation present in these populations, they are not widely used for genetic studies. Commercially available outbred CD-1 mice are drawn from an extremely large breeding population that has accumulated many recombination events, which is desirable for genome-wide association studies. We therefore examined the degree of genome-wide variation within CD-1 mice to investigate their suitability for genetic studies. The CD-1 mouse genome displays patterns of linkage disequilibrium and heterogeneity similar to wild-caught mice. Population substructure and phenotypic differences were observed among CD-1 mice obtained from different breeding facilities. Differences in genetic variation among CD-1 mice from distinct facilities were similar to genetic differences detected between closely related human populations, consistent with a founder effect. This first large-scale genetic analysis of the outbred CD-1 mouse strain provides important considerations for the design and analysis of genetic studies in CD-1 mice. PMID:19266100

  5. The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies

    PubMed Central

    Cauchi, Stéphane; Nead, Kevin T; Choquet, Hélène; Horber, Fritz; Potoczna, Natascha; Balkau, Beverley; Marre, Michel; Charpentier, Guillaume; Froguel, Philippe; Meyre, David

    2008-01-01

    Background Considering that a portion of the heterogeneity amongst previous replication studies may be due to a variable proportion of obese subjects in case-control designs, we assessed the association of genetic variants with type 2 diabetes (T2D) in large groups of obese and non-obese subjects. Methods We genotyped RETN, KCNJ11, HNF4A, HNF1A, GCK, SLC30A8, ENPP1, ADIPOQ, PPARG, and TCF7L2 polymorphisms in 1,283 normoglycemic (NG) and 1,581 T2D obese individuals as well as in 3,189 NG and 1,244 T2D non-obese subjects of European descent, allowing us to examine T2D risk over a wide range of BMI. Results Amongst non-obese individuals, we observed significant T2D associations with HNF1A I27L [odds ratio (OR) = 1.14, P = 0.04], GCK -30G>A (OR = 1.23, P = 0.01), SLC30A8 R325W (OR = 0.87, P = 0.04), and TCF7L2 rs7903146 (OR = 1.89, P = 4.5 × 10-23), and non-significant associations with PPARG Pro12Ala (OR = 0.85, P = 0.14), ADIPOQ -11,377C>G (OR = 1.00, P = 0.97) and ENPP1 K121Q (OR = 0.99, P = 0.94). In obese subjects, associations with T2D were detected with PPARG Pro12Ala (OR = 0.73, P = 0.004), ADIPOQ -11,377C>G (OR = 1.26, P = 0.02), ENPP1 K121Q (OR = 1.30, P = 0.003) and TCF7L2 rs7903146 (OR = 1.30, P = 1.1 × 10-4), and non-significant associations with HNF1A I27L (OR = 0.96, P = 0.53), GCK -30G>A (OR = 1.15, P = 0.12) and SLC30A8 R325W (OR = 0.95, P = 0.44). However, a genotypic heterogeneity was only found for TCF7L2 rs7903146 (P = 3.2 × 10-5) and ENPP1 K121Q (P = 0.02). No association with T2D was found for KCNJ11, RETN, and HNF4A polymorphisms in non-obese or in obese individuals. Conclusion Genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in non-obese individuals. PMID:18498634

  6. A TEM study of samples from acid mine drainage systems: metal-mineral association with implications for transport

    NASA Astrophysics Data System (ADS)

    Hochella, Michael F.; Moore, Johnnie N.; Golla, Ute; Putnis, Andrew

    1999-10-01

    Transmission electron microscopy (TEM), with energy dispersive X-ray (EDX) analysis and energy filtered transmission electron microscopy/electron energy loss spectroscopy (EFTEM/EELS), as well as powder X-ray diffraction (XRD) and scanning electron microscopy (SEM), have been used to study bed sediments from two acid mine drainage (AMD) sites in western Montana, USA. TEM and associated techniques, including sample preparation via epoxy impregnation and ultramicrotome sectioning, afford the opportunity to better interpret and understand complex water-rock interactions in these types of samples. For the sample taken from the first site (Mike Horse mine), ferrihydrite is the dominant phase, Si and Zn are the most abundant elements sorbed to ferrihydrite surfaces, and Pb is notably absent from ferrihydrite association. Three additional important metal-containing phases (gahnite, hydrohetaerolite, and plumbojarosite), that were not apparent in the powder XRD pattern because of their relatively low concentration, were identified in the TEM. The presence of these phases is important, because, for example, gahnite and plumbojarosite act as sinks for Zn and Pb, respectively. Therefore, the mobility of Pb from this part of the drainage system depends on the stability of plumbojarosite and the ability of ferrihydrite to sorb the released Pb. From thermodynamic data in the literature, we predict that Pb will be released by the dissolution of plumbojarosite above a pH of 4 to 5, but it will then be recaptured by ferrihydrite if the pH continues to rise to 5.5 and higher, irrespective of competition effects from other metals. Therefore, only a relatively narrow pH window exists in which Pb can escape this portion of the system as an aqueous species. For the sample taken from the other site included in this study (the Carbonate mine), jarosite and quartz are the dominant phases. Interestingly, however, the jarosites are both Pb-poor and Pb-enriched. In addition, TEM reveals the

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

    PubMed

    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

  8. Body Mass Index in Adults with Intellectual Disability: Distribution, Associations and Service Implications--A Population-Based Prevalence Study

    ERIC Educational Resources Information Center

    Bhaumik, S.; Watson, J. M.; Thorp, C. F.; Tyrer, F.; McGrother, C. W.

    2008-01-01

    Background: Previous studies of weight problems in adults with intellectual disability (ID) have generally been small or selective and given conflicting results. The objectives of our large-scale study were to identify inequalities in weight problems between adults with ID and the general adult population, and to investigate factors associated…

  9. 5HT1Dbeta Receptor gene implicated in the pathogenesis of Obsessive-Compulsive Disorder: further evidence from a family-based association study.

    PubMed

    Mundo, E; Richter, M A; Zai, G; Sam, F; McBride, J; Macciardi, F; Kennedy, J L

    2002-01-01

    Obsessive-Compulsive Disorder (OCD) is a psychiatric condition with strong evidence for a genetic component and for the involvement of genes of the serotonin system. In a recent family-based association study we reported an association between the G allele of the G861C polymorphism of the 5HT1Dbeta receptor gene and OCD. The aim of the present study was to further investigate for the presence of linkage disequilibrium between each of two polymorphisms of the 5HT1Dbeta receptor gene and OCD in a larger sample of OCD families. In a total of 121 families the G861C and the T371G polymorphisms of the 5HT1Dbeta receptor gene were genotyped using standard protocols. The genotyping data were analyzed with a new extension of the Transmission Disequilibrium Test (FBAT). The phenotypes considered in the analyses were the diagnosis of OCD and two quantitative phenotypes related to the diagnosis and clinically relevant, ie, the age at onset and the severity of OCD symptoms. We confirmed the previously found preferential transmission of the G861 allele to the affected subjects (z = 2.262, P = 0.02). No significant association was found between the polymorphism and the quantitative phenotypes considered. These results represent a confirmation of our previous published study and thus, could have important implications for the role of the 5HT1Dbeta receptor gene in the pathogenesis and treatment of OCD. Further genetic investigations on this marker considering additional polymorphisms and other quantitative phenotypes related to OCD are warranted. PMID:12192628

  10. Factors associated with self-reported health: implications for screening level community-based health and environmental studies

    EPA Science Inventory

    BACKGROUND: Advocates for environmental justice, local, state, and national public health officials, exposure scientists, need broad-based heath indices to identify vulnerable communities. Longitudinal studies show that perception of current health status predicts subsequent mort...

  11. A Systematic, Large-Scale Study of Synaesthesia: Implications for the Role of Early Experience in Lexical-Colour Associations

    ERIC Educational Resources Information Center

    Rich, A. N.; Bradshaw, J. L.; Mattingley, J. B.

    2005-01-01

    For individuals with synaesthesia, stimuli in one sensory modality elicit anomalous experiences in another modality. For example, the sound of a particular piano note may be "seen" as a unique colour, or the taste of a familiar food may be "felt" as a distinct bodily sensation. We report a study of 192 adult synaesthetes, in which we administered…

  12. KAr and {40Ar }/{39}Ar study of metamorphic rocks associated with the Oman ophiolite: Tectonic implications

    NASA Astrophysics Data System (ADS)

    Montigny, R.; Le Mer, O.; Thuizat, R.; Whitechurch, H.

    1988-09-01

    K-Ar analyses on extracted minerals are reported for a variety of metamorphic rocks associated with the Sumail ophiolite. Amphibolites lying at the sole of the ophiolite yield ages of 95-100 Ma, which are viewed as reflecting times of crystallization. High-pressure metamorphics of the Saih Hatat reveal complex results: white micas range in age from 80 to 131 Ma whereas blue amphiboles indicate ages that are systematically lower than those of coexisting white micas. Investigation of a few white micas by the {40Ar }/{39Ar } step heating method yields rather intricate age spectra, featuring low apparent ages in the first and the last stages of gas release and high apparent ages in between. Two explanations can be equally envisaged for these convex-upward age spectra. The first is the mixing of two generations of micas, corresponding to two main metamorphisms. The first one ( M1) is a low- to medium-temperature, high-pressure event which conceivably occurred between 130 and 114 m.y. ago. The second ( M2) overprints M1 and has produced rocks typical of the greenschist facies. It took place 80 m.y. ago and also affected the sole of the ophiolites. The second is the presence of excess argon in mica mixtures with complex degassing properties. Thus, the two metamorphic phases identified by microscopic inspection are not significantly different in age. They occurred in the 70-80 Ma interval. Moreover, K-Ar dates on amphibole from gabbroic dikes intersecting the peridotites suggest that they are genetically linked to the mafic part of the ophiolites. Assuming that metamorphism is a tracer of tectonic events, we view the infraophiolitic amphibolites as the result of an intraoceanic thrusting which took place near a spreading center. Nevertheless, the uncertainty as to the age of the blueschist metamorphism precludes the possibility of indicating a timetable, based on metamorphic ages, for the motion shift of Africa relative to Eurasia during the Late Cretaceous. A tentative

  13. High-Fidelity Manikin-Based Simulation: A Study of Implications for Interprofessional Healthcare Practitioner Education at the Associate Degree Level of Study

    ERIC Educational Resources Information Center

    Fowler, Luster

    2013-01-01

    Healthcare practitioner training programs, specifically at the associate degree level of study, have historically focused practitioner training efforts on discipline-specific programming and curricula. However, these institutions have now begun to examine the utility and efficacy of incorporating interprofessional experiences into their programs.…

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

    PubMed

    Do, Duy Ngoc; Strathe, Anders Bjerring; Ostersen, Tage; Jensen, Just; Mark, Thomas; Kadarmideen, Haja N

    2013-01-01

    This study was aimed at identifying genomic regions controlling feeding behavior in Danish Duroc boars and its potential implications for eating behavior in humans. Data regarding individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of daily visits to feeder (NVD), average duration of each visit (TPV), mean feed intake per visit (FPV) and mean feed intake rate (FR) were available for 1130 boars. All boars were genotyped using the Illumina Porcine SNP60 BeadChip. The association analyses were performed using the GenABEL package in the R program. Sixteen SNPs were found to have moderate genome-wide significance (p<5E-05) and 76 SNPs had suggestive (p<5E-04) association with feeding behavior traits. MSI2 gene 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, PTPRZ1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results 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. This is the first translational genomics study of its kind to report potential candidate genes for eating behavior in humans. PMID:23977060

  15. Architectural Implications for Spatial Object Association Algorithms

    SciTech Connect

    Kumar, V S; Kurc, T; Saltz, J; Abdulla, G; Kohn, S R; Matarazzo, C

    2009-01-29

    Spatial object association, also referred to as cross-match of spatial datasets, is the problem of identifying and comparing objects in two or more datasets based on their positions in a common spatial coordinate system. In this work, we evaluate two crossmatch algorithms that are used for astronomical sky surveys, on the following database system architecture configurations: (1) Netezza Performance Server R, a parallel database system with active disk style processing capabilities, (2) MySQL Cluster, a high-throughput network database system, and (3) a hybrid configuration consisting of a collection of independent database system instances with data replication support. Our evaluation provides insights about how architectural characteristics of these systems affect the performance of the spatial crossmatch algorithms. We conducted our study using real use-case scenarios borrowed from a large-scale astronomy application known as the Large Synoptic Survey Telescope (LSST).

  16. Architectural Implications for Spatial Object Association Algorithms*

    PubMed Central

    Kumar, Vijay S.; Kurc, Tahsin; Saltz, Joel; Abdulla, Ghaleb; Kohn, Scott R.; Matarazzo, Celeste

    2013-01-01

    Spatial object association, also referred to as crossmatch of spatial datasets, is the problem of identifying and comparing objects in two or more datasets based on their positions in a common spatial coordinate system. In this work, we evaluate two crossmatch algorithms that are used for astronomical sky surveys, on the following database system architecture configurations: (1) Netezza Performance Server®, a parallel database system with active disk style processing capabilities, (2) MySQL Cluster, a high-throughput network database system, and (3) a hybrid configuration consisting of a collection of independent database system instances with data replication support. Our evaluation provides insights about how architectural characteristics of these systems affect the performance of the spatial crossmatch algorithms. We conducted our study using real use-case scenarios borrowed from a large-scale astronomy application known as the Large Synoptic Survey Telescope (LSST). PMID:25692244

  17. Association between Obesity, hsCRP ≥2 mg/L, and Subclinical Atherosclerosis: Implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Blaha, Michael J.; Rivera, Juan J.; Budoff, Matthew J.; Blankstein, Ron; Agatston, Arthur; O’Leary, Daniel H.; Cushman, Mary; Lakoski, Susan; Criqui, Michael H.; Szklo, Moyses; Blumenthal, Roger S.; Nasir, Khurram

    2011-01-01

    Objective High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The JUPITER trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however the association of hsCRP to atherosclerosis, independent of obesity, remains unknown. Methods and Results We studied 6,760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: non-obese/low hsCRP, non-obese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean BMI was 28.3 ± 5.5 kg/m2, and median hsCRP was 1.9 mg/L (0.84 – 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independent of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2,083 JUPITER-eligible individuals. Conclusions High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independent of hsCRP status. PMID:21474823

  18. Genome-wide association study identifies five novel susceptibility loci for Crohn's disease and implicates a role for autophagy in disease pathogenesis.

    PubMed Central

    Rioux, John D.; Xavier, Ramnik J.; Taylor, Kent D.; Silverberg, Mark S.; Goyette, Philippe; Huett, Alan; Green, Todd; Kuballa, Petric; Barmada, M. Michael; Datta, Lisa Wu; Shugart, Yin Yao; Griffiths, Anne M.; Targan, Stephan R.; Ippoliti, Andrew F.; Bernard, Edmond-Jean; Mei, Ling; Nicolae, Dan L.; Regueiro, Miguel; Schumm, L. Philip; Steinhart, A. Hillary; Rotter, Jerome I.; Duerr, Richard H.; Cho, Judy H.; Daly, Mark J.; Brant, Steven R.

    2008-01-01

    We present a genome-wide association study of ileal Crohn's disease (CD) and two independent replication studies that identify five novel regions of association to CD. Specifically, in addition to the previously established CARD15 and IL23R associations, we report strong associations with independent replication to variation in the genomic regions encoding the PHOX2B, NCF4 and ATG16L1 genes, as well as a predicted gene on 16q24.1 (FAM92B) and an intergenic region on 10q21.1. We further demonstrate that the ATG16L1 gene is expressed in intestinal epithelial cell lines and that functional knock down of this gene abrogates autophagy of Salmonella typhimurium. Together these findings suggest that autophagy and host cell responses to intra-cellular microbes are involved in the pathogenesis of CD. PMID:17435756

  19. Diabetes and cancer: Associations, mechanisms, and implications for medical practice

    PubMed Central

    Xu, Chun-Xiao; Zhu, Hong-Hong; Zhu, Yi-Min

    2014-01-01

    Both diabetes mellitus and cancer are prevalent diseases worldwide. It is evident that there is a substantial increase in cancer incidence in diabetic patients. Epidemiologic studies have indicated that diabetic patients are at significantly higher risk of common cancers including pancreatic, liver, breast, colorectal, urinary tract, gastric and female reproductive cancers. Mortality due to cancer is moderately increased among patients with diabetes compared with those without. There is increasing evidence that some cancers are associated with diabetes, but the underlying mechanisms of this potential association have not been fully elucidated. Insulin is a potent growth factor that promotes cell proliferation and carcinogenesis directly and/or through insulin-like growth factor 1 (IGF-1). Hyperinsulinemia leads to an increase in the bioactivity of IGF-1 by inhibiting IGF binding protein-1. Hyperglycemia serves as a subordinate plausible explanation of carcinogenesis. High glucose may exert direct and indirect effects upon cancer cells to promote proliferation. Also chronic inflammation is considered as a hallmark of carcinogenesis. The multiple drugs involved in the treatment of diabetes seem to modify the risk of cancer. Screening to detect cancer at an early stage and appropriate treatment of diabetic patients with cancer are important to improve their prognosis. This paper summarizes the associations between diabetes and common cancers, interprets possible mechanisms involved, and addresses implications for medical practice. PMID:24936258

  20. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder

    PubMed Central

    Baum, AE; Akula, N; Cabanero, M; Cardona, I; Corona, W; Klemens, B; Schulze, TG; Cichon, S; Rietschel, M; Nöthen, MM; Georgi, A; Schumacher, J; Schwarz, M; Jamra, R Abou; Höfels, S; Propping, P; Satagopan, J; Detera-Wadleigh, SD; Hardy, J; McMahon, FJ

    2008-01-01

    The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550,000 SNPs in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA; selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost savings and gain in efficiency. A total of 88 SNPs representing 80 different genes met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of DGKH (p = 1.5 × 10−8, experiment-wide p<0.01, OR= 1.59). This gene encodes diacylglycerol kinase eta, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease. PMID:17486107

  1. Corona Associations and Their Implications for Venus

    USGS Publications Warehouse

    Chapman, M.G.; Zimbelman, J.R.

    1998-01-01

    Geologic mapping principles were applied to determine genetic relations between coronae and surrounding geomorphologic features within two study areas in order to better understand venusian coronae. The study areas contain coronae in a cluster versus a contrasting chain and are (1) directly west of Phoebe Regio (quadrangle V-40; centered at latitude 15??S, longitude 250??) and (2) west of Asteria and Beta Regiones (between latitude 23??N, longitude 239?? and latitude 43??N, longitude 275??). Results of this research indicate two groups of coronae on Venus: (1) those that are older and nearly coeval with regional plains, and occur globally; and (2) those that are younger and occur between Beta, Atla, and Themis Regiones or along extensional rifts elsewhere, sometimes showing systematic age progressions. Mapping relations and Earth analogs suggest that older plains coronae may be related to a near-global resurfacing event perhaps initiated by a mantle superplume or plumes. Younger coronae of this study that show age progression may be related to (1) a tectonic junction of connecting rifts resulting from local mantle upwelling and spread of a quasi-stationary hotspot plume, and (2) localized spread of post-plains volcanism. We postulate that on Venus most of the young, post-resurfacing coronal plumes may be concentrated within an area defined by the bounds of Beta, Atla, and Themis Regiones. ?? 1998 Academic Press.

  2. Novel Genetic Locus Implicated for HIV-1 Acquisition with Putative Regulatory Links to HIV Replication and Infectivity: A Genome-Wide Association Study

    PubMed Central

    Johnson, Eric O.; Hancock, Dana B.; Gaddis, Nathan C.; Levy, Joshua L.; Page, Grier; Novak, Scott P.; Glasheen, Cristie; Saccone, Nancy L.; Rice, John P.; Moreau, Michael P.; Doheny, Kimberly F.; Romm, Jane M.; Brooks, Andrew I.; Aouizerat, Bradley E.; Bierut, Laura J.; Kral, Alex H.

    2015-01-01

    Fifty percent of variability in HIV-1 susceptibility is attributable to host genetics. Thus identifying genetic associations is essential to understanding pathogenesis of HIV-1 and important for targeting drug development. To date, however, CCR5 remains the only gene conclusively associated with HIV acquisition. To identify novel host genetic determinants of HIV-1 acquisition, we conducted a genome-wide association study among a high-risk sample of 3,136 injection drug users (IDUs) from the Urban Health Study (UHS). In addition to being IDUs, HIV- controls were frequency-matched to cases on environmental exposures to enhance detection of genetic effects. We tested independent replication in the Women’s Interagency HIV Study (N=2,533). We also examined publicly available gene expression data to link SNPs associated with HIV acquisition to known mechanisms affecting HIV replication/infectivity. Analysis of the UHS nominated eight genetic regions for replication testing. SNP rs4878712 in FRMPD1 met multiple testing correction for independent replication (P=1.38x10-4), although the UHS-WIHS meta-analysis p-value did not reach genome-wide significance (P=4.47x10-7 vs. P<5.0x10-8) Gene expression analyses provided promising biological support for the protective G allele at rs4878712 lowering risk of HIV: (1) the G allele was associated with reduced expression of FBXO10 (r=-0.49, P=6.9x10-5); (2) FBXO10 is a component of the Skp1-Cul1-F-box protein E3 ubiquitin ligase complex that targets Bcl-2 protein for degradation; (3) lower FBXO10 expression was associated with higher BCL2 expression (r=-0.49, P=8x10-5); (4) higher basal levels of Bcl-2 are known to reduce HIV replication and infectivity in human and animal in vitro studies. These results suggest new potential biological pathways by which host genetics affect susceptibility to HIV upon exposure for follow-up in subsequent studies. PMID:25786224

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

    PubMed

    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. PMID:26856123

  4. Linkage Disequilibrium between Two High-Frequency Deletion Polymorphisms: Implications for Association Studies Involving the glutathione-S transferase (GST) Genes

    PubMed Central

    Zhao, Yongzhong; Marotta, Michael; Eichler, Evan E.; Eng, Charis; Tanaka, Hisashi

    2009-01-01

    Copy number variations (CNVs) represent a large source of genetic variation in humans and have been increasingly studied for disease association. A deletion polymorphism of the gene encoding the cytosolic detoxification enzyme glutathione S-transferase theta 1 (GSTT1) has been extensively studied for cancer susceptibility (919 studies, from HuGE navigator, http://www.hugenavigator.net/). However, clear conclusions have not been reached. Since the GSTT1 gene is located within a genomic region of segmental duplications (SD), there may be a confounding effect from another, yet-uncharacterized CNV at the same locus. Here we describe a previously uncharacterized 38-kilo-base (kb) long deletion polymorphism of GSTT2B located within a 61-kb DNA inverted repeat. GSTT2B is a duplicated copy of GSTT2, the only paralogue of GSTT1 in humans. A newly developed PCR assay revealed that a microhomology-mediated breakpoint appears to be shared among individuals at high frequency. The GSTT2B deletion polymorphism was in strong linkage disequilibrium (LD) (D′ = 0.841) with the neighboring GSTT1 deletion polymorphism in the Caucasian population. Alleles harboring a single deletion were significantly overrepresented (p = 2.22×10−16), suggesting a selection against alleles with both deletions. The deletion alleles are almost certainly the derived ones, because the GSTT2B-GSTT2-GSTT1 genes were strictly retained in chimpanzees. Extremely low GSTT2 mRNA expression was associated with the GSTT2B deletion, suggesting an influence of the deletion on the flanking region and loss of GSTT2 function. Genome-wide LD analysis between deletion polymorphisms further points to the uniqueness of two deletions, because strong LD between deletion polymorphisms might be very rare in humans. These results show a complex genomic organization and unexpected biological functions of CNVs within segmental duplications and emphasize the importance of detailed structural characterization for disease

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

    PubMed

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

    PubMed Central

    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; Yu Mok, Zuan; 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; Ann Rozario, Michelle; 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

    2016-01-01

    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 × 10−21). 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

  7. Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study

    PubMed Central

    Köbel, M; Madore, J; Ramus, S J; Clarke, B A; Pharoah, P D P; Deen, S; Bowtell, D D; Odunsi, K; Menon, U; Morrison, C; Lele, S; Bshara, W; Sucheston, L; Beckmann, M W; Hein, A; Thiel, F C; Hartmann, A; Wachter, D L; Anglesio, M S; Høgdall, E; Jensen, A; Høgdall, C; Kalli, K R; Fridley, B L; Keeney, G L; Fogarty, Z C; Vierkant, R A; Liu, S; Cho, S; Nelson, G; Ghatage, P; Gentry-Maharaj, A; Gayther, S A; Benjamin, E; Widschwendter, M; Intermaggio, M P; Rosen, B; Bernardini, M Q; Mackay, H; Oza, A; Shaw, P; Jimenez-Linan, M; Driver, K E; Alsop, J; Mack, M; Koziak, J M; Steed, H; Ewanowich, C; DeFazio, A; Chenevix-Trench, G; Fereday, S; Gao, B; Johnatty, S E; George, J; Galletta, L; Goode, E L; Kjær, S K; Huntsman, D G; Fasching, P A; Moysich, K B; Brenton, J D; Kelemen, L E

    2014-01-01

    Background: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. Methods: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. Results: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20–0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10–3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25–0.94). Conclusions: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1

  8. MHC microsatellite diversity and linkage disequilibrium among common HLA-A, HLA-B, DRB1 haplotypes: implications for unrelated donor hematopoietic transplantation and disease association studies.

    PubMed

    Malkki, M; Single, R; Carrington, M; Thomson, G; Petersdorf, E

    2005-08-01

    Twenty-two human major histocompatibility complex (MHC) region microsatellite (Msat) markers were studied for diversity and linkage disequilibrium (LD) with HLA loci in hematopoietic cell transplant recipients and their HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele-matched unrelated donors. These Msats showed highly significant LD over much of the MHC region. The Msat diversity of five common Caucasian haplotypes (HLA-A1-B8-DR3, A3-B7-DR15, A2-B44-DR4, A29-B44-DR7, and A2-B7-DR15) was examined using a new measure called 'haplotype specific heterozygosity' (HSH). Each of the five haplotypes had at least one Msat marker with an HSH value of zero indicating that only one Msat allele was observed for the particular HLA haplotype. In addition, the ability of Msats to predict HLA-A-B-DRB1 haplotypes was studied. Over 90% prediction probability of two common haplotypes (HLA-A1-B8-DR3 and HLA-A3-B7-DR15) was achieved with information from three Msats (D6S265/D6S2787/D6S2894 and D6S510/D6S2810/D6S2876, respectively). We demonstrate how the HSH index can be used in the selection of informative Msats for transplantation and disease association studies. Markers with low HSH values can be used to predict specific HLA haplotypes or multilocus genotypes to supplement the screening of HLA-matched donors for transplantation. Markers with high HSH values will be most informative in studies investigating MHC region disease-susceptibility genes where HLA haplotypic effects are known to exist. PMID:16029431

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

    PubMed

    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. PMID:24050719

  10. 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

    PubMed Central

    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 variables in a sample of employed adults. Self-reported demographic, work-related transport behaviours, and neighbourhood preference data were collected from 1616 employed adults recruited from 48 neighbourhoods located across four New Zealand cities. Data were collected between April 2008 and September 2010. Neighbourhood built environment measures were generated using geographical information systems. Findings demonstrated that more people preferred to live in urban (more walkable), rather than suburban (less walkable) settings. Those living in more suburban neighbourhoods had significantly longer work commute distances and lower density of public transport stops available within the neighbourhood when compared with those who lived in more urban neighbourhoods. Those preferring a suburban style neighbourhood commuted approximately 1.5 km further to work when compared with participants preferring urban settings. Respondents who preferred a suburban style neighbourhood were less likely to take public or active transport to/from work when compared with those who preferred an urban style setting, regardless of the neighbourhood type in which they resided. Although it is unlikely that constructing more walkable environments will result in work-related travel behaviour change for all, providing additional highly walkable environments will help satisfy the demand for these settings, reinforce positive health behaviours, and support those amenable to change to engage in higher levels of

  11. Pedagogical Implications of Contrastive Studies

    ERIC Educational Resources Information Center

    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)

  12. Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita; Zanello, Susana; Yarbough, Patrice; Ploutz-Snyder, Robert; Taibbi, Giovanni; Vizzeri, Gianmarco

    2013-01-01

    time points. There was no correlation between the largest change in IOP (BR-3 versus BR3) and cardiovascular measure changes between baseline (BR-5) and post bed rest (BR+2). While no clinically relevant visual changes were observed during the study, measurement of various retinal parameters was performed with optical coherence tomography (OCT). A decrease in central subfield retinal thickness was observed between BR+2 and baseline at BR-10, but no association was observed with IOP changes. This work investigates the time course of changes in IOP during 14-day HDT bed rest in an attempt to characterize HDT bed rest as a model of the VIIP syndrome and delve into its etiology.

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

    PubMed

    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

  14. Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women

    PubMed Central

    Guffanti, Guia; Galea, Sandro; Yan, Lulu; Roberts, Andrea L.; Solovieff, Nadia; Aiello, Allison E.; Smoller, Jordan W.; De Vivo, Immaculata; Ranu, Hardeep; Uddin, Monica; Wildman, Derek E.; Purcell, Shaun; Koenen, Karestan C.

    2013-01-01

    Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder’s genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for > 700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences. PMID:24080187

  15. Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women.

    PubMed

    Guffanti, Guia; Galea, Sandro; Yan, Lulu; Roberts, Andrea L; Solovieff, Nadia; Aiello, Allison E; Smoller, Jordan W; De Vivo, Immaculata; Ranu, Hardeep; Uddin, Monica; Wildman, Derek E; Purcell, Shaun; Koenen, Karestan C

    2013-12-01

    Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder's genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for >700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences. PMID:24080187

  16. Genome-Wide Association Study Implicates Testis-Sperm Specific FKBP6 as a Susceptibility Locus for Impaired Acrosome Reaction in Stallions

    PubMed Central

    Raudsepp, Terje; Dobson, Lauren; Vishnoi, Monika; Fritz, Krista L.; Schaefer, Robert; Rendahl, Aaron K.; Derr, James N.; Love, Charles C.; Varner, Dickson D.; Chowdhary, Bhanu P.

    2012-01-01

    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 (P<6.75E-08) genotype–phenotype association was found in horse chromosome 13 in FK506 binding protein 6 (FKBP6). The gene belongs to the immunophilins FKBP family known to be involved in meiosis, calcium homeostasis, clathrin-coated vesicles, and membrane fusions. Direct sequencing of FKBP6 exons in cases and controls identified SNPs g.11040315G>A 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. PMID:23284302

  17. Mechanisms and implications of air pollution particle associations with chemokines

    SciTech Connect

    Seagrave, JeanClare

    2008-11-01

    Inflammation induced by inhalation of air pollutant particles has been implicated as a mechanism for the adverse health effects associated with exposure to air pollution. The inflammatory response is associated with upregulation of various pro-inflammatory cytokines and chemokines. We have previously shown that diesel exhaust particles (DEP), a significant constituent of air pollution particulate matter in many urban areas, bind and concentrate IL-8, an important human neutrophil-attracting chemokine, and that the chemokine remains biologically active. In this report, we examine possible mechanisms of this association and the effects on clearance of the chemokine. The binding appears to be the result of ionic interactions between negatively charged particles and positively charged chemokine molecules, possibly combined with intercalation into small pores in the particles. The association is not limited to diesel exhaust particles and IL-8: several other particle types also adsorb the chemokine and several other cytokines are adsorbed onto the diesel particles. However, there are wide ranges in the effectiveness of various particle types and various cytokines. Finally, male Fisher 344 rats were intratracheally instilled with chemokine alone or combined with diesel exhaust or silica particles under isofluorane anesthesia. In contrast to silica particles, which do not bind the chemokine, the presence of diesel exhaust particles, which bind the chemokine, prolonged the retention of the chemokine.

  18. An integrative study of Necremnus Thomson (Hymenoptera: Eulophidae) associated with invasive pests in Europe and North America: taxonomic and ecological implications

    PubMed Central

    Gebiola, Marco; Bernardo, Umberto; Ribes, Antoni; Gibson, Gary A P

    2015-01-01

    The species of Necremnus attacking two invasive pests of tomato and canola in Europe and North America, respectively, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and Ceutorhynchus obstrictus (Marsham) (Coleoptera: Curculionidae), have been revised using an integrative taxonomy approach. Molecular data from the mitochondrial cytochrome oxidase c subunit I and the nuclear D2 expansion region of the 28S ribosomal subunit and internal transcribed spacer 2, the discovery of new morphological features, and study of type material resulted in the delineation of three species groups, the Necremnus artynes, Necremnus cosconius, and Necremnus tidius groups, the discovery of four new species, and the resurrection of three taxa from synonymy. Lectotypes have been designated for 13 species originally described in Eulophus by Walker. Although Necremnus has not been revised, an illustrated key is given to differentiate 23 recognized European species. The key, type images, and treatments of the three species groups will enable more accurate identification of the valid species of Necremnus in the future. They will also benefit biological control practitioners of pest species. The ecological consequences of the new taxonomic concepts are discussed. PMID:25745268

  19. X-ray absorption and EPR studies on the copper ions associated with the particulate methane monooxygenase from Methylococcus capsulatus (Bath). Cu(I) ions and their implications

    SciTech Connect

    Nguyen, H.H.T.; Elliott, S.J.; Lidstrom, M.E.; Chan, S.I.; Nakagawa, K.H.; Hedman, B.; Hodgson, K.O.

    1996-12-18

    Parallel X-ray absorption edge and EPR studies of the particulate methane monooxygenase in situ reveal that the enzyme contains unusually high levels of copper ions with a significant portion of the copper ions existing as Cu(I) in the `as-isolated` form (70-80%). The observation of high levels of reduced copper in a monooxygenase is surprising considering that the natural cosubstrate of the enzyme is dioxygen. Toward clarifying the roles of the various copper ions in the enzyme, we have successfully prepared different states of the protein in the membrane-bound form at various levels of reduction using dithionite, dioxygen, and ferricyanide. EPR intensity analysis of the fully-oxidized preparations indicates that the bulk of copper ions are arranged in cluster units. The fully-reduced protein obtained by reduction by dithionite has been used to initiate the single turnover of the enzyme in the presence of dioxygen. Differential reactivity toward dioxygen was observed upon analyzing the copper reduction levels in these synchronized preparations. The enzyme is capable of supporting turnover in the absence of external electron donors in the highly reduced states. These results suggest the presence of at least two classes of copper ions in the particulate methane monoxygenase. As a working hypothesis, we have referred to these classes of copper ions as (1) the catalytic (C) clusters, and (2) the electron transfer (E) clusters. 56 refs., 4 figs., 1 tab.

  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

    PubMed Central

    Haney, Steven; Zhao, Juan; Tiwari, Shiwani; Eng, Kurt; Guey, Lin T.; Tien, Eric

    2013-01-01

    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. PMID:23840313

  1. Genome-wide association studies in neurology

    PubMed Central

    Tan, Meng-Shan; Jiang, Teng

    2014-01-01

    Genome-wide association studies (GWAS) are a powerful tool for understanding the genetic underpinnings of human disease. In this article, we briefly review the role and findings of GWAS in common neurological diseases, including Stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, multiple sclerosis, migraine, amyotrophic lateral sclerosis, frontotemporal lobar degeneration, restless legs syndrome, intracranial aneurysm, human prion diseases and moyamoya disease. We then discuss the present and future implications of these findings with regards to disease prediction, uncovering basic biology, and the development of potential therapeutic agents. PMID:25568877

  2. Genome wide association scan for chronic periodontitis implicates novel locus

    PubMed Central

    2014-01-01

    Background There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99). Methods Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed. Results The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis. Conclusions Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis. PMID:25008200

  3. Associations of sleep disturbance with ADHD: implications for treatment.

    PubMed

    Hvolby, Allan

    2015-03-01

    Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; increased sleep onset latency and shorter sleep time in actigraphic studies; and bedtime resistance, difficulty with morning awakenings, sleep onset difficulties, sleep-disordered breathing, night awakenings and daytime sleepiness in subjective studies. ADHD is also frequently coincident with sleep disorders (obstructive sleep apnea, peripheral limb movement disorder, restless legs syndrome and circadian-rhythm sleep disorders). Psychostimulant medications are associated with disrupted or disturbed sleep, but also 'paradoxically' calm some patients with ADHD for sleep by alleviating their symptoms. Long-acting formulations may have insufficient duration of action, leading to symptom rebound at bedtime. Current guidelines recommend assessment of sleep disturbance during evaluation of ADHD, and before initiation of pharmacotherapy, with healthy sleep practices the first-line option for addressing sleep problems. This review aims to provide a comprehensive overview of the relationships between ADHD and sleep, and presents a conceptual model of the modes of interaction: ADHD may cause sleep problems as an intrinsic feature of the disorder; sleep problems may cause or mimic ADHD; ADHD and sleep problems may interact, with reciprocal causation and possible involvement of comorbidity; and ADHD and sleep problems may share a common underlying neurological etiology. PMID:25127644

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

    ERIC Educational Resources Information Center

    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…

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Memory for Sentences: Implications for Human Associative Memory

    ERIC Educational Resources Information Center

    Foss, Donald J.; Harwood, David A.

    1975-01-01

    This paper evaluates associative theories of sentence memory, based on the model of J.R. Anderson and G.H. Bower. A model of Human Associative Memory (HAM) is generalized and defined, and alternative models incorporating configural information are presented. (CK)

  7. Feedback: Implications for Further Research and Study.

    ERIC Educational Resources Information Center

    Nishikawa, Sue S.

    This report reviews current literature on feedback and suggests practical implications of feedback research for educators. A definition of feedback is offered, and past definitions in prior research are noted. An analysis of the current state of knowledge of feedback discusses the historical development of feedback theory and suggests that…

  8. [Syringomyelobulbia associated with cervical spondylosis. Pathophysiology and therapeutic implications].

    PubMed

    Rebai, R; Boudawara, M Z; Ben Yahia, M; Mhiri, C; Ben Mansour, H

    2002-05-01

    Spinal spondylosis is rarely implicated in syringomyelia. We report the case of a 70-year-old patient with a 10-year history of gait disturbance; constrictive pain of lower limbs and urinary incontinance. Physical examination disclosed spastic tetraparesis. In the upper limbs, deep tendon reflexes were abolished, with hyposthesia and hands amyotrophy. Brain and cervical MRI showed syringomyelobulbia with cervical spondylotic myelopathy. Extensive cervical laminectomy induced a mild clinical improvement. A second MRI performed 6 months after surgery depicted a complete disappearance of the bulbo-medullar cavitation with secondary atrophy. Extradural spondylotic compression of the spinal cord should be firmly considered as an etiology of syringomyelia. A purely extradural decompression could be sufficient to induce regression of the medullary cavitation. PMID:12053170

  9. Empirical studies of software design: Implications for SSEs

    NASA Technical Reports Server (NTRS)

    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.

  10. Nutrition and age-associated inflammation: implications for disease prevention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulating evidence suggests that aging is associated with dysregulated immune and inflammatory responses. Investigation into the cellular and molecular mechanisms underlying this phenomenon suggests that an up-regulated cyclooxygenase (COX)-2 expression, and resulting increase in production of pr...

  11. Obstructive sleep apnea and asthma: associations and treatment implications.

    PubMed

    Prasad, Bharati; Nyenhuis, Sharmilee M; Weaver, Terri E

    2014-04-01

    Obstructive sleep apnea (OSA) and asthma are highly prevalent respiratory disorders and are frequently co-morbid. Risk factors common to the two diseases include obesity, rhinitis, and gastroesophageal reflux (GER). Observational and experimental evidence implicates airways and systemic inflammation, neuromechanical effects of recurrent upper airway collapse, and asthma-controlling medications (corticosteroids) as additional explanatory factors. Therefore, undiagnosed or inadequately treated OSA may adversely affect control of asthma and vice versa. It is important for clinicians to be vigilant and specifically address weight-control, nasal obstruction, and GER in these populations. Utilizing validated screening instruments to affirm high risk of co-morbid OSA or asthma in persistently symptomatic patients will allow clinicians to cost-effectively test and treat appropriate patients, potentially improving outcomes. While non-invasive ventilation in acute asthma improves outcomes, the role of chronic continuous positive airway pressure (CPAP; the first-line treatment for OSA) in improving long-term asthma control is not known. Future research should focus on the impact of optimal CPAP therapy and adherence on asthma symptoms and outcomes. PMID:23890469

  12. Learning through a Disciplined Curriculum Study Approach: Implications for Educational Leadership

    ERIC Educational Resources Information Center

    Henderson, James G.

    2010-01-01

    In this article, the author begins by describing an important present moment in curriculum studies. He then rethinks this moment and briefly explores the implications of this new line of thought for leadership development. At the 2007 American Association for the Advancement of Curriculum Studies' (AAACS) business meeting, Pinar (2007a) presented…

  13. Implications of Berthlot`s descriptive of associative reactions

    SciTech Connect

    Hessler, J.P.

    1996-10-04

    Berthelot`s equation, k{sub {infinity}}(T) = A{sub {infinity}} exp (-Dk{sub B}T), provides a good description of the high-pressure rate coefficient for associative reactions such as CH{sub 3} + CH{sub 3}, CH{sub 3} + OH, and CH{sub 3} + H. The parameter D may be used to characterize an effective temperature-dependent barrier, {Delta}E{sub eff} = Dk{sub B}{sup 2}T{sup 2}, which is due to the internal energy, i.e. rotational and vibrational energy, or the centrifugal barrier of the associating species. The parameter A{sub {infinity}} may be identified as the rate coefficient for association when the species approach one another with zero translational and internal energy. A microcanonical rate expression is given which may be used to directly compare experimental results with theoretical calculations. In addition, this approach suggests that the Arrhenius expression for the high-pressure rate coefficient for dissociation should contain both the change of enthalpy of the reaction and this effective barrier.

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

    PubMed

    Cai, Yan; An, Seong Soo A; Kim, SangYun

    2015-01-01

    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. PMID:26203236

  15. Closed culture plant studies: Implications for CELSS

    NASA Technical Reports Server (NTRS)

    Hoshizaki, T.

    1986-01-01

    Arabidopsis plants were grown in closed cultures similar to those used in space experiments. A shift in metabolism from photosynthesis to respiration is indicated by the accumulation of CO2 in the culture atmosphere. Reproductive growth is suppressed. Plant growth and development is apparently related to the atmospheric volume available to each plant. The implications of these findings to closed ecological systems are given: (1) there is a need for an open culture having ample gas exchange, (2) CO2 levels must be maintained within prescribed limits, (3) the minimum atmospheric volume required for each plant is dependent on the precision of the gas monitors and of the subsystems used to maintain appropriate levels of various atmospheric components, and (4) volatiles such as ethylene and terpenes emanating from plants be monitored and reduced to benign concentrations.

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

    SciTech Connect

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

    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

  19. Association of actinides with microorganisms and clay: Implications for radionuclide migration from waste-repository sites

    SciTech Connect

    Ohnuki, T.; Francis, A.; Kozai, N.; Sakamoto, F.; Ozaki, T.; Nankawa, T.; Suzuki, Y.

    2010-04-01

    We conducted a series of basic studies on the microbial accumulation of actinides to elucidate their migration behavior around backfill materials used in the geological disposal of radioactive wastes. We explored the interactions of U(VI) and Pu(VI) with Bacillus subtilis, kaolinite clay, and within a mixture of the two, directly analyzing their association with the bacterium in the mixture by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The accumulation of U by the mixture rose as the numbers of B. subtilis cells increased. Treating the kaolinite with potassium acetate (CH{sub 3}COOK) removed approximately 80% of the associated uranium while only 65% was removed in the presence of B. subtilis. TEM-EDS analysis confirmed that most of the U taken from solution was associated with B. subtilis. XANES analyses revealed that the oxidation state of uranium associated with B. subtilis, kaolinite, and with the mixture containing both was U(VI). The amount of Pu sorbed by B. subtilis increased with time, but did not reach equilibrium in 48 h; in kaolinite alone, equilibrium was attained within 8 h. After 48 h, the oxidation state of Pu in the solutions exposed to B. subtilis and to the mixture had changed to Pu(V), whereas the oxidation state of the Pu associated with both was Pu(IV). In contrast, there was no change in the oxidation state of Pu in the solution nor on kaolinite after exposure to Pu(VI). SEM-EDS analysis indicated that most of the Pu in the mixture was associated with the bacteria. These results suggest that U(VI) and Pu(VI) preferentially are sorbed to bacterial cells in the presence of kaolinite clay, and that the mechanism of accumulation of U and Pu differs. U(VI) is sorbed directly to the bacterial cells, whereas Pu(VI) first is reduced to Pu(V) and then to Pu(IV), and the latter is associated with the cells. These results have important implications on the migrations of radionuclides around the repository sites of

  20. Association studies in consanguineous populations

    SciTech Connect

    Genin, E.; Clerget-Darpous, F.

    1996-04-01

    To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

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

    ERIC Educational Resources Information Center

    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…

  2. Geochemical Implications of Gas Leakage Associated with Geologic CO2 Storage - A Qualitative Review

    SciTech Connect

    Harvey, Omar R.; Qafoku, Nikolla; Cantrell, Kirk J.; Lee, Gie Hyeon; Amonette, James E.; Brown, Christopher F.

    2013-01-01

    Leakage from deep storage reservoirs is considered the major risk factor associated with geologic sequestration of CO2. Different schools of thought exist concerning the potential implications of such leakage for near-surface environments. We reviewed the current literature on how CO2 leakage (from storage reservoirs) would likely impact the geochemistry of overlying potable aquifers. Results from experimental and modeling studies point to the potential for both beneficial (e.g. contaminant immobilization) and deleterious (e.g. contaminant mobilization) consequences of CO2 intrusion into potable groundwater. However, there are significant discrepancies between studies particularly concerning, what contaminants are of concern and the geochemical processes involved. These discrepancies reflected the lack of a consensus on CO2-induced changes in subsurface geochemical processes and subsequent effects on groundwater chemistry. The development of consistent experimental protocols and the identification of pertinent factors driving CO2-induced geochemical changes in the subsurface were identified as key research needs. Geochemical modeling was used to systematically highlight why a standardization of experimental protocols and the consideration of experimental factors such as gas leakage rates, redox status and the influence of co-transported gases are pertinent. The role of analog studies, reactions occurring in the vadose zone, and the influence of organic contaminants are also discussed.

  3. Special Education Faculty Needs Assessment Study Implications

    ERIC Educational Resources Information Center

    Smith, D.D.; Tyler, N.; Montrosse, B.E.; Young, C.; Robb, S.M.

    2011-01-01

    This paper presents the highlights of the Special Education Faculty Needs Assessment Study (SEFNA). Actions taken after the release of The 2001 Faculty Shortage Study demonstrate that supply-and-demand imbalances can be improved. The projected shortage of special education faculty will directly and negatively affect students with disabilities and…

  4. Creativity: Its Implications for Social Studies.

    ERIC Educational Resources Information Center

    Eulie, Joseph

    1984-01-01

    Techniques that a social studies teacher can use to help students develop imagination, understanding, and divergent thinking are discussed. Also examined are meanings attached to the creative process and traits of creative people. (RM)

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

    PubMed

    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

  6. Phylogenetic diversity of the expression of the microtubule-associated protein tau: implications for neurodegenerative disorders.

    PubMed

    Janke, C; Beck, M; Stahl, T; Holzer, M; Brauer, K; Bigl, V; Arendt, T

    1999-05-01

    The microtubule-associated protein tau regulates the dynamic stability of the neuronal cytoskeleton by interacting with microtubules. It is encoded by a single gene, but expressed in a variety of isoforms due to differential RNA splicing. Six isoforms can be found in the human central nervous system. These isoforms differ in their ability to promote the assembly of microtubules as well as in their capacity to stabilize existing microtubule structures. Furthermore, some of the isoforms of tau are specifically involved in the pathogenesis of neurodegenerative disorders. Thus, splicing of tau might critically influence the physiological functions of tau protein as well as the pathogenesis of neurodegenerative diseases with tauopathy. The present study addresses the differential expression of the six isoforms of tau in the central nervous system of 12 mammalian species including Homo sapiens. The occurrence of each of the six tau isoforms was highly variable. However, species that were phylogenetically related expressed a similar pattern of tau isoforms. These results suggest a phylogenetic descent of splicing paradigms, which can be matched with known phylogenetic concepts based on morphological and molecular genetical studies. Especially, the unique expression pattern of tau isoforms in the human central nervous system implicates a possible link to the particular vulnerability of humans to neurodegenerative disorders with tauopathy, namely Alzheimer's disease, frontotemporal dementia and Pick's disease. PMID:10320789

  7. Surgical implications of frontoethmoidal pneumosinus dilatans-associated proptosis caused by meningioma.

    PubMed

    Raheja, Amol; Abou Al-Shaar, Hussam; Patel, Bhupendra C; Couldwell, William T

    2016-08-01

    Pneumosinus dilatans (PSD) involves paranasal sinus enlargement without radiologic evidence of localized bone destruction, hyperostosis, or mucous membrane thickening. We discuss the surgical implications of PSD-associated proptosis in patients with anterior skull-base meningioma. A 20-year-old man with proptosis, hypoglobus, and lateral globe displacement had WHO grade I anterior skull-base and orbital meningiomas. Aggressive resection using anterior/medial orbitotomy and an anterior interhemispheric skull-base approach achieved Simpson grade I resection. Postoperatively, his symptoms improved, with no recurrence at 2-year follow-up. Although PSD-associated proptosis is relatively uncommon, it carries important clinical implications in surgical management of skull-base and orbital meningiomas. PMID:27246632

  8. RERF databases and implications for future studies.

    PubMed

    Katayama, H

    2012-10-01

    Many studies have been conducted by the Radiation Effects Research Foundation (RERF) to assess the radiation effects on human beings of atomic bombs, and numerous data have been collected, including records of medical examinations and questionnaires, analytical results, inventories of biosamples and published or unpublished documentation. Some of those data have been stored and analysed since the Atomic Bomb Casualty Commission (later reorganised as RERF) was established in 1947. RERF has made an effort to establish an archival database system so that an RERF researcher can access data at any time without difficulty. Under development is a new database system with the capability to handle a very large amount of data and permit future bioinformatics analyses of data, such as that required in genomics and proteomics analyses. PMID:22914332

  9. Implications of patient-borne costs associated with pediatric neurosurgical care in eastern Africa.

    PubMed

    Awori, Jonathan; Strahle, Jennifer; Okechi, Humphrey; Davis, Matthew C

    2016-07-01

    OBJECTIVE Pediatric neurosurgery can be highly cost-effective even in the developing world, but delivery of these services is hampered by resource limitations at the levels of both health care infrastructure and individual patients. Few studies have evaluated costs borne by neurosurgical patients in the developing world and their potential implications for efficient and effective delivery of care in this population. METHODS The families of 40 pediatric neurosurgery patients were surveyed in February 2015 at the AIC Kijabe Hospital in Kijabe, Kenya. Costs associated with obtaining inpatient care were assessed. RESULTS Patient families were charged an average of US $539.44 for neurosurgical services, representing 132% of their annual income. Indirect expenses (transport, food and lodging, lost wages) constituted US $79.37, representing 14.7% of the overall cost and 19.5% of their annual income. CONCLUSIONS Expansion of pediatric neurosurgical services throughout the developing world necessitates increased attention to seemingly insignificant expenses that are absorbed by patients and their families. Even when all direct costs are covered at the institutional or national level, without additional assistance, some patients may be too poor to obtain even "free" neurosurgical care. PMID:26966883

  10. Military space station implications. Study project

    SciTech Connect

    Bourne, G.D.; Skirvin, G.D.; Wilson, G.R.

    1987-03-23

    Justifying the relevancy of a Manned Military Space Station (MMSS) and subsequently proposing its deployment to capitalize upon the United States' national security interests is the essence and purpose of this group study project. The MMSS is intended to perform a two-fold purpose: (1) facilitate military peacetime operations while simultaneously supporting and promoting civilian space initiatives; and, (2) act as a force multiplier for space and terrestrial force operations in the event of conventional, theater nuclear, and/or strategic nuclear war. Data to support the future value of the MMSS was obtained from individual and group research using unclassified sources such as professional journals, books, US Air Force Staff College reference material, and information from the US Air Force space coordinating staff in Washington, DC. The importance of space to our future and especially of a MMSS by America's national leaders and its people has yet to be fully appreciated and/or realized. The significance of space and its nexus to the United States' national security has been growing dramatically in importance since the launching of the Sputnik in 1957 by Russian. Space, as the forth dimension, cannot and should not be understated in importance as it relates to commercialism, deterrence to war, and to the stability of world order.

  11. Natural Products from Plant-associated Microorganisms: Distribution, Structural Diversity, Bioactivity, and Implications of Their Occurrence⊥

    PubMed Central

    Gunatilaka, A. A. Leslie

    2012-01-01

    A growing body of evidence suggests that plant-associated microorganisms, especially endophytic and rhizosphere bacteria and fungi, represent a huge and largely untapped resource of natural products with chemical structures that have been optimized by evolution for biological and ecological relevance. A diverse array of bioactive small molecule natural products has been encountered in these microorganisms. The structures of over 230 metabolites isolated and characterized from over 70 plant-associated microbial strains during the past four years are presented with information on their hosts, culture conditions, and biological activities. Some significant biological and ecological implications of their occurrence are also reviewed. PMID:16562864

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

    PubMed

    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

  13. Elevated Myo-Inositol, Choline, and Glutamate Levels in the Associative Striatum of Antipsychotic-Naive Patients With First-Episode Psychosis: A Proton Magnetic Resonance Spectroscopy Study With Implications for Glial Dysfunction.

    PubMed

    Plitman, Eric; de la Fuente-Sandoval, Camilo; Reyes-Madrigal, Francisco; Chavez, Sofia; Gómez-Cruz, Gladys; León-Ortiz, Pablo; Graff-Guerrero, Ariel

    2016-03-01

    Glial disturbances are highly implicated in the pathophysiology of schizophrenia and may be linked with glutamatergic dysregulation. Myo-inositol (mI), a putative marker of glial cells, and choline (Cho), representative of membrane turnover, are both present in larger concentrations within glial cells than in neurons, and their elevation is often interpreted to reflect glial activation. Proton magnetic resonance spectroscopy ((1)H-MRS) allows for the evaluation of mI, Cho, glutamate, glutamate + glutamine (Glx), and N-acetylaspartate (NAA). A collective investigation of these measures in antipsychotic-naive patients experiencing their first nonaffective episode of psychosis (FEP) can improve the understanding of glial dysfunction and its implications in the early stages of schizophrenia. 3-Tesla (1)H-MRS (echo time = 35ms) was performed in 60 antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls. mI, Cho, glutamate, Glx, and NAA were estimated using LCModel and corrected for cerebrospinal fluid composition within the voxel. mI, Cho, and glutamate were elevated in the FEP group. After correction for multiple comparisons, mI positively correlated with grandiosity. The relationships between mI and glutamate, and Cho and glutamate, were more positive in the FEP group. These findings are suggestive of glial activation in the absence of neuronal loss and may thereby provide support for the presence of a neuroinflammatory process within the early stages of schizophrenia. Dysregulation of glial function might result in the disruption of glutamatergic neurotransmission, which may influence positive symptomatology in patients with FEP. PMID:26320195

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

    NASA Astrophysics Data System (ADS)

    Ebisu, Keita; Belanger, Kathleen; Bell, Michelle L.

    2014-08-01

    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.

  15. The Association between Airborne PM2.5 Chemical Constituents and Birth Weight–Implication of Buffer Exposure Assignment

    PubMed Central

    Ebisu, Keita; Belanger, Kathleen; Bell, Michelle L.

    2014-01-01

    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 30km in Connecticut (2000–2006), in the New England region of the U.S. 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. PMID:26594233

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

    PubMed

    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

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

    PubMed

    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

  18. Restless leg syndrome associated with atypical antipsychotics: current status, pathophysiology, and clinical implications.

    PubMed

    Aggarwal, Shilpa; Dodd, Seetal; Berk, Michael

    2015-01-01

    Restless leg syndrome (RLS) is a common disorder, frequently of unclear origin, which is often associated with significant distress. There are a few case reports of atypical antipsychotic agents (AAP) causing RLS. The pathophysiological mechanisms resulting in emergence of these movements suggest central dopaminergic dysfunction. Dopamine agonists and L-dopa reduce the symptoms of RLS, and some agents that block the dopaminergic system aggravate RLS. Genetic influences are implicated in RLS and an association between gene polymorphisms and antipyschotic-associated onset of RLS has been postulated. Greater awareness of potential causes of RLS, and its differentiation from akathisia and illness related agitation might help in reducing the distress associated with it and improving patient compliance in patients using atypical antipsychotic agents. PMID:24861990

  19. Misuse of "study drugs:" prevalence, consequences, and implications for policy

    PubMed Central

    Sussman, Steve; Pentz, Mary Ann; Spruijt-Metz, Donna; Miller, Toby

    2006-01-01

    Background Non-medical/illegal use of prescription stimulants popularly have been referred to as "study drugs". This paper discusses the current prevalence and consequences of misuse of these drugs and implications of this information for drug policy. Results Study drugs are being misused annually by approximately 4% of older teens and emerging adults. Yet, there are numerous consequences of misuse of prescription stimulants including addiction, negative reactions to high dosages, and medical complications. Policy implications include continuing to limit access to study drugs, finding more safe prescription drug alternatives, interdiction, and public education. Conclusion Much more work is needed on prescription stimulant misuse assessment, identifying the extent of the social and economic costs of misuse, monitoring and reducing access, and developing prevention and cessation education efforts. PMID:16764722

  20. Japan Studies Association Journal, 1998.

    ERIC Educational Resources Information Center

    Speaker, Richard B., Jr., Ed.; Kawada, Louise Myers, Ed.

    1998-01-01

    This journal presents new perspectives and materials on Japan that are engaging, relatively jargon-free, and shaped so that their usefulness in a college classroom is readily apparent. The journal represents an example of the potential for genuine scholarship that lies within interdisciplinary studies. Articles are divided among three thematic…

  1. Implications of the Tentative Association between GW150914 and a Fermi-GBM Transient

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    The merger-driven gamma-ray bursts (GRBs) and their associated gravitational-wave (GW) radiation, if both are successfully detected, have some far-reaching implications, including, for instance: (i) the statistical comparison of the physical properties of the short/long-short GRBs with and without GW detection can test the general origin model; (ii) revealing the physical processes taking place at the central engine; (iii) measuring the velocity of the gravitational wave directly/accurately. In this work, we discuss these implications in the case of a possible association of GW150914/Gamma-ray Burst Monitor (GBM) transient 150914. We compared GBM transient 150914 with other SGRBs and found that such an event may be a distinct outlier in some statistical diagrams, possibly due to its specific binary black hole merger origin. However, the presence of a “new” group of SGRBs with “unusual” physical parameters is also possible. If the outflow of GBM transient 150914 was launched by the accretion onto the nascent black hole, the magnetic activity rather than the neutrino process is likely responsible for the energy extraction, and the accretion disk mass is estimated to be ∼10‑5 M ⊙. The GW150914/GBM transient 150914 association, if confirmed, would provide the first opportunity to directly measure the GW velocity, and its departure from the speed of the light should be within a factor of ∼10‑17.

  2. Implications of the Tentative Association between GW150914 and a Fermi-GBM Transient

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    The merger-driven gamma-ray bursts (GRBs) and their associated gravitational-wave (GW) radiation, if both are successfully detected, have some far-reaching implications, including, for instance: (i) the statistical comparison of the physical properties of the short/long-short GRBs with and without GW detection can test the general origin model; (ii) revealing the physical processes taking place at the central engine; (iii) measuring the velocity of the gravitational wave directly/accurately. In this work, we discuss these implications in the case of a possible association of GW150914/Gamma-ray Burst Monitor (GBM) transient 150914. We compared GBM transient 150914 with other SGRBs and found that such an event may be a distinct outlier in some statistical diagrams, possibly due to its specific binary black hole merger origin. However, the presence of a “new” group of SGRBs with “unusual” physical parameters is also possible. If the outflow of GBM transient 150914 was launched by the accretion onto the nascent black hole, the magnetic activity rather than the neutrino process is likely responsible for the energy extraction, and the accretion disk mass is estimated to be ˜10‑5 M ⊙. The GW150914/GBM transient 150914 association, if confirmed, would provide the first opportunity to directly measure the GW velocity, and its departure from the speed of the light should be within a factor of ˜10‑17.

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

    PubMed

    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

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

    PubMed Central

    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

  5. The second national hospital costing study: background, results and implications.

    PubMed

    Oates, B; Murray, J; Hindle, D

    1998-01-01

    The costing of hospital outputs, and especially of acute admitted patients categorised by DRG, has been the focus of considerable attention in the last decade. Many individual hospitals now routinely estimate the costs of their main products, several State and Territory health authorities undertake periodic multi-site studies, and there have been a few one-off national studies. This paper summarises the methods and results of the most recent national study, which measured costs at a sample of public and private hospitals around Australia for the 1996-97 financial year. We briefly describe the main results and note some implications. PMID:10185689

  6. Empirical studies of design software: Implications for software engineering environments

    NASA Technical Reports Server (NTRS)

    Krasner, Herb

    1988-01-01

    The empirical studies team of MCC's Design Process Group conducted three studies in 1986-87 in order to gather data on professionals designing software systems in a range of situations. The first study (the Lift Experiment) used thinking aloud protocols in a controlled laboratory setting to study the cognitive processes of individual designers. The second study (the Object Server Project) involved the observation, videotaping, and data collection of a design team of a medium-sized development project over several months in order to study team dynamics. The third study (the Field Study) involved interviews with the personnel from 19 large development projects in the MCC shareholders in order to study how the process of design is affected by organizationl and project behavior. The focus of this report will be on key observations of design process (at several levels) and their implications for the design of environments.

  7. Pre-association of polynuclear platinum anticancer agents on a protein, human serum albumin. Implications for drug design†

    PubMed Central

    Montero, Eva I.; Benedetti, Brad T.; Mangrum, John B.; Oehlsen, Michael J.; Qu, Yun; Farrell, Nicholas P.

    2009-01-01

    The interactions of polynuclear platinum complexes with human serum albumin were studied. The compounds examined were the “non-covalent” analogs of the trinuclear BBR3464 as well as the dinuclear spermidine-bridged compounds differing in only the presence or absence of a central -NH2-+ (BBR3571 and analogs). Thus, closely-related compounds could be compared. Evidence for pre-association, presumably through electrostatic and hydrogen-bonding, was obtained from fluorescence and circular dichroism spectroscopy and Electrospray Ionization Mass Spectrometry (ESI-MS). In the case of those compounds containing Pt-Cl bonds, further reaction took place presumably through displacement by sulfur nucleophiles. The implications for protein pre-association and plasma stability of polynuclear platinum compounds are discussed. PMID:17992278

  8. The association between aerobic fitness and language processing in children: implications for academic achievement.

    PubMed

    Scudder, Mark R; Federmeier, Kara D; Raine, Lauren B; Direito, Artur; Boyd, Jeremy K; Hillman, Charles H

    2014-06-01

    Event-related brain potentials (ERPs) have been instrumental for discerning the relationship between children's aerobic fitness and aspects of cognition, yet language processing remains unexplored. ERPs linked to the processing of semantic information (the N400) and the analysis of language structure (the P600) were recorded from higher and lower aerobically fit children as they read normal sentences and those containing semantic or syntactic violations. Results revealed that higher fit children exhibited greater N400 amplitude and shorter latency across all sentence types, and a larger P600 effect for syntactic violations. Such findings suggest that higher fitness may be associated with a richer network of words and their meanings, and a greater ability to detect and/or repair syntactic errors. The current findings extend previous ERP research explicating the cognitive benefits associated with greater aerobic fitness in children and may have important implications for learning and academic performance. PMID:24747513

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

    PubMed Central

    Sagona, Antonia P.; Nezis, Ioannis P.; Stenmark, Harald

    2014-01-01

    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. PMID:24741567

  10. The Association between Aerobic Fitness and Language Processing in Children: Implications for Academic Achievement

    PubMed Central

    Scudder, Mark R.; Federmeier, Kara D.; Raine, Lauren B.; Direito, Artur; Boyd, Jeremy K.; Hillman, Charles H.

    2014-01-01

    Event-related brain potentials (ERPs) have been instrumental for discerning the relationship between children’s aerobic fitness and aspects of cognition, yet language processing remains unexplored. ERPs linked to the processing of semantic information (the N400) and the analysis of language structure (the P600) were recorded from higher and lower aerobically fit children as they read normal sentences and those containing semantic or syntactic violations. Results revealed that higher fit children exhibited greater N400 amplitude and shorter latency across all sentence types, and a larger P600 effect for syntactic violations. Such findings suggest that higher fitness may be associated with a richer network of words and their meanings, and a greater ability to detect and/or repair syntactic errors. The current findings extend previous ERP research explicating the cognitive benefits associated with greater aerobic fitness in children and may have important implications for learning and academic performance. PMID:24747513

  11. 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

    PubMed Central

    Holtedahl, Knut; Hurum, Harald

    2002-01-01

    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. PMID:11955291

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

    PubMed

    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

  13. Precipitation variability of the Grand Canyon region, 1893 through 2009, and its implications for studying effects of gullying of Holocene terraces and associated archeological sites in Grand Canyon, Arizona

    USGS Publications Warehouse

    Hereford, Richard; Bennett, Glenn E.; Fairley, Helen C.

    2014-01-01

    A daily precipitation dataset covering a large part of the American Southwest was compiled for online electronic distribution (http://pubs.usgs.gov/of/2014/1006/). The dataset contains 10.8 million observations spanning January 1893 through January 2009 from 846 weather stations in six states and 13 climate divisions. In addition to processing the data for distribution, water-year totals and other statistical parameters were calculated for each station with more than 2 years of observations. Division-wide total precipitation, expressed as the average deviation from the individual station means of a climate division, shows that the region—including the Grand Canyon, Arizona, area—has been affected by alternating multidecadal episodes of drought and wet conditions. In addition to compiling and analyzing the long-term regional precipitation data, a second dataset consisting of high-temporal-resolution precipitation measurements collected between November 2003 and January 2009 from 10 localities along the Colorado River in Grand Canyon was compiled. An exploratory study of these high-temporal-resolution precipitation measurements suggests that on a daily basis precipitation patterns are generally similar to those at a long-term weather station in the canyon, which in turn resembles the patterns at other long-term stations on the canyon rims; however, precipitation amounts recorded by the individual inner canyon weather stations can vary substantially from station to station. Daily and seasonal rainfall patterns apparent in these data are not random. For example, the inner canyon record, although short and fragmented, reveals three episodes of widespread, heavy precipitation in late summer 2004, early winter 2005, and summer 2007. The 2004 event and several others had sufficient rainfall to initiate potentially pervasive erosion of the late Holocene terraces and related archeological features located along the Colorado River in Grand Canyon.

  14. Genome Wide Association Study Identifies Variants in NBEA Associated with Migraine in Bipolar Disorder

    PubMed Central

    Jacobsen, Kaya K.; Nievergelt, Caroline M.; Zayats, Tetyana; Greenwood, Tiffany A.; Anttila, Verneri; Akiskal, Hagop S.; Haavik, Jan; Fasmer, Ole Bernt; Kelsoe, John R.; Johansson, Stefan; Oedegaard, Ketil J.

    2014-01-01

    Background Migraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this co-occurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine. Methods We performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS). Results We identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene (P= 2.97×10-8, OR: 1.82, 95% CI: 1.47-2.25), although this was not replicated in a smaller sample of 289 migraine cases. Limitations Our study is based on self-reported migraine. Conclusions NBEA encodes neurobeachin, a scaffolding protein primarily expressed in the brain and involved in trafficking of vesicles containing neurotransmitter receptors. This locus has not previously been implicated in migraine per se. We found no evidence of association in data from the GWAS migraine meta-analysis consortium (n=118 710 participants) suggesting that the association might be specific to migraine co-morbid with bipolar disorder. PMID:25451450

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26372729

  16. Prognostic Implications of Tumor Diameter in Association With Gene Expression Profile for Uveal Melanoma

    PubMed Central

    Walter, Scott D.; Chao, Daniel L.; Feuer, William; Schiffman, Joyce; Char, Devron H.; Harbour, J. William

    2016-01-01

    IMPORTANCE Uveal melanoma (UM) can be divided into prognostically significant subgroups based on a prospectively validated and widely used 15-gene expression profile (GEP) test. Class 1 UMs have a low risk and class 2 UMs have a high risk for metastasis. OBJECTIVE To determine whether any clinicopathologic factors provide independent prognostic information that may enhance the accuracy of the GEP classification. DESIGN, SETTING, AND PARTICIPANTS This retrospective observational study performed at 2 ocular oncology referral centers included 339 patients in a primary cohort and 241 patients in a validation cohort. Both cohorts had a diagnosis of UM arising from the ciliary body and/or choroid. All patients underwent tumor biopsy for GEP prognostic testing. Clinicopathologic variables included patient age and sex, tumor thickness, largest basal tumor diameter (LBD), ciliary body involvement, and pathologic cell type. Patients from the primary cohort were enrolled from November 1, 1998, to March 16, 2012; from the validation cohort, from November 4, 1996, to November 7, 2013. Follow-up for the primary cohort was completed on August 18, 2013; for the validation cohort, December 10, 2013. Data were analyzed from November 12, 2013, to November 25, 2015. MAIN OUTCOME AND MEASURES Progression-free survival (PFS). The secondary outcome was overall survival. RESULTS The primary cohort included 339 patients (175 women [51.6%]; mean [SD] age, 61.8 [13.6] years). The most significant prognostic factor was GEP classification (exp[b], 10.33; 95% CI, 4.30–24.84; P < .001). The only other variable that provided independent prognostic information was LBD (exp[b], 1.13; 95% CI, 1.02–1.26; P = .02). Among class 2 UMs, LBD showed a modest but significant association with PFS (exp[b], 1.13; 95% CI, 1.04–1.24; P = .005). The 5-year actuarial metastasis-free survival estimates (SE) were 97% (3%) for class 1 UMs with LBD of less than 12 mm, 90% (4%) for class 1 UMs with LBD of at

  17. The sequence, and its evolutionary implications, of a Thermococcus celer protein associated with transcription

    NASA Technical Reports Server (NTRS)

    Kaine, B. P.; Mehr, I. J.; Woese, C. R.

    1994-01-01

    Through random search, a gene from Thermococcus celer has been identified and sequenced that appears to encode a transcription-associated protein (110 amino acid residues). The sequence has clear homology to approximately the last half of an open reading frame reported previously for Sulfolobus acidocaldarius [Langer, D. & Zillig, W. (1993) Nucleic Acids Res. 21, 2251]. The protein translations of these two archaeal genes in turn are homologs of a small subunit found in eukaryotic RNA polymerase I (A12.2) and the counterpart of this from RNA polymerase II (B12.6). Homology is also seen with the eukaryotic transcription factor TFIIS, but it involves only the terminal 45 amino acids of the archaeal proteins. Evolutionary implications of these homologies are discussed.

  18. Practical and Scholarly Implications of Information Behaviour Research: A Pilot Study of Research Literature

    ERIC Educational Resources Information Center

    Koh, Kyungwon; Rubenstein, Ellen; White, Kelvin

    2015-01-01

    Introduction: This pilot study examined how current information behaviour research addresses the implications and potential impacts of its findings. The goal was to understand what implications and contributions the field has made and how effectively authors communicate implications of their findings. Methods: We conducted a content analysis of 30…

  19. Brain Expression Genome-Wide Association Study (eGWAS) Identifies Human Disease-Associated Variants

    PubMed Central

    Crook, Julia; Pankratz, V. Shane; Carrasquillo, Minerva M.; Rowley, Christopher N.; Nair, Asha A.; Middha, Sumit; Maharjan, Sooraj; Nguyen, Thuy; Ma, Li; Malphrus, Kimberly G.; Palusak, Ryan; Lincoln, Sarah; Bisceglio, Gina; Georgescu, Constantin; Kouri, Naomi; Kolbert, Christopher P.; Jen, Jin; Haines, Jonathan L.; Mayeux, Richard; Pericak-Vance, Margaret A.; Farrer, Lindsay A.; Schellenberg, Gerard D.; Petersen, Ronald C.; Graff-Radford, Neill R.; Dickson, Dennis W.; Younkin, Steven G.; Ertekin-Taner, Nilüfer

    2012-01-01

    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

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

    PubMed

    Zou, Fanggeng; Chai, High Seng; Younkin, Curtis S; Allen, Mariet; Crook, Julia; Pankratz, V Shane; Carrasquillo, Minerva M; Rowley, Christopher N; Nair, Asha A; Middha, Sumit; Maharjan, Sooraj; Nguyen, Thuy; Ma, Li; Malphrus, Kimberly G; Palusak, Ryan; Lincoln, Sarah; Bisceglio, Gina; Georgescu, Constantin; Kouri, Naomi; Kolbert, Christopher P; Jen, Jin; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Petersen, Ronald C; Graff-Radford, Neill R; Dickson, Dennis W; Younkin, Steven G; Ertekin-Taner, Nilüfer

    2012-01-01

    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

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

    PubMed Central

    Cai, Yan; An, Seong Soo A; Kim, SangYun

    2015-01-01

    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. PMID:26203236

  2. Genome-wide association studies in pharmacogenomics.

    PubMed

    Daly, Ann K

    2010-04-01

    Genome-wide association (GWA) studies for pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. Until now, only the largest effects have been detected, partly because of the challenges of obtaining large numbers of cases for pharmacogenomic studies. Since 2007, a range of pharmacogenomics GWA studies have been published that have identified several interesting and novel associations between drug responses or reactions and clinically relevant loci, showing the value of this approach. PMID:20300088

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

    PubMed

    Geller, Frank; Feenstra, Bjarke; Zhang, Hao; Shaffer, John R; Hansen, Thomas; Esserlind, Ann-Louise; Boyd, Heather A; Nohr, Ellen A; Timpson, Nicholas J; Fatemifar, Ghazaleh; Paternoster, Lavinia; Evans, David M; Weyant, Robert J; Levy, Steven M; Lathrop, Mark; Smith, George Davey; Murray, Jeffrey C; Olesen, Jes; Werge, Thomas; Marazita, Mary L; Sørensen, Thorkild I A; Melbye, Mads

    2011-09-01

    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, analyzed as age-adjusted standard deviation score averaged over multiple time points, based on childhood records for 5,104 women from the Danish National Birth Cohort. Four loci showed association at P<5×10(-8) and were replicated in four independent study groups from the United States and Denmark with a total of 3,762 individuals; all combined P-values were below 10(-11). Two loci agreed with previous findings in primary tooth eruption and were also known to influence height and breast cancer, respectively. The two other loci pointed to genomic regions without any previous significant genome-wide association study results. The intronic SNP rs7924176 in ADK could be linked to gene expression in monocytes. The combined effect of the four genetic variants was most pronounced between age 10 and 12 years, where children with 6 to 8 delayed tooth eruption alleles had on average 3.5 (95% confidence interval: 2.9-4.1) fewer permanent teeth than children with 0 or 1 of these alleles. PMID:21931568

  4. Biochemical Studies in Suicide Victims: Current Findings and Future Implications.

    ERIC Educational Resources Information Center

    Stanley, Michael; Stanley, Barbara

    1989-01-01

    Reviews relevant neurochemical findings in postmortem suicide studies, looking specifically at association between serotonergic dysfunction and suicide. Explores relative strengths and weaknesses of studies and provides overview regarding advantages and shortcomings of given technique or approach. Notes that data presented in review provide…

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

    PubMed Central

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

    2016-01-01

    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

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

    PubMed

    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

  7. HLA Associations and Clinical Implications in T-Cell Mediated Drug Hypersensitivity Reactions: An Updated Review

    PubMed Central

    Cheng, Chi-Yuan; Chen, Chi-Hua; Chen, Wei-Li; Deng, Shin-Tarng; Chung, Wen-Hung

    2014-01-01

    T-cell mediated drug hypersensitivity reactions may range from mild rash to severe fatal reactions. Among them, drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS), Stevens-Johnson syndrome/ toxic epidermal necrolysis (SJS/TEN), are some of the most life-threatening severe cutaneous adverse reactions (SCARs). Recent advances in pharmacogenetic studies show strong genetic associations between human leukocyte antigen (HLA) alleles and susceptibility to drug hypersensitivity. This review summarizes the literature on recent progresses in pharmacogenetic studies and clinical application of pharmacogenetic screening based on associations between SCARs and specific HLA alleles to avoid serious conditions associated with drug hypersensitivity. PMID:24901010

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

    PubMed

    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. PMID:27477491

  9. Fluorescence studies of polymer surfactant association

    NASA Astrophysics Data System (ADS)

    Miguel, M. da G.; Burrows, H. D.; Formosinho, S. J.; Lindman, B.

    2001-05-01

    Fluorescence spectroscopy has been successfully used for the study of central issues of solutions of surfactants and associating polymers. Different fluorescence techniques and methods are uniquely adapted to investigate problems in this field and can, by using extrinsic or intrinsic probes, provide information on molecular association, microstructure and molecular dynamics. This constitutes an important contribution to the understanding and control of macroscopic properties, as well as to their biological functions and technical applications. Important aspects of these mixed systems, related to their self-assembly, are: formation of micelles and hydrophobic microdomains in general; size and shape of surfactant molecular aggregates; formation and stability of vesicles; intra- vs. intermolecular association in polymers; conformational changes in polymers as affected by polymer-surfactant association; surfactant organization in adsorbed layers; kinetic aspects of the formation and disintegration of self-assembly structures; residence times of molecules in microdomains and migration of active molecules. Some of these issues will be addressed in this paper.

  10. Efficacy studies in natural family planning: issues and management implications illustrated with data from five studies.

    PubMed

    Labbok, M H; Klaus, H; Perez, A

    1991-12-01

    Studies of method effectiveness must be carefully assessed for comparability of findings. Several parameters are identified that are important in the assurance of comparable results. This article discusses these issues with the use of data from previously published studies and emphasizes the management implications of use-effectiveness data. PMID:1755468

  11. Genome-wide association study reveals multiple loci associated with primary tooth development during infancy.

    PubMed

    Pillas, Demetris; Hoggart, Clive J; Evans, David M; O'Reilly, Paul F; Sipilä, Kirsi; Lähdesmäki, Raija; Millwood, Iona Y; Kaakinen, Marika; Netuveli, Gopalakrishnan; Blane, David; Charoen, Pimphen; Sovio, Ulla; Pouta, Anneli; Freimer, Nelson; Hartikainen, Anna-Liisa; Laitinen, Jaana; Vaara, Sarianna; Glaser, Beate; Crawford, Peter; Timpson, Nicholas J; Ring, Susan M; Deng, Guohong; Zhang, Weihua; McCarthy, Mark I; Deloukas, Panos; Peltonen, Leena; Elliott, Paul; Coin, Lachlan J M; Smith, George Davey; Jarvelin, Marjo-Riitta

    2010-02-01

    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 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5x10(-8), and 5 with suggestive association (P<5x10(-6)). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years. PMID:20195514

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

    PubMed Central

    Warrier, Varun; Chakrabarti, Bhismadev; Murphy, Laura; Chan, Allen; Craig, Ian; Mallya, Uma; Lakatošová, Silvia; Rehnstrom, Karola; 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

  13. EXPOSURE TO INTERMITTENT AIR POLLUTION AND CHANGES IN SEMEN QUALITY: EVIDENCE FOR AN ASSOCIATION AND IMPLICATIONS FOR REPRODUCTIVE RISK ASSESSMENT

    EPA Science Inventory

    Exposure to Intermittent Air Pollution and Changes in Semen Quality:
    Evidence for an Association and Implications for Reproductive Risk Assessment.

    S. D. Perreault1, S.G. Selevan2, J. Rubes3, D. Zudova3, and D.P. Evenson4
    1US EPA, ORD/NHEERL, Research Triangle Pa...

  14. Depression and Apathy Among People Living with HIV: Implications for Treatment of HIV Associated Neurocognitive Disorders

    PubMed Central

    Whitehead, Nicole E.; Burrell, Larry E.; Dotson, Vonetta M.; Cook, Robert L.; Malloy, Paul; Devlin, Kathryn; Cohen, Ronald A.

    2015-01-01

    Depression and apathy are common among people living with HIV (PLWH). However, in PLWH, it is unclear whether depression and apathy are distinct conditions, which contribute to different patterns of disruption to cognitive processing and brain systems. Understanding these conditions may enable the development of prognostic indicators for HIV associated neurocognitive disorders (HAND). The present study examined substance use behavior and cognitive deficits, associated with depression and apathy, in 120 PLWH, using hierarchical regression analyses. Higher levels of depression were associated with a history of alcohol dependence and greater deficits in processing speed, motor and global cognitive functioning. Higher levels of apathy were associated with a history of cocaine dependence. It is recommended that PLWH get screened appropriately for apathy and depression, in order to receive the appropriate treatment, considering the comorbidities associated with each condition. Future research should examine the neurological correlates of apathy and depression in PLWH. PMID:25533921

  15. The genetic landscape and clinical implications of vertebral anomalies in VACTERL association

    PubMed Central

    Chen, Yixin; Liu, Zhenlei; Chen, Jia; Zuo, Yuzhi; Liu, Sen; Chen, Weisheng; Liu, Gang; Qiu, Guixing; Giampietro, Philip F; Wu, Nan; Wu, Zhihong

    2016-01-01

    VACTERL association is a condition comprising multisystem congenital malformations, causing severe physical disability in affected individuals. It is typically defined by the concurrence of at least three of the following component features: vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheo-oesophageal fistula (TE), renal dysplasia (R) and limb abnormalities (L). Vertebral anomaly is one of the most important and common defects that has been reported in approximately 60–95% of all VACTERL patients. Recent breakthroughs have suggested that genetic factors play an important role in VACTERL association, especially in those with vertebral phenotypes. In this review, we summarised the genetic studies of the VACTERL association, especially focusing on the genetic aetiology of patients with vertebral anomalies. Furthermore, genetic reports of other syndromes with vertebral phenotypes overlapping with VACTERL association are also included. We aim to provide a further understanding of the genetic aetiology and a better evidence for genetic diagnosis of the association and vertebral anomalies. PMID:27084730

  16. A Comparative Study of Sparse Associative Memories

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    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.

  17. A Comparative Study of Sparse Associative Memories

    NASA Astrophysics Data System (ADS)

    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.

  18. Functional Analysis of Variance for Association Studies

    PubMed Central

    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

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

    ERIC Educational Resources Information Center

    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…

  20. Genetic association of impulsivity in young adults: a multivariate study

    PubMed Central

    Khadka, S; Narayanan, B; Meda, S A; Gelernter, J; Han, S; Sawyer, B; Aslanzadeh, F; Stevens, M C; Hawkins, K A; Anticevic, A; Potenza, M N; Pearlson, G D

    2014-01-01

    Impulsivity is a heritable, multifaceted construct with clinically relevant links to multiple psychopathologies. We assessed impulsivity in young adult (N~2100) participants in a longitudinal study, using self-report questionnaires and computer-based behavioral tasks. Analysis was restricted to the subset (N=426) who underwent genotyping. Multivariate association between impulsivity measures and single-nucleotide polymorphism data was implemented using parallel independent component analysis (Para-ICA). Pathways associated with multiple genes in components that correlated significantly with impulsivity phenotypes were then identified using a pathway enrichment analysis. Para-ICA revealed two significantly correlated genotype–phenotype component pairs. One impulsivity component included the reward responsiveness subscale and behavioral inhibition scale of the Behavioral-Inhibition System/Behavioral-Activation System scale, and the second impulsivity component included the non-planning subscale of the Barratt Impulsiveness Scale and the Experiential Discounting Task. Pathway analysis identified processes related to neurogenesis, nervous system signal generation/amplification, neurotransmission and immune response. We identified various genes and gene regulatory pathways associated with empirically derived impulsivity components. Our study suggests that gene networks implicated previously in brain development, neurotransmission and immune response are related to impulsive tendencies and behaviors. PMID:25268255

  1. Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

    PubMed

    Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

    2013-10-01

    Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. PMID:23796633

  2. CELLULAR, MOLECULAR, AND EPIGENETIC MECHANISMS IN NON-ASSOCIATIVE CONDITIONING: IMPLICATIONS FOR PAIN AND MEMORY

    PubMed Central

    Rahn, Elizabeth J.; Guzman-Karlsson, Mikael C.; Sweatt, J. David

    2013-01-01

    Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning-and pain- related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. PMID:23796633

  3. Curcumin and genistein: the combined effects on disease-associated CFTR mutants and their clinical implications.

    PubMed

    Sohma, Yoshiro; Yu, Ying-Chun; Hwang, Tzyh-Chang

    2013-01-01

    Genistein and curcumin are major components of Asian foods, soybean and curry turmeric respectively. These compounds have been intensively investigated for their chemical and biological features conferring their anti-cancer activity. Genistein and curcumin have also been investigated for their potentiation effects on disease-associated CFTR mutants such as ΔF508 and G551D. Recently, we investigated the combined effect of genistein and curcumin on G551D-CFTR, which exhibits gating defects without abnormalities in protein synthesis or trafficking using the patch-clamp technique. We found that genistein and curcumin showed additive effects on their potentiation of G551D-CFTR in high concentration range and also, more importantly, showed a significant synergistic effect in their minimum concentration ranges. These results are consistent with the idea that multiple mechanisms are involved in the action of these CFTR potentiators. In this review, we revisit the pharmacology of genistein and curcumin on CFTR and also propose new pharmaceutical implications of combined use of these compounds in the development of drugs for CF pharmacotherapy. PMID:23331029

  4. Curcumin and Genistein: the Combined Effects on Disease-associated CFTR Mutants and their Clinical Implications

    PubMed Central

    Sohma, Yoshiro; Yu, Ying-Chun; Hwang, Tzyh-Chang

    2016-01-01

    Genistein and curcumin are major components of Asian foods, soybean and curry turmeric respectively. These compounds have been intensively investigated for their chemical and biological features conferring their anti-cancer activity. Genistein and curcumin have also been investigated for their potentiation effects on disease-associated CFTR mutants such as ΔF508 and G551D. Recently, we investigated the combined effect of genistein and curcumin on G551D-CFTR, which exhibits gating defects without abnormalities in protein synthesis or trafficking using the patch-clamp technique. We found that genistein and curcumin showed additive effects on their potentiation of G551D-CFTR in high concentration range and also, more importantly, showed a significant synergistic effect in their minimum concentration ranges. These results are consistent with the idea that multiple mechanisms are involved in the action of these CFTR potentiators. In this review, we revisit the pharmacology of genistein and curcumin on CFTR and also propose new pharmaceutical implications of combined use of these compounds in the development of drugs for CF pharmacotherapy. PMID:23331029

  5. Quantum-holographic and classical Hopfield-like associative nnets: implications for modeling two cognitive modes of consciousness

    NASA Astrophysics Data System (ADS)

    Rakovic, D.; Dugic, M.

    2005-05-01

    Quantum bases of consciousness are considered with psychosomatic implications of three front lines of psychosomatic medicine (hesychastic spirituality, holistic Eastern medicine, and symptomatic Western medicine), as well as cognitive implications of two modes of individual consciousness (quantum-coherent transitional and altered states, and classically reduced normal states) alongside with conditions of transformations of one mode into another (considering consciousness quantum-coherence/classical-decoherence acupuncture system/nervous system interaction, direct and reverse, with and without threshold limits, respectively) - by using theoretical methods of associative neural networks and quantum neural holography combined with quantum decoherence theory.

  6. Software Engineering Laboratory Ada performance study: Results and implications

    NASA Technical Reports Server (NTRS)

    Booth, Eric W.; Stark, Michael E.

    1992-01-01

    The SEL is an organization sponsored by NASA/GSFC to investigate the effectiveness of software engineering technologies applied to the development of applications software. The SEL was created in 1977 and has three organizational members: NASA/GSFC, Systems Development Branch; The University of Maryland, Computer Sciences Department; and Computer Sciences Corporation, Systems Development Operation. The goals of the SEL are as follows: (1) to understand the software development process in the GSFC environments; (2) to measure the effect of various methodologies, tools, and models on this process; and (3) to identify and then to apply successful development practices. The activities, findings, and recommendations of the SEL are recorded in the Software Engineering Laboratory Series, a continuing series of reports that include the Ada Performance Study Report. This paper describes the background of Ada in the Flight Dynamics Division (FDD), the objectives and scope of the Ada Performance Study, the measurement approach used, the performance tests performed, the major test results, and the implications for future FDD Ada development efforts.

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

    PubMed

    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

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

    PubMed

    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

  9. Invited Commentary: Circulating Inflammation Markers and Cancer Risk—Implications for Epidemiologic Studies

    PubMed Central

    Chaturvedi, Anil K.; Moore, Steven C.; Hildesheim, Allan

    2013-01-01

    Chronic inflammation, an established risk factor for cardiovascular disease, is increasingly being recognized as an etiologic factor in several cancers. In this issue of the Journal, Touvier et al. (Am J Epidemiol. 2013;177(1):3–13) report on the association of 7 markers of inflammation, adiposity, and endothelial function with risk of overall cancer and breast and prostate cancers in a nested case-control study carried out within the SU.VI.MAX cohort (France, 1994–2007). Consistent with previous reports on this topic, Touvier et al. focused on a limited number of markers. Future studies of inflammation and cancer should be able to capitalize on emerging multiplexed methods for the simultaneous detection of larger numbers of inflammatory markers in low-volume specimens. This should allow a more comprehensive evaluation of the role of inflammation in cancer development. In this commentary, the authors review emerging methods for measurement of multiplexed inflammation markers, the design and analytic implications of the use of these methods in epidemiologic studies, and potential public health implications of such studies. Given that many large prospective cohort studies have already collected and banked serum/plasma samples, rapid gains in our understanding of chronic inflammation and its role in cancer etiology are possible. PMID:23171878

  10. Genome-Wide Association Studies of Cancer

    PubMed Central

    Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

    2010-01-01

    Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

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

    PubMed

    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

  12. Pollution and skin: from epidemiological and mechanistic studies to clinical implications.

    PubMed

    Krutmann, Jean; Liu, Wei; Li, Li; Pan, Xiaochuan; Crawford, Martha; Sore, Gabrielle; Seite, Sophie

    2014-12-01

    In recent years, the health effects associated with air pollution have been intensively studied. Most studies focus on air pollution effects on the lung and the cardiovascular system. More recently, however, epidemiological and mechanistic studies suggest that air pollution is also affecting skin integrity. This state-of-the-art review focuses on this latter aspect; it was developed with the collaboration of European and Chinese board of experts with specific interests in environmental health, clinical and basic research in dermatology and cosmetic dermatology. A literature review limited to pollution and health effects and (sensitive) skin was performed using PubMed. Review and original articles were chosen. We summarize the existing scientific evidence that air pollution exerts detrimental effects on human skin, discuss potential clinical implications and suggest specific and unspecific cosmetic protective measures. PMID:25278222

  13. Association of Depressive Symptoms and Disease Activity in Children with Asthma: Methodological and Clinical Implications

    ERIC Educational Resources Information Center

    Waxmonsky, James; Wood, Beatrice L.; Stern, Trudy; Ballow, Mark; Lillis, Kathleen; Cramer-Benjamin, Darci; Mador, Jeffrey; Miller, Bruce D.

    2006-01-01

    Objective: This study was designed to assess the prevalence of depressive symptoms in children with asthma and the association between depression and asthma activity. Method: Children ages 7 to 17 (n = 129) were recruited from a hospital emergency department after presenting for asthma symptoms. The majority of subjects were from disadvantaged,…

  14. Longitudinal associations between BMI, waist circumference, and cardiometabolic risk in US youth: Monitoring implications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined whether change in body mass index (BMI) or waist circumference (WC)is associated with change in cardiometabolic risk factors and differences between cardiovascular disease specific and diabetes specific risk factors among adolescents. We also sought to examine any differences by ...

  15. Chronic Periodontitis Genome-wide Association Studies

    PubMed Central

    Rhodin, K.; Divaris, K.; North, K.E.; Barros, S.P.; Moss, K.; Beck, J.D.; Offenbacher, S.

    2014-01-01

    Recent genome-wide association studies (GWAS) of chronic periodontitis (CP) offer rich data sources for the investigation of candidate genes, functional elements, and pathways. We used GWAS data of CP (n = 4,504) and periodontal pathogen colonization (n = 1,020) from a cohort of adult Americans of European descent participating in the Atherosclerosis Risk in Communities study and employed a MAGENTA approach (i.e., meta-analysis gene set enrichment of variant associations) to obtain gene-centric and gene set association results corrected for gene size, number of single-nucleotide polymorphisms, and local linkage disequilibrium characteristics based on the human genome build 18 (National Center for Biotechnology Information build 36). We used the Gene Ontology, Ingenuity, KEGG, Panther, Reactome, and Biocarta databases for gene set enrichment analyses. Six genes showed evidence of statistically significant association: 4 with severe CP (NIN, p = 1.6 × 10−7; ABHD12B, p = 3.6 × 10−7; WHAMM, p = 1.7 × 10−6; AP3B2, p = 2.2 × 10−6) and 2 with high periodontal pathogen colonization (red complex–KCNK1, p = 3.4 × 10−7; Porphyromonas gingivalis–DAB2IP, p = 1.0 × 10−6). Top-ranked genes for moderate CP were HGD (p = 1.4 × 10−5), ZNF675 (p = 1.5 × 10−5), TNFRSF10C (p = 2.0 × 10−5), and EMR1 (p = 2.0 × 10−5). Loci containing NIN, EMR1, KCNK1, and DAB2IP had showed suggestive evidence of association in the earlier single-nucleotide polymorphism–based analyses, whereas WHAMM and AP2B2 emerged as novel candidates. The top gene sets included severe CP (“endoplasmic reticulum membrane,” “cytochrome P450,” “microsome,” and “oxidation reduction”) and moderate CP (“regulation of gene expression,” “zinc ion binding,” “BMP signaling pathway,” and “ruffle”). Gene-centric analyses offer a promising avenue for efficient interrogation of large-scale GWAS data. These results highlight genes in previously identified loci and

  16. Possible implication of disordered neutrophil extracellular traps in the pathogenesis of MPO-ANCA-associated vasculitis.

    PubMed

    Nakazawa, Daigo; Tomaru, Utano; Ishizu, Akihiro

    2013-10-01

    Neutrophil extracellular traps (NETs) are characterized by the presence of extracellular DNA fibers studded with antimicrobial proteins, including myeloperoxidase (MPO). Although NETs play an important role in the innate immune system, the scattered extracellular enzymes, such as MPO, pose risks to the host. Therefore, NETs are strictly regulated by DNase I in the serum, which prevents them from persisting. Recent studies have demonstrated that dysregulation of NETs could be involved in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus. In this review, we interpret the association of disordered NETs with autoimmune diseases, especially propylthiouracil-induced MPO-ANCA-associated vasculitis. PMID:23224024

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

    PubMed Central

    Al-Hazzaa, Hazzaa M; Musaiger, Abdulrahman O

    2011-01-01

    Background 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 simultaneously assess broad lifestyle variables in a large sample of adolescents from numerous urbanized Arab regions. This joint research project will supply us with comprehensive and recent data on physical activity/inactivity and eating habits of Arab adolescents relative to obesity. Such invaluable lifestyle-related data are crucial for developing public health policies and regional strategies for health promotion and disease prevention. PMID

  18. A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain.

    PubMed

    Yuferov, Vadim; Ji, Fei; Nielsen, David A; Levran, Orna; Ho, Ann; Morgello, Susan; Shi, Ruijin; Ott, Jurg; Kreek, Mary Jeanne

    2009-04-01

    Dynorphin peptides and the kappa-opioid receptor are important in the rewarding properties of cocaine, heroin, and alcohol. We tested polymorphisms of the prodynorphin gene (PDYN) for association with cocaine dependence and cocaine/alcohol codependence. We genotyped six single nucleotide polymorphisms (SNPs), located in the promoter region, exon 4 coding, and 3' untranslated region, in 106 Caucasians and 204 African Americans who were cocaine dependent, cocaine/alcohol codependent, or controls. In Caucasians, we found point-wise significant associations of 3'UTR SNPs (rs910080, rs910079, and rs2235749) with cocaine dependence and cocaine/alcohol codependence. These SNPs are in high linkage disequilibrium, comprising a haplotype block. The haplotype CCT was significantly experiment-wise associated with cocaine dependence and with combined cocaine dependence and cocaine/alcohol codependence (false discovery rate, q=0.04 and 0.03, respectively). We investigated allele-specific gene expression of PDYN, using SNP rs910079 as a reporter, in postmortem human brains from eight heterozygous subjects, using SNaPshot assay. There was significantly lower expression for C allele (rs910079), with ratios ranging from 0.48 to 0.78, indicating lower expression of the CCT haplotype of PDYN in both the caudate and nucleus accumbens. Analysis of total PDYN expression in 43 postmortem brains also showed significantly lower levels of preprodynorphin mRNA in subjects having the risk CCT haplotype. This study provides evidence that a 3'UTR PDYN haplotype, implicated in vulnerability to develop cocaine addiction and/or cocaine/alcohol codependence, is related to lower mRNA expression of the PDYN gene in human dorsal and ventral striatum. PMID:18923396

  19. Strong association between microsatellites and an HLA-B, DR haplotype (B18-DR3): Implication for microsatellite evolution

    SciTech Connect

    Crouau-Roy, B.; Bouzekri, N.; Clayton, J.

    1996-09-01

    The HLA haplotype B18-DR3 has a widespread geographical distribution, but has its greatest frequencies in Southern Europe, probably vestigial of the earliest populations of this region, particularly in the Pays Basque and Sardinia. This haplotype is of medical significance, being that most implicated as a factor of risk in insulin-dependent diabetes mellitus. In this study, the closely linked microsatellite markers (TNFa,b,c) in the region of the tumor necrosis factor (TNF) genes have been used in an attempt to subtype this haplotype in the two populations and/or in healthy and diabetic populations. A total of 79 HLA-B18-DR3 haplotypes were analyzed: 54 in Basques (12 from healthy individuals and 42 from diabetics or their first-degree relatives) and 25 in Sardinians (13 from healthy and 13 from diabetic individuals). The TNF haplotype a1-b5-c2 is completely associated with B18-DR3 in both populations. The homogeneity of the B18-DR3 haplotype in two ethnically pure populations implies stability in evolution, which suggest that the mutation rate of these microsatellite markers must be less than is usually assumed (i.e., {approximately} 5x10{sup {minus}6} per site per generation). Such markers should be powerful tools for studying genetic drift and admixture of populations, but it remains to be established whether this stability is a rule for all microsatellites in HLA haplotypes or whether or whether it is restricted to some microsatellites and/or some HLA haplotypes. The population genetics of those microsatellites associated with HLA B18-DR3 was also studied in a random sample of the Basque population. 44 refs., 3 tabs.

  20. Highly Drug-Resistant Pathogens Implicated in Burn-Associated Bacteremia in an Iraqi Burn Care Unit

    PubMed Central

    Ronat, Jean-Baptiste; Kakol, Jabar; Khoury, Marwan N.; Berthelot, Mathilde; Yun, Oliver; Brown, Vincent; Murphy, Richard A.

    2014-01-01

    Objective In low- and middle-income countries, bloodstream infections are an important cause of mortality in patients with burns. Increasingly implicated in burn-associated infections are highly drug-resistant pathogens with limited treatment options. We describe the epidemiology of bloodstream infections in patients with burns in a humanitarian surgery project in Iraq. Methods We performed a retrospective, descriptive study of blood culture isolates identified between July 2008 and September 2009 among patients with burns in a single hospital in Iraq who developed sepsis. Results In 1169 inpatients admitted to the burn unit during the study period, 212 (18%) had suspected sepsis, and 65 (6%) had confirmed bacteremia. Sepsis was considered the primary cause of death in 198 patients (65%; 95% CI 65–70) of the 304 patients that died. The most commonly isolated organisms were Pseudomonas aeruginosa (22 isolates [34%]), Staphylococcus aureus (17 [26%]), Klebsiella pneumoniae (8 [12%]), Staphylococcus epidermidis (7 [11%]), Acinetobacter baumannii (6 [9%]), and Enterobacter cloacae (5 [8%]). A high proportion of Enterobacteriaceae strains produced extended-spectrum beta-lactamase and S. aureus isolates were uniformly methicillin-resistant. For gram-negative bacteria, the most reliably active antibiotics were imipenen and amikacin. Conclusions Burn patients with sepsis in Iraq were commonly found to have bloodstream pathogens resistant to most antibiotics available locally. Effective empirical therapy of burn sepsis in this region of Iraq would consist of vancomycin or teicoplanin and a carbapenem-class antibiotic with antipseudomonal activity. PMID:25111170

  1. Genome-Wide Association Studies: A Primer

    PubMed Central

    Corvin, Aiden; Craddock, Nick; Sullivan, Patrick F.

    2014-01-01

    There have been nearly 400genome-wide association studies published since 2005. The GWAS approach has been exceptionally successful in identifying common genetic variants that predispose to a variety of complex human diseases and biochemical and anthropometric traits. Although this approach is relatively new, there are many excellent reviews of different aspects of the GWAS method. Here, we provide a primer, an annotated overview of the GWAS method with particular reference to psychiatric genetics. We dissect the GWAS methodology into its components and provide a brief description with citations and links to reviews that cover the topic in detail. PMID:19895722

  2. A novel centrosome and microtubules associated subcellular localization of Nogo-A: implications for neuronal development.

    PubMed

    Mi, Yajing; Gao, Xingchun; Ma, Yue; Gao, Jie; Wang, Zhen; Jin, Weilin

    2014-12-01

    Oligodendrocyte-derived neurite-outgrowth inhibitor Nogo-A and its restriction mechanism are well-known. Recently, Nogo-A is reported to be abundantly expressed in neurons, however, the concrete link between neuronal Nogo-A and neuronal development is poorly understood. In the present study, we used Neuro2A and COS7 cell lines to clarify that Nogo-A largely distributed in the centrosome and microtubules-rich regions. When endogenous Nogo-A was down-regulated with RNA interference, the percentage of cell differentiation and the total neurite length of Neuro2A exposed to valproic acid (VPA) decreased sharply. Furthermore, in primary neurons, acetylated α-tubulin decreased at the tips of neurites where endogenous Nogo-A was still highly expressed. In HEK293FT cell lines, Nogo-A overexpression could redistribute acetylated α-tubulin but not change the level of α-tubulin. Together, our data discovered that centrosome- and microtubules-localized Nogo-A positively regulates neuronal differentiation and neurite outgrowth of Neuro2A cell lines, implicating the essential roles of subcellular Nogo-A in neuronal development. PMID:25286302

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

    PubMed Central

    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 disorders. Furthermore, the manifestation of anxiety in numerous psychiatric disorders, such as generalized anxiety disorder, depressive disorder, panic disorder, phobia, obsessive-compulsive disorder, and posttraumatic stress disorder, highlights the importance of studying the underlying biology of these disorders to gain a better understanding of the disease and to identify common biomarkers for these disorders. Most recently, the expression of glutathione reductase 1 and glyoxalase 1, which are genes involved in antioxidative metabolism, were reported to be correlated with anxiety-related phenotypes. This review focuses on direct and indirect evidence of the potential involvement of oxidative stress in the genesis of anxiety and discusses different opinions that exist in this field. Antioxidant therapeutic strategies are also discussed, highlighting the importance of oxidative stress in the etiology, incidence, progression, and prevention of psychiatric disorders. PMID:24669207

  4. Preschool children's views on emotion regulation: Functional associations and implications for social-emotional adjustment.

    PubMed

    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 fear. Forty-seven adults were presented with a parallel questionnaire. Participants rated the degree to which six emotion-regulation strategies were effective in decreasing negative emotions. Results showed that even the youngest preschoolers viewed cognitive and behavioral distraction and repairing the situation as relatively effective; compared to adults, however, preschoolers favored relatively "ineffective" strategies such as venting and rumination. Children also showed a functional view of emotion regulation; that effective strategies depend on the emotion being regulated. All participants favored repairing a negative situation to reduce anger and behavioral distraction to reduce sadness and fear. Finally, the more children indicated that venting would reduce negative emotions, the lower their maternal report of social skills. Findings are discussed in terms of functional emotion theory and implications of emotion-regulation understanding for child adjustment. PMID:19724663

  5. Direct association of Mu-opioid and NMDA glutamate receptors supports their cross-regulation: molecular implications for opioid tolerance.

    PubMed

    Garzón, Javier; Rodríguez-Muñoz, María; Sánchez-Blázquez, Pilar

    2012-09-01

    In the nervous system, the interaction of opioids like morphine and its derivatives, with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of analgesic tolerance, as well as physical dependence. Tolerance implies that increasing doses of the drug are required to achieve the same effect, a phenomenon that contributes significantly to the social problems surrounding recreational opioid abuse. In recent years, our understanding of the mechanisms that control MOR function in the nervous system, and that eventually produce opioid tolerance, has increased greatly. Pharmacological studies have identified a number of signaling proteins involved in morphine-induced tolerance, including the N-methyl-D-aspartate acid glutamate receptor (NMDAR), nitric oxide synthase (NOS), protein kinase C (PKC), protein kinase A (PKA), calcium (Ca²⁺)/calmodulin (CaM)-dependent kinase II (CaMKII), delta-opioid receptor (DOR) and the regulators of G-protein signaling (RGS) proteins. There is general agreement on the critical role of the NMDAR/nNOS/CaMKII pathway in this process, which is supported by the recent demonstration of a physical association between MORs and NMDARs in post-synaptic structures. Indeed, it is feasible that treatments that diminish morphine tolerance may target distinct elements within the same regulatory MOR-NMDAR pathway. Accordingly, we propose a model that incorporates the most relevant signaling components implicated in opioid tolerance in which, certain signals originating from the activated MOR are perceived by the associated NMDAR, which in turn exerts a negative feedback effect on MOR signaling. MOR- and NMDAR-mediated signals work together in a sequential and interconnected manner to ultimately induce MOR desensitization. Future studies of these phenomena should focus on adding further components to this signaling pathway in order to better define the mechanism underlying MOR desensitization in neural cells. PMID:22920535

  6. A literature review of neck pain associated with computer use: public health implications

    PubMed Central

    Green, Bart N

    2008-01-01

    Prolonged use of computers during daily work activities and recreation is often cited as a cause of neck pain. This review of the literature identifies public health aspects of neck pain as associated with computer use. While some retrospective studies support the hypothesis that frequent computer operation is associated with neck pain, few prospective studies reveal causal relationships. Many risk factors are identified in the literature. Primary prevention strategies have largely been confined to addressing environmental exposure to ergonomic risk factors, since to date, no clear cause for this work-related neck pain has been acknowledged. Future research should include identifying causes of work related neck pain so that appropriate primary prevention strategies may be developed and to make policy recommendations pertaining to prevention. PMID:18769599

  7. Association of lipoarabinomannan with high density lipoprotein in blood: Implications for diagnostics

    SciTech Connect

    Sakamuri, Rama Murthy; Price, Dominique N.; Lee, Myungsun; Cho, Sang Nae; Barry, Clifton E.; Via, Laura E.; Swanson, Basil I.; Mukundan, Harshini

    2013-02-14

    Understanding the pathophysiology of tuberculosis, and the bio-distribution of pathogen-associated molecules in the host is essential for the development of efficient methods of intervention. One of the key virulence factors in the pathology of tuberculosis infection is Lipoarabinomannan (LAM). Previously, we have demonstrated the reliable detection of LAM in urine from tuberculosis patients in a sandwich immunoassay format. We also applied an ultra-sensitive detection strategy developed for amphiphilic biomarkers, membrane insertion, to the detection of LAM with a limit of detection of 10 fM. Herein, we evaluate the application of membrane insertion to the detection of LAM in patient serum, and demonstrate that the circulating concentrations of ‘monomeric’ LAM in serum are very low, despite significantly higher concentrations in the urine. Using spiked samples, we demonstrate that this discrepancy is due to the association of LAM with high-density lipoprotein (HDL) nanodiscs in human serum. Indeed, pull-down of HDL nanodiscs from human serum allows for the recovery of HDL-associated LAM. These studies suggest that LAM is likely associated with carrier molecules such as HDL in the blood of patients infected with tuberculosis. Furthermore, this phenomenon may not be limited to LAM in that many pathogen-associated molecular patterns like LAM are amphiphilic in nature and may also be associated with host lipid carriers. Such interactions are likely to affect host–pathogen interactions, pathogen bio-distribution and clearance in the host, and must be thoroughly understood for the effective design of vaccines and diagnostics.

  8. Association of lipoarabinomannan with high density lipoprotein in blood: Implications for diagnostics

    DOE PAGESBeta

    Sakamuri, Rama Murthy; Price, Dominique N.; Lee, Myungsun; Cho, Sang Nae; Barry, Clifton E.; Via, Laura E.; Swanson, Basil I.; Mukundan, Harshini

    2013-02-14

    Understanding the pathophysiology of tuberculosis, and the bio-distribution of pathogen-associated molecules in the host is essential for the development of efficient methods of intervention. One of the key virulence factors in the pathology of tuberculosis infection is Lipoarabinomannan (LAM). Previously, we have demonstrated the reliable detection of LAM in urine from tuberculosis patients in a sandwich immunoassay format. We also applied an ultra-sensitive detection strategy developed for amphiphilic biomarkers, membrane insertion, to the detection of LAM with a limit of detection of 10 fM. Herein, we evaluate the application of membrane insertion to the detection of LAM in patient serum,more » and demonstrate that the circulating concentrations of ‘monomeric’ LAM in serum are very low, despite significantly higher concentrations in the urine. Using spiked samples, we demonstrate that this discrepancy is due to the association of LAM with high-density lipoprotein (HDL) nanodiscs in human serum. Indeed, pull-down of HDL nanodiscs from human serum allows for the recovery of HDL-associated LAM. These studies suggest that LAM is likely associated with carrier molecules such as HDL in the blood of patients infected with tuberculosis. Furthermore, this phenomenon may not be limited to LAM in that many pathogen-associated molecular patterns like LAM are amphiphilic in nature and may also be associated with host lipid carriers. Such interactions are likely to affect host–pathogen interactions, pathogen bio-distribution and clearance in the host, and must be thoroughly understood for the effective design of vaccines and diagnostics.« less

  9. Association of lipoarabinomannan with high density lipoprotein in blood: implications for diagnostics.

    PubMed

    Sakamuri, Rama Murthy; Price, Dominique N; Lee, Myungsun; Cho, Sang Nae; Barry, Clifton E; Via, Laura E; Swanson, Basil I; Mukundan, Harshini

    2013-05-01

    Understanding the pathophysiology of tuberculosis, and the bio-distribution of pathogen-associated molecules in the host is essential for the development of efficient methods of intervention. One of the key virulence factors in the pathology of tuberculosis infection is Lipoarabinomannan (LAM). Previously, we have demonstrated the reliable detection of LAM in urine from tuberculosis patients in a sandwich immunoassay format. We have also applied an ultra-sensitive detection strategy developed for amphiphilic biomarkers, membrane insertion, to the detection of LAM with a limit of detection of 10 fM. Herein, we evaluate the application of membrane insertion to the detection of LAM in patient serum, and demonstrate that the circulating concentrations of 'monomeric' LAM in serum are very low, despite significantly higher concentrations in the urine. Using spiked samples, we demonstrate that this discrepancy is due to the association of LAM with high-density lipoprotein (HDL) nanodiscs in human serum. Indeed, pull-down of HDL nanodiscs from human serum allows for the recovery of HDL-associated LAM. These studies suggest that LAM is likely associated with carrier molecules such as HDL in the blood of patients infected with tuberculosis. This phenomenon may not be limited to LAM in that many pathogen-associated molecular patterns like LAM are amphiphilic in nature and may also be associated with host lipid carriers. Such interactions are likely to affect host-pathogen interactions, pathogen bio-distribution and clearance in the host, and must be thoroughly understood for the effective design of vaccines and diagnostics. PMID:23507184

  10. Researchable Problems and Implications for T & I Education Drawn from the Vocational Education Study.

    ERIC Educational Resources Information Center

    Wichowski, Chester P.

    Findings are reported of a survey to determine researchable problems or implications for trade and industrial education as they might be stimulated by "The Final Report of The Vocational Education Study, Publication No. 8," directed by Henry David in 1981 for the National Institute of Education. Research questions and implications provided by…

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

    ERIC Educational Resources Information Center

    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)

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

    2012-01-01

    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 (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). PMID:21926974

  15. COSMOLOGICAL IMPLICATIONS OF FAST RADIO BURST/GAMMA-RAY BURST ASSOCIATIONS

    SciTech Connect

    Deng, Wei; Zhang, Bing E-mail: zhang@physics.unlv.edu

    2014-03-10

    If a small fraction of fast radio bursts (FRBs) are associated with gamma-ray bursts (GRBs), as recently suggested by Zhang, the combination of redshift measurements of GRBs and dispersion measure (DM) measurements of FRBs opens a new window to study cosmology. At z < 2 where the universe is essentially fully ionized, detections of FRB/GRB pairs can give an independent measurement of the intergalactic medium portion of the baryon mass fraction, Ω {sub b} f {sub IGM}, of the universe. If a good sample of FRB/GRB associations are discovered at higher redshifts, the free electron column density history can be mapped, which can be used to probe the reionization history of both hydrogen and helium in the universe. We apply our formulation to GRBs 101011A and 100704A that each might have an associated FRB, and constrained Ω {sub b} f {sub IGM} to be consistent with the value derived from other methods. The methodology developed here is also applicable, if the redshifts of FRBs not associated with GRBs can be measured by other means.

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

    PubMed Central

    Thow, Anne Marie; Hawkes, Corinna

    2009-01-01

    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 that preventive health

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

    PubMed

    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 < 0.0001). Norovirus was detected in a faecal specimen. Although no pathogen was identified during the environmental investigation, the source oyster lease had been closed just prior to harvesting due to sewage contamination. Australian 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

  18. The late maintenance of hippocampal LTP: requirements, phases, 'synaptic tagging', 'late-associativity' and implications.

    PubMed

    Reymann, Klaus G; Frey, Julietta U

    2007-01-01

    Our review focuses on the mechanisms which enable the late maintenance of hippocampal long-term potentiation (LTP; >3h), a phenomenon which is thought to underlie prolonged memory. About 20 years ago we showed for the first time that the maintenance of LTP - like memory storage--depends on intact protein synthesis and thus, consists of at least two temporal phases. Here we concentrate on mechanisms required for the induction of the transient early-LTP and of the protein synthesis-dependent late-LTP. Our group has shown that the induction of late-LTP requires the associative activation of heterosynaptic inputs, i.e. the synergistic activation of glutamatergic and modulatory, reinforcing inputs within specific, effective time windows. The induction of late-LTP is characterized by novel, late-associative properties such as 'synaptic tagging' and 'late-associative reinforcement'. Both phenomena require the associative setting of synaptic tags as well as the availability of plasticity-related proteins (PRPs) and they are restricted to functional dendritic compartments, in general. 'Synaptic tagging' guarantees input specificity and thus the specific processing of afferent signals for the establishment of late-LTP. 'Late-associative reinforcement' describes a process where early-LTP by the co-activation of modulatory inputs can be transformed into late-LTP in activated synapses where a tag is set. Recent evidence from behavioral experiments, which studied processes of emotional and cognitive reinforcement of LTP, point to the physiological relevance of the above mechanisms during cellular and system's memory formation. PMID:16919684

  19. Association of heterotrophic bacteria with aggregated Arthrospira platensis exopolysaccharides: implications in the induction of axenic cultures.

    PubMed

    Shiraishi, Hideaki

    2015-01-01

    Inducing an axenic culture of the edible cyanobacterium Arthrospira (Spirulina) platensis using differential filtration alone is never successful; thus, it has been thought that, in non-axenic cultures, a portion of contaminating bacteria is strongly associated with Arthrospira cells. However, examination of the behavior of these bacteria during filtration revealed that they were not associated with Arthrospira cells but with aggregates of exopolysaccharides present in the medium away from the Arthrospira cells. Based on this finding, a rapid and reliable method for preparing axenic trichomes of A. platensis was established. After verifying the axenicity of the resulting trichomes on enriched agar plates, they were individually transferred to fresh sterile medium using a handmade tool, a microtrowel, to produce axenic cultures. With this technique, axenic cultures of various A. platensis strains were successfully produced. The technique described in this study is potentially applicable to a wider range of filamentous cyanobacteria. PMID:25333502

  20. Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications

    PubMed Central

    Tsiodras, Sotirios; Mantzoros, Christos

    2006-01-01

    Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients. PMID:17183414

  1. Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management

    PubMed Central

    Shinagare, Atul B.; Krajewski, Katherine M.; Pyo, Junhee; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.

    2015-01-01

    Objective 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. Materials and Methods 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. Results 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. Conclusion Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management. PMID:25741192

  2. The health implications of wastewater reuse in vegetable irrigation: a case study from Malamulele, South Africa.

    PubMed

    Gumbo, Jabulani Ray; Malaka, Eric Mathwalibona; Odiyo, John O; Nare, Lerato

    2010-06-01

    Malamulele is located in an arid region where small-scale irrigation with wastewater is rife. A study was conducted to investigate the health implications of wastewater reuse in vegetable irrigation. Results showed that there are potential health hazards associated with this practice. The wastewater contained 103 helminth eggs/100 ml and zero helminth eggs for control group; vegetable wash water had 3 helminth eggs/100 ml for the exposed group and zero for control. The wastewater results exceeded the WHO guidelines whereas the vegetable wash water counts were within the guideline. Stool samples of farmers and their children indicated common infections with hookworm and Giardia lamblia. Hookworm infections were high (42%) among exposed group in comparison to the control group (27.5%). The farmers were able derive their livelihood from the sale of vegetables. The findings suggest that the health risks of using wastewater are real but can be managed by using the incomes that the farmers earn. PMID:20175010

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

    PubMed

    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

  4. Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development.

    PubMed

    Zhou, Shu-Feng; Wang, Lin-Lin; Di, Yuan Ming; Xue, Charlie Changli; Duan, Wei; Li, Chun Guang; Li, Yong

    2008-01-01

    associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. Drug targeting of these transporters to overcome MRP/ABCC-mediated multidrug resistance may play a role in cancer chemotherapy. Most MRP/ABCC transporters are subject to inhibition by a variety of compounds. Based on currently available preclinical and limited clinical data, it can be expected that modulation of MRP members may represent a useful approach in the management of anticancer and antimicrobial drug resistance and possibly of inflammatory diseases and other diseases. A better understanding of their substrates and inhibitors has important implications in development of drugs for treatment of cancer and inflammation. PMID:18691054

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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

  7. Functional connectivity associated with acoustic stability during vowel production: implications for vocal-motor control.

    PubMed

    Sidtis, John J

    2015-03-01

    Vowels provide the acoustic foundation of communication through speech and song, but little is known about how the brain orchestrates their production. Positron emission tomography was used to study regional cerebral blood flow (rCBF) during sustained production of the vowel /a/. Acoustic and blood flow data from 13, normal, right-handed, native speakers of American English were analyzed to identify CBF patterns that predicted the stability of the first and second formants of this vowel. Formants are bands of resonance frequencies that provide vowel identity and contribute to voice quality. The results indicated that formant stability was directly associated with blood flow increases and decreases in both left- and right-sided brain regions. Secondary brain regions (those associated with the regions predicting formant stability) were more likely to have an indirect negative relationship with first formant variability, but an indirect positive relationship with second formant variability. These results are not definitive maps of vowel production, but they do suggest that the level of motor control necessary to produce stable vowels is reflected in the complexity of an underlying neural system. These results also extend a systems approach to functional image analysis, previously applied to normal and ataxic speech rate that is solely based on identifying patterns of brain activity associated with specific performance measures. Understanding the complex relationships between multiple brain regions and the acoustic characteristics of vocal stability may provide insight into the pathophysiology of the dysarthrias, vocal disorders, and other speech changes in neurological and psychiatric disorders. PMID:25295385

  8. Studying Risk Factors Associated with Human Leptospirosis

    PubMed Central

    Kamath, Ramachandra; Swain, Subhashisa; Pattanshetty, Sanjay; Nair, N Sreekumaran

    2014-01-01

    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 considered as

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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

  11. Factors associated with early growth in Egyptian infants: implications for addressing the dual burden of malnutrition.

    PubMed

    Kavle, Justine A; Flax, Valerie L; Abdelmegeid, Ali; Salah, Farouk; Hafez, Seham; Ramzy, Magda; Hamed, Doaa; Saleh, Gulsen; Galloway, Rae

    2016-01-01

    Optimal nutrition is critical to the attainment of healthy growth, human capital and sustainable development. In Egypt, infants and young children face overlapping forms of malnutrition, including micronutrient deficiencies, stunting and overweight. Yet, in this setting, little is known about the factors associated with growth during the first year of life. A rise in stunting in Lower Egypt from 2005 to 2008 prompted this implementation research study, which followed a longitudinal cohort of infants from birth to 1 year of age within the context of a USAID-funded maternal and child health integrated programme. We sought to determine if growth patterns and factors related to early growth differed in Lower and Upper Egypt, and examined the relationship between weight loss and subsequent stunting at 12 months of age. Growth patterns revealed that length-for-age z-score (LAZ) decreased and weight-for-length z-score (WLZ) increased from 6 to 12 months of age in both regions. One-quarter of infants were stunted and nearly one-third were overweight by 12 months of age in lower Egypt. Minimum dietary diversity was significantly associated with WLZ in Lower Egypt (β = 0.22, P < 0.05), but not in Upper Egypt. Diarrhoea, fever and programme exposure were not associated with any growth outcome. Weight loss during any period was associated with a twofold likelihood of stunting at 12 months in Lower Egypt, but not Upper Egypt. In countries, like Egypt, facing the nutrition transition, infant and young child nutrition programmes need to address both stunting and overweight through improving dietary quality and reducing reliance on energy-dense foods. PMID:26373408

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

    PubMed Central

    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

  13. Family-based association analysis implicates IL-4 in susceptibility to Kawasaki disease

    PubMed Central

    Burns, JC; Shimizu, C; Shike, H; Newburger, JW; Sundel, RP; Baker, AL; Matsubara, T; Ishikawa, Y; Brophy, VA; Cheng, S; Grow, MA; Steiner, LL; Kono, N; Cantor, RM

    2010-01-01

    Several compelling lines of evidence suggest an important influence of genetic variation in susceptibility to Kawasaki disease (KD), an acute vasculitis that causes coronary artery aneurysms in children. We performed a family-based genotyping study to test for association between KD and 58 genes involved in cardiovascular disease and inflammation. By analysis of a cohort of 209 KD trios using the transmission disequilibrium test, we documented the asymmetric transmission of five alleles including the interleukin-4 (IL-4) C(−589)T allele (P = 0.03). Asymmetric transmission of the IL-4 C(−589)T was replicated in a second, independent cohort of 60 trios (P = 0.05, combined P = 0.002). Haplotypes of alleles in IL-4, colony-stimulating factor 2 (CSF2), IL-13, and transcription factor 7 (TCF7), all located in the interleukin gene cluster on 5q31, were also asymmetrically transmitted. The reported associations of KD with atopic dermatitis and allergy, elevated serum IgE levels, eosinophilia, and increased circulating numbers of monocyte/macrophages expressing the low-affinity IgE receptor (FCεR2) may be related to effects of IL-4. Thus, the largest family-based genotyping study of KD patients to date suggests that genetic variation in the IL-4 gene, or regions linked to IL-4, plays an important role in KD pathogenesis and disease susceptibility. PMID:15889128

  14. Neuroanatomical association of hypothalamic HSD2-containing neurons with ERα, catecholamines, or oxytocin: implications for feeding?

    PubMed Central

    Askew, Maegan L.; Muckelrath, Halie D.; Johnston, Jonathon R.; Curtis, Kathleen S.

    2015-01-01

    This study used immunohistochemical methods to investigate the possibility that hypothalamic neurons that contain 11-β-hydroxysteroid dehydrogenase type 2 (HSD2) are involved in the control of feeding by rats via neuroanatomical associations with the α subtype of estrogen receptor (ERα), catecholamines, and/or oxytocin (OT). An aggregate of HSD2-containing neurons is located laterally in the hypothalamus, and the numbers of these neurons were greatly increased by estradiol treatment in ovariectomized (OVX) rats compared to numbers in male rats and in OVX rats that were not given estradiol. However, HSD2-containing neurons were anatomically segregated from ERα-containing neurons in the Ventromedial Hypothalamus and the Arcuate Nucleus. There was an absence of OT-immunolabeled fibers in the area of HSD2-labeled neurons. Taken together, these findings provide no support for direct associations between hypothalamic HSD2 and ERα or OT neurons in the control of feeding. In contrast, there was catecholamine-fiber labeling in the area of HSD2-labeled neurons, and these fibers occasionally were in close apposition to HSD2-labeled neurons. Therefore, we cannot rule out interactions between HSD2 and catecholamines in the control of feeding; however, given the relative sparseness of the appositions, any such interaction would appear to be modest. Thus, these studies do not conclusively identify a neuroanatomical substrate by which HSD2-containing neurons in the hypothalamus may alter feeding, and leave the functional role of hypothalamic HSD2-containing neurons subject to further investigation. PMID:26124709

  15. A Genome-Wide Association Study Reveals Genes Associated with Fusarium Ear Rot Resistance in a Maize Core Diversity Panel

    PubMed Central

    Zila, Charles T.; Samayoa, L. Fernando; Santiago, Rogelio; Butrón, Ana; Holland, James B.

    2013-01-01

    Fusarium ear rot is a common disease of maize that affects food and feed quality globally. Resistance to the disease is highly quantitative, and maize breeders have difficulty incorporating polygenic resistance alleles from unadapted donor sources into elite breeding populations without having a negative impact on agronomic performance. Identification of specific allele variants contributing to improved resistance may be useful to breeders by allowing selection of resistance alleles in coupling phase linkage with favorable agronomic characteristics. We report the results of a genome-wide association study to detect allele variants associated with increased resistance to Fusarium ear rot in a maize core diversity panel of 267 inbred lines evaluated in two sets of environments. We performed association tests with 47,445 single-nucleotide polymorphisms (SNPs) while controlling for background genomic relationships with a mixed model and identified three marker loci significantly associated with disease resistance in at least one subset of environments. Each associated SNP locus had relatively small additive effects on disease resistance (±1.1% on a 0–100% scale), but nevertheless were associated with 3 to 12% of the genotypic variation within or across environment subsets. Two of three identified SNPs colocalized with genes that have been implicated with programmed cell death. An analysis of associated allele frequencies within the major maize subpopulations revealed enrichment for resistance alleles in the tropical/subtropical and popcorn subpopulations compared with other temperate breeding pools. PMID:24048647

  16. A genome-wide association study reveals genes associated with fusarium ear rot resistance in a maize core diversity panel.

    PubMed

    Zila, Charles T; Samayoa, L Fernando; Santiago, Rogelio; Butrón, Ana; Holland, James B

    2013-11-01

    Fusarium ear rot is a common disease of maize that affects food and feed quality globally. Resistance to the disease is highly quantitative, and maize breeders have difficulty incorporating polygenic resistance alleles from unadapted donor sources into elite breeding populations without having a negative impact on agronomic performance. Identification of specific allele variants contributing to improved resistance may be useful to breeders by allowing selection of resistance alleles in coupling phase linkage with favorable agronomic characteristics. We report the results of a genome-wide association study to detect allele variants associated with increased resistance to Fusarium ear rot in a maize core diversity panel of 267 inbred lines evaluated in two sets of environments. We performed association tests with 47,445 single-nucleotide polymorphisms (SNPs) while controlling for background genomic relationships with a mixed model and identified three marker loci significantly associated with disease resistance in at least one subset of environments. Each associated SNP locus had relatively small additive effects on disease resistance (±1.1% on a 0-100% scale), but nevertheless were associated with 3 to 12% of the genotypic variation within or across environment subsets. Two of three identified SNPs colocalized with genes that have been implicated with programmed cell death. An analysis of associated allele frequencies within the major maize subpopulations revealed enrichment for resistance alleles in the tropical/subtropical and popcorn subpopulations compared with other temperate breeding pools. PMID:24048647

  17. Rapid HPLC screening method for contaminants found in implicated L-tryptophan associated with eosinophilia myalgia syndrome and adulterated rapeseed oil associated with toxic oil syndrome.

    PubMed

    Williamson, B L; Tomlinson, A J; Hurth, K M; Posada de la Paz, M; Gleich, G J; Naylor, S

    1998-01-01

    In 1981 a massive food-borne epidemic, termed the toxic oil syndrome (TOS), occurred in Spain. Eight years later a closely related disease, the eosinophilia myalgia syndrome (EMS), was reported in the USA with many additional cases being reported worldwide. Although EMS was linked to the ingestion of contaminated L-tryptophan and TOS to aniline denatured rapeseed oil, the etiological agent(s) responsible for both diseases remains unknown. However, contaminants in both the oil and the dietary supplement are believed to have triggered these diseases, and there has been much speculation that a common contaminant may have caused both epidemics. In this report, methods for the facile preparation and HPLC analysis of EMS-implicated L-tryptophan and adulterated rapeseed oil samples associated with TOS are described which allow a direct comparison between the contaminants of both foodstuffs. A combination of solvent and solid phase extraction methods are demonstrated along with the application of C18 reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with on-line UV and MS detection. These methods have allowed us to determine for the first time, based upon this work, that there are no detectable common contaminants that possess a UV response, between EMS implicated L-tryptophan and TOS implicated rapeseed oil samples. PMID:9787895

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

    PubMed Central

    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 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 μg/kg) or saline and were tested on the attentional set-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 threefold 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. PMID:24959140

  19. Genome-wide association studies (GWAS) and their importance in asthma.

    PubMed

    García-Sánchez, A; Isidoro-García, M; García-Solaesa, V; Sanz, C; Hernández-Hernández, L; Padrón-Morales, J; Lorente-Toledano, F; Dávila, I

    2015-01-01

    Asthma is a complex disease determined by the interaction of different genes and environmental factors. The first genetic investigations in asthma were candidate gene association studies and linkage studies. In recent years research has focused on association studies that scan the entire genome without any prior conditioning hypothesis: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1). None of these genes would have been selected in a classical genetic association study since it was not known they could be implicated in asthma. To date, a number of GWAS studies in asthma have been made, with the identification of about 1000 candidate genes. Coordination of the different research groups in international consortiums and the application of new technologies such as new generation sequencing will help discover new implicated genes and improve our understanding of the molecular mechanisms underlying the disease. PMID:25433770

  20. Pedagogical implications of approaches to study in distance learning: developing models through qualitative and quantitative analysis.

    PubMed

    Carnwell, R

    2000-05-01

    The need for flexibility in the delivery of nurse education has been identified by various initiatives including: widening the entry gate; continuous professional development; and the specialist practitioner. Access to degree level programmes is creating the need to acquire academic credit through flexible learning. The aim of this study was to further develop relationships between the need for guidance, materials design and learning styles and strategies and how these impact upon the construction of meaning. The study is based on interviews of 20 female community nurses purposively selected from the 96 respondents who had previously completed a survey questionnaire. The interviews were underpinned by theories relating to learning styles and approaches to study. Of particular concern was how these variables are mediated by student context, personal factors and materials design, to influence the need for support and guidance. The interview transcripts were first analysed using open and axial coding. Three approaches to study emerged from the data - systematic waders, speedy-focusers and global dippers - which were linked to other concepts and categories. Categories were then assigned numerical codes and subjected to logistical regression analysis. The attributes of the three approaches to study, arising from both qualitative and quantitative analysis, are explained in detail. The pedagogical implications of the three approaches to study are explained by their predicted relationships to other variables, such as support and guidance, organization of study, materials design and role of the tutor. The global dipper approach is discussed in more detail due to its association with a variety of predictor variables, not associated with the other two approaches to study. A feedback model is then developed to explore the impact of guidance on the global dipper approach. The paper makes recommendations for guidance to students using different approaches to study in distance

  1. Some initial findings and policy implications of the Pathways to Desistance Study

    PubMed Central

    Mulvey, Edward P.; Schubert, Carol A.

    2016-01-01

    Little is known about how adolescents curtail their offending and make positive adjustments to early adulthood. The Pathways to Desistance study follows 1,354 serious adolescent offenders to provide information about these processes. This paper summarizes some initial findings from the study and lays out their potential policy implications. The findings covered include the variability in the sample, the importance of the link between substance use and offending, and the possible implications of institutional care. PMID:27087803

  2. Medicine possession ratio as proxy for adherence to antiepileptic drugs: prevalence, associations, and cost implications

    PubMed Central

    Jacobs, Karen; Julyan, Marlene; Lubbe, Martie S; Burger, Johanita R; Cockeran, Marike

    2016-01-01

    Objective To determine the adherence status to antiepileptic drugs (AEDs) among epilepsy patients; to observe the association between adherence status and age, sex, active ingredient prescribed, treatment period, and number of comorbidities; and to determine the effect of nonadherence on direct medicine treatment cost of AEDs. Methods A retrospective study analyzing medicine claims data obtained from a South African pharmaceutical benefit management company was performed. Patients of all ages (N=19,168), who received more than one prescription for an AED, were observed from 2008 to 2013. The modified medicine possession ratio (MPRm) was used as proxy to determine the adherence status to AED treatment. The MPRm was considered acceptable (adherent) if the calculated value was ≥80%, but ≤110%, whereas an MPRm of <80% (unacceptably low) or >110% (unacceptably high) was considered nonadherent. Direct medicine treatment cost was calculated by summing the medical scheme contribution and patient co-payment associated with each AED prescription. Results Only 55% of AEDs prescribed to 19,168 patients during the study period had an acceptable MPRm. MPRm categories depended on the treatment period (P>0.0001; Cramer’s V=0.208) but were independent of sex (P<0.182; Cramer’s V=0.009). Age group (P<0.0001; Cramer’s V=0.067), active ingredient (P<0.0001; Cramer’s V=0.071), and number of comor-bidities (P<0.0001; Cramer’s V=0.050) were statistically but not practically significantly associated with MPRm categories. AEDs with an unacceptably high MPRm contributed to 3.74% (US$736,376.23) of the total direct cost of all AEDs included in the study, whereas those with an unacceptably low MPRm amounted to US$3,227,894.85 (16.38%). Conclusion Nonadherence to antiepileptic treatment is a major problem, encompassing ~20% of cost in our study. Adherence, however, is likely to improve with the treatment period. Further research is needed to determine the factors influencing

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

    PubMed

    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

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

    PubMed Central

    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

  5. A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy

    PubMed Central

    Villard, Eric; Perret, Claire; Gary, Françoise; Proust, Carole; Dilanian, Gilles; Hengstenberg, Christian; Ruppert, Volker; Arbustini, Eloisa; Wichter, Thomas; Germain, Marine; Dubourg, Olivier; Tavazzi, Luigi; Aumont, Marie-Claude; DeGroote, Pascal; Fauchier, Laurent; Trochu, Jean-Noël; Gibelin, Pierre; Aupetit, Jean-François; Stark, Klaus; Erdmann, Jeanette; Hetzer, Roland; Roberts, Angharad M.; Barton, Paul J.R.; Regitz-Zagrosek, Vera; Aslam, Uzma; Duboscq-Bidot, Laëtitia; Meyborg, Matthias; Maisch, Bernhard; Madeira, Hugo; Waldenström, Anders; Galve, Enrique; Cleland, John G.; Dorent, Richard; Roizes, Gerard; Zeller, Tanja; Blankenberg, Stefan; Goodall, Alison H.; Cook, Stuart; Tregouet, David A.; Tiret, Laurence; Isnard, Richard; Komajda, Michel; Charron, Philippe; Cambien, François

    2011-01-01

    Aims Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM. Methods and results One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P < 5.0 10−7), and two of them, rs10927875 and rs2234962, were replicated in independent samples (1165 DCM patients and 1302 controls), with P-values of 0.002 and 0.009, respectively. rs10927875 maps to a region on chromosome 1p36.13 which encompasses several genes among which HSPB7 has been formerly suggested to be implicated in DCM. The second identified locus involves rs2234962, a non-synonymous SNP (c.T757C, p. C151R) located within the sequence of BAG3 on chromosome 10q26. To assess whether coding mutations of BAG3 might cause monogenic forms of the disease, we sequenced BAG3 exons in 168 independent index cases diagnosed with familial DCM and identified four truncating and two missense mutations. Each mutation was heterozygous, present in all genotyped relatives affected by the disease and absent in a control group of 347 healthy individuals, strongly suggesting that these mutations are causing the disease. Conclusion This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM. PMID:21459883

  6. Genetic diversity of Escherichia coli isolates in irrigation water and associated sediments: implications for source tracking.

    PubMed

    Lu, Lingeng; Hume, Michael E; Sternes, Keith L; Pillai, Suresh D

    2004-11-01

    Identifying the sources of fecal contaminants in surface water bodies such as rivers and lakes is of significant importance for environmental quality, food safety and regulatory purposes. Current DNA library-based source tracking approaches rely on the comparison of the genetic relatedness among the fecal contaminants. The objective of this study was to determine the genetic relatedness of Escherichia coli isolated from irrigation water and associated sediments using pulse field gel electrophoresis (PFGE) and to evaluate the genetic stability of the E. coli PFGE patterns. The isolates were obtained over a 4-month period from specific locations within irrigation canals and sediments associated with the Rio Grande River along the Texas-Mexico border. Fifty E. coli isolates were genotyped using PFGE. Different E. coli genotypes were identified among samples collected in 11 different locations. Some isolates obtained over successive months showed similar genotypic patterns. In the laboratory experiment, the PFGE pattern of one E. coli strain changed during survival in irrigation water. The genetic relatedness of this strain changed from >95% to <83% over 8-week survival. These results imply that PFGE is of such extreme resolution that it may be a challenging task to rely solely on a PFGE-based source tracking DNA fingerprint library for large watersheds. PMID:15380980

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

    PubMed

    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 (P<0.0001), especially among those obese 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, P<0.0001; DBP: regression coefficient estimate=-0.028, P<0.0001). Multiple logistic regression showed that calcium intake was negatively associated with the probability of hypertension (odds ratio (OR)=0.81, 95% confidence interval (CI): 0.74-0.87, P<0.0001). In stratified analysis, calcium intake in youngest adults (age 20-44 years) had the lowest likelihood of hypertension (OR=0.77, 95% CI: 0.64-0.93, P<0.0001), the inverse relationship between calcium intake and probability of hypertension was stronger among females (OR: 0.68, 95% CI: 0.55-0.84, P<0.0001), when compared with the whole

  8. Public Stigma Associated With Psychosis Risk Syndrome in a College Population: Implications for Peer Intervention

    PubMed Central

    Yang, Lawrence H.; Anglin, Deidre M.; Wonpat-Borja, Ahtoy J.; Opler, Mark G.; Greenspoon, Michelle; Corcoran, Cheryl M.

    2013-01-01

    Objectives This study compared stigma associated with the psychosis risk label and diagnostic labels for nonpsychotic and psychotic mental disorders among young adult peers. Methods Urban college respondents (N=153) read an experimental vignette describing a young adult experiencing prodromal symptoms who was randomly assigned a diagnostic label (major depression, generalized anxiety disorder, schizophrenia, or psychosis risk with and without accurate information about the psychosis risk label) and answered questions about stigma toward the individual in the vignette. Results Compared with labels for non-psychotic disorders, schizophrenia elicited more negative stereotyping and the at-risk label invoked greater social distance and less willingness to help. Any increased social distance appeared to be reduced by accurate information about the at-risk state. No differences in stigma were found for the psychosis risk and schizophrenia labels. Conclusions The psychosis risk label alone appeared to evoke greater status loss and discrimination. Accurate information may minimize some stigmatizing attitudes among college peers. PMID:23450386

  9. Association between maternal age and pregnancy outcome: implications for the Pakistani society.

    PubMed

    Hanif, Hafsa Muhammad

    2011-03-01

    Maternal age at conception has long been demonstrated to have a significant correlation with pregnancy outcome and maternal health. Classically, very young (<20 years old) and old (= or >35 years) women have been classified as high-risk categories for child bearing. Recently, career, education, financial, and other goals have coerced women to delay childbearing all over the world. This trend is also becoming apparent in Pakistan, especially in the upper middle class, wealthy and educated women, as they become increasingly empowered. This review presents the association between maternal age and pregnancy outcome, particularly in the context of statistics of Pakistan, and its possible repercussions. On one hand, physicians need to develop effective counseling strategies for their patients in this regard, and on the other, more studies are required to ascertain the attitudes of Pakistani women, particularly those belonging to the upper and middle classes, regarding delayed childbearing, that can aid physicians in formulating effective counseling strategies. PMID:21465960

  10. Fracturing of doleritic intrusions and associated contact zones: Implications for fluid flow in volcanic basins

    NASA Astrophysics Data System (ADS)

    Senger, Kim; Buckley, Simon J.; Chevallier, Luc; Fagereng, Åke; Galland, Olivier; Kurz, Tobias H.; Ogata, Kei; Planke, Sverre; Tveranger, Jan

    2015-02-01

    Igneous intrusions act as both carriers and barriers to subsurface fluid flow and are therefore expected to significantly influence the distribution and migration of groundwater and hydrocarbons in volcanic basins. Given the low matrix permeability of igneous rocks, the effective permeability in- and around intrusions is intimately linked to the characteristics of their associated fracture networks. Natural fracturing is caused by numerous processes including magma cooling, thermal contraction, magma emplacement and mechanical disturbance of the host rock. Fracturing may be locally enhanced along intrusion-host rock interfaces, at dyke-sill junctions, or at the base of curving sills, thereby potentially enhancing permeability associated with these features. In order to improve our understanding of fractures associated with intrusive bodies emplaced in sedimentary host rocks, we have investigated a series of outcrops from the Karoo Basin of the Eastern Cape province of South Africa, where the siliciclastic Burgersdorp Formation has been intruded by various intrusions (thin dykes, mid-sized sheet intrusions and thick sills) belonging to the Karoo dolerite. We present a quantified analysis of fracturing in- and around these igneous intrusions based on five outcrops at three individual study sites, utilizing a combination of field data, high-resolution lidar virtual outcrop models and image processing. Our results show a significant difference between the three sites in terms of fracture orientation. The observed differences can be attributed to contrasting intrusion geometries, outcrop geometry (for lidar data) and tectonic setting. Two main fracture sets were identified in the dolerite at two of the sites, oriented parallel and perpendicular to the contact respectively. Fracture spacing was consistent between the three sites, and exhibits a higher degree of variation in the dolerites compared to the host rock. At one of the study sites, fracture frequency in the

  11. Combining genetic association study designs: a GWAS case study.

    PubMed

    Estus, Janice L; Fardo, David W

    2013-01-01

    Genome-wide association studies (GWAS) explore the relationship between genome variability and disease susceptibility with either population- or family-based data. Here, we have evaluated the utility of combining population- and family-based statistical association tests and have proposed a method for reducing the burden of multiple testing. Unrelated singleton and parent-offspring trio cases and controls from the Genetics of Kidneys in Diabetes (GoKinD) study were analyzed for genetic association with diabetic nephropathy (DN) in type 1 diabetics (T1D). The Cochran-Armitage test for trend and the family-based association test were employed using either unrelated cases and controls or trios, respectively. In addition to combining single nucleotide polymorphism (SNP) p-values across these tests via Fisher's method, we employed a novel screening approach to rank SNPs based on conditional power for more efficient testing. Using either the population-based or family-based subset alone predictably limited resolution to detect DN SNPs. For 384,197 SNPs passing quality control (QC), none achieved strict genome-wide significance (1.4 × 10(-7)) using 1171 singletons (577/594 cases/controls) or 1738 pooled singletons and offspring probands (841/897). Similarly, none of the 352,004 SNPs passing QC in 567 family trios (264/303 case/control proband trios) reached genome-wide significance. Testing the top 10 SNPs ranked using aggregated conditional power resulted in two SNPs reaching genome-wide significance, rs11645147 on chromosome 16 (p = 1.74 × 10(-4) < 0.05/10 = 0.005) and rs7866522 on chromosome 9 (p = 0.0033). Efficient usage of mixed designs incorporating both unrelated and family-based data may help to uncover associations otherwise difficult to detect in the presence of massive multiple testing corrections. Capitalizing on the strengths of both types while using screening approaches may be useful especially in light of large-scale, next-generation sequencing and rare

  12. Topographical and geological amplification: case studies and engineering implications

    USGS Publications Warehouse

    Celebi, M.

    1991-01-01

    Topographical and geological amplification that occurred during past earthquakes are quantified using spectral ratios of recorded motions. Several cases are presented from the 1985 Chilean and Mexican earthquakes as well as the 1983 Coalinga (California) and 1987 Supersition Hills (California) earthquake. The strong motions recorded in Mexico City during the 1985 Michoacan earthquake are supplemented by ambient motions recorded within Mexico City to quantify the now well known resonating frequencies of the Mexico City lakebed. Topographical amplification in Canal Beagle (Chile), Coalinga and Superstition Hills (California) are quantified using the ratios derived from the aftershocks following the earthquakes. A special dense array was deployed to record the aftershocks in each case. The implications of both geological and topographical amplification are discussed in light of current code provisions. The observed geological amplifications has already influenced the code provisions. Suggestions are made to the effect that the codes should include further provisions to take the amplification due to topography into account. ?? 1991.

  13. Association studies in late onset sporadic Alzheimer`s disease

    SciTech Connect

    Goate, A.M.; Lendon, C.; Talbot, C.

    1994-09-01

    Alzheimer`s disease (AD) is characterized by an adult onset progressive dementia and the presence of numerous plaques and tangles within the brain at autopsy. The senile plaques are composed of a proteinaceous core surrounded by dystrophic neurites. The major protein component of the core is {beta}-amyloid but antibodies to many other proteins bind to senile plaques, e.g., antibodies to apolioprotein E (ApoE) and to {alpha}1-antichymotrypsin (AACT). Genetic studies have implicated mutations within the {beta}-amyloid precursor protein gene as the cause of AD in a small number of early onset AD families. More recently, assocition studies in late onset AD have demonstrated a positive association between ApoE-{epsilon}4 and AD. We report evidence for a negative association between ApoE-{epsilon}2 and AD in a large sample of sporadic late onset AD cases and matched controls supporting the role of ApoE in the etiology of AD. Ninety-three patients with sporadic AD (average age = 75 years, s.d. 8 yrs.) and 67 normal controls from the same ethnic background (age = 77 yrs., s.d. 10 yrs.) were recruited through the patient registry of the Washington University Alzheimer`s Disease Research Center. We found a statistically significant increase in ApoE-{epsilon}4 allele frequency in patients compared with controls ({chi}{sup 2}=7.75, 1 d.f., one tailed p=0.0027) and a significant decrease in {epsilon}2 allele frequency (Fisher`s exact test, one tailed p=0.0048), whereas the decreased frequency of {epsilon}3 in the patient groups was not statistically significant. Allele {epsilon}2 conferred a strong protective effect in our sample, with the odds ratio for AD for subjects possessing this allele being 0.08 (85% confidence interval 0.01-0.69). Similar studies using a polymorphism within the AACT gene showed no association with alleles at this locus in the entire AD sample or in AD cases homozygous for ApoE-{epsilon}3.

  14. A new genome scan for primary nonsyndromic vesicoureteric reflux emphasizes high genetic heterogeneity and shows linkage and association with various genes already implicated in urinary tract development

    PubMed Central

    Darlow, J M; Dobson, M G; Darlay, R; Molony, C M; Hunziker, M; Green, A J; Cordell, H J; Puri, P; Barton, D E

    2014-01-01

    Primary vesicoureteric reflux (VUR), the retrograde flow of urine from the bladder toward the kidneys, results from a developmental anomaly of the vesicoureteric valve mechanism, and is often associated with other urinary tract anomalies. It is the most common urological problem in children, with an estimated prevalence of 1–2%, and is a major cause of hypertension in childhood and of renal failure in childhood or adult life. We present the results of a genetic linkage and association scan using 900,000 markers. Our linkage results show a large number of suggestive linkage peaks, with different results in two groups of families, suggesting that VUR is even more genetically heterogeneous than previously imagined. The only marker achieving P < 0.02 for linkage in both groups of families is 270 kb from EMX2. In three sibships, we found recessive linkage to KHDRBS3, previously reported in a Somali family. In another family we discovered sex-reversal associated with VUR, implicating PRKX, for which there was weak support for dominant linkage in the overall data set. Several other candidate genes are suggested by our linkage or association results, and four of our linkage peaks are within copy-number variants recently found to be associated with renal hypodysplasia. Undoubtedly there are many genes related to VUR. Our study gives support to some loci suggested by earlier studies as well as suggesting new ones, and provides numerous indications for further investigations. PMID:24498626

  15. Rho-associated kinase signalling and the cancer microenvironment: novel biological implications and therapeutic opportunities.

    PubMed

    Chin, Venessa T; Nagrial, Adnan M; Chou, Angela; Biankin, Andrew V; Gill, Anthony J; Timpson, Paul; Pajic, Marina

    2015-01-01

    The Rho/ROCK pathway is involved in numerous pivotal cellular processes that have made it an area of intense study in cancer medicine, however, Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are yet to make an appearance in the clinical cancer setting. Their performance as an anti-cancer therapy has been varied in pre-clinical studies, however, they have been shown to be effective vasodilators in the treatment of hypertension and post-ischaemic stroke vasospasm. This review addresses the various roles the Rho/ROCK pathway plays in angiogenesis, tumour vascular tone and reciprocal feedback from the tumour microenvironment and explores the potential utility of ROCK inhibitors as effective vascular normalising agents. ROCK inhibitors may potentially enhance the delivery and efficacy of chemotherapy agents and improve the effectiveness of radiotherapy. As such, repurposing of these agents as adjuncts to standard treatments may significantly improve outcomes for patients with cancer. A deeper understanding of the controlled and dynamic regulation of the key components of the Rho pathway may lead to effective use of the Rho/ROCK inhibitors in the clinical management of cancer. PMID:26507949

  16. Incidence and clinical implication of nosocomial infections associated with implantable biomaterials – catheters, ventilator-associated pneumonia, urinary tract infections

    PubMed Central

    Guggenbichler, Josef Peter; Assadian, Ojan; Boeswald, Michael; Kramer, Axel

    2012-01-01

    Health care associated infections, the fourth leading cause of disease in industrialised countries, are a major health issue. One part of this condition is based on the increasing insertion and implantation of prosthetic medical devices, since presence of a foreign body significantly reduces the number of bacteria required to produce infection. The most significant hospital-acquired infections, based on frequency and potential severity, are those related to procedures e.g. surgical site infections and medical devices, including urinary tract infection in catheterized patients, pneumonia in patients intubated on a ventilator and bacteraemia related to intravascular catheter use. At least half of all cases of nosocomial infections are associated with medical devices. Modern medical and surgical practices have increasingly utilized implantable medical devices of various kinds. Such devices may be utilized only short-time or intermittently, for months, years or permanently. They improve the therapeutic outcome, save human lives and greatly enhance the quality of life of these patients. However, plastic devices are easily colonized with bacteria and fungi, able to be colonized by microorganisms at a rate of up to 0.5 cm per hour. A thick biofilm is formed within 24 hours on the entire surface of these plastic devices once inoculated even with a small initial number of bacteria. The aim of the present work is to review the current literature on causes, frequency and preventive measures against infections associated with intravascular devices, catheter-related urinary tract infection, ventilator-associated infection, and infections of other implantable medical devices. Raising awareness for infection associated with implanted medical devices, teaching and training skills of staff, and establishment of surveillance systems monitoring device-related infection seem to be the principal strategies used to achieve reduction and prevention of such infections. The intelligent use

  17. Changes in interconnected pathways implicating microRNAs are associated with the activity of apocynin in attenuating myocardial fibrogenesis.

    PubMed

    Yang, Qinbo; Cui, Jingang; Wang, Peiwei; Du, Xiaoye; Wang, Wenjian; Zhang, Teng; Chen, Yu

    2016-08-01

    Myocardial fibrosis is the endpoint pathology common to many cardiovascular disorders. We have previously shown that apocynin (APO), a naturally occurring NADPH oxidase inhibitor, significantly prevents the development of isoproterenol (ISO)-induced myocardial injury and fibrogenesis. The current study investigated the changes in microRNAs (miRNAs) and their potential implication in the cardioprotective effects of APO. Integrative analyses of whole-genome miRNA and gene expression profiles were first performed, revealing that altered expression of miRNAs likely contributed to dysregulated expression of genes associated with multiple interconnected fibrogenic signaling pathways. Importantly, APO treatment exhibited a broad impact on these signaling pathways, which could in part be mediated through miRNA-mediated gene expression regulation. The expression of differentially expressed miRNAs was further validated by real-time PCR analyses. Consistent with the data from miRNA array, compared to that from vehicle-treated normal controls, significantly decreased expression of miR-10b, miR-29c*, miR-30c-1*, miR-30e*, miR-148b, miR-181d, miR-218 and miR-3107* was observed in ISO-challenged vehicle-treated mouse hearts. In contrast, significantly increased expression of these miRNAs was observed in ISO-challenged APO-treated hearts compared to that from ISO-challenged vehicle-treated mice. Moreover, increased expression of miR-21 was observed as a result of ISO administration, which was significantly reduced by APO treatment. Altered protein levels of Col1, TIMP1, Rac2 and gp91(phox) were also validated. Lastly, APO treatment was shown to attenuate pre-established myocardial fibrosis induced by ISO. The results therefore demonstrated for the first time that complex changes in miRNA-mRNA interactome network are associated with the protective effects of APO against ISO-induced myocardial injury and fibrogenesis. PMID:27174579

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

    PubMed Central

    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

  19. Genome-wide Association Study of Neurocognitive Impairment and Dementia in HIV-Infected Adults

    PubMed Central

    Levine, Andrew J.; Service, Susan; Miller, Eric N.; Reynolds, Sandra M.; Singer, Elyse J.; Shapshak, Paul; Martin, Eileen M.; Sacktor, Ned; Becker, James T.; Jacobson, Lisa P.; Thompson, Paul; Freimer, Nelson

    2012-01-01

    Background The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. Candidate gene studies have implicated genetic susceptibility loci within immune-related genes; however, these have not been reliably validated. Here we employed genome-wide association (GWA) methods to discover novel genetic susceptibility loci associated with HAND, and validate susceptibility loci implicated in prior candidate gene studies. Methods Data from 1287 participants enrolled in the Multicenter AIDS Cohort Study between 1985 and 2010 were used. Genotyping was conducted with Illumina 1M, 1MDuo, or 550K platform. Linear mixed models determined subject-specific slopes for change over time in processing speed and executive functioning, considering all visits including baseline and the most recent study visit. Covariates modeled as fixed effects included: time since the first visit, depression severity, nadir CD4+ T-cell count, Hepatitis C co-infection, substance use, and antiretroviral medication regimen. Prevalence of HIV-associated dementia (HAD) and neurocognitive impairment (NCI) was also examined as neurocognitive phenotypes in a case-control analysis. Results No genetic susceptibility loci were associated with decline in processing speed or executive functioning among almost 2.5 million single nucleotide polymorphisms (SNPs) directly genotyped or imputed. No association between the SNPs and HAD or NCI were found. Previously reported associations between specific genetic susceptibility loci, HIV-associated neurocognitive impairment and HAD were not validated. Conclusions In this first GWAS of HAND, no novel or previously identified genetic susceptibility loci were associated with any of the phenotypes examined. Due to the relatively small sample size, future collaborative efforts that incorporate this dataset may still yield important findings. PMID:22628157

  20. Marker imputation in barley association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Association mapping requires higher marker density than linkage mapping, potentially leading to more missing marker data and to higher genotyping costs. In human genetics, methods exist to impute missing marker data and whole markers that were typed in a reference panel but not in the experimental d...

  1. ASAP: Accelerated Study in Associate Programs

    ERIC Educational Resources Information Center

    MDRC, 2015

    2015-01-01

    Graduation rates at community colleges are low, especially for students who need developmental (remedial) courses to build their basic skills. ASAP is a comprehensive program at the City University of New York designed to help more associate degree-seeking students graduate and help them graduate more quickly. Using a random assignment research…

  2. Bone morphogenetic proteins in tumour associated angiogenesis and implication in cancer therapies.

    PubMed

    Ye, Lin; Jiang, Wen G

    2016-10-01

    Bone morphogenetic protein (BMP) belongs to transforming growth factor-β superfamily. To date, more than 20 BMPs have been identified in humans. BMPs play a critical role in embryonic and postnatal development, and also in maintaining homeostasis in different organs and tissues by regulating cell differentiation, proliferation, survival and motility. They play important roles in the development and progression of certain malignancies, including prostate cancer, breast cancer, lung cancer, etc. Recently, more evidence shows that BMPs are also involved in tumour associated angiogenesis. For example BMP can either directly regulate the functions of vascular endothelial cells or indirectly influence the angiogenesis via regulation of angiogenic factors, such as vascular endothelial growth factor (VEGF). Such crosstalk can also be reflected in the interaction with other angiogenic factors, like hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF). All these factors are involved in the orchestration of the angiogenic process during tumour development and progression. Review of the relevant studies will provide a comprehensive prospective on current understanding and shed light on the corresponding therapeutic opportunity. PMID:26639195

  3. Satisfaction with Life in Orofacial Pain Disorders: Associations and Theoretical Implications

    PubMed Central

    Boggero, Ian A.; Rojas-Ramirez, Marcia V.; de Leeuw, Reny; Carlson, Charles R.

    2016-01-01

    Aims To test if patients with masticatory myofascial pain, local myalgia, centrally mediated myalgia, disc displacement, capsulitis/synovitis, or continuous neuropathic pain differed in self-reported satisfaction with life. The study also tested if satisfaction with life was similarly predicted by measures of physical, emotional, and social functioning across disorders. Methods Satisfaction with life, fatigue, affective distress, social support, and pain data were extracted from the medical records of 343 patients seeking treatment for chronic orofacial pain. Patients were grouped by primary diagnosis assigned following their initial appointment. Satisfaction with life was compared between disorders, with and without pain intensity entered as a covariate. Disorder-specific linear regression models using physical, emotional, and social predictors of satisfaction with life were computed. Results Patients with centrally mediated myalgia reported significantly lower satisfaction with life than did patients with any of the other five disorders. Inclusion of pain intensity as a covariate weakened but did not eliminate the effect. Satisfaction with life was predicted by measures of physical, emotional, and social functioning, but these associations were not consistent across disorders. Conclusions Results suggest that reduced satisfaction with life in patients with centrally mediated myalgia is not due only to pain intensity. There may be other factors that predispose people to both reduced satisfaction with life and centrally mediated myalgia. Furthermore, the results suggest that satisfaction with life is differentially influenced by physical, emotional, and social functioning in different orofacial pain disorders. PMID:27128473

  4. Environmental degradation: Implications for national security. Study report

    SciTech Connect

    Schlegel, J.D.

    1990-03-30

    As the United States prepares to move into the 21st century, the threat of armed conflict between the United States and the Soviet Union appears to have receded into the realm of the improbable. At the same time, however, a new and perhaps more ominous threat is emerging to challenge the security of nations: environmental degradation. Burgeoning world populations and the quest for industrial/economic development have begun seriously to erode the capability of the earth's environment to sustain itself. The phenomena of global warming, ozone depletion, deforestation, desertification and many forms of pollution are destroying the delicate life support systems upon which humanity depends for its very survival. National security, therefore, must be redefined and in this instance must be viewed in a context outside the traditional concept of military capability. This paper examines economic, social, political and military implications of environmental degradation as threats to the security of the United States and to world security. The paper concludes that a new level of international cooperation and technological innovation are required to reduce the negative impact of environmental degradation. An appendix provides additional data on specific forms of environmental degradation.

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

    ERIC Educational Resources Information Center

    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…

  6. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

    PubMed Central

    2012-01-01

    Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9 (HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes. PMID:22306652

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

    PubMed

    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 (< 50 km), a large portion of the population of C. albimarginatus (71%) was detected on multiple 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 (< 20 km) may perform better for species like C. albimarginatus than having either a single or a network of isolated MPAs. This design would also provide protection for larger male C. amblyrhynchos

  8. Study of costs associated with alternative fuels development: A case study. Research report

    SciTech Connect

    Lede, N.W.

    1995-07-01

    The primary objective of the study was to conduct a case study of large-scale fuel conversion project to assess selected costs and related issues. An inventory of public transit agencies engaged in demonstration projects involving alternative fuels as conducted with representative sample of large public transit systems in the nation. Included in the survey were questions pertaining to fuel supply arrangements, fuel reserve storage requirements and/or deficiencies; future plans for managing energy resources and costs associated with fuel conversion/alternative fuels use -- whether planned or currently in operation. The case study approach was used to document the methodological and logistical problems encountered during the course of projects involving alternative fuels use compared with a control sample using diesel fuel. Monthly status reports on the alternative fuel project included data on accumulated mileage, road calls/unscheduled maintenance, fuel consumption, fuel cost per mile, alternative fuel purchases, schedule of activities, personnel, safety , and diesel emission test results. The data collected indicate several conclusions and future implications about technical and safety issues associated with the testing and use of liquefied natural gas (LNG).

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

    NASA Astrophysics Data System (ADS)

    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

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

    ERIC Educational Resources Information Center

    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…

  11. Modeling riverine pathogen fate and transport in Mexican rural communities and associated public health implications.

    PubMed

    Robles-Morua, Agustin; Mayer, Alex S; Auer, Martin T; Vivoni, Enrique R

    2012-12-30

    The discharge of untreated or poorly treated wastewater to river systems remains a major problem affecting public and environmental health, particularly in rural communities of less developed countries. One of the primary goals in setting policies for wastewater management is to reduce risks to human health associated with microbial contamination of receiving water. In this study, we apply a surface water quality model to develop an Escherichia coli based indicator that reflects the quality of surface water and the potential impact to recreational users in a large, rural river in northwest Mexico (upper Sonora River). The model assesses the relative importance of streamflow variations and the uncertainty in E. coli removal coefficient parameters for the predictions of E. coli concentrations in the river. Given the sparse information on streamflow, we use a physically-based, distributed hydrologic model to generate tributary contributions to the river. We determined the best estimate and uncertainty of E. coli removal rates to explore the impacts of parameter uncertainty on the transport of E. coli downstream from two wastewater discharge zones. Our results depict the regions in the river that are in noncompliance with fresh water pathogen norms. The impact of streamflow variability and uncertainty in the removal rates of pathogen indicators was used to derive a range of river distances in noncompliance. The comparison between two sites with different streamflow behaviors was used to illustrate the impacts of streamflow spatiotemporal variability on pathogen indicators. We derive a simple relationship that can be used to assess the relative importance of dilution (ratio of wastewater discharge to river discharge) and pathogen removal (ratio of residence time to reaction time). PMID:22996002

  12. A STUDY OF PATHOGENESIS OF ACANTHOSIS NIGRICANS AND ITS CLINICAL IMPLICATIONS

    PubMed Central

    Puri, Neerja

    2011-01-01

    Background: Acanthosis nigricans (AN) is a dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize AN; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of AN and its clinical implications and management. Materials and Methods: We selected 30 patients for the study. Diagnosis of associated disorders was established by history, physical examination, body mass index (BMI), hormone measurements by radioimmunoassays of thyroidnfunction tests, free testosterone, 17 (OH) progesterone, dehydroepiandrosterone sulfate (DHEAS), cortisol, gonadotropins, prolactin, immunoreactive insulin, and C-peptide levels. Results and Discussion: In our study, the flexural involvement (flexures of groins, knees and elbows) was seen in 40% patients, lip involvement was seen in 6.6% patients, and dorsal involvement was seen in 3.3% patients each. Increased serum testosterone levels were seen in 13.3% patients and increased DHEAS levels were seen in 20% patients. Regarding the types of AN, obesity induced AN or pseudo-AN was seen 70% patients, syndromic AN was seen in 23.35% patients and malignant AN was seen in 6.6% patients. The commonest histopathological feature of patients with AN was hyperkeratosis, seen in 100% patients, papillomatosis was seen in 90% patients, dermal infiltrate of lymphocytes and plasma cells was seen in 60% patients, horn pseudocysts were seen in 30% patients, and irregular acanthosis was seen in 26.6% patients. PMID:22345770

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

    PubMed

    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. PMID:26096053

  14. Community College Study Abroad: Implications for Student Success

    ERIC Educational Resources Information Center

    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…

  15. A National Study of Fluoride Mouthrinse Adoption: Implications for School Health Personnel.

    ERIC Educational Resources Information Center

    Coombs, Jeanne A.; And Others

    1983-01-01

    The ongoing adoption of school-based fluoride mouthrinse programs has provided the opportunity to study issues surrounding the adoption and implementation of health technology by public schools. This article reports data on and implications of the National Study on the Diffusion of Preventive Health Measures to Schools. (Authors/CJ)

  16. Studies of hypernuclei by associated production

    SciTech Connect

    Chrien, R.E.

    1987-01-01

    The effectiveness of the associated production, the (..pi../sup +/,K/sup +/) technique, for obtaining hypernuclear spectra across the whole periodic table is demonstrated. Binding energy spectra for hypernuclei of beryllium-9, carbon-12, carbon-13, oxygen-16, silicon-28, calcium-40, vanadium-51, and yttrium-89 were measured. The Low-Energy-Separated Beam I at the Brookhaven National Laboratory AGS was used with the Moby Dick spectrometer. A rate of 2 million pions per beam spill was used for targets of beryllium-9, carbon-12, water, silicon, and calcium. A rate of 10 million pions per beam spill was used for carbon-13, vanadium-51, calcium, and yttrium-89. The higher beam rates were necessary for the low cross sections for the ground states of heavier targets. All of the spectra for hypernuclei above the p-shell show the presence of a continuum apparently underlying the peaks of the bound state region. 4 refs., 5 figs., 1 tab.

  17. Submergence and Uplift Associated to Paleoearthquakes in the Northern Sunda Subduction System: Implications for Future Earthquakes.

    NASA Astrophysics Data System (ADS)

    Mondal, D. R.; McHugh, C. M.; Mortlock, R. A.; Steckler, M. S.; Seeber, L.; Goodbred, S. L., Jr.; Akhter, S. H.; Mustaque, S.

    2015-12-01

    Recent studies documented that the northern part of the Sunda subduction zone ruptured several times in the past 1500 years including one in 1762. To better understand megathrust surface ruptures and the hazards associated to them, we surveyed the SE coast of Bangladesh along the Teknaf peninsula and the Saint Martin anticline by dating coral microatolls of Porites lutea species by the U-Th dating method. Porites luteagrows a few centimeters below the low tide level creating a 5-12 mm thick skeletal band per year, which makes them a good indicator of relative sea level change that might be caused during tectonic submergence and uplift. U-Th ages were obtained from coral slabs and their growth bands interpreted from x-rays. The corals and marine terraces uplift were measured with high precision RTK GPS and modeled with high resolution DEM. The coral microatolls along the St. Martin anticline were dated to be ~ 250, 800 and 1300 years old. Since storm and other climatic phenomenon cannot cause uplift, we interpret that 2.5 m uplift was caused by 1762 earthquake that killed the coral microatolls. The coral slabs show three growth interruptions, where skeletal growth bands continued to grow onlapping the older growth bands. These growth onlaps could be the result of smaller uplift events after 1762 that did not result in coral mortality. The subsidence history extracted from vertical growth of the slabs suggests that the island is submerging at a rate of 11 mm/year. Corals growing 250 m from the dead coral colony post date the 1762 earthquake. Today living Porites lutea can be found 2.5 m below the dead coral heads and 9 cm above the spring low tide. The elevation of marine terraces (T1, T2 and T3) along the Teknaf coast is 2.5 m, 5-7 m and 11-13 m above sea level, respectively. A shell bed on top of T1 was dated at 1763 (dated by C14). This and the other two terraces could have been uplifted during the three earthquakes dated from coral microatolls. Considering the

  18. Current and future greenhouse gas emissions associated with electricity generation in China: implications for electric vehicles.

    PubMed

    Shen, Wei; Han, Weijian; Wallington, Timothy J

    2014-06-17

    China's oil imports and greenhouse gas (GHG) emissions have grown rapidly over the past decade. Addressing energy security and GHG emissions is a national priority. Replacing conventional vehicles with electric vehicles (EVs) offers a potential solution to both issues. While the reduction in petroleum use and hence the energy security benefits of switching to EVs are obvious, the GHG benefits are less obvious. We examine the current Chinese electric grid and its evolution and discuss the implications for EVs. China's electric grid will be dominated by coal for the next few decades. In 2015 in Beijing, Shanghai, and Guangzhou, EVs will need to use less than 14, 19, and 23 kWh/100 km, respectively, to match the 183 gCO2/km WTW emissions for energy saving vehicles. In 2020, in Beijing, Shanghai, and Guangzhou EVs will need to use less than 13, 18, and 20 kWh/100 km, respectively, to match the 137 gCO2/km WTW emissions for energy saving vehicles. EVs currently demonstrated in China use 24-32 kWh/100 km. Electrification will reduce petroleum imports; however, it will be very challenging for EVs to contribute to government targets for GHGs emissions reduction. PMID:24853334

  19. Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma

    PubMed Central

    Johnson, David C.; Weinhold, Niels; Mitchell, Jonathan S.; Chen, Bowang; Kaiser, Martin; Begum, Dil B.; Hillengass, Jens; Bertsch, Uta; Gregory, Walter A.; Cairns, David; Jackson, Graham H.; Försti, Asta; Nickel, Jolanta; Hoffmann, Per; Nöethen, Markus M.; Stephens, Owen W.; Barlogie, Bart; Davis, Faith E.; Hemminki, Kari; Goldschmidt, Hartmut; Houlston, Richard S.; Morgan, Gareth J.

    2016-01-01

    Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22–1.48, P=4.69 × 10–9). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors. PMID:26743840

  20. Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma.

    PubMed

    Johnson, David C; Weinhold, Niels; Mitchell, Jonathan S; Chen, Bowang; Kaiser, Martin; Begum, Dil B; Hillengass, Jens; Bertsch, Uta; Gregory, Walter A; Cairns, David; Jackson, Graham H; Försti, Asta; Nickel, Jolanta; Hoffmann, Per; Nöethen, Markus M; Stephens, Owen W; Barlogie, Bart; Davis, Faith E; Hemminki, Kari; Goldschmidt, Hartmut; Houlston, Richard S; Morgan, Gareth J

    2016-01-01

    Survival following a diagnosis of multiple myeloma (MM) varies between patients and some of these differences may be a consequence of inherited genetic variation. In this study, to identify genetic markers associated with MM overall survival (MM-OS), we conduct a meta-analysis of four patient series of European ancestry, totalling 3,256 patients with 1,200 MM-associated deaths. Each series is genotyped for ∼600,000 single nucleotide polymorphisms across the genome; genotypes for six million common variants are imputed using 1000 Genomes Project and UK10K as the reference. The association between genotype and OS is assessed by Cox proportional hazards model adjusting for age, sex, International staging system and treatment. We identify a locus at 6q25.1 marked by rs12374648 associated with MM-OS (hazard ratio=1.34, 95% confidence interval=1.22-1.48, P=4.69 × 10(-9)). Our findings have potential clinical implications since they demonstrate that inherited genotypes can provide prognostic information in addition to conventional tumor acquired prognostic factors. PMID:26743840

  1. RAP1 stimulates single- to double-strand association of yeast telomeric DNA: implications for telomere-telomere interactions.

    PubMed Central

    Gilson, E; Müller, T; Sogo, J; Laroche, T; Gasser, S M

    1994-01-01

    Repressor Activator Protein 1 (RAP1) of Saccharomyces cerevisiae is an abundant nuclear protein implicated in telomere length maintenance, transactivation, and in the establishment of silent chromatin domains. The RAP1 binding site 5' of the yeast HIS4 gene is also a region of hyperrecombination in meiosis. We report here that as RAP1 binds its recognition consensus, it appears to untwist double-stranded DNA, which we detect as the introduction of a negative supercoil in circularization assays. Coincident with the RAP1-dependent untwisting, we observe stimulation of the association of a single-stranded yeast telomeric sequence with its homologous double-stranded sequence in a supercoiled plasmid. This unusual distortion of the DNA double helix by RAP1 may contribute to the RAP1-dependent enhancement of recombination rates and promote non-duplex strand interactions at telomeres. Images PMID:7816621

  2. Implications of Common Core State Standards on the Social Studies

    ERIC Educational Resources Information Center

    Kenna, Joshua L.; Russell, William B., III.

    2014-01-01

    Social studies teachers have often been on the outside looking in during much of the era billed as the standards-based educational reform (SBER), but with the adoption and implementation of the Common Core State Standards (CCSS), social studies teachers seem to have been invited back inside. Yet, how will the standards impact social studies…

  3. Changes in heart rate variability associated with acute alcohol consumption: current knowledge and implications for practice and research.

    PubMed

    Romanowicz, Magdalena; Schmidt, John E; Bostwick, John M; Mrazek, David A; Karpyak, Victor M

    2011-06-01

    Alcohol consumption is associated with a broad array of physiologic and behavioral effects including changes in heart rate. However, the physiologic mechanisms of alcohol effects and the reasons for individual differences in the cardiac response remain unknown. Measuring changes in resting heart rate (measured as beats/min) has not been found to be as sensitive to alcohol's effects as changes in heart rate variability (HRV). HRV is defined as fluctuations in interbeat interval length which reflect the heart's response to extracardiac factors that affect heart rate. HRV allows simultaneous assessment of both sympathetic and parasympathetic activity and the interplay between them. Increased HRV has been associated with exercise and aerobic fitness, while decreased HRV has been associated with aging, chronic stress, and a wide variety of medical and psychiatric disorders. Decreased HRV has predictive value for mortality in general population samples and patients with myocardial infarction and used as an indicator of altered autonomic function. A significant inverse correlation was found between HRV and both the severity of depression and the duration of the depressive episode. HRV analysis provides insights into mechanisms of autonomic regulation and is extensively used to clarify relationships between depression and cardiovascular disease. This article will review the methodology of HRV measurements and contemporary knowledge about effects of acute alcohol consumption on HRV. Potential implications of this research include HRV response to alcohol that could serve as a marker for susceptibility to alcoholism. At present however there is almost no research data supporting this hypothesis. PMID:21332532

  4. Experimental evidence for friction-enhancing integumentary modifications of chameleons and associated functional and evolutionary implications.

    PubMed

    Khannoon, Eraqi R; Endlein, Thomas; Russell, Anthony P; Autumn, Kellar

    2014-01-22

    The striking morphological convergence of hair-like integumentary derivatives of lizards and arthropods (spiders and insects) demonstrates the importance of such features for enhancing purchase on the locomotor substrate. These pilose structures are responsible for the unique tractive abilities of these groups of animals, enabling them to move with seeming ease on overhanging and inverted surfaces, and to traverse inclined smooth substrates. Three groups of lizards are well known for bearing adhesion-promoting setae on their digits: geckos, anoles and skinks. Similar features are also found on the ventral subdigital and distal caudal skin of chameleons. These have only recently been described in any detail, and structurally and functionally are much less well understood than are the setae of geckos and anoles. The seta-like structures of chameleons are not branched (a characteristic of many geckos), nor do they terminate in spatulate tips (which is characteristic of geckos, anoles and skinks). They are densely packed and have attenuated blunt, globose tips or broad, blade-like shafts that are flattened for much of their length. Using a force transducer, we tested the hypothesis that these structures enhance friction and demonstrate that the pilose skin has a greater frictional coefficient than does the smooth skin of these animals. Our results are consistent with friction being generated as a result of side contact of the integumentary filaments. We discuss the evolutionary and functional implications of these seta-like structures in comparison with those typical of other lizard groups and with the properties of seta-mimicking synthetic structures. PMID:24285195

  5. Experimental evidence for friction-enhancing integumentary modifications of chameleons and associated functional and evolutionary implications

    PubMed Central

    Khannoon, Eraqi R.; Endlein, Thomas; Russell, Anthony P.; Autumn, Kellar

    2014-01-01

    The striking morphological convergence of hair-like integumentary derivatives of lizards and arthropods (spiders and insects) demonstrates the importance of such features for enhancing purchase on the locomotor substrate. These pilose structures are responsible for the unique tractive abilities of these groups of animals, enabling them to move with seeming ease on overhanging and inverted surfaces, and to traverse inclined smooth substrates. Three groups of lizards are well known for bearing adhesion-promoting setae on their digits: geckos, anoles and skinks. Similar features are also found on the ventral subdigital and distal caudal skin of chameleons. These have only recently been described in any detail, and structurally and functionally are much less well understood than are the setae of geckos and anoles. The seta-like structures of chameleons are not branched (a characteristic of many geckos), nor do they terminate in spatulate tips (which is characteristic of geckos, anoles and skinks). They are densely packed and have attenuated blunt, globose tips or broad, blade-like shafts that are flattened for much of their length. Using a force transducer, we tested the hypothesis that these structures enhance friction and demonstrate that the pilose skin has a greater frictional coefficient than does the smooth skin of these animals. Our results are consistent with friction being generated as a result of side contact of the integumentary filaments. We discuss the evolutionary and functional implications of these seta-like structures in comparison with those typical of other lizard groups and with the properties of seta-mimicking synthetic structures. PMID:24285195

  6. Cation reordering in natural titanomagnetites and implications for paleointensity studies

    NASA Astrophysics Data System (ADS)

    Bowles, J. A.; Jackson, M. J.; Gee, J. S.

    2013-05-01

    Successful paleointensity experiments hinge on the underlying assumption of reciprocity; the remanence acquired over a particular temperature range should be fully removed over the same temperature range, and vice versa. This means that the blocking (TB) and unblocking (TUB) temperature spectra are identical and do not change during the course of the experiment. We will present the results of recent work demonstrating that some natural titanomagnetites undergo cation reordering on laboratory timescales and at temperatures at or below the Curie temperature (TC). The bulk composition of the titanomagnetites (Fe3-xTixO4) varies between approximately 0.2 < x < 0.4, with moderate degrees of Mg and Al substitution. Although there is no attendant structural or chemical alteration, the re-distribution of ferric and ferrous iron cations results in reversible changes in Curie temperature of up to 150°C. This necessarily changes the blocking temperature spectrum as a function of prior thermal history. These changes in TC, TUB and TB clearly pose problems for all paleointensity experiments, but the effects may be most apparent during Thellier-type experiments where the sample is step-wise heated to increasingly higher temperatures. The blocking temperature distribution will be expected to change over the course of the experiment even in the absence of chemical alteration, and one can expect the experiment to fail. We will explore the effects of cation redistribution on paleointensity experiments through numerical models and by comparison with paleointensity data from pumice samples taken from the 1980 pyroclastic flows at Mt. St. Helens (MSH). In the MSH samples, two phases are typically present: a predominantly multi-domain, homogeneous titanomagnetite (associated with the cation reordering) and an oxyexsolved, single-domain to pseudo-single-domain phase with ilmenite lamellae in a magnetite-rich host. Samples that result in technically successful paleointensity experiments

  7. Evaluating Technology in Schools: Implications of a Research Study.

    ERIC Educational Resources Information Center

    Kell, Diane; And Others

    This report provides an overview of the issues related to a recently completed study of the use of computers in primary classrooms in six school districts and some special program classes, i.e., K-2 English-as-a-Second-Language and bilingual classes at one study site and Chapter 1 pullout classes for grades K-5 at another site. The sites used were…

  8. HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV-Associated Pathogenesis.

    PubMed

    Medvedev, Regina; Ploen, Daniela; Hildt, Eberhard

    2016-01-01

    HCV (hepatitis C virus) is a member of the Flaviviridae family that contains a single-stranded positive-sense RNA genome of approximately 9600 bases. HCV is a major causative agent for chronic liver diseases such as steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma which are caused by multifactorial processes. Elevated levels of reactive oxygen species (ROS) are considered as a major factor contributing to HCV-associated pathogenesis. This review summarizes the mechanisms involved in formation of ROS in HCV replicating cells and describes the interference of HCV with ROS detoxifying systems. The relevance of ROS for HCV-associated pathogenesis is reviewed with a focus on the interference of elevated ROS levels with processes controlling liver regeneration. The overview about the impact of ROS for the viral life cycle is focused on the relevance of autophagy for the HCV life cycle and the crosstalk between HCV, elevated ROS levels, and the induction of autophagy. PMID:26955431

  9. Erythrophore cell response to food-associated pathogenic bacteria: implications for detection.

    PubMed

    Hutchison, Janine R; Dukovcic, Stephanie R; Dierksen, Karen P; Carlyle, Calvin A; Caldwell, Bruce A; Trempy, Janine E

    2008-09-01

    Cell-based biosensors have been proposed for use as function-based detectors of toxic agents. We report the use of Betta splendens chromatophore cells, specifically erythrophore cells, for detection of food-associated pathogenic bacteria. Evaluation of erythrophore cell response, using Bacillus spp., has revealed that this response can distinguish pathogenic Bacillus cereus from a non-pathogenic B. cereus ΔplcR deletion mutant and a non-pathogenic Bacillus subtilis. Erythrophore cells were exposed to Salmonella enteritidis, Clostridium perfringens and Clostridium botulinum. Each bacterial pathogen elicited a response from erythrophore cells that was distinguished from the corresponding bacterial growth medium, and this observed response was unique for each bacterial pathogen. These findings suggest that erythrophore cell response has potential for use as a biosensor in the detection and toxicity assessment for food-associated pathogenic bacteria. PMID:21261862

  10. Explosive volcanism and associated pressures - Implications for models of endogenically shocked quartz

    NASA Technical Reports Server (NTRS)

    De Silva, S. L.; Wolff, J. A.; Sharpton, V. L.

    1990-01-01

    The nature of explosive volcanic phenomena and associated pressures, both from field and theoretical perspectives, is discussed. An endogenic origin for shocked quartz at the K/T boundary requires impulsive pressures greater than 60 kbars to be generated during explosive volcanism. Explosive volcanic eruptions which are events of sustained decompression may be initiated by impulsive explosions while the magnitudes of the overpressures are small. These maximum overpressures can be controlled mainly by the tensile strength of the rock surrounding the magma chamber-conduit system. Thus maximum overpressures in the volcanic environment are limited to less than 500 bars which are orders of magnitude less than those required for shock quartz (greater than 60 kbars). This observation is found to be consistent with the complete lack of field or petrographic evidence in support of shock metamorphism associated with volcanic eruptions and their products.

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

    PubMed

    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

  12. HCV and Oxidative Stress: Implications for HCV Life Cycle and HCV-Associated Pathogenesis

    PubMed Central

    Medvedev, Regina; Ploen, Daniela; Hildt, Eberhard

    2016-01-01

    HCV (hepatitis C virus) is a member of the Flaviviridae family that contains a single-stranded positive-sense RNA genome of approximately 9600 bases. HCV is a major causative agent for chronic liver diseases such as steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma which are caused by multifactorial processes. Elevated levels of reactive oxygen species (ROS) are considered as a major factor contributing to HCV-associated pathogenesis. This review summarizes the mechanisms involved in formation of ROS in HCV replicating cells and describes the interference of HCV with ROS detoxifying systems. The relevance of ROS for HCV-associated pathogenesis is reviewed with a focus on the interference of elevated ROS levels with processes controlling liver regeneration. The overview about the impact of ROS for the viral life cycle is focused on the relevance of autophagy for the HCV life cycle and the crosstalk between HCV, elevated ROS levels, and the induction of autophagy. PMID:26955431

  13. OB associations and the nonuniversality of the cosmic abundances - Implications for cosmic rays and meteorites

    NASA Technical Reports Server (NTRS)

    Olive, K. A.; Schramm, D. N.

    1982-01-01

    The formation of the solar system inside an OB association is examined with particular attention to the elemental abundances which would have been ejected by the association's first few supernovae. It is found that the solar system material may have been significantly contaminated by these supernovae and thus the average interstellar composition may differ from the solar system composition. In particular, we find that many of the so-called isotopic and elemental abundance anomalies (e.g., Ne, C, O, s-process/r-process, etc.) found in meteoritic inclusions and in cosmic rays may be more representative of the average interstellar abundance. In other words, it may be that the average solar system abundances are what is 'anomalous'.

  14. Ice-Associated Impact Craters on Mars: Implications from MOLA Observations

    NASA Technical Reports Server (NTRS)

    Garvin, J. B.; Sakimoto, S. E. H.

    1998-01-01

    Impact features adjacent to the permanent North Polar Cap on Mars provide a unique perspective on the crater formation and modification process. Little attention has been previously paid to the dozen's of ice-associated or 'frost-filled' craters north of 70N on Mars. We have examined Mars Orbiter Laser Altimeter (MOLA) cross-sections of 13 of these features between 7ON and 82N in an effort to understand cavity modification processes potentially associated with the advance and retreat of the North Polar ice cap. Here we treat the general geometric properties of these impact features and focus attention on one almost entirely filled example (i.e., 32 km diameter, located at 77N, 89E) for which high resolution Viking Orbiter images (50 m per pixel) provide key constraints for interpreting MOLA's meter-precision topographic measurements.

  15. Foraging Strategies of Laysan Albatross Inferred from Stable Isotopes: Implications for Association with Fisheries.

    PubMed

    Edwards, Ann E; Fitzgerald, Shannon M; Parrish, Julia K; Klavitter, John L; Romano, Marc D

    2015-01-01

    Fatal entanglement in fishing gear is the leading cause of population decline for albatross globally, a consequence of attraction to bait and fishery discards of commercial fishing operations. We investigated foraging strategies of Laysan albatross (Phoebastria immutabilis), as inferred from nitrogen and carbon isotope values of primary feathers, to determine breeding-related, seasonal, and historic factors that may affect the likelihood of association with Alaskan or Hawaiian longline fisheries. Feather samples were collected from live birds monitored for breeding status and breeding success on Midway Atoll in the northwestern Hawaiian Islands, birds salvaged as fisheries-bycatch, and birds added to museum collections before 1924. During the chick-rearing season (sampled April-May), means and variances of stable isotope values of birds with the highest, most consistent reproductive success were distinct from less productive conspecifics and completely different from birds caught in Hawaiian or Alaskan longline fisheries, suggesting birds with higher multi-annual reproductive success were less likely to associate with these fisheries. Contemporary birds with the highest reproductive success had mean values most similar to historic birds. Values of colony-bound, courting prebreeders were similar to active breeders but distinct from prebreeders caught in Alaskan longline fisheries. During the breeding season, δ15N values were highly variable for both contemporary and historic birds. Although some historic birds exhibited extremely low δ15N values unmatched by contemporary birds (< 11.2‰), others had values as high as the highest fishery-associated contemporary birds. During the non-breeding season (sampled July-September), isotopic variability coalesced into a more narrow set of values for both contemporary and historic birds. Our results suggest that foraging strategies of Laysan albatross are a complex function of season, breeding status, and multi

  16. Foraging Strategies of Laysan Albatross Inferred from Stable Isotopes: Implications for Association with Fisheries

    PubMed Central

    Edwards, Ann E.; Fitzgerald, Shannon M.; Parrish, Julia K.; Klavitter, John L.; Romano, Marc D.

    2015-01-01

    Fatal entanglement in fishing gear is the leading cause of population decline for albatross globally, a consequence of attraction to bait and fishery discards of commercial fishing operations. We investigated foraging strategies of Laysan albatross (Phoebastria immutabilis), as inferred from nitrogen and carbon isotope values of primary feathers, to determine breeding-related, seasonal, and historic factors that may affect the likelihood of association with Alaskan or Hawaiian longline fisheries. Feather samples were collected from live birds monitored for breeding status and breeding success on Midway Atoll in the northwestern Hawaiian Islands, birds salvaged as fisheries-bycatch, and birds added to museum collections before 1924. During the chick-rearing season (sampled April-May), means and variances of stable isotope values of birds with the highest, most consistent reproductive success were distinct from less productive conspecifics and completely different from birds caught in Hawaiian or Alaskan longline fisheries, suggesting birds with higher multi-annual reproductive success were less likely to associate with these fisheries. Contemporary birds with the highest reproductive success had mean values most similar to historic birds. Values of colony-bound, courting prebreeders were similar to active breeders but distinct from prebreeders caught in Alaskan longline fisheries. During the breeding season, δ15N values were highly variable for both contemporary and historic birds. Although some historic birds exhibited extremely low δ15N values unmatched by contemporary birds (< 11.2‰), others had values as high as the highest fishery-associated contemporary birds. During the non-breeding season (sampled July-September), isotopic variability coalesced into a more narrow set of values for both contemporary and historic birds. Our results suggest that foraging strategies of Laysan albatross are a complex function of season, breeding status, and multi

  17. Preferential association of endophytic bradyrhizobia with different rice cultivars and its implications for rice endophyte evolution.

    PubMed

    Piromyou, Pongdet; Greetatorn, Teerana; Teamtisong, Kamonluck; Okubo, Takashi; Shinoda, Ryo; Nuntakij, Achara; Tittabutr, Panlada; Boonkerd, Nantakorn; Minamisawa, Kiwamu; Teaumroong, Neung

    2015-05-01

    Plant colonization by bradyrhizobia is found not only in leguminous plants but also in nonleguminous species such as rice. To understand the evolution of the endophytic symbiosis of bradyrhizobia, the effect of the ecosystems of rice plantations on their associations was investigated. Samples were collected from various rice (Oryza sativa) tissues and crop rotational systems. The rice endophytic bradyrhizobia were isolated on the basis of oligotrophic properties, selective medium, and nodulation on siratro (Macroptilium atropurpureum). Six bradyrhizobial strains were obtained exclusively from rice grown in a crop rotational system. The isolates were separated into photosynthetic bradyrhizobia (PB) and nonphotosynthetic bradyrhizobia (non-PB). Thai bradyrhizobial strains promoted rice growth of Thai rice cultivars better than the Japanese bradyrhizobial strains. This implies that the rice cultivars possess characteristics that govern rice-bacterium associations. To examine whether leguminous plants in a rice plantation system support the persistence of rice endophytic bradyrhizobia, isolates were tested for legume nodulation. All PB strains formed symbioses with Aeschynomene indica and Aeschynomene evenia. On the other hand, non-PB strains were able to nodulate Aeschynomene americana, Vigna radiata, and M. atropurpureum but unable to nodulate either A. indica or A. evenia. Interestingly, the nodABC genes of all of these bradyrhizobial strains seem to exhibit low levels of similarity to those of Bradyrhizobium diazoefficiens USDA110 and Bradyrhizobium sp. strain ORS285. From these results, we discuss the evolution of the plant-bradyrhizobium association, including nonlegumes, in terms of photosynthetic lifestyle and nod-independent interactions. PMID:25710371

  18. Preferential Association of Endophytic Bradyrhizobia with Different Rice Cultivars and Its Implications for Rice Endophyte Evolution

    PubMed Central

    Piromyou, Pongdet; Greetatorn, Teerana; Teamtisong, Kamonluck; Okubo, Takashi; Shinoda, Ryo; Nuntakij, Achara; Tittabutr, Panlada; Boonkerd, Nantakorn

    2015-01-01

    Plant colonization by bradyrhizobia is found not only in leguminous plants but also in nonleguminous species such as rice. To understand the evolution of the endophytic symbiosis of bradyrhizobia, the effect of the ecosystems of rice plantations on their associations was investigated. Samples were collected from various rice (Oryza sativa) tissues and crop rotational systems. The rice endophytic bradyrhizobia were isolated on the basis of oligotrophic properties, selective medium, and nodulation on siratro (Macroptilium atropurpureum). Six bradyrhizobial strains were obtained exclusively from rice grown in a crop rotational system. The isolates were separated into photosynthetic bradyrhizobia (PB) and nonphotosynthetic bradyrhizobia (non-PB). Thai bradyrhizobial strains promoted rice growth of Thai rice cultivars better than the Japanese bradyrhizobial strains. This implies that the rice cultivars possess characteristics that govern rice-bacterium associations. To examine whether leguminous plants in a rice plantation system support the persistence of rice endophytic bradyrhizobia, isolates were tested for legume nodulation. All PB strains formed symbioses with Aeschynomene indica and Aeschynomene evenia. On the other hand, non-PB strains were able to nodulate Aeschynomene americana, Vigna radiata, and M. atropurpureum but unable to nodulate either A. indica or A. evenia. Interestingly, the nodABC genes of all of these bradyrhizobial strains seem to exhibit low levels of similarity to those of Bradyrhizobium diazoefficiens USDA110 and Bradyrhizobium sp. strain ORS285. From these results, we discuss the evolution of the plant-bradyrhizobium association, including nonlegumes, in terms of photosynthetic lifestyle and nod-independent interactions. PMID:25710371

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

    PubMed

    Baragli, Paolo; Padalino, Barbara; Telatin, Angelo

    2015-01-01

    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. PMID:25857383

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

    ERIC Educational Resources Information Center

    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…

  1. Contributions and Implications of the Medford, Oregon, Boys' Growth Study.

    ERIC Educational Resources Information Center

    Clarke, H. H.

    The overall and long-range purposes of the Medford Boys' Growth Study are: (1) to construct physical and motor growth curves and growth acceleration curves of boys seven to 18 years old; (2) to relate these traits to physiological maturity, physique type, nutritional status, socio-personal adjustment, interests, and scholastic aptitude and…

  2. Social Constructionism and Ludology: Implications for the Study of Games

    ERIC Educational Resources Information Center

    Montola, Markus

    2012-01-01

    This article combines the paradigm of social constructionism with the developing field of ludology. As games are intersubjective meaning-making activities, their study requires understanding of the nature of social constructions, and how such constructions are produced and interpreted: The formalist nature of ludological core concepts such as game…

  3. Implications of Early Sociocultural Adaptation for Study Abroad Students

    ERIC Educational Resources Information Center

    Savicki, Victor

    2010-01-01

    Helping students and others facing the task of adapting to a foreign culture is becoming ever more pressing. The current study delves into sociocultural adaptation in order to clarify that process and provide information useful for educators, trainers, coaches, and others guiding those facing a sojourn in a foreign culture. A question to be…

  4. A Performance Measurement Feasibility Study: Implications for Manpower Policy.

    ERIC Educational Resources Information Center

    Schmidt, Frank L.; And Others

    Utilizing eight apprentices in the mentals trades, this study empirically evaluated a number of techniques designed to produce performance tests that are economically feasible, reliable, content-valid, and less disadvantageous to minority group members than paper-and-pencil measures. The final test was economically feasible, reliable with respect…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  7. Children's Linguistic Attitudes: A Study and Some Implications.

    ERIC Educational Resources Information Center

    Light, Richard L.

    Linguists and psychologists have disagreed concerning the development and nature of children's social perceptions of others on the basis of speech differences. The present study sought to determine in what ways 8- and 9-year olds from different socioeconomic backgrounds might react to dialect differences. Ninety-two randomly selected 8- and…

  8. Bilingual Lexicon: Implications for Studies of Language Choice.

    ERIC Educational Resources Information Center

    Quay, Suzanne

    1995-01-01

    Bilingual case study of infant acquiring Spanish and English from birth to 1;10 is used to address whether young bilinguals differentiate between their languages based on language choice. Daily diary records and weekly video recordings in the two language contexts were used to construct the child's lexicon and establish that translation…

  9. Implications of recent multimodel attribution studies for climate sensitivity

    NASA Astrophysics Data System (ADS)

    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.

  10. Exogenous Visual Orienting Is Associated with Specific Neurotransmitter Genetic Markers: A Population-Based Genetic Association Study

    PubMed Central

    Lundwall, Rebecca A.; Guo, Dong-Chuan; Dannemiller, James L.

    2012-01-01

    Background Currently, there is a sense that the spatial orienting of attention is related to genotypic variations in cholinergic genes but not to variations in dopaminergic genes. However, reexamination of associations with both cholinergic and dopaminergic genes is warranted because previous studies used endogenous rather than exogenous cues and costs and benefits were not analyzed separately. Examining costs (increases in response time following an invalid pre-cue) and benefits (decreases in response time following a valid pre-cue) separately could be important if dopaminergic genes (implicated in disorders such as attention deficit disorder) independently influence the different processes of orienting (e.g., disengage, move, engage). Methodology/Principal Findings We tested normal subjects (N = 161) between 18 and 61 years. Participants completed a computer task in which pre-cues preceded the presence of a target. Subjects responded (with a key press) to the location of the target (right versus left of fixation). The cues could be valid (i.e., appear where the target would appear) or invalid (appear contralateral to where the target would appear). DNA sequencing assays were performed on buccal cells to genotype known genetic markers and these were examined for association with task scores. Here we show significant associations between visual orienting and genetic markers (on COMT, DAT1, and APOE; R2s from 4% to 9%). Conclusions/Significance One measure in particular – the response time cost of a single dim, invalid cue – was associated with dopaminergic markers on COMT and DAT1. Additionally, variations of APOE genotypes based on the ε2/ε3/ε4 alleles were also associated with response time differences produced by simultaneous cues with unequal luminances. We conclude that individual differences in visual orienting are related to several dopaminergic markers as well as to a cholinergic marker. These results challenge the view that orienting is not

  11. Generic Information Can Retrieve Known Biological Associations: Implications for Biomedical Knowledge Discovery

    PubMed Central

    van Haagen, Herman H. H. B. M.; 't Hoen, Peter A. C.; Mons, Barend; Schultes, Erik A.

    2013-01-01

    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

  12. Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology.

    PubMed

    Burlot, Marie-Anne; Braudeau, Jérôme; Michaelsen-Preusse, Kristin; Potier, Brigitte; Ayciriex, Sophie; Varin, Jennifer; Gautier, Benoit; Djelti, Fathia; Audrain, Mickael; Dauphinot, Luce; Fernandez-Gomez, Francisco-Jose; Caillierez, Raphaëlle; Laprévote, Olivier; Bièche, Ivan; Auzeil, Nicolas; Potier, Marie-Claude; Dutar, Patrick; Korte, Martin; Buée, Luc; Blum, David; Cartier, Nathalie

    2015-11-01

    Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The amyloid component and altered cholesterol metabolism are closely linked, but the relationship between Tau pathology and cholesterol is currently unclear. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene. In AD patients, the concentration of 24S-hydroxycholesterol in the plasma and the cerebrospinal fluid are lower than in healthy controls. The THY-Tau22 mouse is a model of AD-like Tau pathology without amyloid pathology. We used this model to investigate the potential association between Tau pathology and CYP46A1 modulation. The amounts of CYP46A1 and 24S-hydroxycholesterol in the hippocampus were lower in THY-Tau22 than control mice. We used an adeno-associated virus (AAV) gene transfer strategy to increase CYP46A1 expression in order to investigate the consequences on THY-Tau22 mouse phenotype. Injection of the AAV-CYP46A1 vector into the hippocampus of THY-Tau22 mice led to CYP46A1 and 24S-hydroxycholesterol content normalization. The cognitive deficits, impaired long-term depression and spine defects that characterize the THY-Tau22 model were completely rescued, whereas Tau hyperphosphorylation and associated gliosis were unaffected. These results argue for a causal link between CYP46A1 protein content and memory impairments that result from Tau pathology. Therefore, CYP46A1 may be a relevant therapeutic target for Tauopathies and especially for AD. PMID:26358780

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

    PubMed

    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 < 70), compared with those with a low degree of sleep disturbance, secreted a higher amount of cortisol. Pulsatile analysis revealed a significantly higher number of peaks per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analysis showed no differences in the temporal pattern of ACTH or cortisol secretion between insomniacs and controls. We conclude that 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

  14. The Epigenetic Modifications of Genes Associated with Tuberculosis Susceptibility and Implications for Epi-Drugs.

    PubMed

    Zeng, Jie; Xie, Longxiang; Luo, Hongping; Xie, Jianping

    2015-01-01

    Epigenetics of genes associated with tuberculosis susceptibility such as DNA methylation, posttranslational histone modifications, and non-coding RNA remain largely untapped field for better tuberculosis control. Many genes involved in tuberculosis susceptibility (e.g., NRAMP1 (SLC11A1), IFNG, NOS2A, VDR, ISG15, TACO, TLR1, TLR, IL18R1, chemokines, PADI, DUSP14, MBL, and MASP-2) have been subjected to epigenetic modification. Our summary of these modifications provides fresh insights into the pathogenesis of tuberculosis and inspires targets discovery for host-derived therapy. PMID:26559095

  15. Genome-wide association study of leukotriene modifier response in asthma.

    PubMed

    Dahlin, A; Litonjua, A; Irvin, C G; Peters, S P; Lima, J J; Kubo, M; Tamari, M; Tantisira, K G

    2016-04-01

    Heterogeneous therapeutic responses to leukotriene modifiers (LTMs) are likely due to variation in patient genetics. Although prior candidate gene studies implicated multiple pharmacogenetic loci, to date, no genome-wide association study (GWAS) of LTM response was reported. In this study, DNA and phenotypic information from two placebo-controlled trials (total N=526) of zileuton response were interrogated. Using a gene-environment (G × E) GWAS model, we evaluated 12-week change in forced expiratory volume in 1 second (ΔFEV1) following LTM treatment. The top 50 single-nucleotide polymorphism associations were replicated in an independent zileuton treatment cohort, and two additional cohorts of montelukast response. In a combined analysis (discovery+replication), rs12436663 in MRPP3 achieved genome-wide significance (P=6.28 × 10(-08)); homozygous rs12436663 carriers showed a significant reduction in mean ΔFEV1 following zileuton treatment. In addition, rs517020 in GLT1D1 was associated with worsening responses to both montelukast and zileuton (combined P=1.25 × 10(-07)). These findings implicate previously unreported loci in determining therapeutic responsiveness to LTMs. PMID:26031901

  16. Peyronie's disease: a case study with clinical implications.

    PubMed

    Fisher, D Eileen; Lofton, Susan P; Hale, Theresa; Durant, Norma; Grant, LaVerne F

    2008-04-01

    Peyronie's disease involves the development of fibrous plaques in the connective tissue of the penis usually near the dorsal midline of the penile shaft in middle-aged and older men. This case study describes a 57-year-old man who presented with a history of prostatitis and complaints of anxiety related to penile pain and erectile difficulties. The diagnostic work-up and clinical interaction are described. PMID:18488585

  17. Radiocarbon dating organic detritus: Implications for studying ice sheet dynamics

    SciTech Connect

    Punning, J.; Rajamaee, R. . Inst. of Ecology)

    1993-01-01

    They present here a description of the [sup 14]C dating method used at the Institute of Geology, Estonian Academy of Science. They discuss results of geochronological studies of several stratigraphic sections, from which one estimates the age of the Late Weichselian (Late Valdaian) glacial maximum. [sup 14]C and paleobotanical data indicate that biodetrital materials comprise organic debris from various sources and suggests only a maximum age of investigated strata (16,000 BP).

  18. An Invitation to the Ethnographic Study of University Examination Behavior: Concepts, Methodology, and Implications.

    ERIC Educational Resources Information Center

    Albas, Cheryl; Albas, Dan

    1996-01-01

    Reports a series of ethnographic studies of student behavior concerning examinations, conducted in a Canadian university since the mid-1980s. Describes techniques of data gathering and the link between methodology and theory. Examines implications for higher education, including dealing with students' exam-related stress, factors influencing…

  19. Identifying Implications of Tensions in a Series of Collaborative Self-Study Groups

    ERIC Educational Resources Information Center

    East, Katheryn; Fitzgerald, Linda May; Manke, Mary P.

    2010-01-01

    Drawing on 14 years of collaborative self-study group work at their university, East and Fitzgerald reviewed the data, stories and findings from that collaborative work, seeking to go beyond those original stories to identify practical implications of the tensions that emerged and played out within the various groups. Findings were shared and…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

  3. Nutrition Implications of Low Fruit and Vegetable Intakes in the Geisinger Rural Aging Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recommendations for fruit and vegetable (FV) intakes have nearly doubled despite that more than half the U.S. population does not meet previous recommendations. The purpose of this study was to examine the implications of low FV intakes in a group of rural older adults at nutrition risk who are part...

  4. Family Matters Update: Design, Baseline Findings, Policy Implications and Program Developments from a Family Supports Study.

    ERIC Educational Resources Information Center

    Cochran, Moncrieff

    The major portion of this presentation describes research results and policy implications of the Family Matters Project, a longitudinal study of social contexts as they affect children and families during the period of transition from home to school. Also provided in this portion are highlights of what was learned from delivering to 160 families…

  5. Common Polymorphisms at the CYP17A1 Locus Associate With Steroid Phenotype: Support for Blood Pressure Genome-Wide Association Study Signals at This Locus.

    PubMed

    Diver, Louise A; MacKenzie, Scott M; Fraser, Robert; McManus, Frances; Freel, E Marie; Alvarez-Madrazo, Samantha; McClure, John D; Friel, Elaine C; Hanley, Neil A; Dominiczak, Anna F; Caulfield, Mark J; Munroe, Patricia B; Connell, John M; Davies, Eleanor

    2016-04-01

    Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located ≤ 2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure-associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835--which we associate with changes in aldosterone level--is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects. PMID:26902494

  6. A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE

    PubMed Central

    Sandling, Johanna K; Garnier, Sophie; Sigurdsson, Snaevar; Wang, Chuan; Nordmark, Gunnel; Gunnarsson, Iva; Svenungsson, Elisabet; Padyukov, Leonid; Sturfelt, Gunnar; Jönsen, Andreas; Bengtsson, Anders A; Truedsson, Lennart; Eriksson, Catharina; Rantapää-Dahlqvist, Solbritt; Mälarstig, Anders; Strawbridge, Rona J; Hamsten, Anders; Criswell, Lindsey A; Graham, Robert R; Behrens, Timothy W; Eloranta, Maija-Leena; Alm, Gunnar; Rönnblom, Lars; Syvänen, Ann-Christine

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (Pmeta=0.00010 and Pmeta=0.00040, respectively). STAT1 was also associated with SLE in this cohort (Pmeta=3.3 × 10−5), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis. PMID:21179067

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Activities associated with drownings in Imperial County, CA, 1980-90: implications for prevention.

    PubMed Central

    Agócs, M M; Trent, R B; Russell, D M

    1994-01-01

    Statewide surveillance in California determined that the highest drowning rate from 1980 through 1989 was for the rural, desert county of Imperial (21.9 drownings per 100,000 population). To identify activities associated with drowning in this county, the authors abstracted data from the county sheriff-coroner's reports. From 1980 through 1990, there were 317 unintentional drownings; 85 percent occurred in irrigation canals. The activity prior to drowning was known for 262 persons (83 percent), and the most common activity was illegal entry into the United States. Overall, 140 persons (53 percent) were illegal entrants. Ninety-three percent of illegal entrants drowned in the All American Canal; the monthly drowning rate increased as the monthly average water velocity in the canal increased (r = 0.36; P < 0.001). Forty-eight persons (18 percent) drowned while riding in or on a land vehicle (automobile, pick-up truck, motorcycle, dune buggy, or tractor), the second most common activity associated with drowning. Seventy percent of the 23 drivers had an alcohol concentration of 100 milligrams per deciliter or more, California's limit for intoxication. To reduce drownings in Imperial County, prevention strategies should target persons engaged in at-risk activities near bodies of water. These strategies should include the identification and use of effective canal safety devices. PMID:8153281

  9. Innate immune memory: Implications for host responses to damage-associated molecular patterns.

    PubMed

    Crișan, Tania O; Netea, Mihai G; Joosten, Leo A B

    2016-04-01

    Cells of the innate immune system build immunological memory via epigenetic reprogramming after stimulations with microbial ligands. This functional readjustment allows for enhanced nonspecific inflammatory responses upon secondary challenges, a process termed "trained immunity." The epigenomic blueprint of trained monocytes has been recently reported, which revealed several important immunologic and metabolic mechanisms that underlie these changes. Interestingly, similar long-term reprogramming of cytokine production has also been described to be induced by endogenous damage-associated molecular patterns (DAMPs). Here, we present an overview of the novel data showing that endogenous alarm signals associated with tissue damage and sterile inflammation can induce trained immunity through epigenetic regulation of transcriptional programs. We describe new and old evidence of persistent effects of DAMPs in driving inflammation and enforce the concept that the influence of tissue-derived signals is critical in adjusting the magnitude and type of immune response built by the host. The better characterization of trained immunity for the persistence of inflammation induced by DAMPs would provide new possibilities for intervention in aging and autoinflammatory disorders. PMID:26970440

  10. Heme Oxygenase-1 Dysregulation in the Brain: Implications for HIV-Associated Neurocognitive Disorders

    PubMed Central

    Ambegaokar, Surendra S; Kolson, Dennis L

    2014-01-01

    Heme oxygenase-1 (HO-1) is a highly inducible and ubiquitous cellular enzyme that subserves cytoprotective responses to toxic insults, including inflammation and oxidative stress. In neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis, HO-1 expression is increased, presumably reflecting an endogenous neuroprotective response against ongoing cellular injury. In contrast, we have found that in human immunodeficiency virus (HIV) infection of the brain, which is also associated with inflammation, oxidative stress and neurodegeneration, HO-1 expression is decreased, likely reflecting a unique role for HO-1 deficiency in neurodegeneration pathways activated by HIV infection. We have also shown that HO-1 expression is significantly suppressed by HIV replication in cultured macrophages which represent the primary cellular reservoir for HIV in the brain. HO-1 deficiency is associated with release of neurotoxic levels of glutamate from both HIV-infected and immune-activated macrophages; this glutamate-mediated neurotoxicity is suppressed by pharmacological induction of HO-1 expression in the macrophages. Thus, HO-1 induction could be a therapeutic strategy for neuroprotection against HIV infection and other neuroinflammatory brain diseases. Here, we review various stimuli and signaling pathways regulating HO-1 expression in macrophages, which could promote neuronal survival through HO-1-modulation of endogenous antioxidant and immune modulatory pathways, thus limiting the oxidative stress that can promote HIV disease progression in the CNS. The use of pharmacological inducers of endogenous HO-1 expression as potential adjunctive neuroprotective therapeutics in HIV infection is also discussed. PMID:24862327

  11. The Incomplete Impact Record and Implications for Ice Core Studies

    NASA Astrophysics Data System (ADS)

    Bay, R. C.; Rohde, R. A.; Price, P. B.

    2007-12-01

    sufficiently extensive and synchronized to suggest an emerging pattern between explosive volcanic layers and abrupt climate change, although atmospheric focusing and preservation of deposits complicate analysis. By comparing ice core ash and acid signals of explosive volcanic fallout in Antarctica and Greenland, we have identified a number of common horizons which likely resulted from "eruptions" that dispersed material world-wide. These events appear to have preferentially occurred during onsets or intensifications of cooling phases, contributing to long-standing debates over possible feedbacks between climatic and geologic phenomena. The correlation may be evidence that abrupt climate change and associated changes in sea level and ice sheets can trigger volcanism. An intriguing and conspicuous alternative possibility is that catastrophic explosions force long term cooling. A relatively high rate for small impact events (objects hundreds of meters in size) could imply that impacts (instead of volcanism) are a causal factor in some of the climate variations observed during the last million years. Our method of optically probing outward from the boreholes created by ice coring missions is capable of detecting particulate layers which are invisible or largely missing in the cores, identifying candidate horizons for chemical analyses. Deliberate and discriminative analysis of the "ash" layers in ice cores could shed light on the recent impact rate. This research was supported by grant NSF ANT-0440609.

  12. Thermal Infrared Studies of Chloride Salts; Implications for Mars

    NASA Astrophysics Data System (ADS)

    Baldridge, A. M.; Osterloo, M. M.; Christensen, P. R.

    2007-12-01

    Morphological and spectral evidence supporting the past occurrence of widespread water on the surface of Mars continues to build. Furthermore, geochemical footprints of water are especially compelling. As a past reservoir of water receded, it would have left behind evaporitic chemistries specific to Martian water-rock interactions (e.g. chlorides, sulfates and phyllosilicates). To understand the extent and abundance of past water, the detection of such minerals is key. In support of both orbital and in situ thermal infrared (TIR) observations, we have examined the TIR behavior of chloride minerals. In the thermal infrared, most minerals are identified based on characteristic absorption features. However, chloride detection is particularly challenging because these minerals are transparent over much of the infrared and therefore their identification must be based on the effect that they have on the spectra of coexisting materials. Additionally, the transparent nature of chlorides results in greybody (non-unit emissivity) behavior and consequently the standard calibration techniques to convert from radiance to emissivity produces a slope in the spectra. Here we discuss laboratory spectral studies including emission, reflectance, and transmission spectra of a suite of chloride minerals and mixtures. These studies are then used to interpret a spectrally distinct deposit identified with 2001 Odyssey Thermal Emission Imaging System (THEMIS) data in the low albedo, mid-to-low latitude, southern highlands of Mars which correspond to mid- late Noachian aged terrains and early Hesperian aged ridged plains units.

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

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed

    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

  15. Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging

    PubMed Central

    2013-01-01

    Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and transplanting a patient’s own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell aging. PMID:23673056

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

    PubMed Central

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

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

    PubMed

    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

  18. Interspecific habitat associations of juvenile salmonids in Lake Ontario tributaries: implications for Atlantic salmon restoration

    USGS Publications Warehouse

    Johnson, James H.; Chalupnicki, Marc

    2014-01-01

    Diel variation in habitat use of subyearling Chinook salmon (Oncorhynchus tshawytscha), subyearling coho salmon (O. kisutch), yearling steelhead (O. mykiss), and yearling Atlantic salmon (Salmo salar) was examined during the spring in two tributaries of Lake Ontario. A total of 1318 habitat observations were made on juvenile salmonids including 367 on steelhead, 351 on Chinook salmon, 333 on Atlantic salmon, and 261 on coho salmon. Steelhead exhibited the most diel variation in habitat use and Chinook the least. Juvenile salmonids were generally associated with more cover and larger substrate during the day in both streams. Interspecific differences in habitat use in both streams occurred with Atlantic salmon (fast velocities) and coho salmon (pools) using the least similar habitat. Chinook salmon and Atlantic salmon used similar habitat in both streams. These findings should help guide future management actions specific to habitat protection and restoration of Atlantic salmon in Lake Ontario tributaries.

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development

    PubMed Central

    Trotter, Caroline L.; Ramsay, Mary E.; Chandra, Manosree; Jolley, Keith A.; van der Ende, Arie; Carion, Françoise; Berthelsen, Lene; Hoffmann, Steen; Harðardóttir, Hjördís; Vazquez, Julio A.; Murphy, Karen; Toropainen, Maija; Caniça, Manuela; Ferreira, Eugenia; Diggle, Mathew; Edwards, Giles F.; Taha, Muhamed-Kheir; Stefanelli, Paola; Kriz, Paula; Gray, Steve J.; Fox, Andrew J.; Jacobsson, Susanne; Claus, Heike; Vogel, Ulrich; Tzanakaki, Georgina; Heuberger, Sigrid; Caugant, Dominique A.; Frosch, Matthias; Maiden, Martin C. J.

    2014-01-01

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups. PMID:24695776

  1. Effects of meals on hemodynamics: implications for antihypertensive drug studies.

    PubMed

    Fagan, T C; Conrad, K A; Mar, J H; Nelson, L

    1986-03-01

    The ingestion of food is known to affect blood pressure and heart rate, but food is often allowed in patients under observation for antihypertensive drug effects. Seventy-seven patients with essential hypertension were observed for 8 hours after a 16-hour fast. Thirty-six continued to fast, 20 ate a high-carbohydrate meal, and 21 ate a meal of their own choice. Blood pressure and heart rate did not change during fasting, but both meals lowered mean supine and standing diastolic blood pressures during the subsequent 4 hours by 3 to 7 mm Hg (P less than 0.001). The high-carbohydrate meal reduced supine systolic blood pressure by 6 mm Hg (P less than 0.0001). Both meals increased supine and standing heart rates by 5 to 8 bpm (P less than 0.001). After the self-selected meal, standing systolic blood pressure increased in younger patients but decreased in older patients. Food ingestion during antihypertensive drug studies may interfere with the interpretation of results and should be avoided whenever possible. PMID:3948465

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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

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

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Position of the American Dietetic Association: health implications of dietary fiber.

    PubMed

    Marlett, Judith A; McBurney, Michael I; Slavin, Joanne L

    2002-07-01

    Dietary fiber consists of the structural and storage polysaccharides and lignin in plants that are not digested in the human stomach and small intestine. A wealth of information supports the American Dietetic Association position that the public should consume adequate amounts of dietary fiber from a variety of plant foods. Recommended intakes, 20-35 g/day for healthy adults and age plus 5 g/day for children, are not being met, because intakes of good sources of dietary fiber, fruits, vegetables, whole and high-fiber grain products, and legumes are low. Consumption of dietary fibers that are viscous lowers blood cholesterol levels and helps to normalize blood glucose and insulin levels, making these kinds of fibers part of the dietary plans to treat cardiovascular disease and type 2 diabetes. Fibers that are incompletely or slowly fermented by microflora in the large intestine promote normal laxation and are integral components of diet plans to treat constipation and prevent the development of diverticulosis and diverticulitis. A diet adequate in fiber-containing foods is also usually rich in micronutrients and nonnutritive ingredients that have additional health benefits. It is unclear why several recently published clinical trials with dietary fiber intervention failed to show a reduction in colon polyps. Nonetheless, a fiber-rich diet is associated with a lower risk of colon cancer. A fiber-rich meal is processed more slowly, which promotes earlier satiety, and is frequently less calorically dense and lower in fat and added sugars. All of these characteristics are features of a dietary pattern to treat and prevent obesity. Appropriate kinds and amounts of dietary fiber for the critically ill and the very old have not been clearly delineated; both may need nonfood sources of fiber. Many factors confound observations of gastrointestinal function in the critically ill, and the kinds of fiber that would promote normal small and large intestinal function are usually

  7. Factors associated with HIV testing and condom use in Mozambique: implications for programs

    PubMed Central

    2012-01-01

    Background To identify predictors of HIV testing and condom use in Mozambique. Methods Nationally representative survey data collected in Mozambique in 2009 was analyzed. Logistic regression analysis was used for two outcomes: HIV testing and condom use. Results Women at a higher risk of HIV were less likely to be tested for HIV than women at a lower risk: compared to married women, HIV testing was lower among never married women (OR = 0.37, CI: 0.25-0.54); compared to women with one lifetime partner, HIV testing was lower among women with four or more lifetime partners (OR = 0.62, CI: 0.47-0.83). Large wealth differentials were observed: compared to the poorest women, HIV testing was higher among the wealthiest women (OR = 3.03, CI: 1.96-4.68). Perceived quality of health services was an important predictor of HIV testing: HIV testing was higher among women who rated health services as being of very good quality (OR = 2.12, CI: 1.49-3.00). Type of sexual partner was the strongest predictor of condom use: condom use was higher among men who reported last sex with a girlfriend (OR = 9.75, CI: 6.81-13.97) or a casual partner (OR = 11.05, CI: 7.21-16.94). Being tested for HIV during the last two years was the only programmatic variable that predicted condom use. Interestingly, being tested for HIV more than two years ago was not associated with condom use. Frequent mass media exposure was neither associated with HIV testing nor with condom use. Conclusions The focus of HIV testing should shift from married women (routinely tested during antenatal care visits) to unmarried women and women with multiple sexual partners. Financial barriers to HIV testing appear to be substantial. Since HIV testing is done without a fee being charged, these barriers are presumably related to the cost of transportation to static health facilities. Mechanisms should be developed to cover the cost of transportation to health facilities. Substantially increasing

  8. New Geophysical L Study Northwestern Antarctic Peninsula: Geodinamic Implicances

    NASA Astrophysics Data System (ADS)

    Vilas, J. F.; Tassone, A. A.; Lippai, H. F.

    2007-05-01

    The current tectonic arrangement of Tierra del Fuego and Antarctica is the product of an extensive and complex evolution that involved the most southern part in South America (SA) from the Early Mesozoic when a subduction area settles down along the Pacific border of Gondwana (GDW) including the then continuous SA and Antarctic Peninsula (AP) (Dalziel and Elliot, 1973; Dalziel, 1982). The paleogeographic position of the AP immediately before the separation of the GDW has been a topic of controversy. The presently available information for the beginning of GDW fragmentation is contradictory. In the last years a new accretion model has been proposed for the Mesozoic development of the AP. This model requires of more data to sustain the extension of the old magmatic arc and GDW paleomargin. A geophysical campaign has been developed along Danco Coast - between Py Point to the south, and Vivot Cape to the north- with the aim of acquire new data to define the geometry, lateral relationships and tectonic development of the geologic units of the Mesozoic magmatic arc exposed in the western border of the AP. Rock outcrops mostly belong to plutonic bodies of granitic through tonalitic composition, and rhyolites, andesites and basaltic rocks. The geologic survey included the lithologic and structural sampling, a total of 216 rock cores were obtained for AMS and paleomagnetic studies. The acquired data have been GPS referred. The magnetic survey was carried out with two magnetometers of proton free- precession: a Scintrex ENVI GRAD (used as permanent base) and a Geometrics G856 magnetometer employed for sampling stations (which measured the intensity of the total magnetic field and worked synchronized with the base magnetometer in order to make the corresponding corrections). A total of 1670 registrations were acquired in the 334 GPS fixed onland stations. A Zodiac MK5 was employed for the offshore magnetic survey. 5162 stations constitute the magnetic grid in offshore areas

  9. Implications of ground water chemistry and flow patterns for earthquake studies.

    PubMed

    Guangcai, Wang; Zuochen, Zhang; Min, Wang; Cravotta, Charles A; Chenglong, Liu

    2005-01-01

    Ground water can facilitate earthquake development and respond physically and chemically to tectonism. Thus, an understanding of ground water circulation in seismically active regions is important for earthquake prediction. To investigate the roles of ground water in the development and prediction of earthquakes, geological and hydrogeological monitoring was conducted in a seismogenic area in the Yanhuai Basin, China. This study used isotopic and hydrogeochemical methods to characterize ground water samples from six hot springs and two cold springs. The hydrochemical data and associated geological and geophysical data were used to identify possible relations between ground water circulation and seismically active structural features. The data for delta18O, deltaD, tritium, and 14C indicate ground water from hot springs is of meteoric origin with subsurface residence times of 50 to 30,320 years. The reservoir temperature and circulation depths of the hot ground water are 57 degrees C to 160 degrees C and 1600 to 5000 m, respectively, as estimated by quartz and chalcedony geothermometers and the geothermal gradient. Various possible origins of noble gases dissolved in the ground water also were evaluated, indicating mantle and deep crust sources consistent with tectonically active segments. A hard intercalated stratum, where small to moderate earthquakes frequently originate, is present between a deep (10 to 20 km), high-electrical conductivity layer and the zone of active ground water circulation. The ground water anomalies are closely related to the structural peculiarity of each monitoring point. These results could have implications for ground water and seismic studies in other seismogenic areas. PMID:16029173

  10. The implication of frontostriatal circuits in young smokers: A resting-state study.

    PubMed

    Yuan, Kai; Yu, Dahua; Bi, Yanzhi; Li, Yangding; Guan, Yanyan; Liu, Jixin; Zhang, Yi; Qin, Wei; Lu, Xiaoqi; Tian, Jie

    2016-06-01

    The critical roles of frontostriatal circuits had been revealed in addiction. With regard to young smokers, the implication of frontostriatal circuits resting-state functional connectivity (RSFC) in smoking behaviors and cognitive control deficits remains unclear. In this study, the volume of striatum subsets, i.e., caudate, putamen, and nucleus accumbens, and corresponding RSFC differences were investigated between young smokers (n1  = 60) and nonsmokers (n2  = 60), which were then correlated with cigarette smoking measures, such as pack_years-cumulative effect of smoking, Fagerström Test for Nicotine Dependence (FTND)-severity of nicotine addiction, Questionnaire on Smoking Urges (QSU)-craving state, and Stroop task performances. Additionally, mediation analysis was carried out to test whether the frontostriatal RSFC mediates the relationship between striatum morphometry and cognitive control behaviors in young smokers when applicable. We revealed increased volume of right caudate and reduced RSFC between caudate and dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex in young smokers. Significant positive correlation between right caudate volume and QSU as well as negative correlation between anterior cingulate cortex-right caudate RSFC and FTND were detected in young smokers. More importantly, DLPFC-caudate RSFC strength mediated the relationship between caudate volume and incongruent errors during Stroop task in young smokers. Our results demonstrated that young smokers showed abnormal interactions within frontostriatal circuits, which were associated with smoking behaviors and cognitive control impairments. It is hoped that our study focusing on frontostriatal circuits could provide new insights into the neural correlates and potential novel therapeutic targets for treatment of young smokers. Hum Brain Mapp 37:2013-2026, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918784

  11. Genomics of chromophobe renal cell carcinoma: implications from a rare tumor for pan-cancer studies

    PubMed Central

    Rathmell, Kimryn W.; Chen, Fengju; Creighton, Chad J.

    2015-01-01

    Chromophobe Renal Cell Carcinoma (ChRCC) is a rare subtype of the renal cell carcinomas, a heterogenous group of cancers arising from the nephron. Recently, The Cancer Genome Atlas (TCGA) profiled this understudied disease using multiple data platforms, including whole exome sequencing, whole genome sequencing (WGS), and mitochondrial DNA (mtDNA) sequencing. The insights gained from this study would have implications for other types of kidney cancer as well as for cancer biology in general. Global molecular patterns in ChRCC provided clues as to this cancer's cell of origin, which is distinct from that of the other renal cell carcinomas, illustrating an approach that might be applied towards elucidating the cell of origin of other cancer types. MtDNA sequencing revealed loss-of-function mutations in NADH dehydrogenase subunits, highlighting the role of deregulated metabolism in this and other cancers. Analysis of WGS data led to the discovery of recurrent genomic rearrangements involving TERT promoter region, which were associated with very high expression levels of TERT, pointing to a potential mechanism for TERT deregulation that might be found in other cancers. WGS data, generated by large scale efforts such as TCGA and the International Cancer Genomics Consortium (ICGC), could be more extensively mined across various cancer types, to uncover structural variants, mtDNA mutations, themes of tumor metabolic properties, as well as noncoding point mutations. TCGA's data on ChRCC should continue to serve as a resource for future pan-cancer as well as kidney cancer studies, and highlight the value of investigations into rare tumor types to globally inform principals of cancer biology. PMID:25859550

  12. Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

    PubMed Central

    2014-01-01

    Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the

  13. Consumption of human milk glycoconjugates by infant-associated bifidobacteria: mechanisms and implications

    PubMed Central

    Garrido, Daniel; Dallas, David C.

    2013-01-01

    Human milk is a rich source of nutrients and energy, shaped by mammalian evolution to provide all the nutritive requirements of the newborn. In addition, several molecules in breast milk act as bioactive agents, playing an important role in infant protection and guiding a proper development. While major breast milk nutrients such as lactose, lipids and proteins are readily digested and consumed by the infant, other molecules, such as human milk oligosaccharides and glycosylated proteins and lipids, can escape intestinal digestion and transit through the gastrointestinal tract. In this environment, these molecules guide the composition of the developing infant intestinal microbiota by preventing the colonization of enteric pathogens and providing carbon and nitrogen sources for other colonic commensals. Only a few bacteria, in particular Bifidobacterium species, can gain access to the energetic content of milk as it is displayed in the colon, probably contributing to their predominance in the intestinal microbiota in the first year of life. Bifidobacteria deploy exquisite molecular mechanisms to utilize human milk oligosaccharides, and recent evidence indicates that their activities also target other human milk glycoconjugates. Here, we review advances in our understanding of how these microbes have been shaped by breast milk components and the strategies associated with their consumption of milk glycoconjugates. PMID:23460033

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

    PubMed

    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

  15. Evidence and Implications of Mortality Associated with Acute Plasmodium vivax Malaria

    PubMed Central

    2013-01-01

    Vivax malaria threatens patients despite relatively low-grade parasitemias in peripheral blood. The tenet of death as a rare outcome, derived from antiquated and flawed clinical classifications, disregarded key clinical evidence, including (i) high rates of mortality in neurosyphilis patients treated with vivax malaria; (ii) significant mortality from zones of endemicity; and (iii) the physiological threat inherent in repeated, very severe paroxysms in any patient, healthy or otherwise. The very well-documented course of this infection, with the exception of parasitemia, carries all of the attributes of “perniciousness” historically linked to falciparum malaria, including severe disease and fatal outcomes. A systematic analysis of the parasite biomass in severely ill patients that includes blood, marrow, and spleen may ultimately explain this historic misunderstanding. Regardless of how this parasite is pernicious, recent data demonstrate that the infection comes with a significant burden of morbidity and associated mortality. The extraordinary burden of malaria is not heavily weighted upon any single continent by a single species of parasite—it is a complex problem for the entire endemic world, and both species are of fundamental importance. Humanity must rally substantial resources, intellect, and energy to counter this daunting but profound threat. PMID:23297258

  16. The MS Risk Allele of CD40 Is Associated with Reduced Cell-Membrane Bound Expression in Antigen Presenting Cells: Implications for Gene Function

    PubMed Central

    Field, Judith; Shahijanian, Fernando; Schibeci, Stephen; Johnson, Laura; Gresle, Melissa; Laverick, Louise; Parnell, Grant; Stewart, Graeme; McKay, Fiona; Kilpatrick, Trevor; Butzkueven, Helmut; Booth, David

    2015-01-01

    Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s) associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS. PMID:26068105

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

    PubMed

    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

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

    ERIC Educational Resources Information Center

    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…

  19. Population structure and linkage disequilibrium in US barley germplasm: implications for association mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have shown that there is considerable population structure in cultivated barley, with the strongest structure corresponding to differences in row number and growth habit. US barley breeding programs include 6-row and 2-row types and winter and spring types in all combinations. To fa...

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

    ERIC Educational Resources Information Center

    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…

  1. Science Education in the Rural United States. Implications for the Twenty-First Century. A Yearbook of the Association for the Education of Teachers in Science.

    ERIC Educational Resources Information Center

    Otto, Paul B., Ed.

    This yearbook of the Association for the Education of Teachers in Science (AETS) is designed to give a perspective on rural science education. It is presented in a sequence which leads from the definition and philosophy of rural science education, to the status of rural science education, research implications, the integration of science within…

  2. Implications of Recent Research for Speech Communication Education; Proceedings of the Speech Communication Association Summer Conference (6th, Chicago, July 9-11, 1970).

    ERIC Educational Resources Information Center

    Sillars, Malcolm O., Ed.

    This publication contains the proceedings of the 1970 Summer Conference of the Speech Communication Association which explored the practical implications of recent research in the field for classroom teachers. Included are (1) four papers by Barbara Wood, Frederick Williams, Gerald R. Miller, and Lawrence Rosenfield, who were commissioned to write…

  3. Inferring Quantitative Trait Pathways Associated with Bull Fertility from a Genome-Wide Association Study

    PubMed Central

    Peñagaricano, Francisco; Weigel, Kent A.; Rosa, Guilherme J. M.; Khatib, Hasan

    2013-01-01

    Whole-genome association studies typically focus on genetic markers with the strongest evidence of association. However, single markers often explain only a small component of the genetic variance and hence offer a limited understanding of the trait under study. As such, the objective of this study was to perform a pathway-based association analysis in Holstein dairy cattle in order to identify relevant pathways involved in bull fertility. The results of a single-marker association analysis, using 1,755 bulls with sire conception rate data and genotypes for 38,650 single nucleotide polymorphisms (SNPs), were used in this study. A total of 16,819 annotated genes, including 2,767 significantly associated with bull fertility, were used to interrogate a total of 662 Gene Ontology (GO) terms and 248 InterPro (IP) entries using a test of proportions based on the cumulative hypergeometric distribution. After multiple-testing correction, 20 GO categories and one IP entry showed significant overrepresentation of genes statistically associated with bull fertility. Several of these functional categories such as small GTPases mediated signal transduction, neurogenesis, calcium ion binding, and cytoskeleton are known to be involved in biological processes closely related to male fertility. These results could provide insight into the genetic architecture of this complex trait in dairy cattle. In addition, this study shows that quantitative trait pathways inferred from single-marker analyses could enhance our interpretations of the results of genome-wide association studies. PMID:23335935

  4. Novel Loci Associated with Usual Sleep Duration: The CHARGE Consortium Genome-Wide Association Study

    PubMed Central

    Gottlieb, Daniel J.; Hek, Karin; Chen, Ting-hsu; Watson, Nathaniel F.; Eiriksdottir, Gudny; Byrne, Enda M.; Cornelis, Marilyn; Warby, Simon C.; Bandinelli, Stefania; Cherkas, Lynn; Evans, Daniel S.; Grabe, Hans J.; Lahti, Jari; Li, Man; Lehtimäki, Terho; Lumley, Thomas; Marciante, Kristin D.; Pérusse, Louis; Psaty, Bruce M.; Robbins, John; Tranah, Gregory J.; Vink, Jacqueline M.; Wilk, Jemma B.; Stafford, Jeanette M.; Bellis, Claire; Biffar, Reiner; Bouchard, Claude; Cade, Brian; Curhan, Gary C.; Eriksson, Johan G.; Ewert, Ralf; Ferrucci, Luigi; Fülöp, Tibor; Gehrman, Philip R.; Goodloe, Robert; Harris, Tamara B.; Heath, Andrew C.; Hernandez, Dena; Hofman, Albert; Hottenga, Jouke-Jan; Hunter, David J.; Jensen, Majken K.; Johnson, Andrew D.; Kähönen, Mika; Kao, Linda; Kraft, Peter; Larkin, Emma K.; Lauderdale, Diane S.; Luik, Annemarie I.; Medici, Marco; Montgomery, Grant W.; Palotie, Aarno; Patel, Sanjay R.; Pistis, Giorgio; Porcu, Eleonora; Quaye, Lydia; Raitakari, Olli; Redline, Susan; Rimm, Eric B.; Rotter, Jerome I.; Smith, Albert V.; Spector, Tim D.; Teumer, Alexander; Uitterlinden, André G.; Vohl, Marie-Claude; Widen, Elisabeth; Willemsen, Gonneke; Young, Terry; Zhang, Xiaoling; Liu, Yongmei; Blangero, John; Boomsma, Dorret I.; Gudnason, Vilmundur; Hu, Frank; Mangino, Massimo; Martin, Nicholas G.; O’Connor, George T.; Stone, Katie L.; Tanaka, Toshiko; Viikari, Jorma; Gharib, Sina A.; Punjabi, Naresh M.; Räikkönen, Katri; Völzke, Henry; Mignot, Emmanuel; Tiemeier, Henning

    2015-01-01

    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 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 35–80 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 minutes longer per night. The alleles associated with longer sleep duration were associated in previous genome-wide association studies 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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

    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

  7. Genetic/epidemiological findings in a study of smoking-associated tumors.

    PubMed

    Lynch, H T; Fain, P R; Albano, W A; Ruma, T; Black, L; Lynch, J; Shonka, M

    1982-06-01

    While the etiology of bronchogenic carcinoma remains enigmatic, an expanding array of carcinogenic pollutants in interaction with host susceptibility factors has been implicated. We have studied family histories of cancer in a consecutive series of cancer patients from two university oncology clinics in Nebraska. Particular attention has been given to carcinoma of the lung and other putative smoking-associated cancers (oral cavity, esophagus, urinary bladder, pancreas). Smoking histories were obtained for relatives of an overlapping series of patients with these tumor sites. Findings revealed that, although a significant cohort effect was observed with respect to smoking habits for both relatives of lung cancer probands and for relatives of probands with other smoking-associated tumors, a corresponding trend for lung cancer frequency was observed only for relatives of lung cancer probands. This result suggests the importance of host factors in combination with environmental exposures in determining lung risk. A cohort trend for lung cancer was also apparent among relatives of breast cancer probands, but not for relatives of colon cancer probands, suggesting the possibility of an intrinsic association between carcinomas of the breast and lung. We believe that further elucidation of host factor susceptibility in lung cancer may have important etiological and preventive implications. PMID:7104988

  8. Spatial Implications Associated with Using Euclidean Distance Measurements and Geographic Centroid Imputation in Health Care Research

    PubMed Central

    Jones, Stephen G; Ashby, Avery J; Momin, Soyal R; Naidoo, Allen

    2010-01-01

    Objective To determine the effect of using Euclidean measurements and zip-code centroid geo-imputation versus more precise spatial analytical techniques in health care research. Data Sources Commercially insured members from a southeastern managed care organization. Study Design Distance from admitting inpatient facility to member's home and zip-code centroid (geographic placement) was compared using Euclidean straight-line and shortest-path drive distances (measurement technique). Data Collection Administrative claims from October 2005 to September 2006. Principal Findings Measurement technique had a greater impact on distance values compared with geographic placement. Drive distance from the geocoded address was highly correlated (r=0.99) with the Euclidean distance from the zip-code centroid. Conclusions Actual differences were relatively small. Researchers without capabilities to produce drive distance measurements and/or address geocoding techniques could rely on simple linear regressions to estimate correction factors with a high degree of confidence. PMID:19780852

  9. Changes in Hawaiian palagonite FE mineralogy associated with thermal alteration: Implications for Mars

    NASA Technical Reports Server (NTRS)

    Bell, James F., III; Morris, Richard V.; Adams, John B.

    1993-01-01

    We have studied six Hawaiian palagonitic tephra samples (PH-1 through PH-6) from a site where a Mauna Loa lava flow has partially embayed a Mauna Kea cinder cone Tephra samples that were not affected by the lava flow (PH-5, PH-6) consist of partially palagonitized coarse-grained glassy Hawaiitic particles whose iron mineralogy is dominated by nanophase ferric oxide (np-Ox) and olivine. Samples closest to the lava flow (PH-1 through PH-4) have been strongly altered and their iron mineralogy is dominated by np-Ox, magnetite, and hematite. This suite of samples has many spectral similarities to Martian bright regions; thus, this localized thermal alteration event may be an analog to similar processes on Mars that lead to the production of small amounts of crystalline ferric oxides within a poorly-crystalline or amorphous palagonitic matrix.

  10. Pneumococcal serotypes associated with invasive disease in under five children in India & implications for vaccine policy

    PubMed Central

    Balaji, V.; Jayaraman, Ranjith; Verghese, Valsan Philip; Baliga, P.R.; Kurien, T.

    2015-01-01

    Background & objectives: Streptococcus pneumoniae is a major cause of morbidity and mortality especially in children less than five years, particularly in India. We present data on S. pneumoniae infections in children less than five years age group, with response to its serotype distribution, antibiotic resistance profile and available vaccines expected coverage. Methods: Children aged less than five, who were suspected for invasive pneumococcal disease were included in the study and their sterile body fluids were investigated for the presence of S. pneumoniae. Invasive S. pneumoniae isolates from sterile body fluids were identified by bile solubility and optochin susceptibility test. Pneumococcal serotyping was performed with co-agglutination technique and reconfirmed with multiplex PCR. Results: The most common pneumococcal serotypes causing invasive infections in children less than five years of age were 14, 19F, 5, 6A and 6B. Of the 114 S. pneumoniae isolates studied, 110 (96.4%) were non-susceptible to co-trimoxazole and 30 per cent were non-susceptible to erythromycin, 5.2 per cent of the isolates were non-susceptible to penicillin and only 0.8 per cent was non-susceptible to cefotaxime. Interpretation & conclusions: Our results indicate that PCV-10 can protect against 64 per cent of serotypes causing invasive pneumococcal infections. Use of PCV-13 in this region can provide increase in protection upto 74.6 per cent against serotypes causing invasive pneumococcal infections. Incorporating PCV-13 in the Universal Immunization Programme may provide incremental protection against IPD serotypes in the southern region of the country. PMID:26458344

  11. Identification of aerosol types over Indo-Gangetic Basin: implications to optical properties and associated radiative forcing.

    PubMed

    Tiwari, S; Srivastava, A K; Singh, A K; Singh, Sachchidanand

    2015-08-01

    The aerosols in the Indo-Gangetic Basin (IGB) are a mixture of sulfate, dust, black carbon, and other soluble and insoluble components. It is a challenge not only to identify these various aerosol types, but also to assess the optical and radiative implications of these components. In the present study, appropriate thresholds for fine-mode fraction and single-scattering albedo have been used to first identify the aerosol types over IGB. Four major aerosol types may be identified as polluted dust (PD), polluted continental (PC), black carbon-enriched (BCE), and organic carbon-enriched (OCE). Further, the implications of these different types of aerosols on optical properties and radiative forcing have been studied. The aerosol products derived from CIMEL sun/sky radiometer measurements, deployed under Aerosol Robotic Network program of NASA, USA were used from four different sites Karachi, Lahore, Jaipur, and Kanpur, spread over Pakistan and Northern India. PD is the most dominant aerosol type at Karachi and Jaipur, contributing more than 50% of all the aerosol types. OCE, on the other hand, contributes only about 12-15% at all the stations except at Kanpur where its contribution is ∼38%. The spectral dependence of AOD was relatively low for PD aerosol type, with the lowest AE values (<0.5); whereas, large spectral dependence in AOD was observed for the remaining aerosol types, with the highest AE values (>1.0). SSA was found to be the highest for OCE (>0.9) and the lowest for BCE (<0.9) type aerosols, with drastically different spectral variability. The direct aerosol radiative forcing at the surface and in the atmosphere was found to be the maximum at Lahore among all the four stations in the IGB. PMID:25893625

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

    PubMed

    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

  13. Pickup ion processes associated with spacecraft thrusters: Implications for solar probe plus

    NASA Astrophysics Data System (ADS)

    Clemens, Adam; Burgess, David

    2016-03-01

    Chemical thrusters are widely used in spacecraft for attitude control and orbital manoeuvres. They create an exhaust plume of neutral gas which produces ions via photoionization and charge exchange. Measurements of local plasma properties will be affected by perturbations caused by the coupling between the newborn ions and the plasma. A model of neutral expansion has been used in conjunction with a fully three-dimensional hybrid code to study the evolution and ionization over time of the neutral cloud produced by the firing of a mono-propellant hydrazine thruster as well as the interactions of the resulting ion cloud with the ambient solar wind. Results are presented which show that the plasma in the region near to the spacecraft will be perturbed for an extended period of time with the formation of an interaction region around the spacecraft, a moderate amplitude density bow wave bounding the interaction region and evidence of an instability at the forefront of the interaction region which causes clumps of ions to be ejected from the main ion cloud quasi-periodically.

  14. Association of Intron Loss with High Mutation Rate in Arabidopsis: Implications for Genome Size Evolution

    PubMed Central

    Yang, Yu-Fei; Zhu, Tao; Niu, Deng-Ke

    2013-01-01

    Despite the prevalence of intron losses during eukaryotic evolution, the selective forces acting on them have not been extensively explored. Arabidopsis thaliana lost half of its genome and experienced an elevated rate of intron loss after diverging from A. lyrata. The selective force for genome reduction was suggested to have driven the intron loss. However, the evolutionary mechanism of genome reduction is still a matter of debate. In this study, we found that intron-lost genes have high synonymous substitution rates. Assuming that differences in mutability among different introns are conserved among closely related species, we used the nucleotide substitution rate between orthologous introns in other species as the proxy of the mutation rate of Arabidopsis introns, either lost or extant. The lost introns were found to have higher mutation rates than extant introns. At the genome-wide level, A. thaliana has a higher mutation rate than A. lyrata, which correlates with the higher rate of intron loss and rapid genome reduction of A. thaliana. Our results indicate that selection to minimize mutational hazards might be the selective force for intron loss, and possibly also for genome reduction, in the evolution of A. thaliana. Small genome size and lower genome-wide intron density were widely reported to be correlated with phenotypic features, such as high metabolic rates and rapid growth. We argue that the mutational-hazard hypothesis is compatible with these correlations, by suggesting that selection for rapid growth might indirectly increase mutational hazards. PMID:23516254

  15. Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: Functional and antioxidative implications

    PubMed Central

    Roche, Camille J.; Dantsker, David; Alayash, Abdu I.; Friedman, Joel M.

    2012-01-01

    The presence of acellular hemoglobin (Hb) within the circulation is generally viewed as a pathological state that can result in toxic consequences. Haptoglobin (Hp), a globular protein found in the plasma, binds with high avidity the αβ dimers derived from the dissociation of Hb tetramer and thus helps clear free Hb. More recently there have been compelling indications that the redox properties of the Hp bound dimer (Hb–Hp) may play a more active role in controlling toxicity by limiting the potential tissue damage caused by propagation of the free-radicals generated within the heme containing globin chains. The present study further examines the potential protective effect of Hp through its impact on the production of nitric oxide (NO) from nitrite through nitrite reductase activity of the Hp bound αβ Hb dimer. The presented results show that the Hb dimer in the Hb–Hp complex has oxygen binding, CO recombination and spectroscopic properties consistent with an Hb species having properties similar to but not exactly the same as the R quaternary state of the Hb tetramer. Consistent with these observations is the finding that the initial nitrite reductase rate for Hb–Hp is approximately ten times that of HbA under the same conditions. These results in conjunction with the earlier redox properties of the Hb–Hp are discussed in terms of limiting the pathophysiological consequences of acellular Hb in the circulation. PMID:22521791

  16. Sex Differences in monocytes and TLR4 associated immune responses; implications for systemic lupus erythematosus (SLE)

    PubMed Central

    Jiang, Wei; Gilkeson, Gary

    2014-01-01

    It has been shown that TLR7 and TLR9 signaling play a role in SLE pathogenesis. Our recent study revealed that estrogen receptor α knockout mice have impaired inflammatory responses to TLR3, TLR4, TLR7 and TLR9 ligand stimulation in DCs, B cells and whole spleen cells. These findings indicate that estrogen receptor mediated signaling may impact universal TLR responsiveness. Whether estrogen has a direct or indirect effect on TLR responsiveness by immune cells is not clear. There is evidence of a role of TLR4 in SLE disease pathogenesis, such as the kidney damage, the induction of CD40 and autoantibodies, the suppression of regulatory T cells, and the role of pro-inflammatory cytokines (e.g., IL-6, IL-1β, TNF-α) in SLE pathogenesis that can be induced by TLR4-mediated monocyte activation, suggesting that TLR4 and TLR4 responsiveness are also important for SLE disease. This review will focus on TLR4 responses and monocytes, which are understudied in systemic autoimmune diseases such as SLE. PMID:25309746

  17. Dietary correlates associated with the mental foramen in primates: implications for interpreting the fossil record.

    PubMed

    Muchlinski, Magdalena N; Deane, Andrew S

    2016-07-01

    The mandibular nerve is a sensory and motor nerve that innervates the muscles of mastication, the lower dentition, and the lower lip and surrounding structures. Although this nerve contains both efferent and afferent fibers, the mental nerve, a terminal branch of the mandibular nerve, is a strictly sensory nerve that exits the mental foramen and innervates the lower lip, the skin overlaying the mandible, and the oral mucosa around the mandible. Osteological foramina are often used as proxies for nerve cross section area and they often correlate well with some aspect of a primate's ecology (e.g., optic foramen and visual acuity). The primary objective of this study is to explore the correlation between the mental foramen and dietary preference among primates. The mental foramen of 40 primate species (n = 180) was measured from 3-D surface models of the mandible. Both conventional and phylogenetic tests indicate that although frugivores have larger mental foramina than folivores, the differences were not significant. These results show that while structures like the infraorbital foramen correlate well with diet and touch sensitivity, the mental foramen does not. Based on these findings, the mental foramen is not a suggested morphological character for interpreting of the fossil record. J. Morphol. 277:978-985, 2016. © 2016 Wiley Periodicals, Inc. PMID:27130849

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

    PubMed Central

    Park, Chul-Kee; Jung, Shin; Park, Eun Sung; Lee, Ju-Seog; Kim, Se-Hyuk; Woo, Hyun Goo

    2015-01-01

    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. PMID:26466313

  19. Type B lamins remain associated with the integral nuclear envelope protein p58 during mitosis: implications for nuclear reassembly.

    PubMed Central

    Meier, J; Georgatos, S D

    1994-01-01

    p58 (also referred to as the lamin B receptor) is an integral membrane protein of the nuclear envelope known to form a multimeric complex with the lamins and other nuclear proteins during interphase. To examine the fate of this complex during mitosis, we have investigated the partitioning and the molecular interactions of p58 in dividing chicken hepatoma (DU249) cells. Using confocal microscopy and double immunolabelling, we show here that lamins B1 and B2 co-localize with p58 during all phases of mitosis and co-assemble around reforming nuclei. A close juxtaposition of p58/lamin B-containing vesicles and chromosomes is already detectable in metaphase; however, p58 and lamin reassembly proceeds slowly and is completed in late telophase--G1. Flotation of mitotic membranes in sucrose density gradients and analysis of mitotic vesicles by immunoelectron microscopy confirms that p58 and most of the type B lamins reside in the same compartment. Co-immunoprecipitation of both proteins by affinity-purified anti-p58 antibodies shows that they are physically associated in the context of a mitotic p58 'sub-complex'. This sub-assembly does not include the type A lamins which are fully solubilized during mitosis. Our data provide direct, in vivo and in vitro evidence that the majority of type B lamins remain connected to nuclear membrane 'receptors' during mitosis. The implications of these findings in nuclear envelope reassembly are discussed below. Images PMID:8168487

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

    PubMed

    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

  1. Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions.

    PubMed Central

    Peles, E; Nativ, M; Lustig, M; Grumet, M; Schilling, J; Martinez, R; Plowman, G D; Schlessinger, J

    1997-01-01

    Receptor protein tyrosine phosphatase beta (RPTPbeta) expressed on the surface of glial cells binds to the glycosylphosphatidylinositol (GPI)-anchored recognition molecule contactin on neuronal cells leading to neurite outgrowth. We describe the cloning of a novel contactin-associated transmembrane receptor (p190/Caspr) containing a mosaic of domains implicated in protein-protein interactions. The extracellular domain of Caspr contains a neurophilin/coagulation factor homology domain, a region related to fibrinogen beta/gamma, epidermal growth factor-like repeats, neurexin motifs as well as unique PGY repeats found in a molluscan adhesive protein. The cytoplasmic domain of Caspr contains a proline-rich sequence capable of binding to a subclass of SH3 domains of signaling molecules. Caspr and contactin exist as a complex in rat brain and are bound to each other by means of lateral (cis) interactions in the plasma membrane. We propose that Caspr may function as a signaling component of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. The binding of RPTPbeta to the contactin-Caspr complex could provide a mechanism for cell-cell communication between glial cells and neurons during development. PMID:9118959

  2. Flare-associated Fast-mode Coronal Wave Trains Discovered by SDO/AIA: Physical Properties and Implications

    NASA Astrophysics Data System (ADS)

    Liu, W.; Ofman, L.; Downs, C.; Cheung, C. M. M.; Broder, B.; De Pontieu, B.

    2015-12-01

    Quasi-periodic Fast Propagating wave trains (QFPs) are a new observational phenomenon discovered in extreme ultraviolet (EUV) by the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). They are fast-mode magnetosonic waves, closely related to quasi-periodic pulsations in solar flare emission ranging from radio to X-ray wavelengths. The significance of QFPs lies in their diagnostic potential, because they can provide critical clues to flare energy release and serve as new tools for coronal seismology. In this presentation, we report recent advances in observing and modeling QFPs. For example, using differential emission measure (DEM) inversion, we found clear evidence of heating and cooling cycles that are consistent with alternating compression and rarefaction expected for magnetosonic wave pulses. Moreover, recent IRIS observations of QFP source regions revealed sawtooth-like flare ribbon motions, indicative of pulsed magnetic reconnection, that are correlated with QFP excitation. More interestingly, from a survey of over 100 QFP events, we found a preferential association with eruptive flares rather than confined flares. We will discuss the implications of these results and the potential roles of QFPs in coronal heating, energy transport, and solar eruptions.

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

    PubMed Central

    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.; Alvero, Ruben; Barnhart, Huiman X.; Baker, Valerie; Barnhart, Kurt T.; Bates, G. Wright; Brzyski, Robert G.; Carr, Bruce R.; Carson, Sandra A.; Casson, Peter; Cataldo, Nicholas A.; Christman, Gregory; Coutifaris, Christos; Diamond, Michael P.; Eisenberg, Esther; Gosman, Gabriella G.; Giudice, Linda C.; Haisenleder, Daniel J.; Huang, Hao; Krawetz, Stephen A.; Lucidi, Scott; McGovern, Peter G.; Myers, Evan R.; Nestler, John E.; Ohl, Dana; Santoro, Nanette; Schlaff, William D.; Snyder, Peter; Steinkampf, Michael P.; Trussell, J. C.; Usadi, Rebecca; Yan, Qingshang; Zhang, Heping; 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 8p32.1 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

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

    PubMed

    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. PMID:26230249

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Habitat Association and Conservation Implications of Endangered Francois’ Langur (Trachypithecus francoisi)

    PubMed Central

    Zeng, Yajie; Xu, Jiliang; Wang, Yong; Zhou, Chunfa

    2013-01-01

    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. PMID:24130730

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

    ERIC Educational Resources Information Center

    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…

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

    PubMed

    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

  9. Molecular sequences derived from Paleocene Fort Union Formation coals vs. associated produced waters: Implications for CBM regeneration

    USGS Publications Warehouse

    Klein, Donald A.; Flores, Romeo M.; Venot, Christophe; Gabbert, Kendra; Schmidt, Raleigh; Stricker, Gary D.; Pruden, Amy; Mandernack, Kevin

    2008-01-01

    Coalbed methane regeneration is of increasing interest, and is gaining global attention with respect to enhancement of gas recovery. The objective of this study is to determine if there are differences in methanogen nucleic acid sequences associated with low rank coals from the Powder River Basin, Wyoming, in comparison with sequences that can be recovered from coal bed-associated produced waters. Based on results obtained to date, the sequences from the coals appear to be associated with putatively deep-rooted thermophilic autotrophic methanogens, whereas the sequences from the waters are associated with thermophilic autotrophic and heterotrophic methanogens. The recovered sequences associated with coal thus appear to be both phylogenetically and functionally distinct from those that are more closely associated with the produced water. To be able to relate such recovered sequences to organisms that might be present and possibly active in these environments, it is suggested that direct observation, followed by isolation and single cell-based physiological/molecular analyses, be used to characterize methanogenic consortia possibly associated with coals and/or produced waters. It is also important to characterize the microenvironment where these microbes might be found, in both ecological and geological contexts, to be able to develop effective, ecologically relevant coalbed methane regeneration processes.

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

    PubMed

    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

  11. Associations of Postural Knowledge and Basic Motor Skill with Dyspraxia in Autism: Implication for Abnormalities in Distributed Connectivity and Motor Learning

    PubMed Central

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

    2009-01-01

    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 controls. The ASD group continued to show significantly poorer praxis than 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

  12. The cys-loop ligand-gated ion channel gene family of Tetranychus urticae: implications for acaricide toxicology and a novel mutation associated with abamectin resistance.

    PubMed

    Dermauw, W; Ilias, A; Riga, M; Tsagkarakou, A; Grbić, M; Tirry, L; Van Leeuwen, T; Vontas, J

    2012-07-01

    The cys-loop ligand-gated ion channel (cysLGIC) super family of Tetranychus urticae, the two-spotted spider mite, represents the largest arthropod cysLGIC super family described to date and the first characterised one within the group of chelicerates. Genome annotation, phylogenetic analysis and comparison of the cysLGIC subunits with their counterparts in insects reveals that the T. urticae genome encodes for a high number of glutamate- and histamine-gated chloride channel genes (GluCl and HisCl) compared to insects. Three orthologues of the insect γ-aminobutyric acid (GABA)-gated chloride channel gene Rdl were detected. Other cysLGIC groups, such as the nAChR subunits, are more conserved and have clear insect orthologues. Members of cysLGIC family mediate endogenous chemical neurotransmission and they are prime targets of insecticides. Implications for toxicology associated with the identity and specific features of T. urticae family members are discussed. We further reveal the accumulation of known and novel mutations in different GluCl channel subunits (Tu_GluCl1 and Tu_GluCl3) associated with abamectin resistance in T. urticae, and provide genetic evidence for their causality. Our study provides useful toxicological insights for the exploration of the T. urticae cysLGIC subunits as putative molecular targets for current and future chemical control strategies. PMID:22465149

  13. Global implications of the emergence of community-associated methicillin-resistant Staphylococcus aureus in Indigenous populations.

    PubMed

    Tong, Steven Y C; McDonald, Malcolm I; Holt, Deborah C; Currie, Bart J

    2008-06-15

    The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in Australia may have been facilitated by conditions in socially disadvantaged populations--particularly, remote Australian Aboriginal communities. The appearance of community-associated MRSA was first noticed in Australia during the early 1980s; subsequently, several genetically diverse strains have independently emerged from geographically distinct regions. Molecular and epidemiological studies support the role of genetic transfer of resistance determinants (SCCmecIV) in this process. Conditions in Aboriginal communities--namely, domestic crowding, poor hygiene, and high rates of scabies, pyoderma, and antibiotic use--have facilitated both the clonal expansion and de novo emergence of strains of community-associated MRSA. Combating the worldwide emergence and spread of community-associated MRSA may require novel community-level control strategies targeted at specific groups, such as remote Indigenous populations. PMID:18462175

  14. Longitudinal study of appraisal at Three Mile Island: implications for life event research.

    PubMed

    Goldsteen, R; Schorr, J K; Goldsteen, K S

    1989-01-01

    This study tests a path model which indicates the occurrence of appraisal following the accident at Three Mile Island (TMI). The model posits a causal relationship between trust in TMI-related authorities, perceived danger, perceived harm to health, and psychological distress. The implications of the findings for life event research are discussed in terms of the etiological significance of meaning, event consequences, and control. PMID:2705011

  15. "No Child Left Behind Act of 2001" and Implications for the Pacific Territories and Freely Associated States. PREL Briefing Paper.

    ERIC Educational Resources Information Center

    Heine, Hilda C.

    Pacific Resources for Education and Learning (PREL) prepared a summary and brief analysis of the "No Child Left Behind Act of 2001" (NCLB) and its implications for education for the American Pacific region. This briefing paper is intended to help educational leaders understand the law and its expectations and implications for schools, educators,…

  16. RETROSPECTIVE EPIDEMIOLOGICAL STUDY OF DISEASE ASSOCIATED WITH WASTEWATER UTILIZATION

    EPA Science Inventory

    A retrospective epidemiological study was carried out on the association between enteric disease incidence and wastewater utilization in 79 kibbutzim (cooperative agricultural settlements) in Israel having a population of 32,672. Medical records on disease incidence were collecte...

  17. Matching Strategies for Genetic Association Studies in Structured Populations

    PubMed Central

    Hinds, David A.; Stokowski, Renee P.; Patil, Nila; Konvicka, Karel; Kershenobich, David; Cox, David R.; Ballinger, Dennis G.

    2004-01-01

    Association studies in populations that are genetically heterogeneous can yield large numbers of spurious associations if population subgroups are unequally represented among cases and controls. This problem is particularly acute for studies involving pooled genotyping of very large numbers of single-nucleotide–polymorphism (SNP) markers, because most methods for analysis of association in structured populations require individual genotyping data. In this study, we present several strategies for matching case and control pools to have similar genetic compositions, based on ancestry information inferred from genotype data for ∼300 SNPs tiled on an oligonucleotide-based genotyping array. We also discuss methods for measuring the impact of population stratification on an association study. Results for an admixed population and a phenotype strongly confounded with ancestry show that these simple matching strategies can effectively mitigate the impact of population stratification. PMID:14740319

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

    PubMed

    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 < 5 × 10(-6) in African Americans were carried forward for de novo genotyping in 570 non-diabetic West Africans. We replicated SNPs in or near SC4MOL and TCERG1L in West Africans. The meta-analysis of 1497 African Americans and West Africans yielded genome-wide significant associations for SNPs in the SC4MOL gene: rs17046216 (P = 1.7 × 10(-8) and 2.9 × 10(-8) for FI and IR, respectively); and near the TCERG1L gene with rs7077836 as the top scoring (P = 7.5 × 10(-9) and 4.9 × 10(-10) for FI and IR, respectively). In silico replication in the MAGIC study (n = 37 037) showed weak but significant association (adjusted P-value of 0.0097) for rs34602777 in the MYO5A gene. In addition, we replicated previous GWAS findings for IR and FI in Europeans for GCKR, and for variants in four T2D loci (FTO, IRS1, 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

  19. SCN9A Variants May be Implicated in Neuropathic Pain Associated With Diabetic Peripheral Neuropathy and Pain Severity

    PubMed Central

    Cheng, Peter; Favis, Reyna; Wickenden, Alan; Romano, Gary; Wang, Hao

    2015-01-01

    Objectives: Previous studies have established the role of SCN9A in various pain conditions, including idiopathic small fiber neuropathy. In the present study, we interrogate the relationship between common and rare variants in SCN9A gene and chronic neuropathic pain associated with diabetic peripheral neuropathy. Design: Using a cohort of 938 patients of European ancestry with chronic neuropathic pain associated with diabetic peripheral neuropathy enrolled in 6 clinical studies and 2 controls (POPRES, n=2624 and Coriell, n=1029), we examined the relationship between SCN9A variants and neuropathic pain in a case-control study using a 2-stage design. The exonic regions of SCN9A were sequenced in a subset of 244 patients with neuropathic pain, and the variants discovered were compared with POPRES control (stage 1). The top associated variants were followed up by genotyping in the entire case collection and Coriell controls restricting the analysis to the matching patients from the United States and Canada only (stage 2). Results: Seven variants were found to be associated with neuropathic pain at the sequencing stage. Four variants (Asp1908Gly, Val991Leu/Met932Leu, and an intronic variant rs74449889) were confirmed by genotyping to occur at a higher frequency in cases than controls (odds ratios ∼2.1 to 2.6, P=0.05 to 0.009). Val991Leu/Met932Leu was also associated with the severity of pain as measured by pain score Numeric Rating Scale (NRS-11, P=0.047). Val991Leu/Met932Leu variants were in complete linkage disequilibrium and previously shown to cause hyperexcitability in dorsal root ganglia neurons. Conclusions: The association of SCN9A variants with neuropathic pain and pain severity suggests a role of SCN9A in the disease etiology of neuropathic pain. PMID:25585270

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

    PubMed Central

    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

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

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

    2016-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Do Emotional Eating Urges Regulate Affect? Concurrent and Prospective Associations and Implications for Risk Models of Binge Eating

    PubMed Central

    Haedt-Matt, Alissa A.; Keel, Pamela K.; Racine, Sarah E.; Burt, S. Alexandra; Hu, Jean Yueqin; Boker, Steven; Neale, Michael; Klump, Kelly L.

    2014-01-01

    Objective Emotional eating (EE) reflects an urge to eat in response to emotional rather than physical cues and is a risk factor for the development of binge eating. EE has been conceptualized as an attempt to regulate negative affect (NA), a posited maintenance factor for binge eating. However, no study has examined whether EE urges regulate affect. Further, no studies have examined longitudinal associations between EE urges and positive affect (PA). Method We examined within-subject longitudinal associations between affect and EE urges in a community-based sample of female twins (mean age=17.8 years). Participants (N=239) completed ratings of affect and EE urges for 45 consecutive days. Results Greater NA was concurrently associated with greater EE urges. Additionally, greater EE urges predicted worse NA for both concurrent and prospective (next-day) analyses. Finally, lower PA was associated with greater EE urges in concurrent analyses, but there were no prospective associations between changes in PA and EE urges. Discussion EE urges do not appear to effectively regulate affect. EE urges in a community-based sample appears to have the same functional relationship with affect as binge eating in clinical samples, further supporting EE as a useful dimensional construct for examining processes related to binge eating. PMID:24431328

  5. Discerning the Ancestry of European Americans in Genetic Association Studies

    PubMed Central

    Price, Alkes L; Butler, Johannah; Patterson, Nick; Capelli, Cristian; Pascali, Vincenzo L; Scarnicci, Francesca; Ruiz-Linares, Andres; Groop, Leif; Saetta, Angelica A; Korkolopoulou, Penelope; Seligsohn, Uri; Waliszewska, Alicja; Schirmer, Christine; Ardlie, Kristin; Ramos, Alexis; Nemesh, James; Arbeitman, Lori; Goldstein, David B

    2008-01-01

    European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data. PMID:18208327

  6. A Survival Association Study of 102 Polymorphisms Previously Associated with Survival Outcomes in Colorectal Cancer

    PubMed Central

    Xu, Jingxiong; Werdyani, Salem; Shestopaloff, Konstantin; Dicks, Elizabeth; Green, Jane; Parfrey, Patrick; Green, Roger

    2015-01-01

    Several published studies identified associations of a number of polymorphisms with a variety of survival outcomes in colorectal cancer. In this study, we aimed to explore 102 previously reported common genetic polymorphisms and their associations with overall survival (OS) and disease-free survival (DFS) in a colorectal cancer patient cohort from Newfoundland (n = 505). Genotypes were obtained using a genomewide SNP genotyping platform. For each polymorphism, the best possible genetic model was estimated for both overall survival and disease-free survival using a previously published approach. These SNPs were then analyzed under their genetic models by Cox regression method. Correction for multiple comparisons was performed by the False Discovery Rate (FDR) method. Univariate analysis results showed that RRM1-rs12806698, IFNGR1-rs1327474, DDX20-rs197412, and PTGS2-rs5275 polymorphisms were nominally associated with OS or DFS (p < 0.01). In stage-adjusted analysis, the nominal associations of DDX20-rs197412, PTGS2-rs5275, and HSPA5-rs391957 with DFS were detected. However, after FDR correction none of these polymorphisms remained significantly associated with the survival outcomes. We conclude that polymorphisms investigated in this study are not associated with OS or DFS in our colorectal cancer patient cohort. PMID:26064972

  7. Association study of the estrogen receptor gene ESR1 with post-partum depression – a pilot study

    PubMed Central

    Pinsonneault, Julia K.; Sullivan, Danielle; Sadee, Wolfgang; Soares, Claudio N.; Hampson, Elizabeth; Steiner, Meir

    2013-01-01

    Perinatal mood disorders, such as postpartum depression (PPD) are costly for society, with potentially serious consequences for mother and child. While multiple genes appear to play a role in PPD susceptibility, the contributions of specific genetic variations remain unclear. Previously implicated as a candidate gene, the estrogen receptor alpha gene (ESR1) is a key player in mediating hormonal differences during pregnancy and the postpartum period. This study addresses genetic factors in perinatal mood disorders, testing 9 polymorphisms in ESR1. 257 postpartum women were screened for mood disorders, including 52 women with PPD and 32 without any symptoms of mood disorders. We detected a significant association for the upstream TA microsatellite repeat with the Edinburgh Postnatal Depression Scale (p=0.007). The same variant was also associated with the occurrence of PPD. Separately, 11 candidate functional polymorphisms in 7 additional genes were genotyped to investigate gene-gene interaction with the ESR1 TA repeat, identifying a potential interaction with the serotonin transporter. Our results support a role for ESR1 in the etiology of PPD, possibly through the modulation of serotonin signaling. Our findings for ESR1 could have broad implications for other disorders and therapies that involve estrogens. PMID:23917948

  8. Genome-wide association studies in diverse populations

    PubMed Central

    Rosenberg, Noah A; Huang, Lucy; Jewett, Ethan M; Szpiech, Zachary A; Jankovic, Ivana; Boehnke, Michael

    2011-01-01

    Genome-wide association (GWA) studies have identified a large number of single-nucleotide polymorphisms (SNPs) associated with disease phenotypes. As most GWA studies have been performed primarily in populations of European descent, this review examines the issues involved in extending consideration of GWA studies to diverse worldwide populations. Although challenges exist with such issues as imputation, admixture, and replication, investigation of diverse populations in GWA studies has significant potential to advance the project of mapping the genetic determinants of complex diseases for the human population as a whole. PMID:20395969

  9. Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies

    PubMed Central

    Kottgen, Anna; Kao, Wen Hong L; Hwang, Shih-Jen; Boerwinkle, Eric; Yang, Qiong; Levy, Daniel; Benjamin, Emelia J; Larson, Martin G; Astor, Brad C; Coresh, Josef; Fox, Caroline S

    2008-01-01

    Background The Framingham Heart Study (FHS) recently obtained initial results from the first genome-wide association scan for renal traits. The study of 70,987 single nucleotide polymorphisms (SNPs) in 1,010 FHS participants provides a list of SNPs showing the strongest associations with renal traits which need to be verified in independent study samples. Methods Sixteen SNPs were selected for replication based on the most promising associations with chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and serum cystatin C in FHS. These SNPs were genotyped in 15,747 participants of the Atherosclerosis in Communities (ARIC) Study and evaluated for association using multivariable adjusted regression analyses. Primary outcomes in ARIC were CKD and eGFR. Secondary prospective analyses were conducted for association with kidney disease progression using multivariable adjusted Cox proportional hazards regression. The definition of the outcomes, all covariates, and the use of an additive genetic model was consistent with the original analyses in FHS. Results The intronic SNP rs6495446 in the gene MTHFS was significantly associated with CKD among white ARIC participants at visit 4: the odds ratio per each C allele was 1.24 (95% CI 1.09–1.41, p = 0.001). Borderline significant associations of rs6495446 were observed with CKD at study visit 1 (p = 0.024), eGFR at study visits 1 (p = 0.073) and 4 (lower mean eGFR per C allele by 0.6 ml/min/1.73 m2, p = 0.043) and kidney disease progression (hazard ratio 1.13 per each C allele, 95% CI 1.00–1.26, p = 0.041). Another SNP, rs3779748 in EYA1, was significantly associated with CKD at ARIC visit 1 (odds ratio per each T allele 1.22, p = 0.01), but only with eGFR and cystatin C in FHS. Conclusion This genome-wide association study provides unbiased information implicating MTHFS as a candidate gene for kidney disease. Our findings highlight the importance of replication to identify common SNPs associated with

  10. An epigenome-wide association study of total serum immunoglobulin E concentration.

    PubMed

    Liang, Liming; Willis-Owen, Saffron A G; Laprise, Catherine; 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

    2015-04-30

    Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations--with a meta-analysis false discovery rate less than 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 asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases. PMID:25707804

  11. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

    PubMed Central

    Graham, Deborah S Cunninghame; Pinder, Christopher L; Tombleson, Philip; Behrens, Timothy W; Martín, Javier; Fairfax, Benjamin P; Knight, Julian C; Chen, Lingyan; Replogle, Joseph; Syvänen, Ann-Christine; Rönnblom, Lars; Graham, Robert R; Wither, Joan E; Rioux, John D; Alarcón-Riquelme, Marta E; Vyse, Timothy J

    2015-01-01

    Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry: a new GWAS, meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including 10 novel associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n=16) of transcription factors among SLE susceptibility genes. This supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE. PMID:26502338

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

    PubMed

    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

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

    NASA Astrophysics Data System (ADS)

    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%.

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

    PubMed

    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

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

    PubMed

    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 < 0.001). Moreover, by conditional logistic regression analysis, the odds ratio of prior 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. Generalization of Rare Variant Association Tests for Longitudinal Family Studies.

    PubMed

    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. PMID:26783077

  17. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics.

    PubMed

    Giambartolomei, Claudia; Vukcevic, Damjan; Schadt, Eric E; Franke, Lude; Hingorani, Aroon D; Wallace, Chris; Plagnol, Vincent

    2014-05-01

    Genetic association studies, in particular the genome-wide association study (GWAS) design, have provided a wealth of novel insights into the aetiology of a wide range of human diseases and traits, in particular cardiovascular diseases and lipid biomarkers. The next challenge consists of understanding the molecular basis of these associations. The integration of multiple association datasets, including gene expression datasets, can contribute to this goal. We have developed a novel statistical methodology to assess whether two association signals are consistent with a shared causal variant. An application is the integration of disease scans with expression quantitative trait locus (eQTL) studies, but any pair of GWAS datasets can be integrated in this framework. We demonstrate the value of the approach by re-analysing a gene expression dataset in 966 liver samples with a published meta-analysis of lipid traits including >100,000 individuals of European ancestry. Combining all lipid biomarkers, our re-analysis supported 26 out of 38 reported colocalisation results with eQTLs and identified 14 new colocalisation results, hence highlighting the value of a formal statistical test. In three cases of reported eQTL-lipid pairs (SYPL2, IFT172, TBKBP1) for which our analysis suggests that the eQTL pattern is not consistent with the lipid association, we identify alternative colocalisation results with SORT1, GCKR, and KPNB1, indicating that these genes are more likely to be causal in these genomic intervals. A key feature of the method is the ability to derive the output statistics from single SNP summary statistics, hence making it possible to perform systematic meta-analysis type comparisons across multiple GWAS datasets (implemented online at http://coloc.cs.ucl.ac.uk/coloc/). Our methodology provides information about candidate causal genes in associated intervals and has direct implications for the understanding of complex diseases as well as the design of drugs to

  18. A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation

    PubMed Central

    Han, Jiali; Kraft, Peter; Nan, Hongmei; Guo, Qun; Chen, Constance; Qureshi, Abrar; Hankinson, Susan E.; Hu, Frank B.; Duffy, David L.; Zhao, Zhen Zhen; Martin, Nicholas G.; Montgomery, Grant W.; Hayward, Nicholas K.; Thomas, Gilles; Hoover, Robert N.; Chanock, Stephen; Hunter, David J.

    2008-01-01

    We conducted a multi-stage genome-wide association study of natural hair color in more than 10,000 men and women of European ancestry from the United States and Australia. An initial analysis of 528,173 single nucleotide polymorphisms (SNPs) genotyped on 2,287 women identified IRF4 and SLC24A4 as loci highly associated with hair color, along with three other regions encompassing known pigmentation genes. We confirmed these associations in 7,028 individuals from three additional studies. Across these four studies, SLC24A4 rs12896399 and IRF4 rs12203592 showed strong associations with hair color, with p = 6.0×10−62 and p = 7.46×10−127, respectively. The IRF4 SNP was also associated with skin color (p = 6.2×10−14), eye color (p = 6.1×10−13), and skin tanning response to sunlight (p = 3.9×10−89). A multivariable analysis pooling data from the initial GWAS and an additional 1,440 individuals suggested that the association between rs12203592 and hair color was independent of rs1540771, a SNP between the IRF4 and EXOC2 genes previously found to be associated with hair color. After adjustment for rs12203592, the association between rs1540771 and hair color was not significant (p = 0.52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with other SNPs in this region, including three previously reported SNPs. The signals detected in a region around the MC1R gene were explained by MC1R red hair color alleles. Our results suggest that the IRF4 and SLC24A4 loci are associated with human hair color and skin pigmentation. PMID:18483556

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

    PubMed

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

    PubMed Central

    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

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

    PubMed Central

    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. PMID:27445940

  2. Failure of replicating the association between hippocampal volume and 3 single-nucleotide polymorphisms identified from the European genome-wide association study in Asian populations.

    PubMed

    Li, Ming; Ohi, Kazutaka; Chen, Chunhui; He, Qinghua; Liu, Jie-Wei; Chen, Chuansheng; Luo, Xiong-Jian; Dong, Qi; Hashimoto, Ryota; Su, Bing

    2014-12-01

    Hippocampal volume is a key brain structure for learning ability and memory process, and hippocampal atrophy is a recognized biological marker of Alzheimer's disease. However, the genetic bases of hippocampal volume are still unclear although it is a heritable trait. Genome-wide association studies (GWASs) on hippocampal volume have implicated several significantly associated genetic variants in Europeans. Here, to test the contributions of these GWASs identified genetic variants to hippocampal volume in different ethnic populations, we screened the GWAS-identified candidate single-nucleotide polymorphisms in 3 independent healthy Asian brain imaging samples (a total of 990 subjects). The results showed that none of these single-nucleotide polymorphisms were associated with hippocampal volume in either individual or combined Asian samples. The replication results suggested a complexity of genetic architecture for hippocampal volume and potential genetic heterogeneity between different ethnic populations. PMID:25131003

  3. Characterization of energy critical elements in ore resources and associated waste tailings: Implications for recovery and remediation

    NASA Astrophysics Data System (ADS)

    McClenaghan, Sean H.

    2015-04-01

    The occurrence of Energy Critical Elements (ECE) in primary ore minerals and their subsequent enrichment in waste tailings is of great metallurgical interest. Recovery of many ECEs, in particular In, Ge, and Ga have come chiefly as a by-product of base-metal production (smelting and refining); these elements are found only at very low levels in the Earth's crust and do not typically form economic deposits on their own. As the ECEs become more important for a growing number of technological applications, it is critical to map the distribution of these elements in ore and waste (gangue) minerals to optimize their recovery and remediation. The characterization and beneficiation of ECEs is best illustrated for Zn-rich ore systems, where a mineral such as sphalerite (ZnS) will concentrate a number of major (Fe, Mn) and important trace elements (Cd, Se, In, Ge, Te, Sn, Bi, Sb, Hg). Interestingly, the mineral chemistry of sphalerite will often differ between different styles of mineralization (i.e., granite-hosted veins versus volcanic-hosted massive sulfides) and can even exhibit considerable variability within a deposit in response to metal zonation across hydrothermal facies. This has significant metallurgical implications for the blending of ore resources, the efficient production of Zn concentrates, and their ultimate value during the smelting and refining stages. Gangue minerals transferred to waste tailings may also exhibit significant enrichment in ECEs and precious metals; including Au in pyrite-arsenopyrite, and rare earth elements in a range of carbonate and phosphate minerals. In situ micro-analytical techniques are ideal for the quantitative measurement of trace elements in ore minerals as well as associated gangue materials. Recent advances in ICP-MS and ICP-OES technology coupled with newer classes of UV Excimer lasers (native 193 nm light) have allowed for more discrete analyses, permitting micro-chemical mapping at small scales (<10 microns). Further

  4. A genome-wide association study of copy number variations with umbilical hernia in swine.

    PubMed

    Long, Yi; Su, Ying; Ai, Huashui; Zhang, Zhiyan; Yang, Bin; Ruan, Guorong; Xiao, Shijun; Liao, Xinjun; Ren, Jun; Huang, Lusheng; Ding, Nengshui

    2016-06-01

    Umbilical hernia (UH) is one of the most common congenital defects in pigs, leading to considerable economic loss and serious animal welfare problems. To test whether copy number variations (CNVs) contribute to pig UH, we performed a case-control genome-wide CNV association study on 905 pigs from the Duroc, Landrace and Yorkshire breeds using the Porcine SNP60 BeadChip and penncnv algorithm. We first constructed a genomic map comprising 6193 CNVs that pertain to 737 CNV regions. Then, we identified eight CNVs significantly associated with the risk for UH in the three pig breeds. Six of seven significantly associated CNVs were validated using quantitative real-time PCR. Notably, a rare CNV (CNV14:13030843-13059455) encompassing the NUGGC gene was strongly associated with UH (permutation-corrected P = 0.0015) in Duroc pigs. This CNV occurred exclusively in seven Duroc UH-affected individuals. SNPs surrounding the CNV did not show association signals, indicating that rare CNVs may play an important role in complex pig diseases such as UH. The NUGGC gene has been implicated in human omphalocele and inguinal hernia. Our finding supports that CNVs, including the NUGGC CNV, contribute to the pathogenesis of pig UH. PMID:27028052

  5. Searching for missing heritability: designing rare variant association studies.

    PubMed

    Zuk, Or; Schaffner, Stephen F; Samocha, Kaitlin; Do, Ron; Hechter, Eliana; Kathiresan, Sekar; Daly, Mark J; Neale, Benjamin M; Sunyaev, Shamil R; Lander, Eric S

    2014-01-28

    Genetic studies have revealed thousands of loci predisposing to hundreds of human diseases and traits, revealing important biological pathways and defining novel therapeutic hypotheses. However, the genes discovered to date typically explain less than half of the apparent heritability. Because efforts have largely focused on common genetic variants, one hypothesis is that much of the missing heritability is due to rare genetic variants. Studies of common variants are typically referred to as genomewide association studies, whereas studies of rare variants are often simply called sequencing studies. Because they are actually closely related, we use the terms common variant association study (CVAS) and rare variant association study (RVAS). In this paper, we outline the similarities and differences between RVAS and CVAS and describe a conceptual framework for the design of RVAS. We apply the framework to address key questions about the sample sizes needed to detect association, the relative merits of testing disruptive alleles vs. missense alleles, frequency thresholds for filtering alleles, the value of predictors of the functional impact of missense alleles, the potential utility of isolated populations, the value of gene-set analysis, and the utility of de novo mutations. The optimal design depends critically on the selection coefficient against deleterious alleles and thus varies across genes. The analysis shows that common variant and rare variant studies require similarly large sample collections. In particular, a well-powered RVAS should involve discovery sets with at least 25,000 cases, together with a substantial replication set. PMID:24443550

  6. Factors affecting the power of haplotype markers in association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An important, unresolved question in genome-wide association studies is whether there are predictable differences in power between single-SNP and haplotype markers. In this study, we use coalescent simulations to compare power for single-SNP and haplotype markers under a number of different models ...

  7. Searching for missing heritability: Designing rare variant association studies

    PubMed Central

    Zuk, Or; Schaffner, Stephen F.; Samocha, Kaitlin; Do, Ron; Hechter, Eliana; Kathiresan, Sekar; Daly, Mark J.; Neale, Benjamin M.; Sunyaev, Shamil R.; Lander, Eric S.

    2014-01-01

    Genetic studies have revealed thousands of loci predisposing to hundreds of human diseases and traits, revealing important biological pathways and defining novel therapeutic hypotheses. However, the genes discovered to date typically explain less than half of the apparent heritability. Because efforts have largely focused on common genetic variants, one hypothesis is that much of the missing heritability is due to rare genetic variants. Studies of common variants are typically referred to as genomewide association studies, whereas studies of rare variants are often simply called sequencing studies. Because they are actually closely related, we use the terms common variant association study (CVAS) and rare variant association study (RVAS). In this paper, we outline the similarities and differences between RVAS and CVAS and describe a conceptual framework for the design of RVAS. We apply the framework to address key questions about the sample sizes needed to detect association, the relative merits of testing disruptive alleles vs. missense alleles, frequency thresholds for filtering alleles, the value of predictors of the functional impact of missense alleles, the potential utility of isolated populations, the value of gene-set analysis, and the utility of de novo mutations. The optimal design depends critically on the selection coefficient against deleterious alleles and thus varies across genes. The analysis shows that common variant and rare variant studies require similarly large sample collections. In particular, a well-powered RVAS should involve discovery sets with at least 25,000 cases, together with a substantial replication set. PMID:24443550

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

    PubMed

    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

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

    PubMed Central

    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 of Biochemical Traits in Korčula Island, Croatia

    PubMed Central

    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

  11. Preschool children’s views on emotion regulation: Functional associations and implications for social-emotional adjustment

    PubMed Central

    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 fear. Forty-seven adults were presented with a parallel questionnaire. Participants rated the degree to which six emotion-regulation strategies were effective in decreasing negative emotions. Results showed that even the youngest preschoolers viewed cognitive and behavioral distraction and repairing the situation as relatively effective; compared to adults, however, preschoolers favored relatively “ineffective” strategies such as venting and rumination. Children also showed a functional view of emotion regulation; that effective strategies depend on the emotion being regulated. All participants favored repairing a negative situation to reduce anger and behavioral distraction to reduce sadness and fear. Finally, the more children indicated that venting would reduce negative emotions, the lower their maternal report of social skills. Findings are discussed in terms of functional emotion theory and implications of emotion-regulation understanding for child adjustment. PMID:19724663

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed

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

    PubMed

    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

  16. Computational Characterization of Osteoporosis Associated SNPs and Genes Identified by Genome-Wide Association Studies

    PubMed Central

    Wang, Ya; Wu, Guiju; Chen, Jie; Ye, Weiyuan; Yang, Jiancai; Huang, Qingyang

    2016-01-01

    Objectives Genome-wide association studies (GWASs) have revealed many SNPs and genes associated with osteoporosis. However, influence of these SNPs and genes on the predisposition to osteoporosis is not fully understood. We aimed to identify osteoporosis GWASs-associated SNPs potentially influencing the binding affinity of transcription factors and miRNAs, and reveal enrichment signaling pathway and “hub” genes of osteoporosis GWAS-associated genes. Methods We conducted multiple computational analyses to explore function and mechanisms of osteoporosis GWAS-associated SNPs and genes, including SNP conservation analysis and functional annotation (influence of SNPs on transcription factors and miRNA binding), gene ontology analysis, pathway analysis and protein-protein interaction analysis. Results Our results suggested that a number of SNPs potentially influence the binding affinity of transcription factors (NFATC2, MEF2C, SOX9, RUNX2, ESR2, FOXA1 and STAT3) and miRNAs. Osteoporosis GWASs-associated genes showed enrichment of Wnt signaling pathway, basal cell carcinoma and Hedgehog signaling pathway. Highly interconnected “hub” genes revealed by interaction network analysis are RUNX2, SP7, TNFRSF11B, LRP5, DKK1, ESR1 and SOST. Conclusions Our results provided the targets for further experimental assessment and further insight on osteoporosis pathophysiology. PMID:26930606

  17. Genome-wide gene-based association study.

    PubMed

    Yang, Hsin-Chou; Liang, Yu-Jen; Chung, Chia-Min; Chen, Jia-Wei; Pan, Wen-Harn

    2009-01-01

    Genome-wide association studies, which analyzes hundreds of thousands of single-nucleotide polymorphisms to identify disease susceptibility genes, are challenging because the work involves intensive computation and complex modeling. We propose a two-stage genome-wide association scanning procedure, consisting of a single-locus association scan for the first stage and a gene-based association scan for the second stage. Marginal effects of single-nucleotide polymorphisms are examined by using the exact Armitage trend test or logistic regression, and gene effects are examined by using a p-value combination method. Compared with some existing single-locus and multilocus methods, the proposed method has the following merits: 1) convenient for definition of biologically meaningful regions, 2) powerful for detection of minor-effect genes, 3) helpful for alleviation of a multiple-testing problem, and 4) convenient for result interpretation. The method was applied to study Genetic Analysis Workshop 16 Problem 1 rheumatoid arthritis data, and strong association signals were found. The results show that the human major histocompatibility complex region is the most important genomic region associated with rheumatoid arthritis. Moreover, previously reported genes including PTPN22, C5, and IL2RB were confirmed; novel genes including HLA-DRA, BTNL2, C6orf10, NOTCH4, TAP2, and TNXB were identified by our analysis. PMID:20018002

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

    PubMed

    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

  19. Intent inferencing by an intelligent operator's associate - A validation study

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.

    1988-01-01

    In the supervisory control of a complex, dynamic system, one potential form of aiding for the human operator is a computer-based operator's associate. The design philosophy of the operator's associate is that of 'amplifying' rather than automating human skills. In particular, the associate possesses understanding and control properties. Understanding allows it to infer operator intentions and thus form the basis for context-dependent advice and reminders; control properties allow the human operator to dynamically delegate individual tasks or subfunctions to the associate. This paper focuses on the design, implementation, and validation of the intent inferencing function. Two validation studies are described which empirically demonstrate the viability of the proposed approach to intent inferencing.

  20. Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases

    PubMed Central

    Lee, Wen-Chung

    2016-01-01

    The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use. PMID:27278756

  1. Short-term Exposure to Microgravity and the Associated Risk of Sudden Cardiac Arrest: Implications for Commercial Spaceflight

    NASA Astrophysics Data System (ADS)

    Laing, Kevin J. C.; Russamono, Thais

    2013-02-01

    The likelihood of trained astronauts developing a life threatening cardiac event during spaceflight is relatively rare, whilst the incidence in untrained individuals is unknown. Space tourists who live a sedentary lifestyle have reduced cardiovascular function, but the associated danger of sudden cardiac arrest (SCA) during a suborbital spaceflight (SOSF) is unclear. Risk during SOSF was examined by reviewing several microgravity studies and methods of determining poor cardiovascular condition. Accurately assessing cardiovascular function and improving baroreceptor sensitivity through exercise is suggested to reduce the incidence of SCA during future SOSFs. Future studies will benefit from past participants sharing medical history; allowing creation of risk profiles and suitable guidelines.

  2. Associations of maternal and adolescent religiosity and spirituality with adolescent alcohol use in Chile: Implications for social work practice among Chilean social workers

    PubMed Central

    Adaniya, Fernando Andrade; Sanhueza, Guillermo; Han, Yoonsun

    2013-01-01

    To inform social work practice with adolescents who may consume alcohol, we examined if alcohol use among Chilean adolescents varied as a function of their mothers’ and their own religiosity and spirituality. Data were from 787 Chilean adolescents and their mothers. Adolescent spirituality was a protective factor against more deleterious alcohol use. Parental monitoring and alcohol using opportunities mediated the associations. The practice of religious behaviors by themselves without meaningful faith were not associated with alcohol use among adolescents. Implications for social work practice are discussed. PMID:25729092

  3. Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels.

    PubMed

    Chambers, John C; Zhang, Weihua; Li, Yun; Sehmi, Joban; Wass, Mark N; Zabaneh, Delilah; Hoggart, Clive; Bayele, Henry; McCarthy, Mark I; Peltonen, Leena; Freimer, Nelson B; Srai, Surjit K; Maxwell, Patrick H; Sternberg, Michael J E; Ruokonen, Aimo; Abecasis, Gonçalo; Jarvelin, Marjo-Riitta; Scott, James; Elliott, Paul; Kooner, Jaspal S

    2009-11-01

    We carried out a genome-wide association study of hemoglobin levels in 16,001 individuals of European and Indian Asian ancestry. The most closely associated SNP (rs855791) results in nonsynonymous (V736A) change in the serine protease domain of TMPRSS6 and a blood hemoglobin concentration 0.13 (95% CI 0.09-0.17) g/dl lower per copy of allele A (P = 1.6 x 10(-13)). Our findings suggest that TMPRSS6, a regulator of hepcidin synthesis and iron handling, is crucial in hemoglobin level maintenance. PMID:19820698

  4. [Genome-wide association study on complex diseases: study design and genetic markers].

    PubMed

    Yan, Wei-Li

    2008-04-01

    Genome-wide association study used to be a dream of geneticists years ago, but now it came true. Since the first paper reported the finding of genetic variation contributing to human age-related macular degeneration by genome-wide association study in 2005, a numbers of whole genome studies have been published. The present paper reviewed some common comments in whole genome association study on complex diseases, including achievements of genome-wide association studies on complex traits or diseases, principles of study design, selection of genetic marker in genome, and comparisons of different commercial products for whole genome association study. Finally a newly defined genetic variation, copy number variation, was briefly introduced. This paper also summarized the shortcomings of current genome-wide association studies and perspectives of its future. PMID:18424408

  5. Genome wide association study on early puberty in Bos indicus.

    PubMed

    Nascimento, A V; Matos, M C; Seno, L O; Romero, A R S; Garcia, J F; Grisolia, A B

    2016-01-01

    The aim of this study was to evaluate a genome wide association study (GWAS) approach to identify single nucleotide polymorphisms (SNPs) associated with fertility traits (early puberty) in Nellore cattle (Bos indicus). Fifty-five Nellore cows were selected from a herd monitored for early puberty onset (positive pregnancy at 18 months of age). Extremes of this phenotype were selected; 30 and 25 individuals were pregnant and non-pregnant, respectively, at that age. DNA samples were genotyped using a high-density SNP chip (>777.000 SNP). GWAS using a case-control strategy highlighted a number of significant markers based on their proximity with the Bonferroni correction line. Results indicated that chromosomes 5, 6, 9, 10, and 22 were associated with the traits of interest. The most significant SNPs on these chromosomes were rs133039577, rs110013280, rs134702839, rs109551605, and rs41639155. Candidate genes, as well as quantitative trait loci (QTL) previously reported in the Ensembl and Cattle QTLdb databases, were further investigated. Analysis of the regions close to the SNP on chromosomes 9 and 10 revealed that four QTL had been previously classified under the reproduction category. In conclusion, we have identified SNPs in close proximity to genes associated with reproductive traits. Moreover, U6 spliceosomal RNA was present on three different chromosomes, which is possibly associated with age at first calving, suggesting that it might be a strong candidate for future studies. PMID:26909970

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

    PubMed

    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. PMID:26667091

  7. Prospects and pitfalls in whole genome association studies

    PubMed Central

    Lawrence, Robert W; Evans, David M; Cardon, Lon R

    2005-01-01

    Recent large-scale studies of common genetic variation throughout the human genome are making it feasible to conduct whole genome studies of genotype–phenotype associations. Such studies have the potential to uncover novel contributors to common complex traits and thus lead to insights into the aetiology of multifactorial phenotypes. Despite this promise, it is important to recognize that the availability of genetic markers and the ability to assay them at realistic cost does not guarantee success of this approach. There are a number of practical issues that require close attention, some forms of allelic architecture are not readily amenable to the association approach with even the most rigorous design, and doubtless new hurdles will emerge as the studies begin. Here we discuss the promise and current challenges of the whole genome approach, and raise some issues to consider in interpreting the results of the first whole genome studies. PMID:16096108

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

    NASA Astrophysics Data System (ADS)

    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

  9. Genome-Wide Association Analysis of Tolerance to Methylmercury Toxicity in Drosophila Implicates Myogenic and Neuromuscular Developmental Pathways

    PubMed Central

    Montgomery, Sara L.; Vorojeikina, Daria; Huang, Wen; Mackay, Trudy F. C.; Anholt, Robert R. H.; Rand, Matthew D.

    2014-01-01

    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 that nutritional

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

    ERIC Educational Resources Information Center

    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…

  11. Population-based analysis of CETP identifies association between I405V and cognitive decline: The Cache County Study

    PubMed Central

    Munger, Caitlin; Perkes, Ammon; Peterson, Michael; Schmutz, Cameron; Leary, Maegan; Ebbert, Mark T. W.; Ridge, Perry G.; Norton, Maria C.; Tschanz, JoAnn T.; Munger, Ronald G.; Corcoran, Christopher D.; Kauwe, John S. K.

    2014-01-01

    Cholesterol has been implicated in the pathogenesis of Late-onset Alzheimer's disease (LOAD) and the Cholesteryl Ester Transfer Protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer’s disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to twelve years of longitudinal cognitive assessment. Analyses revealed an average 0.6-point decrease per year in the rate of cognitive decline for each additional valine (p < 0.011). We failed to detect association between CETP I405V and LOAD status (p < 0.28). We conclude that CETP I405V is associated with preserved cognition over time but is not associated with LOAD status. PMID:25260850

  12. Genetic association study of BDNF in depression: finding from two cohort studies and a meta-analysis.

    PubMed

    Chen, Lina; Lawlor, Debbie A; Lewis, Sarah J; Yuan, Wei; Abdollahi, Mohammad R; Timpson, Nicholas J; Day, Ian N M; Ebrahim, Shah; Smith, George Davey; Shugart, Yin Y

    2008-09-01

    Depression is common and a major cause of morbidity and mortality and is also known to have serious effects on quality of life. Both clinical and pharmacologic studies have implicated the role of brain-derived neurotrophic factor (BDNF) as a susceptibility locus for the development of mental illness, including depression, bipolar disorder, and schizophrenia. Population-based genetic studies have examined the association between BDNF and a variety of depression outcomes, but the results have not clearly established the role of BDNF in the development of this complex disorder. The aim of this study was to test for associations between two genetic variants in BDNF, Val66Met (rs6265) and -270 C > T, and depression measured in two independent samples. In this analysis we included 3,548 participants from British Women's Heart and Health Study (BWHHS) and 6,836 mothers from Avon Longitudinal Study of Parents and Children (ALSPAC) who had complete data on genotype and depression outcomes. We did not detect any strong evidence of associations between any of the two polymorphisms and indicators of depression in either BWHHS or ALSPAC samples. Further, we carried out a systematic review and meta-analysis of all association studies of these two BDNF polymorphisms and depression. The meta-analysis of Val66Met in depression obtained an overall summary OR of 1.06 (95% CI: 0.89-1.26, P = 0.537) comparing MM with VV genotypes and an OR of 0.97 (95% CI: 0.89-1.05, P = 0.403) comparing MV with VV genotypes. Our findings suggest that BDNF genotype does not exert a major influence on the development of depression. PMID:18205169

  13. Association weight matrix: a network-based approach towards functional genome-wide association studies.

    PubMed

    Reverter, Antonio; Fortes, Marina R S

    2013-01-01

    In this chapter we describe the Association Weight Matrix (AWM), a novel procedure to exploit the results from genome-wide association studies (GWAS) and, in combination with network inference algorithms, generate gene networks with regulatory and functional significance. In simple terms, the AWM is a matrix with rows represented by genes and columns represented by phenotypes. Individual {i, j}th elements in the AWM correspond to the association of the SNP in the ith gene to the jth phenotype. While our main objective is to provide a recipe-like tutorial on how to build and use AWM, we also take the opportunity to briefly reason the logic behind each step in the process. To conclude, we discuss the impact on AWM of issues like the number of phenotypes under scrutiny, the density of the SNP chip and the choice of contrast upon which to infer the cause-effect regulatory interactions. PMID:23756904

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

    PubMed Central

    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. PMID:27621611

  15. A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.

    PubMed

    Kuiper, Jonas J W; Van Setten, Jessica; Ripke, Stephan; Van 'T Slot, Ruben; Mulder, Flip; Missotten, Tom; Baarsma, G Seerp; Francioli, Laurent C; Pulit, Sara L; De Kovel, Carolien G F; Ten Dam-Van Loon, Ninette; Den Hollander, Anneke I; Huis in het Veld, Paulien; Hoyng, Carel B; Cordero-Coma, Miguel; Martín, Javier; Llorenç, Victor; Arya, Bharti; Thomas, Dhanes; Bakker, Steven C; Ophoff, Roel A; Rothova, Aniki; De Bakker, Paul I W; Mutis, Tuna; Koeleman, Bobby P C

    2014-11-15

    Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6-272.6, P = 6.6 × 10(-74)). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7-3.1, for the T allele, P = 8.6 × 10(-8)) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2-11.7, for the A allele, P = 3.2 × 10(-8)). The association near ERAP2 was confirmed in an independent British case-control samples (combined meta-analysis P = 1.7 × 10(-9)). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum. PMID:24957906

  16. A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy

    PubMed Central

    Kuiper, Jonas J.W.; Van Setten, Jessica; Ripke, Stephan; Van ‘T Slot, Ruben; Mulder, Flip; Missotten, Tom; Baarsma, G. Seerp; Francioli, Laurent C.; Pulit, Sara L.; De Kovel, Carolien G.F.; Ten Dam-Van Loon, Ninette; Den Hollander, Anneke I.; Huis in het Veld, Paulien; Hoyng, Carel B.; Cordero-Coma, Miguel; Martín, Javier; Llorenç, Victor; Arya, Bharti; Thomas, Dhanes; Bakker, Steven C.; Ophoff, Roel A.; Rothova, Aniki; De Bakker, Paul I.W.; Mutis, Tuna; Koeleman, Bobby P.C.

    2014-01-01

    Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6–272.6, P = 6.6 × 10−74). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7–3.1, for the T allele, P = 8.6 × 10−8) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2–11.7, for the A allele, P = 3.2 × 10−8). The association near ERAP2 was confirmed in an independent British case–control samples (combined meta-analysis P = 1.7 × 10−9). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum. PMID:24957906

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

    PubMed

    Ahmetov, Ii; Kulemin, Na; Popov, Dv; Naumov, Va; Akimov, Eb; Bravy, Yr; Egorova, Es; Galeeva, Aa; Generozov, Ev; Kostryukova, Es; Larin, Ak; Mustafina, Lj; Ospanova, Ea; Pavlenko, Av; Starnes, Lm; Żmijewski, P; Alexeev, Dg; Vinogradova, Ol; Govorun, Vm

    2015-03-01

    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]O2max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P < 10(-5)-10(-8)) between 218 endurance athletes and opposite cohorts (192 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 rs7144481, 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 in elite endurance athletes (95.5%) in comparison with non-elite endurance athletes (89.8%, P = 0.0257), Russian (88.8%, P = 0.007) and European (90.6%, P = 0.0197) controls and power athletes (86.2%, P = 0.0005). The rs1572312 SNP is located on the nuclear factor I A antisense RNA 2 (NFIA-AS2) gene which is supposed to regulate the expression of the NFIA gene (encodes transcription factor involved in activation of erythropoiesis and repression of the granulopoiesis). Our data show that the NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 polymorphisms are associated with aerobic performance and elite endurance athlete status. PMID:25729143

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

    PubMed Central

    Kulemin, NA; Popov, DV; Naumov, VA; Akimov, EB; Bravy, YR; Egorova, ES; Galeeva, AA; Generozov, EV; Kostryukova, ES; Larin, AK; Mustafina, LJ; Ospanova, EA; Pavlenko, AV; Starnes, LM; Żmijewski, P; Alexeev, DG; Vinogradova, OL; Govorun, VM

    2014-01-01

    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 (V.O2max) in 80 international-level Russian endurance athletes (46 males and 34 females). To validate obtained results, we further performed case-control studies by comparing the frequencies of the most significant SNPs (with P < 10−5-10−8) between 218 endurance athletes and opposite cohorts (192 Russian controls, 1367 European controls, and 230 Russian power athletes). Initially, six ‘endurance alleles’ were identified showing discrete associations with V.O2max both in males and females. Next, case-control studies resulted in remaining three SNPs (NFIA-AS2 rs1572312, TSHR rs7144481, RBFOX1 rs7191721) associated with endurance athlete status. The C allele of the most significant SNP, rs1572312, was associated with high values of V.O2max (males: P = 0.0051; females: P = 0.0005). Furthermore, the frequency of the rs1572312 C allele was significantly higher in elite endurance athletes (95.5%) in comparison with non-elite endurance athletes (89.8%, P = 0.0257), Russian (88.8%, P = 0.007) and European (90.6%, P = 0.0197) controls and power athletes (86.2%, P = 0.0005). The rs1572312 SNP is located on the nuclear factor I A antisense RNA 2 (NFIA-AS2) gene which is supposed to regulate the expression of the NFIA gene (encodes transcription factor involved in activation of erythropoiesis and repression of the granulopoiesis). Our data show that the NFIA-AS2 rs1572312, TSHR rs7144481 and RBFOX1 rs7191721 polymorphisms are associated with aerobic performance and elite endurance athlete status. PMID:25729143

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

    PubMed

    Yue, Wei; Wang, Anxin; Zhu, Runxiu; Yan, Zhongrui; Zheng, Shouhuan; Wang, Jingwei; Huo, Jia; Liu, Yunlin; Li, Xin; Ji, Yong

    2016-01-01

    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. PMID:26751070

  20. Genome-Wide Association Study and Pathway-Level Analysis of Tocochromanol Levels in Maize Grain

    PubMed Central

    Lipka, Alexander E.; Gore, Michael A.; Magallanes-Lundback, Maria; Mesberg, Alex; Lin, Haining; Tiede, Tyler; Chen, Charles; Buell, C. Robin; Buckler, Edward S.; Rocheford, Torbert; DellaPenna, Dean

    2013-01-01

    Tocopherols and tocotrienols, collectively known as tocochromanols, are the major lipid-soluble antioxidants in maize (Zea mays L.) grain. Given that individual tocochromanols differ in their degree of vitamin E activity, variation for tocochromanol composition and content in grain from among diverse maize inbred lines has important nutritional and health implications for enhancing the vitamin E and antioxidant contents of maize-derived foods through plant breeding. Toward this end, we conducted a genome-wide association study of six tocochromanol compounds and 14 of their sums, ratios, and proportions with a 281 maize inbred association panel that was genotyped for 591,822 SNP markers. In addition to providing further insight into the association between ZmVTE4 (γ-tocopherol methyltransferase) haplotypes and α-tocopherol content, we also detected a novel association between ZmVTE1 (tocopherol cyclase) and tocotrienol composition. In a pathway-level analysis, we assessed the genetic contribution of 60 a priori candidate genes encoding the core tocochromanol pathway (VTE genes) and reactions for pathways supplying the isoprenoid tail and aromatic head group of tocochromanols. This analysis identified two additional genes, ZmHGGT1 (homogentisate geranylgeranyltransferase) and one prephenate dehydratase parolog (of four in the genome) that also modestly contribute to tocotrienol variation in the panel. Collectively, our results provide the most favorable ZmVTE4 haplotype and suggest three new gene targets for increasing vitamin E and antioxidant levels through marker-assisted selection. PMID:23733887

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

    PubMed

    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

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

    ERIC Educational Resources Information Center

    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…

  3. Monozygotic twins' colour-number association: a case study.

    PubMed

    Hancock, Peter

    2006-02-01

    A case study of a pair of monozygotic twins, both of whom show a strong and enduring colour-number association, is reported. The origin of the colours, in a jigsaw puzzle, is known. Neither reports conscious photisms typical of synaesthesia, but a Stroop task of naming the colours of digits shows an interference effect with incongruent colours. PMID:16683487

  4. A super powerful method for genome wide association study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome-Wide Association Studies shed light on the identification of genes underlying human diseases and agriculturally important traits. This potential has been shadowed by false positive findings. The Mixed Linear Model (MLM) method is flexible enough to simultaneously incorporate population struct...

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

    PubMed

    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

  6. Genome-wide association study of periodontal pathogen colonization.

    PubMed

    Divaris, K; Monda, K L; North, K E; Olshan, A F; Lange, E M; Moss, K; Barros, S P; Beck, J D; Offenbacher, S

    2012-07-01

    Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom "checkerboard" DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: "high red" and "high orange" bacterial complexes, and "high" Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10(-8)). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10(-6)) of association. All associations reported for "red" and "orange" complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease. PMID:22699663

  7. Association Between Promoter Methylation of Serotonin Transporter Gene and Depressive Symptoms: A Monozygotic Twin Study

    PubMed Central

    Zhao, Jinying; Goldberg, Jack; Bremner, James D.; Vaccarino, Viola

    2013-01-01

    Objective Epigenetic mechanisms have been implicated in the pathogenesis of psychiatric disorders. The serotonin transporter gene (SLC6A4) is a key candidate gene for depression. We examined the association between SLC6A4 promoter methylation variation and depressive symptoms using 84 monozygotic twin pairs. Methods DNA methylation level in the SLC6A4 promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The number of current depressive symptoms was assessed using the Beck Depressive Inventory II (BDI-II). The association between methylation variation and depressive symptoms was examined using matched twin-pair analyses, adjusting for body mass index, smoking, physical activity, and alcohol consumption. Multiple testing was controlled by adjusted false discovery rate (q value). Results Intrapair difference in DNA methylation variation at 10 of the 20 studied CpG sites is significantly correlated with intrapair difference in BDI scores. Linear regression using intrapair differences demonstrates that intrapair difference in BDI score was significantly associated with intrapair differences in DNA methylation variation after adjusting for potential confounders and correction for multiple testing. On average, a 10% increase in the difference in mean DNA methylation level was associated with 4.4 increase in the difference in BDI score (95% confidence interval = 0.9–7.9, p = .01). Conclusions This study provides evidence that variation in methylation level within the promoter region of the serotonin transporter gene is associated with variation in depressive symptoms in a large sample of monozygotic twin pairs. This relationship is not confounded by genetic and shared environment. The 5-HTTLPR genotype also does not modulate this association. PMID:23766378

  8. Guilt by rewiring: gene prioritization through network rewiring in Genome Wide Association Studies

    PubMed Central

    Hou, Lin; Chen, Min; Zhang, Clarence K.; Cho, Judy; Zhao, Hongyu

    2014-01-01

    Although Genome Wide Association Studies (GWAS) have identified many susceptibility loci for common diseases, they only explain a small portion of heritability. It is challenging to identify the remaining disease loci because their association signals are likely weak and difficult to identify among millions of candidates. One potentially useful direction to increase statistical power is to incorporate functional genomics information, especially gene expression networks, to prioritize GWAS signals. Most current methods utilizing network information to prioritize disease genes are based on the ‘guilt by association’ principle, in which networks are treated as static, and disease-associated genes are assumed to locate closer with each other than random pairs in the network. In contrast, we propose a novel ‘guilt by rewiring’ principle. Studying the dynamics of gene networks between controls and patients, this principle assumes that disease genes more likely undergo rewiring in patients, whereas most of the network remains unaffected in disease condition. To demonstrate this principle, we consider the changes of co-expression networks in Crohn's disease patients and controls, and how network dynamics reveals information on disease associations. Our results demonstrate that network rewiring is abundant in the immune system, and disease-associated genes are more likely to be rewired in patients. To integrate this network rewiring feature and GWAS signals, we propose to use the Markov random field framework to integrate network information to prioritize genes. Applications in Crohn's disease and Parkinson's disease show that this framework leads to more replicable results, and implicates potentially disease-associated pathways. PMID:24381306

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

    PubMed

    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

    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

  10. Evolution of bimodal volcanism in Gona, Ethiopia: geochemical associations and geodynamic implications for the East African Rift System

    NASA Astrophysics Data System (ADS)

    Ghosh, N.; Basu, A. R.; Gregory, R. T.; Richards, I.; Quade, J.; Ebinger, C. J.

    2013-12-01

    The East African rift system in Ethiopia formed in the Earth's youngest flood basalt province, and provides a natural laboratory to study the geochemistry of bimodal volcanism and its implications for plume-derived magmatism, mantle-lithosphere interactions and evolution of continental rifts from plate extension to rupture. Our geochemical studies of the ~6 Ma to recent eruptive products from Gona within the Afar Rift Zone are understood in context of crustal and upper mantle seismic imaging studies that provide constraints on spatial variations. Geochemical (major element, trace element and isotope) analyses of basalts and rhyolitic tuff from Gona indicate a common magma source for these bimodal volcanics. Light rare earth elements (LREEs) are enriched with a strong negative Eu anomaly and a positive Ce anomaly in some of the silicic volcanic rocks. We observe strong depletions in Sr and higher concentrations of Zr, Hf, Th, Nb and Ta. We hypothesize that the silicic rocks may be residues from a plume-derived enriched magma source, following partial melting with fractional crystallization of plagioclase at shallow magma chambers. The absence of Nb-Ta anomaly shows no crustal assimilation by magmas. Sr isotopes, in conjunction with Nd and Pb isotopes and a strong Ce anomaly could reflect interaction of the parent magma with a deep saline aquifer or brine. Nd isotopic ratios (ɛNd = 1.9 to 4.6) show similarity of the silicic tuffs and basalts in their isotopic compositions except for some ~6 Ma lavas showing MORB-like values (ɛNd = 5 to 8.7) that suggest involvement of the asthenosphere with the plume source. Except for one basaltic tuff, the whole rock oxygen isotopic ratios of the Gona basalts range from +5.8‰ to +7.9‰, higher than the δ values for typical MORB, +5.7. The oxygen isotopes in whole rocks from the rhyolite tuffs vary from 14.6‰ to 20.9‰ while their Sr isotope ratios <0.706, indicative of post-depositional low T alteration of these silicic

  11. Emotion regulatory function of parent attention to child pain and associated implications for parental pain control behaviour.

    PubMed

    Vervoort, Tine; Trost, Zina; Sütterlin, Stefan; Caes, Line; Moors, Agnes

    2014-08-01

    We investigated the function of parental attention to child pain in regulating parental distress and pain control behaviour when observing their child performing a painful (cold pressor) task (CPT); we also studied the moderating role of parental state anxiety. Participants were 62 schoolchildren and one of their parents. Parental attention towards or away from child pain (ie, attend to pain vs avoid pain) was experimentally manipulated during a viewing task pairing unfamiliar children's neutral and pain faces. Before and after the viewing task, parental distress regulation was assessed by heart rate (HR) and heart rate variability (HRV). In a subsequent phase, parents observed their own child perform a CPT task, allowing assessment of parental pain control behaviour (indexed by latency to stop their child's CPT performance) and parental distress, which was assessed via self-report before and after observation of child CPT performance. Eye tracking during the viewing task and self-reported attention to own child's pain confirmed successful attention manipulation. Further, findings indicated that the effect of attentional strategy on parental emotion regulation (indexed by HR, self-report) and pain control behaviour depended on parents' state anxiety. Specifically, whereas low anxious parents reported more distress and demonstrated more pain control behaviour in the Attend to Pain condition, high anxious parents reported more distress and showed more pain control behaviour in the Avoid Pain condition. This inverse pattern was likewise apparent in physiological distress indices (HR) in response to the initial viewing task. Theoretical/clinical implications and further research directions are discussed. PMID:24769189

  12. A Comparative Study of English and Spanish Vowel Systems: Theoretical and Practical Implications for Teaching Pronunciation.

    ERIC Educational Resources Information Center

    Odisho, Edward Y.

    A study examines two major types of vowel systems in languages, centripetal and centrifugal. English is associated with the centripetal system, in which vowel quality and quantity (rhythm) are heavily influenced by stress. In this system, vowels have a strong tendency to move toward the center of the vowel area. Spanish is associated with the…

  13. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects

    PubMed Central

    Ramachandran, Dhanya; Zeng, Zhen; Locke, Adam E.; Mulle, Jennifer G.; Bean, Lora J.H.; Rosser, Tracie C.; Dooley, Kenneth J.; Cua, Clifford L.; Capone, George T.; Reeves, Roger H.; Maslen, Cheryl L.; Cutler, David J.; Feingold, Eleanor; Sherman, Stephanie L.; Zwick, Michael E.

    2015-01-01

    The goal of this study was to identify the contribution of common genetic variants to Down syndrome−associated atrioventricular septal defect, a severe heart abnormality. Compared with the euploid population, infants with Down syndrome, or trisomy 21, have a 2000-fold increased risk of presenting with atrioventricular septal defects. The cause of this increased risk remains elusive. Here we present data from the largest heart study conducted to date on a trisomic background by using a carefully characterized collection of individuals from extreme ends of the phenotypic spectrum. We performed a genome-wide association study using logistic regression analysis on 452 individuals with Down syndrome, consisting of 210 cases with complete atrioventricular septal defects and 242 controls with structurally normal hearts. No individual variant achieved genome-wide significance. We identified four disomic regions (1p36.3, 5p15.31, 8q22.3, and 17q22) and two trisomic regions on chromosome 21 (around PDXK and KCNJ6 genes) that merit further investigation in large replication studies. Our data show that a few common genetic variants of large effect size (odds ratio >2.0) do not account for the elevated risk of Down syndrome−associated atrioventricular septal defects. Instead, multiple variants of low-to-moderate effect sizes may contribute to this elevated risk, highlighting the complex genetic architecture of atrioventricular septal defects even in the highly susceptible Down syndrome population. PMID:26194203

  14. Automated quality control for genome wide association studies

    PubMed Central

    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.

  15. Association studies including genotype by environment interactions: prospects and limits

    PubMed Central

    2014-01-01

    Background Association mapping studies offer great promise to identify polymorphisms associated with phenotypes and for understanding the genetic basis of quantitative trait variation. To date, almost all association mapping studies based on structured plant populations examined the main effects of genetic factors on the trait but did not deal with interactions between genetic factors and environment. In this paper, we propose a methodological prospect of mixed linear models to analyze genotype by environment interaction effects using association mapping designs. First, we simulated datasets to assess the power of linear mixed models to detect interaction effects. This simulation was based on two association panels composed of 90 inbreds (pearl millet) and 277 inbreds (maize). Results Based on the simulation approach, we reported the impact of effect size, environmental variation, allele frequency, trait heritability, and sample size on the power to detect the main effects of genetic loci and diverse effect of interactions implying these loci. Interaction effects specified in the model included SNP by environment interaction, ancestry by environment interaction, SNP by ancestry interaction and three way interactions. The method was finally used on real datasets from field experiments conducted on the two considered panels. We showed two types of interactions effects contributing to genotype by environment interactions in maize: SNP by environment interaction and ancestry by environment interaction. This last interaction suggests differential response at the population level in function of the environment. Conclusions Our results suggested the suitability of mixed models for the detection of diverse interaction effects. The need of samples larger than that commonly used in current plant association studies is strongly emphasized to ensure rigorous model selection and powerful interaction assessment. The use of ancestry interaction component brought valuable

  16. Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study

    PubMed Central

    Martin, Joanna; Tilling, Kate; Hubbard, Leon; Stergiakouli, Evie; Thapar, Anita; Davey Smith, George; O'Donovan, Michael C.; Zammit, Stanley

    2016-01-01

    Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991–2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1–15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. PMID:27188935

  17. Methodological issues associated with studying an illegal act: assisted dying.

    PubMed

    Volker, Deborah L

    2004-01-01

    The experience of receiving patient requests for assistance in prematurely ending life can represent both an ethical and legal dilemma for nurses in the United States. Similarly, the study of nurses' involvement with such a sensitive topic also poses risks to the study participants, the researcher, and the nursing profession's covenant with society. The purpose of this article is to explore methodological issues and approaches associated with studying an ethically and legally sensitive issue, and to describe application of these approaches to a study of oncology nurses' experiences with receiving requests for assisted dying from terminally ill patients with cancer. PMID:15206683

  18. A Genome-Wide Association Study of Depressive Symptoms

    PubMed Central

    Cornelis, Marilyn C.; Amin, Najaf; Bakshis, Erin; Baumert, Jens; Ding, Jingzhong; Liu, Yongmei; Marciante, Kristin; Meirelles, Osorio; Nalls, Michael A.; Sun, Yan V.; Vogelzangs, Nicole; Yu, Lei; Bandinelli, Stefania; Benjamin, Emelia J.; Bennett, David A.; Boomsma, Dorret; Cannas, Alessandra; Coker, Laura H.; de Geus, Eco; De Jager, Philip L.; Diez-Roux, Ana V.; Purcell, Shaun; Hu, Frank B.; Rimma, Eric B.; Hunter, David J.; Jensen, Majken K.; Curhan, Gary; Rice, Kenneth; Penman, Alan D.; Rotter, Jerome I.; Sotoodehnia, Nona; Emeny, Rebecca; Eriksson, Johan G.; Evans, Denis A.; Ferrucci, Luigi; Fornage, Myriam; Gudnason, Vilmundur; Hofman, Albert; Illig, Thomas; Kardia, Sharon; Kelly-Hayes, Margaret; Koenen, Karestan; Kraft, Peter; Kuningas, Maris; Massaro, Joseph M.; Melzer, David; Mulas, Antonella; Mulder, Cornelis L.; Murray, Anna; Oostra, Ben A.; Palotie, Aarno; Penninx, Brenda; Petersmann, Astrid; Pilling, Luke C.; Psaty, Bruce; Rawal, Rajesh; Reiman, Eric M.; Schulz, Andrea; Shulman, Joshua M.; Singleton, Andrew B.; Smith, Albert V.; Sutin, Angelina R.; Uitterlinden, André G.; Völzke, Henry; Widen, Elisabeth; Yaffe, Kristine; Zonderman, Alan B.; Cucca, Francesco; Harris, Tamara; Ladwig, Karl-Heinz; Llewellyn, David J.; Räikkönen, Katri; Tanaka, Toshiko

    2013-01-01

    Background Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. Methods In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p < 1 × 10−5) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. Results The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05 × 10−7). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19 × 10−3). This 5q21 region reached genome-wide significance (p = 4.78 × 10−8) in the overall meta-analysis combining discovery and replication studies (n = 51,258). Conclusions The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms. PMID:23290196

  19. A Genome-Wide Association Study Identifies Protein Quantitative Trait Loci (pQTLs)

    PubMed Central

    Corsi, Anna-Maria; Stevens, Kara; Rafferty, Ian; Lauretani, Fulvio; Murray, Anna; Gibbs, J. Raphael; Paolisso, Giuseppe; Rafiq, Sajjad; Simon-Sanchez, Javier; Lango, Hana; Scholz, Sonja; Weedon, Michael N.; Arepalli, Sampath; Rice, Neil; Washecka, Nicole; Hurst, Alison; Britton, Angela; Henley, William; van de Leemput, Joyce; Li, Rongling; Newman, Anne B.; Tranah, Greg; Harris, Tamara; Panicker, Vijay; Dayan, Colin; Bennett, Amanda; McCarthy, Mark I.; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Guralnik, Jack; Bandinelli, Stefania; Frayling, Timothy M.; Singleton, Andrew; Ferrucci, Luigi

    2008-01-01

    There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts – cis effects, and elsewhere in the genome – trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10−57), CCL4L1 (p = 3.9×10−21), IL18 (p = 6.8×10−13), LPA (p = 4.4×10−10), GGT1 (p = 1.5×10−7), SHBG (p = 3.1×10−7), CRP (p = 6.4×10−6) and IL1RN (p = 7.3×10−6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10−40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These

  20. Genome-wide Association Study of Chicken Plumage Pigmentation.

    PubMed

    Park, Mi Na; Choi, Jin Ae; Lee, Kyung-Tai; Lee, Hyun-Jeong; Choi, Bong-Hwan; Kim, Heebal; Kim, Tae-Hun; Cho, Seoae; Lee, Taeheon

    2013-11-01

    To increase plumage color uniformity and understand the genetic background of Korean chickens, we performed a genome-wide association study of different plumage color in Korean native chickens. We analyzed 60K SNP chips on 279 chickens with GEMMA methods for GWAS and estimated the genetic heritability for plumage color. The estimated heritability suggests that plumage coloration is a polygenic trait. We found new loci associated with feather pigmentation at the genome-wide level and from the results infer that there are additional genetic effect for plumage color. The results will be used for selecting and breeding chicken for plumage color uniformity. PMID:25049737

  1. The effects of sewer infrastructure on water quality: implications for land use studies.

    NASA Astrophysics Data System (ADS)

    Vrebos, Dirk; Staes, Jan; Meire, Patrick

    2010-05-01

    The European Water Framework Directive requires a good ecological status of the European water bodies and the necessary measures to obtain this have to be implemented. The water quality of a river is the result of complex anthropogenic systems (buildings, waste water treatment infrastructure, regulations, etc.) and biogeochemical and eco-hydrological interactions. It is therefore essential to obtain more insight in the factors that determine the water quality in a river. Research into the relation between land use and water quality is necessary. Human activities have a huge impact on the flow regimes and associated water quality of river systems. Effects of land use bound activities on water quality are often investigated, but these studies generally ignore the hydrological complexity of a human influenced catchment. Infrastructure like sewer systems and wastewater treatment plants (WWTP) can displace huge quantities of polluted water. The transfers change flow paths, displace water between catchments and change the residence time of the system. If we want to correctly understand the effect of land use distribution on water quality we have to take these sewer systems into account. In this study we analyse the relation between land use and water quality in the Nete catchment (Belgium) and investigate the impact of the sewage infrastructure on this relation. The Nete catchment (1.673 km²) is a mosaic of semi natural, agricultural and urbanized areas and the land use is very fragmented. For the moment 74% of the households within the catchment are connected to a WWTP. The discharges from these WWTP's compose 15% of the total discharge of the Nete. Based on a runoff model the surface of upstream land use was calculated for 378 points. These data were then corrected for the impact of WWTP's. Using sewage infrastructure plans, urban areas connected to a WWTP were added to the upstream land use of the WWTP's water receiving stream. In order to understand the effect of

  2. HIV-1 Tat Alters Neuronal Autophagy by Modulating Autophagosome Fusion to the Lysosome: Implications for HIV-Associated Neurocognitive Disorders

    PubMed Central

    Fields, Jerel; Dumaop, Wilmar; Elueteri, Simona; Campos, Sofia; Serger, Elisabeth; Trejo, Margarita; Kosberg, Kori; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; He, Johnny J.

    2015-01-01

    Antiretroviral therapy has increased the life span of HIV+ individuals; however, HIV-associated neurocognitive disorder (HAND) occurrence is increasing in aging HIV patients. Previous studies suggest HIV infection alters autophagy function in the aging CNS and HIV-1 proteins affect autophagy in monocyte-derived cells. Despite these findings, the mechanisms leading to dysregulated autophagy in the CNS remain unclear. Here we sought to determine how HIV Tat dysregulates autophagy in neurons. Tat caused a dose-dependent decrease in autophagosome markers, microtubule-associated protein-1 light chain β II (LC3II), and sequestosome 1(SQSTM1), in a membrane-enriched fraction, suggesting Tat increases autophagic degradation. Bafilomycin A1 increased autophagosome number, LC3II, and SQSTM1 accumulation; Tat cotreatment diminished this effect. Tat had no effect when 3-methyladenine or knockdown of beclin 1 blocked early stages of autophagy. Tat increased numbers of LC3 puncta and resulted in the formation of abnormal autophagosomes in vitro. Likewise, in vivo studies in GFAP-Tat tg mice showed increased autophagosome accumulation in neurons, altered LC3II levels, and neurodegeneration. These effects were reversed by rapamycin treatment. Tat colocalized with autophagosome and lysosomal markers and enhanced the colocalization of autophagosome with lysosome markers. Furthermore, co-IP studies showed that Tat interacts with lysosomal-associated membrane protein 2A (LAMP2A) in vitro and in vivo, and LAMP2A overexpression reduces Tat-induced neurotoxicity. Hence, Tat protein may induce autophagosome and lysosome fusion through interaction with LAMP2A leading to abnormal neuronal autophagy function and dysregulated degradation of critical intracellular components. Therapies targeting Tat-mediated autophagy alterations may decrease neurodegeneration in aging patients with HAND. PMID:25653352

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

    PubMed

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

    2010-12-01

    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 affairs professionals in developing study abroad-specific interventions and resources to maintain student well-being while abroad. PMID:23505594

  4. Ulcerated yellow spot syndrome: implications of aquaculture-related pathogens associated with soft coral Sarcophyton ehrenbergi tissue lesions.

    PubMed

    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

  5. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes.

    PubMed

    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

  6. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes

    PubMed Central

    Arendt, Maja; Fall, Tove; Lindblad-Toh, Kerstin; Axelsson, Erik

    2014-01-01

    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

  7. A preliminary study on the association between ventilation rates in classrooms and student performance.

    PubMed

    Shaughnessy, R J; Haverinen-Shaughnessy, U; Nevalainen, A; Moschandreas, D

    2006-12-01

    Poor conditions leading to substandard indoor air quality (IAQ) in classrooms have been frequently cited in the literature over the past two decades. However, there is limited data linking poor IAQ in the classrooms to student performance. Whereas, it is assumed that poor IAQ results in reduced attendance and learning potential, and subsequent poor student performance, validating this hypothesis presents a challenge in today's school environment. This study explores the association between student performance on standardized aptitude tests that are administered to students on a yearly basis, to classroom carbon dioxide (CO2) concentrations, which provide a surrogate of ventilation being provided to each room. Data on classroom CO2 concentrations (over a 4-5 h time span within a typical school day) were recorded in fifth grade classrooms in 54 elementary schools within a school district in the USA. Results from this preliminary study yield a significant (P < 0.10) association between classroom-level ventilation rate and test results in math. They also indicate that non-linear effects may need to be considered for better representation of the association. A larger sample size is required in order to draw more definitive conclusions. Practical Implications Future studies could focus on (1) gathering more evidence on the possible association between classroom ventilation rates and students' academic performance; (2) the linear/non-linear nature of the association; and (3) whether it is possible to detect 'no observed adverse effect level' for adequate ventilation with respect to academic performance in schools. All of this information could be used to improve guidance and take regulatory actions to ensure adequate ventilation in schools. The high prevalence of low ventilation rates, combined with the growing evidence of the positive impact that sufficient ventilation has on human performance, suggests an opportunity for improving design and management of school

  8. An Epigenome-Wide Association Study of Total Serum Immunoglobulin E Concentration

    PubMed Central

    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

  9. Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.

    PubMed

    Yucesoy, Berran; Kaufman, Kenneth M; Lummus, Zana L; Weirauch, Matthew T; Zhang, Ge; Cartier, André; Boulet, Louis-Philippe; Sastre, Joaquin; Quirce, Santiago; Tarlo, Susan M; Cruz, Maria-Jesus; Munoz, Xavier; Harley, John B; Bernstein, David I

    2015-07-01

    Diisocyanates, reactive chemicals used to produce polyurethane products, are the most common causes of occupational asthma. The aim of this study is to identify susceptibility gene variants that could contribute to the pathogenesis of diisocyanate asthma (DA) using a Genome-Wide Association Study (GWAS) approach. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed in 74 diisocyanate-exposed workers with DA and 824 healthy controls using Omni-2.5 and Omni-5 SNP microarrays. We identified 11 SNPs that exceeded genome-wide significance; the strongest association was for the rs12913832 SNP located on chromosome 15, which has been mapped to the HERC2 gene (p = 6.94 × 10(-14)). Strong associations were also found for SNPs near the ODZ3 and CDH17 genes on chromosomes 4 and 8 (rs908084, p = 8.59 × 10(-9) and rs2514805, p = 1.22 × 10(-8), respectively). We also prioritized 38 SNPs with suggestive genome-wide significance (p < 1 × 10(-6)). Among them, 17 SNPs map to the PITPNC1, ACMSD, ZBTB16, ODZ3, and CDH17 gene loci. Functional genomics data indicate that 2 of the suggestive SNPs (rs2446823 and rs2446824) are located within putative binding sites for the CCAAT/Enhancer Binding Protein (CEBP) and Hepatocyte Nuclear Factor 4, Alpha transcription factors (TFs), respectively. This study identified SNPs mapping to the HERC2, CDH17, and ODZ3 genes as potential susceptibility loci for DA. Pathway analysis indicated that these genes are associated with antigen processing and presentation, and other immune pathways. Overlap of 2 suggestive SNPs with likely TF binding sites suggests possible roles in disruption of gene regulation. These results provide new insights into the genetic architecture of DA and serve as a basis for future functional and mechanistic studies. PMID:25918132

  10. Large public display boards: a case study of an OR board and design implications.

    PubMed Central

    Lasome, C. E.; Xiao, Y.

    2001-01-01

    A compelling reason for studying artifacts in collaborative work is to inform design. We present a case study of a public display board (12 ft by 4 ft) in a Level-I trauma center operating room (OR) unit. The board has evolved into a sophisticated coordination tool for clinicians and supporting personnel. This paper draws on study findings about how the OR board is used and organizes the findings into three areas: (1) visual and physical properties of the board that are exploited for collaboration, (2) purposes the board was configured to serve, and (3) types of physical and perceptual interaction with the board. Findings and implications related to layout, size, flexibility, task management, problem-solving, resourcing, shared awareness, and communication are discussed in an effort to propose guidelines to facilitate the design of electronic, computer driven display boards in the OR environment. PMID:11825209

  11. Diacetyl and 2,3-pentanedione exposures associated with cigarette smoking: implications for risk assessment of food and flavoring workers.

    PubMed

    Pierce, Jennifer S; Abelmann, Anders; Spicer, Lauren J; Adams, Rebecca E; Finley, Brent L

    2014-05-01

    Diacetyl and 2,3-pentanedione inhalation have been suggested as causes of severe respiratory disease, including bronchiolitis obliterans, in food/flavoring manufacturing workers. Both compounds are present in many food items, tobacco, and other consumer products, but estimates of exposures associated with the use of these goods are scant. A study was conducted to characterize exposures to diacetyl and 2,3-pentanedione associated with cigarette smoking. The yields (μg/cigarette) of diacetyl and 2,3-pentanedione in mainstream (MS) cigarette smoke were evaluated for six tobacco products under three smoking regimens (ISO, Massachusetts Department of Public Health, and Health Canada Intense) using a standard smoking machine. Mean diacetyl concentrations in MS smoke ranged from 250 to 361 ppm for all tobacco products and smoking regimens, and mean cumulative exposures associated with 1 pack-year ranged from 1.1 to 1.9 ppm-years. Mean 2,3-pentanedione concentrations in MS smoke ranged from 32.2 to 50.1 ppm, and mean cumulative exposures associated with 1 pack-year ranged from 0.14 to 0.26 ppm-years. We found that diacetyl and 2,3-pentanedione exposures from cigarette smoking far exceed occupational exposures for most food/flavoring workers who smoke. This suggests that previous claims of a significant exposure-response relationship between diacetyl inhalation and respiratory disease in food/flavoring workers were confounded, because none of the investigations considered or quantified the non-occupational diacetyl exposure from cigarette smoke, yet all of the cohorts evaluated had considerable smoking histories. Further, because smoking has not been shown to be a risk factor for bronchiolitis obliterans, our findings are inconsistent with claims that diacetyl and/or 2,3-pentanedione exposure are risk factors for this disease. PMID:24635357

  12. Genome-Wide Association Study of Parity in Bangladeshi Women

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Argos, Maria; Pierce, Brandon L.; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Parvez, Faruque; Ahmed, Alauddin; Islam, Tariqul; Kibriya, Muhammad G.; Ahsan, Habibul

    2015-01-01

    Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10-7 and number of pregnancies at P <10-6. This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10-6. The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10-5 for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis. PMID:25742292

  13. Genome-wide association study of parity in Bangladeshi women.

    PubMed

    Aschebrook-Kilfoy, Briseis; Argos, Maria; Pierce, Brandon L; Tong, Lin; Jasmine, Farzana; Roy, Shantanu; Parvez, Faruque; Ahmed, Alauddin; Islam, Tariqul; Kibriya, Muhammad G; Ahsan, Habibul

    2015-01-01

    Human fertility is a complex trait determined by gene-environment interactions in which genetic factors represent a significant component. To better understand inter-individual variability in fertility, we performed one of the first genome-wide association studies (GWAS) of common fertility phenotypes, lifetime number of pregnancies and number of children in a developing country population. The fertility phenotype data and DNA samples were obtained at baseline recruitment from individuals participating in a large prospective cohort study in Bangladesh. GWAS analyses of fertility phenotypes were conducted among 1,686 married women. One SNP on chromosome 4 was non-significantly associated with number of children at P <10(-7) and number of pregnancies at P <10(-6). This SNP is located in a region without a gene within 1 Mb. One SNP on chromosome 6 was non-significantly associated with extreme number of children at P <10(-6). The closest gene to this SNP is HDGFL1, a hepatoma-derived growth factor. When we excluded hormonal contraceptive users, a SNP on chromosome 5 was non-significantly associated at P <10(-5) for number of children and number of pregnancies. This SNP is located near C5orf64, an open reading frame, and ZSWIM6, a zinc ion binding gene. We also estimated the heritability of these phenotypes from our genotype data using GCTA (Genome-wide Complex Trait Analysis) for number of children (hg2 = 0.149, SE = 0.24, p-value = 0.265) and number of pregnancies (hg2 = 0.007, SE = 0.22, p-value = 0.487). Our genome-wide association study and heritability estimates of number of pregnancies and number of children in Bangladesh did not confer strong evidence of common variants for parity variation. However, our results suggest that future studies may want to consider the role of 3 notable SNPs in their analysis. PMID:25742292

  14. Problematic situations associated with dating experiences and relationships among urban African American adolescents: a qualitative study.

    PubMed

    Sullivan, Terri N; Erwin, Elizabeth H; Helms, Sarah W; Masho, Saba W; Farrell, Albert D

    2010-12-01

    This qualitative study focused on the identification of problem situations associated with adolescent dating experiences and relationships, including those that placed youth at risk for dating violence perpetration or victimization. Interviews were conducted with 44 African American middle and high school students in an urban school system. Qualitative analysis identified 18 individual themes representing six categories of problem situations: (a) approach and initiation; (b) conflict, conflict resolution, and break-ups; (c) communication, connection, and emotion; (d) aggression and victimization; (e) the role of others; and (f) media and technology. Identification of these problem situation themes has important implications for developing and evaluating prevention efforts designed to foster healthy adolescent dating relationships. PMID:20931286

  15. Genome-wide association studies in pediatric chronic kidney disease.

    PubMed

    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. PMID:26490952

  16. Testing for association in case-control genome-wide association studies with shared controls.

    PubMed

    Chen, Zhongxue; Huang, Hanwen; Ng, Hon Keung Tony

    2016-04-01

    The statistical analysis of genome-wide association studies (GWASs) with multiple diseases and shared controls (SCs) is discussed. The usual method for analyzing data from these studies is to compare each individual disease with either the SCs or the pooled controls which include other diseases. We observed that applying individual association tests can be problematic because these tests may suffer from power loss in detecting significant associations between diseases and single-nucleotide polymorphism or copy number variant. We propose here a two-stage procedure wherein we first apply an overall chi-square test for multiple diseases with SCs; if the overall test is rejected, then individual tests using the chi-square partition method will be applied to each disease against SCs. A real GWAS data set with SCs and a Monte Carlo simulation study are used to demonstrate that the proposed method is more effective and preferable than other existing methods for analyzing data from GWASs with multiple diseases and SCs. PMID:23376960

  17. Genotype imputation in genome-wide association studies.

    PubMed

    Porcu, Eleonora; Sanna, Serena; Fuchsberger, Christian; Fritsche, Lars G

    2013-07-01

    Imputation is an in silico method that can increase the power of association studies by inferring missing genotypes, harmonizing data sets for meta-analyses, and increasing the overall number of markers available for association testing. This unit provides an introductory overview of the imputation method and describes a two-step imputation approach that consists of the phasing of the study genotypes and the imputation of reference panel genotypes into the study haplotypes. Detailed steps for data preparation and quality control illustrate how to run the computationally intensive two-step imputation with the high-density reference panels of the 1000 Genomes Project, which currently integrates more than 39 million variants. Additionally, the influence of reference panel selection, input marker density, and imputation settings on imputation quality are demonstrated with a simulated data set to give insight into crucial points of successful genotype imputation. PMID:23853078

  18. Genome-wide association studies in pharmacogenetics research debate

    PubMed Central

    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

  19. Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans

    PubMed Central

    Schick, Ursula M.; Jain, Deepti; Hodonsky, Chani J.; Morrison, Jean V.; Davis, James P.; Brown, Lisa; Sofer, Tamar; Conomos, Matthew P.; Schurmann, Claudia; McHugh, Caitlin P.; Nelson, Sarah C.; Vadlamudi, Swarooparani; Stilp, Adrienne; Plantinga, Anna; Baier, Leslie; Bien, Stephanie A.; Gogarten, Stephanie M.; Laurie, Cecelia A.; Taylor, Kent D.; Liu, Yongmei; Auer, Paul L.; Franceschini, Nora; Szpiro, Adam; Rice, Ken; Kerr, Kathleen F.; Rotter, Jerome I.; Hanson, Robert L.; Papanicolaou, George; Rich, Stephen S.; Loos, Ruth J.F.; Browning, Brian L.; Browning, Sharon R.; Weir, Bruce S.; Laurie, Cathy C.; Mohlke, Karen L.; North, Kari E.; Thornton, Timothy A.; Reiner, Alex P.

    2016-01-01

    Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10−28) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits. PMID:26805783

  20. Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans.

    PubMed

    Schick, Ursula M; Jain, Deepti; Hodonsky, Chani J; Morrison, Jean V; Davis, James P; Brown, Lisa; Sofer, Tamar; Conomos, Matthew P; Schurmann, Claudia; McHugh, Caitlin P; Nelson, Sarah C; Vadlamudi, Swarooparani; Stilp, Adrienne; Plantinga, Anna; Baier, Leslie; Bien, Stephanie A; Gogarten, Stephanie M; Laurie, Cecelia A; Taylor, Kent D; Liu, Yongmei; Auer, Paul L; Franceschini, Nora; Szpiro, Adam; Rice, Ken; Kerr, Kathleen F; Rotter, Jerome I; Hanson, Robert L; Papanicolaou, George; Rich, Stephen S; Loos, Ruth J F; Browning, Brian L; Browning, Sharon R; Weir, Bruce S; Laurie, Cathy C; Mohlke, Karen L; North, Kari E; Thornton, Timothy A; Reiner, Alex P

    2016-02-01

    Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10(-28)) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits. PMID:26805783

  1. Genetic and molecular studies of apterous: a gene implicated in the juvenile hormone system of Drosophila.

    PubMed

    Shtorch, A; Werczberger, R; Segal, D

    1995-01-01

    The apterous (ap) gene in Drosophila melanogaster encodes a homeodomain transcription factor. It is required for the development of the wings and of a subset of embryonic muscles. The gene has been implicated in the juvenile hormone (JH) system because mutations in ap lead to JH deficiency, and are associated with defective histolysis of the larval fat body, arrested vitellogenesis, sterility, and aberrant sexual behavior, all of which are dependent on JH. We describe here the use of hemizygotes and germ-line clones, of X-ray- and hybrid dysgenesis-induced lethal ap alleles to determine the primary role of the gene during development. We find that ap lethality is polyphasic, but occurs primarily at the larval and pupal stages. The lethal phenotype is not associated with any overt morphological abnormality, suggesting that death occurs from a systemic malfunction. Strong interallelic complementation for the wing phenotype was found between some ap mutations induced by X-rays or by hybrid-dysgenesis. By Northern blot analysis, we demonstrate an increase in ap expression in pupae and adults as compared to embryos and larvae, suggesting that it is developmentally regulated. Finally, primer extension is used to determine the transcription start site of the gene. PMID:7579572

  2. Genome-wide association study of schizophrenia in Ashkenazi Jews.

    PubMed

    Goes, Fernando S; McGrath, John; Avramopoulos, Dimitrios; Wolyniec, Paula; Pirooznia, Mehdi; Ruczinski, Ingo; Nestadt, Gerald; Kenny, Eimear E; Vacic, Vladimir; Peters, Inga; Lencz, Todd; Darvasi, Ariel; Mulle, Jennifer G; Warren, Stephen T; Pulver, Ann E

    2015-12-01

    Schizophrenia is a common, clinically heterogeneous disorder associated with lifelong morbidity and early mortality. Several genetic variants associated with schizophrenia have been identified, but the majority of the heritability remains unknown. In this study, we report on a case-control sample of Ashkenazi Jews (AJ), a founder population that may provide additional insights into genetic etiology of schizophrenia. We performed a genome-wide association analysis (GWAS) of 592 cases and 505 controls of AJ ancestry ascertained in the US. Subsequently, we performed a meta-analysis with an Israeli AJ sample of 913 cases and 1640 controls, followed by a meta-analysis and polygenic risk scoring using summary results from Psychiatric GWAS Consortium 2 schizophrenia study. The U.S. AJ sample showed strong evidence of polygenic inheritance (pseudo-R(2) ∼9.7%) and a SNP-heritability estimate of 0.39 (P = 0.00046). We found no genome-wide significant associations in the U.S. sample or in the combined US/Israeli AJ meta-analysis of 1505 cases and 2145 controls. The strongest AJ specific associations (P-values in 10(-6) -10(-7) range) were in the 22q 11.2 deletion region and included the genes TBX1, GLN1, and COMT. Supportive evidence (meta P < 1 × 10(-4) ) was also found for several previously identified genome-wide significant findings, including the HLA region, CNTN4, IMMP2L, and GRIN2A. The meta-analysis of the U.S. sample with the PGC2 results provided initial genome-wide significant evidence for six new loci. Among the novel potential susceptibility genes is PEPD, a gene involved in proline metabolism, which is associated with a Mendelian disorder characterized by developmental delay and cognitive deficits. PMID:26198764

  3. Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat

    PubMed Central

    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

  4. Interaction of ochratoxin A with human intestinal Caco-2 cells: possible implication of a multidrug resistance-associated protein (MRP2).

    PubMed

    Berger, Valérie; Gabriel, Anne-Françoise; Sergent, Thérèse; Trouet, André; Larondelle, Yvan; Schneider, Yves-Jacques

    2003-04-11

    Ochratoxin A (OTA), a nephrotoxic mycotoxin, is absorbed from small intestine and, in plasma, binds to serum albumin. Prolonged half-live results from reabsorption by proximal tubules and enterohepatic circulation. The mechanism whereby OTA crosses intestine was investigated by means of a cell culture system consisting of Caco-2 cells, as in vitro model of human intestinal epithelium. Cytotoxicity assays on proliferating Caco-2 cells showed that 0.4 microM OTA inhibits MTT reduction by 50%. Transepithelial transport and intracellular accumulation of OTA were studied in Caco-2 cells, differentiated in bicameral inserts. At pH 7.4, OTA is transported preferentially in basolateral (BL) to apical (AP) direction, suggesting a net secretion. Conditions closer to in vivo situation in duodenum (AP pH 6.0, BL pH 7.4) increase intracellular accumulation and transepithelial transport. AP to BL transport becomes higher than BL to AP transport, suggesting OTA absorption. Addition of serum albumin in BL compartment further increases OTA absorption across Caco-2 cells and suggests that in vivo OTA transport from serosal to luminal side of enterocytes is prevented, due to its binding to plasma proteins. Competition experiments showed that carrier systems for large neutral amino acids, H(+)/dipeptides cotransporter, organic anion (p-aminohippurate) carrier and organic anion transporter (oatp) are not implicated in OTA transport across Caco-2 cells, in contrast to what was reported in kidney and liver. AP and BL transport and intracellular accumulation of OTA are increased in the presence of non specific inhibitors of MRPs (indomethacin, genistein and probenecid) and of 1-chloro-2,4-dinitrobenzene (biotransformed into 2,4-dinitrophenyl-gluthatione, a specific inhibitor of MRPs), but are affected by verapamil, an inhibitor of P-gp. This suggests that the multidrug resistance-associated protein (MRP2) could be implicated in transepithelial transport. Therefore, absorption of OTA

  5. Liposomes- and ethosomes-associated distamycins: a comparative study.

    PubMed

    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

  6. Evaluation of Genome Wide Association Study Associated Type 2 Diabetes Susceptibility Loci in Sub Saharan Africans.

    PubMed

    Adeyemo, Adebowale A; Tekola-Ayele, Fasil; Doumatey, Ayo P; Bentley, Amy R; Chen, Guanjie; Huang, Hanxia; Zhou, Jie; Shriner, Daniel; Fasanmade, Olufemi; Okafor, Godfrey; Eghan, Benjamin; Agyenim-Boateng, Kofi; Adeleye, Jokotade; Balogun, Williams; Elkahloun, Abdel; Chandrasekharappa, Settara; Owusu, Samuel; Amoah, Albert; Acheampong, Joseph; Johnson, Thomas; Oli, Johnnie; Adebamowo, Clement; Collins, Francis; Dunston, Georgia; Rotimi, Charles N

    2015-01-01

    Genome wide association studies (GWAS) for type 2 diabetes (T2D) undertaken in European and Asian ancestry populations have yielded dozens of robustly associated loci. However, the genomics of T2D remains largely understudied in sub-Saharan Africa (SSA), where rates of T2D are increasing dramatically and where the environmental background is quite different than in these previous studies. Here, we evaluate 106 reported T2D GWAS loci in continental Africans. We tested each of th