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Sample records for association study implicates

  1. Implications of genome-wide association studies in cancer therapeutics.

    PubMed

    Patel, Jai N; McLeod, Howard L; Innocenti, Federico

    2013-09-01

    Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable.

  2. Lessons and implications from association studies and post-GWAS analyses of cervical cancer.

    PubMed

    Chen, Dan; Gyllensten, Ulf

    2015-01-01

    Cervical cancer has a heritable genetic component. A large number of genetic associations with cervical cancer have been reported in hypothesis-driven candidate gene studies, but many of these results are either inconsistent or have failed to be independently replicated. Genome-wide association studies (GWAS) have identified additional susceptibility loci previously not implicated in cervical cancer development, highlighting the power of genome-wide unbiased association analyses. Post-GWAS analyses including pathway-based analysis and functional characterization of associated variants have provided new insights into the pathogenesis of cervical cancer. In this review we summarize findings from candidate gene association studies, GWAS, and post-GWAS analyses of cervical cancer. We also discuss gaps in our understanding, possible clinical implications of the findings, and lessons for studies of other complex diseases.

  3. 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

  4. 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

  5. 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

  6. Genomic dissection of population substructure of Han Chinese and its implication in association studies.

    PubMed

    Xu, Shuhua; Yin, Xianyong; Li, Shilin; Jin, Wenfei; Lou, Haiyi; Yang, Ling; Gong, Xiaohong; Wang, Hongyan; Shen, Yiping; Pan, Xuedong; He, Yungang; Yang, Yajun; Wang, Yi; Fu, Wenqing; An, Yu; Wang, Jiucun; Tan, Jingze; Qian, Ji; Chen, Xiaoli; Zhang, Xin; Sun, Yangfei; Zhang, Xuejun; Wu, Bailin; Jin, Li

    2009-12-01

    To date, most genome-wide association studies (GWAS) and studies of fine-scale population structure have been conducted primarily on Europeans. Han Chinese, the largest ethnic group in the world, composing 20% of the entire global human population, is largely underrepresented in such studies. A well-recognized challenge is the fact that population structure can cause spurious associations in GWAS. In this study, we examined population substructures in a diverse set of over 1700 Han Chinese samples collected from 26 regions across China, each genotyped at approximately 160K single-nucleotide polymorphisms (SNPs). Our results showed that the Han Chinese population is intricately substructured, with the main observed clusters corresponding roughly to northern Han, central Han, and southern Han. However, simulated case-control studies showed that genetic differentiation among these clusters, although very small (F(ST) = 0.0002 approximately 0.0009), is sufficient to lead to an inflated rate of false-positive results even when the sample size is moderate. The top two SNPs with the greatest frequency differences between the northern Han and southern Han clusters (F(ST) > 0.06) were found in the FADS2 gene, which associates with the fatty acid composition in phospholipids, and in the HLA complex P5 gene (HCP5), which associates with HIV infection, psoriasis, and psoriatic arthritis. Ingenuity Pathway Analysis (IPA) showed that most differentiated genes among clusters are involved in cardiac arteriopathy (p < 10(-101)). These signals indicating significant differences among Han Chinese subpopulations should be carefully explained in case they are also detected in association studies, especially when sample sources are diverse. PMID:19944404

  7. Patterns of linkage disequilibrium of LRRK2 across different races: implications for genetic association studies.

    PubMed

    Li, Huihua; Teo, Yik Ying; Tan, Eng King

    2013-01-01

    Genome Wide Association Studies (GWASs) have identified trait-associated polymorphisms via a hypothesis-free approach. However, it is challenging when attempting to reproduce GWAS findings in different populations as it fundamentally relies on the similar patterns of linkage disequilibrium (LD) between the unknown causal variants and the genotyped single nucleotide polymorphisms (SNPs). To address this potential limitation, we examined the regional LD pattern of leucine-rich repeat kinase 2 (LRRK2) gene, which is responsible for both autosomal dominant and sporadic Parkinson's disease (PD), in Caucasians (CEU), Japanese (JPT) and Chinese (CHB) from HapMap and Chinese (CHS), Malays (MAS) and Indians (INS) from the Singapore Genome Variation Project (SGVP) utilizing the traditional heatmaps and targeted analysis of LRRK2 gene via Monte Carlo simulation through varLD scores of these ethnic groups. Both heatmaps and targeted analysis showed that LD pattern of JPT was different from that of INS (P=0.0001); while LD pattern of CEU was different from that in Asian except for INS (all P=0.0001). Our study suggests that there is a higher chance to detect associations between PD and those trait-associated SNPs of LRRK2 gene found in Caucasian studies in INS, while those found in Japanese studies are likely to be better replicated among CHB.

  8. A Genome-Wide Association Study in American Indians Implicates DNER as a Susceptibility Locus for Type 2 Diabetes

    PubMed Central

    Hanson, Robert L.; Muller, Yunhua L.; Kobes, Sayuko; Guo, Tingwei; Bian, Li; Ossowski, Victoria; Wiedrich, Kim; Sutherland, Jeffrey; Wiedrich, Christopher; Mahkee, Darin; Huang, Ke; Abdussamad, Maryam; Traurig, Michael; Weil, E. Jennifer; Nelson, Robert G.; Bennett, Peter H.; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.

    2014-01-01

    Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ∼1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 × 10−8, which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians. PMID:24101674

  9. 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

  10. 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

  11. 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

  12. Implications of discoveries from genome-wide association studies in current cardiovascular practice

    PubMed Central

    Jeemon, Panniyammakal; Pettigrew, Kerry; Sainsbury, Christopher; Prabhakaran, Dorairaj; Padmanabhan, Sandosh

    2011-01-01

    Genome-wide association studies (GWAS) have identified several genetic variants associated with coronary heart disease (CHD), and variations in plasma lipoproteins and blood pressure (BP). Loci corresponding to CDKN2A/CDKN2B/ANRIL, MTHFD1L, CELSR2, PSRC1 and SORT1 genes have been associated with CHD, and TMEM57, DOCK7, CELSR2, APOB, ABCG5, HMGCR, TRIB1, FADS2/S3, LDLR, NCAN and TOMM40-APOE with total cholesterol. Similarly, CELSR2-PSRC1-SORT1, PCSK9, APOB, HMGCR, NCAN-CILP2-PBX4, LDLR, TOMM40-APOE, and APOC1-APOE are associated with variations in low-density lipoprotein cholesterol levels. Altogether, forty, forty three and twenty loci have been associated with high-density lipoprotein cholesterol, triglycerides and BP phenotypes, respectively. Some of these identified loci are common for all the traits, some do not map to functional genes, and some are located in genes that encode for proteins not previously known to be involved in the biological pathway of the trait. GWAS have been successful at identifying new and unexpected genetic loci common to diseases and traits, thus rapidly providing key novel insights into disease biology. Since genotype information is fixed, with minimum biological variability, it is useful in early life risk prediction. However, these variants explain only a small proportion of the observed variance of these traits. Therefore, the utility of genetic determinants in assessing risk at later stages of life has limited immediate clinical impact. The future application of genetic screening will be in identifying risk groups early in life to direct targeted preventive measures. PMID:21860704

  13. Factors associated with arsenicosis and arsenic exposure status in Nepal: implications from community based study.

    PubMed

    Maden, Narendra; Singh, Anjana; Smith, Linda S; Maharjan, Makhan; Shrestha, Shreekrishna

    2011-02-01

    A significant public health problem due to exposure to arsenic via groundwater in communities of lowland Terai region of Nepal has issued forth need to assess the exposure status and factors associated with arsenicosis. We observed arsenical dermal manifestations and collected and assessed total arsenic content in tubewell water, urine, and hair samples of study subjects at arsenic affected communities in Nawalparasi district of Nepal. The explanatory variables associated with arsenicosis were elevated arsenic in tubewell, male gender and increased age (P < 0.05). 67% (73/109) and 66% (77/117) of subjects exceeded the normal urinary and hair arsenic levels respectively. Among them 52% (57/109) and 47% (55/117) exceeded normal urinary and hair arsenic levels having no arsenical dermal manifestations. Males and symptomatic cases had significantly higher hair arsenic levels (P < 0.05). We also observed significant positive correlation of both urine and hair arsenic levels to tubewell arsenic levels (r = 0.27, 0.37, P < 0.01) and negative correlation of urine arsenic levels with the age of the subjects (r = -0.18, P = 0.06). We conclude that elucidating factors associated with arsenicosis could be of prime importance in intervention and preventive measures. In arsenic affected communities of Nepal exposure to arsenic is still a major problem despite mitigation efforts and the potential for sub-clinical effects in exposed population is high.

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

    PubMed Central

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

    2000-01-01

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

  16. Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies.

    PubMed

    Hoh, Boon-Peng; Deng, Lian; Julia-Ashazila, Mat Jusoh; Zuraihan, Zakaria; Nur-Hasnah, Ma'amor; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Endom, Ismail; Zilfalil, Bin Alwi; Khalid, Yusoff; Xu, Shuhua

    2015-07-22

    Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated the population sub-structure of Malay involving 431 samples collected from all states from peninsular Malaysia and Singapore. We identified two major clusters of individuals corresponding to the north and south peninsular Malaysia. On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the pairwise FST of Malay sub-populations, of which the north and south regions showed the highest differentiation (FST [North-south] = 0.0011). The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis. We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

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

    PubMed

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

    2011-02-01

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

  18. Genome-Wide Association Studies (GWAS) breast cancer susceptibility loci in Arabs: susceptibility and prognostic implications in Tunisians.

    PubMed

    Shan, Jingxuan; Mahfoudh, Wijden; Dsouza, Shoba P; Hassen, Elham; Bouaouina, Noureddine; Abdelhak, Sonia; Benhadjayed, Ahlem; Memmi, Hager; Mathew, Rebecca Ann; Aigha, Idil I; Gabbouj, Sallouha; Remadi, Yassmine; Chouchane, Lotfi

    2012-10-01

    Genome-wide Association Studies (GWAS) revealed novel genetic markers for breast cancer susceptibility. But little is known about the risk factors and molecular events associated with breast cancer in Arab Population. Therefore, we designed a broad study to investigate the susceptibility and prognostic implications of the GWAS breast cancer loci in the Tunisian population. In a cohort of 640 unrelated patients with breast cancer and 371 healthy control subjects, we characterized the variation of 9 single nucleotide polymorphisms (SNPs), namely rs1219648, rs2981582; rs8051542, rs12443621, and rs3803662; rs889312; rs3817198; rs13387042 and rs13281615. Only 5 out of 9 GWAS breast cancer loci were found to be significantly associated with breast cancer in Tunisians: The rs1219648 (G vs. A allele: OR = 1.36, P = 1 × 10(-3)) and rs2981582 (A vs. G allele: OR = 1.55, P = 3 × 10(-6)) of FGFR2 gene; the rs8051542 of the TNRC9 gene (T vs. C allele: OR = 1.40, P = 4 × 10(-4)); the rs889312 of the MAP3K1 gene (C vs. A allele: OR = 1.33, P = 3 × 10(-3)) and the rs13281615 located on 8q24 (G vs. A allele: OR = 1.21, P = 0.03). Homozygous variant genotypes of rs2981582 were strongly related to lymph node negative breast cancer (OR = 3.33, P = 6 × 10(-7)) and the minor allele of rs2981582 was associated with increased risk of ER+ tumors (OR = 1.57, P = 0.02; OR = 2.15, P = 0.001, for heterozygous and homozygous variant genotypes, respectively) and increased risk of distant metastasis development (OR = 2.30, P = 4 × 10(-3); OR = 3.57, P = 6 × 10(-5), for heterozygous and homozygous variant genotypes, respectively) in a dose dependent manner. The association for rs8051542 was stronger for high-grade SBR tumors (OR = 2.54, P = 2 × 10(-4)). GG genotype of rs13387042 on 2q35 showed a significant association with the risk of developing distant metastasis (OR = 1.94, P = 0.02). The G allele of rs1219648 in FGFR2 and the A allele of rs13387042 on 2q35 indicated a better prognosis

  19. The CHARGE Association: Implications for Teachers.

    ERIC Educational Resources Information Center

    Jones, Thomas W.; Dunne, Michele T.

    1988-01-01

    CHARGE association is described as a diagnostic label for a group of congenital malformations, including coloboma, heart defects, atresia choanae, retarded postnatal growth/central nervous system defects, genital hypoplasia, and ear deformities. Etiology and characteristics of the CHARGE association are discussed, along with implications for…

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

    PubMed Central

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

    2016-01-01

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

  1. 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

  2. Hip flexion weakness is associated with impaired mobility in oculopharyngeal muscular dystrophy: a retrospective study with implications for trial design.

    PubMed

    Youssof, Sarah; Schrader, Ronald; Bear, David; Morrison, Leslie

    2015-03-01

    Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy for which validated outcome measures are lacking, posing a barrier to clinical trials. Our goal was to identify factors associated with impaired mobility in OPMD in order to guide development of surrogate endpoints in future clinical trials. One hundred forty-four individuals with OPMD were included in this retrospective, single-center study. We made novel use of parametric time-to-event analysis to model age at initial use of assistive device for ambulation. We hypothesized that limb weakness and other markers of disease severity are associated with earlier use of assistive devices. 23.6% of individuals (34/144) progressed to use of assistive devices (mean age 66.0 ± 9.6 y). Earlier age at assistive device was associated with hip flexion Medical Research Council grade ≤3 (p <0.0001), earlier disease onset (p <0.0001), and lack of blepharoptosis surgery (p = 0.011). Markers of dysphagia severity were not associated with earlier progression to assistive devices. Our study is the first to show a statistical association between hip flexion weakness and impaired mobility in OPMD, indicating that hip flexion strength could be explored as a surrogate endpoint for use in clinical trials. Since severity of disease features may be discordant within individuals, composite outcome measures are warranted.

  3. Genome-Wide Association Studies of Refractive Error and Myopia, Lessons Learned, and Implications for the Future

    PubMed Central

    Hysi, Pirro G.; Wojciechowski, Robert; Rahi, Jugnoo S.; Hammond, Chris J.

    2014-01-01

    The investigation of the genetic basis of refractive error and myopia entered a new stage with the introduction of genome-wide association studies (GWAS). Multiple GWAS on many ethnic groups have been published over the years, providing new insight into the genetic architecture and pathophysiology of refractive error. This is a review of the GWAS published to date, the main lessons learned, and future possible directions of genetic studies of myopia and refractive error. PMID:24876304

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

    PubMed

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

    2011-03-01

    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 F(ST) 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, F(ST) was smallest for the comparison with the Russians (F(ST)=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.

  5. 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

  6. 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

  7. 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

  8. Assessment of the functionality of genome-wide canine SNP arrays and implications for canine disease association studies.

    PubMed

    Ke, X; Kennedy, L J; Short, A D; Seppälä, E H; Barnes, A; Clements, D N; Wood, S H; Carter, S D; Happ, G M; Lohi, H; Ollier, W E R

    2011-04-01

    Domestic dogs share a wide range of important disease conditions with humans, including cancers, diabetes and epilepsy. Many of these conditions have similar or identical underlying pathologies to their human counterparts and thus dogs represent physiologically relevant natural models of human disorders. Comparative genomic approaches whereby disease genes can be identified in dog diseases and then mapped onto the human genome are now recognized as a valid method and are increasing in popularity. The majority of dog breeds have been created over the past few hundred years and, as a consequence, the dog genome is characterized by extensive linkage disequilibrium (LD), extending usually from hundreds of kilobases to several megabases within a breed, rather than tens of kilobases observed in the human genome. Genome-wide canine SNP arrays have been developed, and increasing success of using these arrays to map disease loci in dogs is emerging. No equivalent of the human HapMap currently exists for different canine breeds, and the LD structure for such breeds is far less understood than for humans. This study is a dedicated large-scale assessment of the functionalities (LD and SNP tagging performance) of canine genome-wide SNP arrays in multiple domestic dog breeds. We have used genotype data from 18 breeds as well as wolves and coyotes genotyped by the Illumina 22K canine SNP array and Affymetrix 50K canine SNP array. As expected, high tagging performance was observed with most of the breeds using both Illumina and Affymetrix arrays when multi-marker tagging was applied. In contrast, however, large differences in population structure, LD coverage and pairwise tagging performance were found between breeds, suggesting that study designs should be carefully assessed for individual breeds before undertaking genome-wide association studies (GWAS).

  9. 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

  10. Pharmacogenetic analysis of genes implicated in rodent models of antidepressant response: association of TREK1 and treatment resistance in the STAR(*)D study.

    PubMed

    Perlis, Roy H; Moorjani, Priya; Fagerness, Jesen; Purcell, Shaun; Trivedi, Madhukar H; Fava, Maurizio; Rush, A John; Smoller, Jordan W

    2008-11-01

    Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (KCNK2 (TREK1), SLC18A2 (VMAT2), S100A10, and HDAC5) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C(16)) score < or =5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in KCNK2 were associated with treatment response (Bonferroni-corrected, gene-based empirical p<0.001). In follow-up analyses, KCNK2 was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (n=225). These findings indicate that genetic variation in KCNK2 may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.

  11. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes

    PubMed Central

    Florez, J. C.; Price, A. L.; Campbell, D.; Riba, L.; Parra, M. V.; Yu, F.; Duque, C.; Saxena, R.; Gallego, N.; Tello-Ruiz, M.; Franco, L.; Rodríguez-Torres, M.; Villegas, A.; Bedoya, G.; Aguilar-Salinas, C. A.; Tusié-Luna, M. T.; Ruiz-Linares, A.; Reich, D.

    2011-01-01

    Aims/hypothesis Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. Methods We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. Results Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02–0.21], p=2.0 × 10−5) and Colombians (OR 0.26 [0.08–0.78], p=0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19–2.12], p=0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04–0.71], p=0.02). Adjustment for BMI did not change the results. Conclusions/interpretation The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects. PMID:19526211

  12. 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

  13. 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

  14. An AEM-TEM study of nanometer-scale mineral associations in an aquifer sand: Implications for colloid mobilization

    NASA Astrophysics Data System (ADS)

    Swartz, Christopher H.; Ulery, April L.; Gschwend, Philip M.

    1997-02-01

    Analytical and transmission electron microscopy (AEM-TEM) techniques were used to identify mineral juxtapositions at the nanometer-scale in the interstitial matrix of a shallow, Southeastern Coastal plain aquifer sand (Georgetown, South Carolina, USA). In doing so, we sought to infer particle-particle interaction mechanisms holding the matrix intact. The aquifer is a fine-to-medium quartz sand with approximately 12% by weight <63 μm size fraction composing the interstitial matrix. The clay-size fraction contains kaolinite, goethite, gibbsite, and vermiculite. The arrangement of the clay minerals is that of a framework of face-associated domains. Selective extraction revealed that goethite constituted 95% by weight of the free iron oxyhydroxides in the <63 μm size fraction, but AEM-TEM and high resolution TEM (HRTEM) indicated that the goethite occurred only in discrete aggregates among the clays. Conversely, the remaining 5% of the free iron oxyhydroxides comprised an amorphous iron phase which was found to be distributed throughout the matrix and directly associated with the clay particles. This evidence suggests that the amorphous iron oxyhydroxide phase could act as an effective binding intermediary among the clay-clay associations, possibly electrostatically or through bond linkages with the clay surfaces. In addition, HRTEM indicated the presence of another amorphous phase which appeared to hold the clay particle aggregates in a cementitious web. AEM suggested that this amorphous phase was silicon enriched, probably biogenic opal. This evidence suggests that instigating dissolution of the opaline silica phase may be necessary to induce substantial colloid mobilization in this aquifer sediment.

  15. 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…

  16. 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...

  17. 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.…

  18. 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

  19. 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).

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

    PubMed

    Yakushiji, Yusuke

    2015-01-01

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

  1. 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

  2. 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.

  3. Genome-wide pathway-based association study implicates complement system in the development of Kashin-Beck disease in Han Chinese.

    PubMed

    Zhang, Feng; Wen, Yan; Guo, Xiong; Zhang, Yingang; Wang, Sen; Yang, Tielin; Shen, Hui; Chen, Xiangding; Tan, Lijun; Tian, Qing; Deng, Hong-Wen

    2015-02-01

    Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of KBD remains unknown. To identify relevant biological pathways for KBD, we conducted a genome-wide pathway-based association study (GWPAS) following by replication analysis, totally using 2743 Chinese Han adults. A modified gene set enrichment algorithm was used to detect association between KBD and 963 biological pathways. Cartilage gene expression analysis and serum complement measurement were performed to evaluate the functional relevance of identified pathway with KBD. We found that the Complement and Coagulation Cascades (CACC) pathway was significantly associated with KBD (P value=3.09×10(-5), false-discovery rate=0.042). Within the CACC pathway, the most significant association was observed at rs1656966 (P value=1.97×10(-4)) of KNG1 gene. Further replication study observed that rs1656966 (P value=0.037) was significantly associated with KBD in an independent validation sample of 1026 subjects. Gene expression analysis observed that CFD (ratio=3.39±2.68), A2M (ratio=3.67±5.63), C5 (ratio=2.65±2.52) and CD46 (ratio=2.29±137) genes of the CACC pathway were up-regulated in KBD articular cartilage compared to healthy articular cartilage. The serum level of complement C5 in KBD patients were significantly higher than that in healthy controls (P value=0.038). Our study is the first to suggest that complement system-related CACC pathway contributed to the development of KBD.

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

    PubMed

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

    2010-09-01

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

  5. 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

  6. Pain symptoms associated with opioid use among vulnerable persons with HIV: An exploratory study with implications for palliative care and opioid abuse prevention

    PubMed Central

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

    2016-01-01

    Current or former injection drug using (IDU) persons with HIV/AIDS are at high risk for pain, which adversely affects quality of life and may increase risk for illicit drug use or relapse. We explored associations between pain symptoms and substance use among IDU study participants with HIV/AIDS and histories of heroin use. Using generalized estimating equations and controlling for prior substance use, pain in each six month period was associated with use of heroin and prescription opioids, but not use of non-opioid drugs or alcohol. Routine clinical assessment and improved management of pain symptoms may be needed in 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

  7. 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

  8. 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.

  9. 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

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

    PubMed

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

    2012-07-01

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

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

    PubMed

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

    2012-07-01

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

  12. 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.

  13. 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

  14. 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.

  15. [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

  16. Dermatomyositis and myastenia gravis: An uncommon association with therapeutic implications.

    PubMed

    Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Méndez Perles, Clara; Barbadillo, Carmen; Godoy, Hildegarda; Andréu, José Luis

    2015-01-01

    The association of dermatomyositis with myasthenia gravis (MG) is uncommon, having been reported so far in only 26 cases. We report the case of a 69 year-old man diagnosed with MG two years ago and currently treated with piridostigmyne. The patient developed acute proximal weakness, shoulder pain and elevated creatine-kinase (CK). He also developed generalized facial erythema and Gottron's papules. Laboratory tests showed positive antinuclear and anti-Mi2 antibodies. Further analysis confirmed CK levels above 1000 U/l. The clinical management of the patient and the therapeutic implications derived from the coexistence of both entities are discusssed.

  17. 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

  18. 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

  19. 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.

  20. Mechanisms and Implications of Air Pollution Particle Associations with Chemokines

    PubMed Central

    Seagrave, JeanClare

    2008-01-01

    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. PMID:18755206

  1. 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

  2. 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

  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. Role of the Microbiota in Colorectal Cancer: Updates on Microbial Associations and Therapeutic Implications

    PubMed Central

    Coleman, Olivia I.; Nunes, Tiago

    2016-01-01

    Abstract Genetic, environmental, and dietary factors have been found to influence the development and progression of colorectal cancer (CRC). More recently, accumulating evidence associates the intestinal microbiota with the initiation and progression of this disease. While studies have shown that individuals with CRC display alterations in gut bacterial composition, it remains somewhat unclear whether such differences drive cancer development or whether they are a response to tumorigenesis. In this review, the authors assess new evidence linking the community structure or specific bacterial factors of the intestinal microbiota to CRC development and progression, with insights into therapeutic implications. PMID:27790385

  5. Training Standards of the American Mental Health Counselors Association: History, Rationale, and Implications.

    ERIC Educational Resources Information Center

    Seiler, Gary; And Others

    1987-01-01

    Traces historical development of training standards for mental health counseling and gives a detailed rationale of the importance of such standards. Presents newly adopted training standards of the American Mental Health Counselors Association and discusses implications of these standards. (Author)

  6. COPD patients with ventilator-associated pneumonia: implications for management.

    PubMed

    Koulenti, D; Blot, S; Dulhunty, J M; Papazian, L; Martin-Loeches, I; Dimopoulos, G; Brun-Buisson, C; Nauwynck, M; Putensen, C; Sole-Violan, J; Armaganidis, A; Rello, J

    2015-12-01

    Data on the occurrence and outcome of patients with chronic obstructive pulmonary disease (COPD) and ventilator-associated pneumonia (VAP) are quite limited. The aim of this study was to determine if COPD intensive care unit (ICU) patients have a higher rate of VAP development, different microbiological aetiology or have worse outcomes than other patients without VAP. A secondary analysis of a large prospective, observational study conducted in 27 European ICUs was carried out. Trauma patients were excluded. Of 2082 intubated patients included in the study, 397 (19.1%) had COPD; 79 (19.9%) patients with COPD and 332 (19.7%) patients without COPD developed VAP. ICU mortality increased by 17% (p < 0.05) when COPD patients developed VAP, remaining an independent predictor of mortality [odds ratio (OR) 2.28; 95% confidence interval (CI) 1.35-3.87]. The development of VAP in COPD patients was associated with a median increase of 12 days in the duration of mechanical ventilation and >13 days in ICU stay (p < 0.05). Pseudomonas aeruginosa was more common in VAP when COPD was present (29.1% vs. 18.7%, p = 0.04) and was the most frequent isolate in COPD patients with early-onset VAP, with a frequency 2.5 times higher than in patients without early-onset VAP (33.3% vs. 13.3%, p = 0.03). COPD patients are not more predisposed to VAP than other ICU patients, but if COPD patients develop VAP, they have a worse outcome. Antibiotic coverage for non-fermenters needs to be included in the empiric therapy of all COPD patients, even in early-onset VAP.

  7. 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…

  8. 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.

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

    PubMed

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

    2016-01-01

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

  10. 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…

  11. 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)

  12. 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.

  13. Internalised homonegativity predicts HIV-associated risk behavior in European men who have sex with men in a 38-country cross-sectional study: some public health implications of homophobia

    PubMed Central

    Ross, Michael W; Berg, Rigmor C; Schmidt, Axel J; Hospers, Harm J; Breveglieri, Michele; Furegato, Martina; Weatherburn, Peter

    2013-01-01

    Objectives Internalised homonegativity (IH) is hypothesised to be associated with HIV risk behaviour and HIV testing in men who have sex with men (MSM). We sought to determine the social and individual variables associated with IH and the associations between IH and HIV-related behaviours. Design and setting We examined IH and its predictors as part of a larger Internet-delivered, cross-sectional study on HIV and health in MSM in 38 European countries. Participants 181 495 MSM, IH data analysis subsample 144 177. All participants were male, over the age of consent for homosexual activity in their country of domicile, and have had at least one homosexual contact in the past 6 months. Methodology An anonymous Internet-based questionnaire was disseminated in 25 languages through MSM social media, websites and organisations and responses saved to a UK-based server. IH was measured using a standardised, cross-culturally appropriate scale. Results Three clusters of European countries based on the level of experienced discrimination emerged. IH was predicted by country LGB (lesbian, gay and bisexual) legal climate, Gini coefficient and size of place of settlement. Lower IH was associated with degree the respondent was ‘out’ as gay to others and older age. ‘Outness’ was associated with ever having an HIV test and age, education and number of gay friends, while IH (controlling for the number of non-steady unprotected sex partners and perceived lack of control over safe sex) was associated with condom use for anal intercourse. Conclusions IH is associated with LGB legal climate, economic development indices and urbanisation. It is also associated with ‘outness’ and with HIV risk and preventive behaviours including HIV testing, perceived control over sexual risk and condom use. Homonegative climate is associated with IH and higher levels of HIV-associated risk in MSM. Reducing IH through attention to LGB human rights may be appropriate HIV reduction

  14. 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…

  15. High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L–DOCK4 gene region in autism susceptibility

    PubMed Central

    Maestrini, E; Pagnamenta, A T; Lamb, J A; Bacchelli, E; Sykes, N H; Sousa, I; Toma, C; Barnby, G; Butler, H; Winchester, L; Scerri, T S; Minopoli, F; Reichert, J; Cai, G; Buxbaum, J D; Korvatska, O; Schellenberg, G D; Dawson, G; Bildt, A de; Minderaa, R B; Mulder, E J; Morris, A P; Bailey, A J; Monaco, A P

    2010-01-01

    Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family. PMID:19401682

  16. Population structure and linkage disequilibrium in Lupinus albus L. germplasm and its implication for association mapping.

    PubMed

    Iqbal, Muhammad Javed; Mamidi, Sujan; Ahsan, Rubina; Kianian, Shahryar F; Coyne, Clarice J; Hamama, Anwar A; Narina, Satya S; Bhardwaj, Harbans L

    2012-08-01

    White lupin (Lupinus albus L.) has been around since 300 B.C. and is recognized for its ability to grow on poor soils and application as green manure in addition to seed harvest. The seed has very high levels of protein (33-47 %) and oil (6-13 %). It also has many secondary metabolites that are potentially of nutraceutical value to animals and humans. Despite such a great potential, lupins role in modern agriculture began only in the twentieth century. Although a large collection of Lupinus germplasm accessions is available worldwide, rarely have they been genetically characterized. Additionally, scarce genomic resources in terms of recombinant populations and genome information have been generated for L. albus. With the advancement in association mapping methods, the natural populations have the potential to replace the recombinant populations in gene mapping and marker-trait associations. Therefore, we studied the genetic similarity, population structure and marker-trait association in a USDA germplasm collection for their current and future application in this crop improvement. A total of 122 PI (Plant Inventory) lines were screened with 18 AFLP primer pairs that generated 2,277 fragments. A subset of 892 polymorphic markers with MAF >0.05 (minor allele frequency) were used for association mapping. The cluster analysis failed to group accessions on the basis of their passport information, and a weak structure and low linkage disequilibrium (LD) were observed indicating the usefulness of the collection for association mapping. Moreover, we were also able to identify two markers (a p value of 1.53 × 10(-4) and 2.3 × 10(-4)) that explained 22.69 and 20.5 % of seed weight variation determined using R (LR) (2) . The implications of lack of geographic clustering, population structure, low LD and the ability of AFLP to map seed weight trait using association mapping and the usefulness of the PI collections in breeding programs are discussed.

  17. 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.

  18. Genome-wide association studies in pediatric endocrinology.

    PubMed

    Dauber, Andrew; Hirschhorn, Joel N

    2011-01-01

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

  19. 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.

  20. 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.

  1. Global physician budgets as common-property resources: some implications for physicians and medical associations.

    PubMed Central

    Hurley, J; Card, R

    1996-01-01

    Since 1990 payment for physician services in the fee-for-service sector has shifted from an open-ended system to fixed global budgets. This shift has created a new economic context for practising medicine in Canada. A global cap creates a conflict between physicians' individual economic self-interest and their collective interest in constraining total billings within the capped budget. These types of incentive problems occur in managing what are known in economics as "common-property resources." Analysts studying common-property resources have documented several management principles associated with successful, long-run use of such resources in the face of these conflicting incentives. These management principles include early defining the boundaries of the common-property resource, explicitly specifying rules for using the resource, developing collective decision-making arrangements and monitoring mechanisms, and creating low-cost conflict-resolution mechanisms. The authors argue that global physician budgets can usefully be viewed as common-property-resources. They describe some of the key management principles and note some implications for physicians and the provincial and territorial medical associations as they adapt to global budgets. PMID:8612251

  2. 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

  3. 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.

  4. 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.

  5. 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…

  6. Reading Study: Findings, Recommendations, and Implications.

    ERIC Educational Resources Information Center

    MacDougall, Allan

    1977-01-01

    As part of an ongoing effort to understand the nature of student performance and persistence at Southwestern College (SC), a study was conducted in fall 1976 to determine the effect of reading ability on student course performance. An analysis of the Nelson-Denny Reading Test (NDRT) scores of 4,610 students revealed that, on an average, students…

  7. Cross-Cultural Studies of Child Development: Implications for Clinicians.

    ERIC Educational Resources Information Center

    Fenichel, Emily, Ed.

    1994-01-01

    This theme issue contains six articles on the development of infants and toddlers: (1) "Cross-Cultural Studies of Child Development: Implications for Clinicians" (J. Kevin Nugent); (2) "Therapeutic Work with African-American Families: Using Knowledge of the Culture" (Cheryl Polk); (3) "Psychotherapy in Specific Cultural Contexts: Resources for the…

  8. An Exploratory Study of the Implications of Test Speededness.

    ERIC Educational Resources Information Center

    Donlon, Thomas F.

    To evaluate test speededness and to derive implications for test program activity, this study reviewed the literature on speed and power, identifying four major approaches to the assessment of speed: the Gulliksen approach, the Cronbach and Warrington approach, the Stafford approach, and the approach of the Educational Testing Service (ETS) as…

  9. 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.

  10. 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

  11. 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.

  12. Virus-associated immunopathology: animal models and implications for human disease

    PubMed Central

    1972-01-01

    Part 2 of this memorandum describes further mechanisms whereby the interaction of a virus with the host's immune system may lead to tissue damage. Cell-mediated immunity plays a vital role in promoting recovery from virus infections, but under some circumstances tissue damage may be caused by the reaction of immune cells with viral antigens. When mice are infected with lymphocytic choriomeningitis virus neonatally or as adults while receiving immunosuppressive drugs, widespread invasion of cells is seen but there is little overt disease. If, however, normal adults are infected or if immune cells are transfused into tolerant mice, cell injury and death follow. Viruses have long been suspected of contributing to the pathogenesis of autoimmune diseases. Antibodies directed against normal cell constituents have been reported in several virus infections. Viruses may conceivably unmask or release host antigens, alter host antigens and act as “helper determinants”, or perhaps in other ways provoke immune responses against normal body constituents. The immunopathological manifestations caused by viruses may also be influenced by the host's genetic makeup. Certain observations indicate that, in addition to controlling susceptibility to virus infection, genetic factors partly determine the effectiveness of the immune response. The memorandum calls attention to the possible implications of these concepts and findings for clinical research. Some of the diseases of animals and man that serve as models for studies of virus-associated immunopathology are briefly described. PMID:4539416

  13. 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.

  14. 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

  15. 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

  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.

  17. 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.

  18. Phenylpropanolamine and stroke: the study, the FDA ruling, the implications.

    PubMed

    Mersfelder, T L

    2001-03-01

    Following a recent case-control study that linked the use of phenylpropanolamine (PPA) in diet aids to the risk of hemorrhagic stroke, the Food and Drug Administration requested that drug companies stop marketing products that contain PPA. Dozens of over-the-counter and prescription diet aids and cough and cold remedies will need to be reformulated or discontinued. This paper reviews the study and its implications for physicians.

  19. 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

  20. 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

  1. Tamoxifen experimental carcinogenicity studies: Implications for human effects

    SciTech Connect

    Williams, G.M.

    1995-02-01

    Tamoxifen is an effective antiestrogen in the treatment of breast cancer and is considered highly safe. In recent years, several trials have been initiated in women to evaluate its potential for the prevention of breast cancer. Such long-term administration of a medication to healthy people requires a substantial degree of safety. This review examines experimental carcinogenicity and mechanistic studies on tamoxifen and the implications for human effects. 25 refs.

  2. 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…

  3. Japan Studies Association Journal, 2001.

    ERIC Educational Resources Information Center

    Reichel, Philip L., Ed.

    2001-01-01

    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 grouped under the topic of "Minority…

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

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

    PubMed Central

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

    2009-01-01

    Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association. At baseline, 4,705 (18.3%) women reported history of migraine; 39.6% of the 3,306 women with active migraine indicated aura. Regarding any history of migraine, the multivariable-adjusted odds ratios (95% confidence intervals) for TNF rs673 were 0.52 (0.30-0.89), for TGFB1 rs1800469 0.93 (0.89-0.98), and for CCR2 rs1799864 1.12 (1.03-1.21). Among active migraine with aura the odds ratios (95% confidence intervals) were 1.35 (1.0-1.81) for TNF rs1800750, 1.13 (1.02-1.26) for TNF rs1800629, and 1.22 (1.07-1.40) for CCR2 rs1799864; among active migraine without aura 0.9 (0.84-0.97) for TGFB1 rs1800469, 1.13 (1.01-1.27) for NOS3 rs3918226, and 1.12 (1.02-1.24) for IL9 rs2069885. After correction for multiple testing using the false discovery rate, none of the results remained significant. Our data suggest an association of polymorphisms implicated in inflammatory pathways and migraine in women. TNF, CCR2, TGFB1, NOS3, and IL9 warrant further investigation. Perspective This article presents results from an association study of 77 polymorphisms, implicated in CVD, and migraine. Variants in TNF, CCR2, TGFB1, NOS3, and IL9 were found to be associated with migraine, but did not remain significant after adjustment for multiple testing. Variations in these genes warrant further investigation. PMID:19559392

  11. Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data.

    PubMed

    Denny, Joshua C; Bastarache, Lisa; Ritchie, Marylyn D; Carroll, Robert J; Zink, Raquel; Mosley, Jonathan D; Field, Julie R; Pulley, Jill M; Ramirez, Andrea H; Bowton, Erica; Basford, Melissa A; Carrell, David S; Peissig, Peggy L; Kho, Abel N; Pacheco, Jennifer A; Rasmussen, Luke V; Crosslin, David R; Crane, Paul K; Pathak, Jyotishman; Bielinski, Suzette J; Pendergrass, Sarah A; Xu, Hua; Hindorff, Lucia A; Li, Rongling; Manolio, Teri A; Chute, Christopher G; Chisholm, Rex L; Larson, Eric B; Jarvik, Gail P; Brilliant, Murray H; McCarty, Catherine A; Kullo, Iftikhar J; Haines, Jonathan L; Crawford, Dana C; Masys, Daniel R; Roden, Dan M

    2013-12-01

    Candidate gene and genome-wide association studies (GWAS) have identified genetic variants that modulate risk for human disease; many of these associations require further study to replicate the results. Here we report the first large-scale application of the phenome-wide association study (PheWAS) paradigm within electronic medical records (EMRs), an unbiased approach to replication and discovery that interrogates relationships between targeted genotypes and multiple phenotypes. We scanned for associations between 3,144 single-nucleotide polymorphisms (previously implicated by GWAS as mediators of human traits) and 1,358 EMR-derived phenotypes in 13,835 individuals of European ancestry. This PheWAS replicated 66% (51/77) of sufficiently powered prior GWAS associations and revealed 63 potentially pleiotropic associations with P < 4.6 × 10⁻⁶ (false discovery rate < 0.1); the strongest of these novel associations were replicated in an independent cohort (n = 7,406). These findings validate PheWAS as a tool to allow unbiased interrogation across multiple phenotypes in EMR-based cohorts and to enhance analysis of the genomic basis of human disease.

  12. Genome-wide association studies in Alzheimer's disease: a review.

    PubMed

    Tosto, Giuseppe; Reitz, Christiane

    2013-10-01

    Over the past decade, research aiming to disentangle the genetic underpinnings of late-onset Alzheimer's disease has mostly focused on the identification of common variants through genome-wide association studies. The identification of several new susceptibility genes through these efforts has reinforced the importance of amyloid precursor protein and tau metabolism in the cause of the disease and has implicated immune response, inflammation, lipid metabolism, endocytosis/intracellular trafficking, and cell migration in the cause of the disease. Ongoing and future large-scale genome-wide association studies, translational studies, and next-generation whole genome or whole exome sequencing efforts, hold the promise to map the specific causative variants in these genes, to identify several additional risk variants, including rare and structural variants, and to identify novel targets for genetic testing, prevention, and treatment.

  13. Implications of fundamental signalling alterations in diabetes mellitus-associated cardiovascular disease .

    PubMed

    Balakumar, Pitchai

    2014-12-01

    The chronic diabetes mellitus (DM) is a major risk factor for cardiovascular disease. The incidence of cardiovascular disease might be a foremost cause of morbidity and mortality in patients afflicted with DM. In fact, DM is associated with multi-factorial cardiovascular signalling alterations via significant modulation of expression pattern, activation or release of PI3K, PKB, eNOS, EDRF, NADPH oxidase, EDHF, CGRP, adenosine, iNOS, ROCK, PKC-β2, CaMKII, microRNA (miR)-126 and miR-130a, which could result in inadequate maintenance of cardiovascular physiology and subsequent development of cardiovascular pathology. This review highlights the possible adverse implications of fundamental cardiovascular signalling alteration in DM-associated cardiovascular disease pathology.

  14. 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

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

    PubMed

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

    2013-10-15

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

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

    PubMed

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

    2014-01-01

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

  17. Medullary carcinoma is associated with expression of intercellular adhesion molecule-1. Implication to its morphology and its clinical behavior.

    PubMed Central

    Bacus, S. S.; Zelnick, C. R.; Chin, D. M.; Yarden, Y.; Kaminsky, D. B.; Bennington, J.; Wen, D.; Marcus, J. N.; Page, D. L.

    1994-01-01

    The histological hallmarks for the diagnosis of medullary breast cancer are circumscription, syncytial architecture, diffuse inflammatory infiltrate, and highly atypical nuclei. The biological and prognostic implication is a lower propensity to metastasize. We studied 19 medullary carcinomas for expression of the intercellular adhesion molecule-1 and lymphocyte-function-associated antigen-1, Neu differentiation factor, tumor necrosis factor-alpha, and the expression of HER-2/neu, HER-4, and HER-3 receptors. Our study revealed that all of the 19 medullary carcinomas expressed the intercellular adhesion molecule-1 and lymphocyte function associated antigen. Eighteen of 19 cancers expressed Neu differentiation factor and tumor necrosis factor-alpha. All medullary cancers expressed the HER-2/neu receptor, however, in the majority of the cases, the staining was confined to the cytoplasm. Only 4 of 12 cancers expressed HER-4 and none of the eight medullary cancers tested expressed HER-3. By comparison, in a control group of infiltrating ductal carcinomas, expression of intercellular adhesion molecule-1, lymphocyte function associated antigen-1, and Neu differentiation factor was positive in about 25 to 30% of the cases, HER-4 was expressed in 75% and HER-3 in 95% of the cases. Taken together, our observations suggest that the expression of intercellular adhesion molecule-1, lymphocyte function associated antigen, Neu differentiation factor, and tumor necrosis factor-alpha as factors that may affect the special morphology and the biological behavior that characterizes medullary carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7992839

  18. 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.

  19. 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

  20. The Legal Implications of Report Back in Household Exposure Studies

    PubMed Central

    Goho, Shaun A.

    2016-01-01

    Background: Scientists conducting research into household air or dust pollution must decide whether, when, and how to disclose to study participants their individual results. A variety of considerations factor into this decision, but one factor that has not received attention until now is the possibility that study participants’ receipt of their results might create legal duties under environmental, property, landlord–tenant, or other laws. Objectives: This article examines relevant laws and regulations and explores the scope of participants’ legal duties and the resulting legal and ethical consequences for researchers. Participants could be required in some situations to disclose the presence of certain chemicals when selling or renting their homes or to frequent visitors. The article discusses hypothetical case studies involving the reporting back of results regarding lead, polychlorinated biphenyls, and phthalates. Discussion: The potential legal duties of study participants have both ethical and legal implications for researchers. Issues include whether the legal consequences for participants should affect the decision whether to report back individual results, how researchers should disclose the legal risks to participants during the informed consent process, and whether researchers would be liable to study participants for legal or economic harm arising from reporting study results to them. The review provides recommendations for language that researchers could use in the informed consent process to disclose the legal risks. Conclusions: Researchers should still report back to participants who want to see their results, but they should disclose the risks of obtaining the information as part of the informed consent process. Citation: Goho SA. 2016. The legal implications of report back in household exposure studies. Environ Health Perspect 124:1662–1670; http://dx.doi.org/10.1289/EHP187 PMID:27153111

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

    PubMed

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

    2015-10-13

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

  2. 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

  3. 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

  4. 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.

  5. The ASPIRA Association School Retention Study.

    ERIC Educational Resources Information Center

    Velez, William; Fernandez, Ricardo R.

    1991-01-01

    The ASPIRA Association in the District of Columbia conducted a longitudinal multimethod study with 1,152 students based on school records, interviews, the High School and Beyond study, and 1-year followup to study dropouts among Hispanic-American students in 5 cities: Chicago, Miami, Newark, Milwaukee, and San Antonio. Findings represent an…

  6. Population genetic simulations of complex phenotypes with implications for rare variant association tests

    PubMed Central

    Uricchio, Lawrence H.; Torres, Raul; Witte, John S.; Hernandez, Ryan D.

    2014-01-01

    Demographic events and natural selection alter patterns of genetic variation within populations, and may play a substantial role in shaping the genetic architecture of complex phenotypes and disease. However, the joint impact of these basic evolutionary forces is often ignored in the assessment of statistical tests of association. Here, we provide a simulation-based framework for generating DNA sequences that incorporates selection and demography with flexible models for simulating phenotypic variation (sfs_coder). This tool also allows the user to perform locus-specific simulations by automatically querying annotated genomic functional elements and genetic maps. We demonstrate the effects of evolutionary forces on patterns of genetic variation by simulating recently inferred models of human selection and demography. We use these simulations to show that the demographic model and locus-specific features, such as the proportion of sites under selection, may have practical implications for estimating the statistical power of sequencing-based rare variant association tests. In particular, for some phenotype models, there may be higher power to detect rare variant associations in African populations compared to non-Africans, but power is considerably reduced in regions of the genome with rampant negative selection. Furthermore, we show that existing methods for simulating large samples based on resampling from a small set of observed haplotypes fail to recapitulate the distribution of rare variants in the presence of rapid population growth (as has been observed in several human populations). PMID:25417809

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

    PubMed Central

    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 nutrition and medical service provision to this population. Design and Methods: In-home interviews and oral examinations were conducted with 635 adults in rural North Carolina counties with substantial African American and American Indian populations. Avoidance and modification data were obtained for foods representing different dental challenges and dietary contributions. Data were weighted to census data for ethnicity and sex. Bivariate analyses of oral health measures and foods avoided used chi-square and logistic regression tests. Multivariable analyses used proportional odds or nominal regression models. Results: Whole fruits and raw vegetables were the most commonly avoided foods; substantial proportions of older adults also avoided meats, cooked vegetables, and other foods. Food avoidance was significantly associated with self-rated oral health, periodontal disease, bleeding gums, dry mouth, having dentures, and having fewer anterior and posterior occlusal contacts. Associations persisted when controlling for demographic and socioeconomic status indicators. From 24% to 68% of participants reported modifying specific fruits, vegetables, and meats. Modifying harder foods was related to location of teeth and periodontal disease and softer foods to oral pain and dry mouth. Implications: Food services for older adults should consider their oral health status. Policy changes are needed to provide oral health care in benefits for older adults. PMID:19574543

  8. 2-D Structure of the A Region of Xist RNA and Its Implication for PRC2 Association

    PubMed Central

    Maenner, Sylvain; Blaud, Magali; Fouillen, Laetitia; Savoye, Anne; Marchand, Virginie; Dubois, Agnès; Sanglier-Cianférani, Sarah; Van Dorsselaer, Alain; Clerc, Philippe; Avner, Philip; Visvikis, Athanase; Branlant, Christiane

    2010-01-01

    In placental mammals, inactivation of one of the X chromosomes in female cells ensures sex chromosome dosage compensation. The 17 kb non-coding Xist RNA is crucial to this process and accumulates on the future inactive X chromosome. The most conserved Xist RNA region, the A region, contains eight or nine repeats separated by U-rich spacers. It is implicated in the recruitment of late inactivated X genes to the silencing compartment and likely in the recruitment of complex PRC2. Little is known about the structure of the A region and more generally about Xist RNA structure. Knowledge of its structure is restricted to an NMR study of a single A repeat element. Our study is the first experimental analysis of the structure of the entire A region in solution. By the use of chemical and enzymatic probes and FRET experiments, using oligonucleotides carrying fluorescent dyes, we resolved problems linked to sequence redundancies and established a 2-D structure for the A region that contains two long stem-loop structures each including four repeats. Interactions formed between repeats and between repeats and spacers stabilize these structures. Conservation of the spacer terminal sequences allows formation of such structures in all sequenced Xist RNAs. By combination of RNP affinity chromatography, immunoprecipitation assays, mass spectrometry, and Western blot analysis, we demonstrate that the A region can associate with components of the PRC2 complex in mouse ES cell nuclear extracts. Whilst a single four-repeat motif is able to associate with components of this complex, recruitment of Suz12 is clearly more efficient when the entire A region is present. Our data with their emphasis on the importance of inter-repeat pairing change fundamentally our conception of the 2-D structure of the A region of Xist RNA and support its possible implication in recruitment of the PRC2 complex. PMID:20052282

  9. Anxiety reduction associated with meditation: home study.

    PubMed

    Puryear, H B; Cayce, C T; Thurston, M A

    1976-10-01

    The effects of a new meditation technique were investigated; 159 A.R.E. members were randomly assigned either to a treatment or control group with the former learning the new technique using a home-study workbook manual and the latter continuing their customary meditational techniques. Analysis of variance (repeated measures) was used to compare group means of the scale scores yielded by two instruments, the IPAT Anxiety Scale (Self-analysis Form) and the Mooney Problem Check List, Adult Form (Mooney & Gordon, 1950). Unlike the control group, the treatment group reported highly significant reduction on the IPAT Anxiety Scale scores after 28 days of meditating with the new approach but no significant differences were found on the check list variables for either the treatment or control group. Implications of the findings for mental health professionals (psychiatrists, clinical and counseling psychologists) are briefly discussed.

  10. Genomewide association study of opioid dependence: multiple associations mapped to calcium and potassium pathways

    PubMed Central

    Gelernter, Joel; Kranzler, Henry R.; Sherva, Richard; Koesterer, Ryan; Almasy, Laura; Zhao, Hongyu; Farrer, Lindsay A.

    2013-01-01

    Background We report a GWAS of two populations, African- and European-American (AA, EA) for opioid dependence (OD) in three sets of subjects, to identify pathways, genes, and alleles important in OD risk. Methods Design employed three phases (based on separate sample collections). Phase 1 included our discovery GWAS dataset consisting of 5,697 subjects (58% AA) diagnosed with opioid and/or other substance dependence (SD), and controls. Subjects were genotyped using the Illumina OmniQuad microarray, yielding 890,000 SNPs suitable for analysis. Additional genotypes were imputed using the 1000 Genomes reference panel. Top-ranked findings were further evaluated in Phase 2 by incorporating information from the publicly available SAGE dataset, with GWAS data from 4,063 subjects (32% AA). In Phase 3, the most significant SNPs from Phase 2 were genotyped in 2,549 independent subjects (32% AA). Analyses were performed using case-control and ordinal trait designs. Results Most significant results emerged from the AA subgroup. Genomewide-significant associations (p<5.0×10−8) were observed with SNPs from multiple loci - KCNC1*rs60349741 most significant after combining results from datasets in every phase of the study. The most compelling results were obtained with genes involved in potassium signaling pathways (e.g., KCNC1, KCNG2, and KCNA4). Pathway analysis also implicated genes involved in calcium signaling and long-term potentiation. Conclusions This is the first study to identify risk variants for OD using GWAS. Our results strongly implicate risk pathways, provide insights into novel therapeutic and prevention strategies, and may provide biologically bridge OD and other non-SD psychiatric traits where similar pathways have been implicated. PMID:24143882

  11. 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

  12. 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

  13. 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.

  14. No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing

    PubMed Central

    Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen A; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Ahmad, Jamil; Thompson, Ella R; Damiola, Francesca; Pertesi, Maroulio; Voegele, Catherine; Mebirouk, Noura; Robinot, Nivonirina; Durand, Geoffroy; Forey, Nathalie; Luben, Robert N; Ahmed, Shahana; Aittomäki, Kristiina; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Beckman, Matthias W; Benitez, Javier; Van Den Berg, David; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Brenner, Hermann; Chang-Claude, Jenny; Chia, Kee Seng; Choi, Ji-Yeob; Conroy, Don M; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Fostira, Florentia; García-Closas, Montserrat; Giles, Graham G; Glendon, Gord; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hart, Steven N; Hartman, Mikael; Hooning, Maartje J; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; James, Paul A; John, Esther M; Johnson, Nichola; Jones, Michael; Kabisch, Maria; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lambrechts, Diether; Li, Na; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Meindl, Alfons; Mitchell, Gillian; Muir, Kenneth; Nevelsteen, Ines; van den Ouweland, Ans; Peterlongo, Paolo; Phuah, Sze Yee; Pylkäs, Katri; Rowley, Simone M; Sangrajrang, Suleeporn; Schmutzler, Rita K; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Verhoef, Senno; Wong-Brown, Michelle; Zheng, Wei; Zheng, Ying; Nevanlinna, Heli; Scott, Rodney J; Andrulis, Irene L; Wu, Anna H; Hopper, John L; Couch, Fergus J; Winqvist, Robert; Burwinkel, Barbara; Sawyer, Elinor J; Schmidt, Marjanka K; Rudolph, Anja; Dörk, Thilo; Brauch, Hiltrud; Hamann, Ute; Neuhausen, Susan L; Milne, Roger L; Fletcher, Olivia; Pharoah, Paul D P; Campbell, Ian G; Dunning, Alison M; Le Calvez-Kelm, Florence; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia

    2016-01-01

    Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels. PMID:26921362

  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. 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

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

    PubMed

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

    2016-07-01

    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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  20. 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

  1. 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...

  2. Associative visual agnosia: a case study.

    PubMed

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

    2008-01-01

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

  3. 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.

  4. Functional analysis of variance for association studies.

    PubMed

    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.

  5. Functional analysis of variance for association studies.

    PubMed

    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

  6. 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…

  7. 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.

  8. 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

  9. Coronary heart disease in Indians: implications of the INTERHEART study.

    PubMed

    Ajay, Vamadevan S; Prabhakaran, Dorairaj

    2010-11-01

    Coronary heart diseases (CHD) have reached epidemic proportions among Indians. The recently concluded INTERHEART study emphasizes the role of behavioural and conventional risk factors in the prediction of CHD risk among Indians. These findings have implication for the health care providers and policy makers in the country due to the fact that all these conventional risk factors are potentially modifiable and are good starting points for prevention. The policy measures by means of legislation and regulatory approaches on agriculture and food industry or tobacco or physical activity will have large impact on CHD risk factor reduction in the population. In addition, the health system needs to focus on: (i) providing information for increasing awareness and an enabling environment for adoption of healthy living habits by the community; (ii) early detection of persons with risk factors and cost-effective interventions for reducing risk; and (iii) early detection of persons with clinical disease and cost-effective secondary prevention measures to prevent complications. The evidence from INTERHEART provides rationale for developing treatment algorithms and treatment guidelines for CHD at various levels of health care. In addition, INTERHEART provides answer for the quest for a single reliable biomarker, Apo B/ApoA 1 ratio that can predict the future CHD risk among individuals. Further to this, the INTERHEART study also opens up several unanswered questions on the pathobiology of the premature onset of myocardial infarction among Indians and calls for the need to developing capacity in clinical research in CHD in India.

  10. 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

  11. 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

  12. Examining the relationship between affect and implicit associations: implications for risk perception.

    PubMed

    Dohle, Simone; Keller, Carmen; Siegrist, Michael

    2010-07-01

    It has been suggested that affect may play an important role in risk perception. Slovic et al. argued that people make use of the "affect heuristic" when assessing risks because it is easier and more efficient to rely on spontaneous affective reactions than to analyze all available information. In the present studies, a single category implicit association test (SC-IAT) to measure associations evoked by different hazards was employed. In the first study, we tested the extent to which the SC-IAT corresponds to the theoretical construct of affect in a risk framework. Specifically, we found that the SC-IAT correlates with other explicit measures that claim to measure affect, as well as with a measure of trust, but not with a measure that captures a different construct (subjective knowledge). In the second study, we addressed the question of whether hazards that vary along the dread dimension of the psychometric paradigm also differ in the affect they evoke. The results of the SC-IAT indicated that a high-dread hazard (nuclear power) elicits negative associations. Moreover, the high-dread hazard evoked more negative associations than a medium-dread hazard (hydroelectric power). In contrast, a nondread hazard (home appliances) led to positive associations. The results of our study highlight the importance of affect in shaping attitudes and opinions toward risks. The results further suggest that implicit measures may provide valuable insight into people's risk perception above and beyond explicit measures. PMID:20409044

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases.

    PubMed

    Searles Quick, V B; Davis, J M; Olincy, A; Sikela, J M

    2015-01-01

    The copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species. PMID:26670282

  18. DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases

    PubMed Central

    Searles Quick, V B; Davis, J M; Olincy, A; Sikela, J M

    2015-01-01

    The copy number of DUF1220, a protein domain implicated in human brain evolution, has been linearly associated with autism severity. Given the possibility that autism and schizophrenia are related disorders, the present study examined DUF1220 copy number variation in schizophrenia severity. There are notable similarities between autism symptoms and schizophrenia negative symptoms, and divergence between autism symptoms and schizophrenia positive symptoms. We therefore also examined DUF1220 copy number in schizophrenia subgroups defined by negative and positive symptom features, versus autistic individuals and controls. In the schizophrenic population (N=609), decreased DUF1220 copy number was linearly associated with increasing positive symptom severity (CON1 P=0.013, HLS1 P=0.0227), an association greatest in adult-onset schizophrenia (CON1 P=0.00155, HLS1 P=0.00361). In schizophrenic males, DUF1220 CON1 subtype copy number increase was associated with increased negative symptom severity (P=0.0327), a finding similar to that seen in autistic populations. Subgroup analyses demonstrated that schizophrenic individuals with predominantly positive symptoms exhibited reduced CON1 copy number compared with both controls (P=0.0237) and schizophrenic individuals with predominantly negative symptoms (P=0.0068). These findings support the view that (1) autism and schizophrenia exhibit both opposing and partially overlapping phenotypes and may represent a disease continuum, (2) variation in DUF1220 copy number contributes to schizophrenia disease risk and to the severity of both disorders, and (3) schizophrenia and autism may be, in part, a harmful by-product of the rapid and extreme evolutionary increase in DUF1220 copy number in the human species. PMID:26670282

  19. 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

  20. 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

  1. 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 ...

  2. A controlled study of associated dental anomalies.

    PubMed

    Baccetti, T

    1998-06-01

    The purpose of this study was to reveal patterns of association among seven types of dental anomalies (aplasia of second premolars, small size of maxillary lateral incisors, infraocclusion of primary molars, enamel hypoplasia, ectopic eruption of first molars, supernumerary teeth, and palatal displacement of maxillary canines) in an untreated orthodontic population, ages 7 to 14. The prevalence of associated tooth anomalies in seven groups of 100 subjects selected according to one primarily diagnosed dental anomaly was compared with the prevalence of the examined dental anomalies in a control group of 1,000 subjects. Significant reciprocal associations (p < 0.005) were found among five of the anomalies (aplasia of second premolars, small size of maxillary lateral incisors, infraocclusion of primary molars, enamel hypoplasia, and palatal displacement of maxillary canines), suggesting a common genetic origin for these conditions. Supernumerary teeth appeared to be a separate etiological entity with respect to all other examined tooth anomalies. The existence of associations between different tooth anomalies is clinically relevant, as the early diagnosis of one anomaly may indicate an increased risk for others. PMID:9622764

  3. 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

  4. 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

  5. Microorganisms associated particulate matter: a preliminary study.

    PubMed

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

    2014-05-01

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

  6. 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

  7. Outbreaks of salmonellosis associated with eating uncooked tomatoes: implications for public health. The Investigation Team.

    PubMed Central

    Hedberg, C. W.; Angulo, F. J.; White, K. E.; Langkop, C. W.; Schell, W. L.; Stobierski, M. G.; Schuchat, A.; Besser, J. M.; Dietrich, S.; Helsel, L.; Griffin, P. M.; McFarland, J. W.; Osterholm, M. T.

    1999-01-01

    Laboratory-based surveillance of salmonella isolates serotyped at four state health departments (Illinois, Michigan, Minnesota and Wisconsin) led to the identification of multistate outbreaks of salmonella infections during 1990 (176 cases of S. javiana) and 1993 (100 cases of S. montevideo). Community-based case-control studies and product traceback implicated consumption of tomatoes from a single South Carolina tomato packer (Packer A) MOR 16.0; 95% CI2.1, 120.6; P < 0.0001 in 1990 and again in 1993 (MOR 5.7; 95 % CI 1.5, 21.9; P = 0.01) as the likely vehicle. Contamination likely occurred at the packing shed, where field grown tomatoes were dumped into a common water bath. These outbreaks represent part of a growing trend of large geographically dispersed outbreaks caused by sporadic or low-level contamination of widely distributed food items. Controlling contamination of agricultural commodities that are also ready-to-eat foods, particularly fruits and vegetables, presents a major challenge to industry, regulators and public health officials. PMID:10459640

  8. 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

  9. What are the health implications associated with the consumption of energy drinks? A systematic review.

    PubMed

    Burrows, Tracy; Pursey, Kirrilly; Neve, Melinda; Stanwell, Peter

    2013-03-01

    There is increasing interest regarding the potential health effects of energy drink (ED) consumption. The aim of the present review was to investigate the existing evidence on health outcomes associated with ED consumption. Studies published between 1966 and February 2011 were retrieved and included if they met the following criteria: were randomized or pseudo randomized control trials; studied a human population; reported a health-related measure; and investigated a whole ED (as opposed to individual ingredients). Study quality was evaluated and data extracted using standardized tools. Fifteen studies were identified, the majority of which had less than 30 participants and included a short term of follow-up (range: 30 min-3 h). The following outcome measures were included: cardiorespiratory effects, physiological measures, pathological measures, and body composition. The mean dosage of ED was 390 mL (range: 250-750 mL). Commercial ED funding and/or study associations were identified in six studies. Studies investigating long-term consumption and follow-up were lacking. The findings from this review do not allow definitive dietary recommendations to be made regarding safe levels of ED consumption; caution should be exercised when consuming these drinks until further high-quality research is undertaken to substantiate findings. PMID:23452281

  10. Implications of Multi-resolution AOD retrievals for Air Quality Studies

    NASA Astrophysics Data System (ADS)

    Kumar, N.; Chu, A. D.

    2009-12-01

    Implications of Multi-resolution AOD retrievals for Air Quality Studies This paper examines the robustness of multi-resolution (2-km, 5-km and 10-km) AOD retrievals using MODIS measurements and with the sunphotometer measurements over the period 2000 to 2007 in two distinct aerosol loading environments: Bondville (USA) and Kanpur (India), with multi-annual mean (±standard deviation) of 0.161±0.0006 and 0.547±0.001, respectively. Our analysis suggests that 2-km and 5-km AODMODIS are significantly better correlated with the sunphotometer measurements as compared to 10-km AODMODIS irrespective of background aerosol loading. The best correlation (~0.91) is observed when both datasets are aggregated within the smallest space and time intervals of 0.025° and 15 minutes, and then the correlation decreases sharply with distance >0.075° and time interval >30 minutes. Based on these findings it is expected that the association between ground measurements of ambient particulates of different sizes and multi-resolution MODIS AOD is likely to vary significantly, and will have significant implications for air quality studies.

  11. 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

  12. 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)

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Presence of cytoplasmic factors functional in peroxisomal protein import implicates organelle-associated defects in several human peroxisomal disorders.

    PubMed Central

    Wendland, M; Subramani, S

    1993-01-01

    Cells from patients with peroxisome-deficient disorders contain membrane ghosts devoid of most matrix contents instead of normal peroxisomes indicating that the underlying molecular defects impair the import of matrix proteins into these peroxisome ghosts. Genetic heterogeneity for the molecular defects was inferred from the assignment of patients with peroxisome-deficient disorders into nine complementation groups. The aim of our studies was to analyze cell lines from six different complementation groups in a systematic manner for the presence of peroxisome ghosts, the ability to import Ser-Lys-Leu-containing proteins into peroxisome ghosts and for the presence of cytosolic factors required for peroxisomal protein import. We show that each of the cell lines analyzed contains peroxisome ghosts, but is unable to import matrix proteins as judged by a peroxisomal import assay using permeabilized cells. The addition of wild type cytosol did not restore the capacity to import matrix proteins but cytosol prepared from these cell lines was functional in stimulation of peroxisomal protein import in a heterologous system. These results implicate organelle-associated molecular defects in each of the six cell lines analyzed. Images PMID:7693762

  19. Noninvasive effects measurements for air pollution human studies: methods, analysis, and implications.

    PubMed

    Mirowsky, Jaime; Gordon, Terry

    2015-01-01

    Human exposure studies, compared with cell and animal models, are heavily relied upon to study the associations between health effects in humans and air pollutant inhalation. Human studies vary in exposure methodology, with some work conducted in controlled settings, whereas other studies are conducted in ambient environments. Human studies can also vary in the health metrics explored, as there exists a myriad of health effect end points commonly measured. In this review, we compiled mini reviews of the most commonly used noninvasive health effect end points that are suitable for panel studies of air pollution, broken into cardiovascular end points, respiratory end points, and biomarkers of effect from biological specimens. Pertinent information regarding each health end point and the suggested methods for mobile collection in the field are assessed. In addition, the clinical implications for each health end point are summarized, along with the factors identified that can modify each measurement. Finally, the important research findings regarding each health end point and air pollutant exposures were reviewed. It appeared that most of the adverse health effects end points explored were found to positively correlate with pollutant levels, although differences in study design, pollutants measured, and study population were found to influence the magnitude of these effects. Thus, this review is intended to act as a guide for researchers interested in conducting human exposure studies of air pollutants while in the field, although there can be a wider application for using these end points in many epidemiological study designs. PMID:25605444

  20. Noninvasive effects measurements for air pollution human studies: methods, analysis, and implications.

    PubMed

    Mirowsky, Jaime; Gordon, Terry

    2015-01-01

    Human exposure studies, compared with cell and animal models, are heavily relied upon to study the associations between health effects in humans and air pollutant inhalation. Human studies vary in exposure methodology, with some work conducted in controlled settings, whereas other studies are conducted in ambient environments. Human studies can also vary in the health metrics explored, as there exists a myriad of health effect end points commonly measured. In this review, we compiled mini reviews of the most commonly used noninvasive health effect end points that are suitable for panel studies of air pollution, broken into cardiovascular end points, respiratory end points, and biomarkers of effect from biological specimens. Pertinent information regarding each health end point and the suggested methods for mobile collection in the field are assessed. In addition, the clinical implications for each health end point are summarized, along with the factors identified that can modify each measurement. Finally, the important research findings regarding each health end point and air pollutant exposures were reviewed. It appeared that most of the adverse health effects end points explored were found to positively correlate with pollutant levels, although differences in study design, pollutants measured, and study population were found to influence the magnitude of these effects. Thus, this review is intended to act as a guide for researchers interested in conducting human exposure studies of air pollutants while in the field, although there can be a wider application for using these end points in many epidemiological study designs.

  1. 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

  2. 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

  3. 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

  4. Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility.

    PubMed

    Jenkins, Timothy G; Aston, Kenneth I; Pflueger, Christian; Cairns, Bradley R; Carrell, Douglas T

    2014-07-01

    Recent evidence demonstrates a role for paternal aging on offspring disease susceptibility. It is well established that various neuropsychiatric disorders (schizophrenia, autism, etc.), trinucleotide expansion associated diseases (myotonic dystrophy, Huntington's, etc.) and even some forms of cancer have increased incidence in the offspring of older fathers. Despite strong epidemiological evidence that these alterations are more common in offspring sired by older fathers, in most cases the mechanisms that drive these processes are unclear. However, it is commonly believed that epigenetics, and specifically DNA methylation alterations, likely play a role. In this study we have investigated the impact of aging on DNA methylation in mature human sperm. Using a methylation array approach we evaluated changes to sperm DNA methylation patterns in 17 fertile donors by comparing the sperm methylome of 2 samples collected from each individual 9-19 years apart. With this design we have identified 139 regions that are significantly and consistently hypomethylated with age and 8 regions that are significantly hypermethylated with age. A representative subset of these alterations have been confirmed in an independent cohort. A total of 117 genes are associated with these regions of methylation alterations (promoter or gene body). Intriguingly, a portion of the age-related changes in sperm DNA methylation are located at genes previously associated with schizophrenia and bipolar disorder. While our data does not establish a causative relationship, it does raise the possibility that the age-associated methylation of the candidate genes that we observe in sperm might contribute to the increased incidence of neuropsychiatric and other disorders in the offspring of older males. However, further study is required to determine whether, and to what extent, a causative relationship exists. PMID:25010591

  5. An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders

    PubMed Central

    Donner, Jonas; Pirkola, Sami; Silander, Kaisa; Kananen, Laura; Terwilliger, Joseph D.; Lönnqvist, Jouko; Peltonen, Leena; Hovatta, Iiris

    2008-01-01

    Background Human anxiety disorders are complex diseases with largely unknown etiology. We have taken a cross-species approach to identify genes that regulate anxiety-like behavior with inbred mouse strains that differ in their innate anxiety levels as a model. We previously identified 17 genes with expression levels that correlate with anxiety behavior across the studied strains. In the present study, we tested their 13 known human homologues as candidate genes for human anxiety disorders with a genetic association study. Methods We describe an anxiety disorder study sample derived from a Finnish population-based cohort and consisting of 321 patients and 653 carefully matched control subjects, all interviewed to obtain DSM-IV diagnoses. We genotyped altogether 208 single nucleotide polymorphisms (SNPs) (all non-synonymous SNPs, SNPs that alter potential microRNA binding sites, and gap-filling SNPs selected on the basis of HapMap information) from the investigated anxiety candidate genes. Results Specific alleles and haplotypes of six of the examined genes revealed some evidence for association (p ≤ .01). The most significant evidence for association with different anxiety disorder subtypes were: p = .0009 with ALAD (δ-aminolevulinate dehydratase) in social phobia, p = .009 with DYNLL2 (dynein light chain 2) in generalized anxiety disorder, and p = .004 with PSAP (prosaposin) in panic disorder. Conclusions Our findings suggest that variants in these genes might predispose to specific human anxiety disorders. These results illustrate the potential utility of cross-species approaches in identification of candidate genes for psychiatric disorders. PMID:18639233

  6. Implications of flexible work systems for work studies.

    PubMed

    Kogi, K

    1997-12-01

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

  7. Ovarian Carcinoma Subtypes Are Different Diseases: Implications for Biomarker Studies

    PubMed Central

    Köbel, Martin; Kalloger, Steve E; Boyd, Niki; McKinney, Steven; Mehl, Erika; Palmer, Chana; Leung, Samuel; Bowen, Nathan J; Ionescu, Diana N; Rajput, Ashish; Prentice, Leah M; Miller, Dianne; Santos, Jennifer; Swenerton, Kenneth; Gilks, C. Blake; Huntsman, David

    2008-01-01

    Background Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous) are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. Methods and Findings In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1) in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognostic marker in the entire cohort (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.2%–2.4%) but is not of prognostic significance within any subtype. Prognostic associations can even show an inverse correlation within the entire cohort, when compared to a specific subtype. For example, WT1 is more frequently expressed in high-grade serous carcinomas, an aggressive subtype, and is an unfavourable prognostic marker within the entire cohort of ovarian carcinomas (RR 1.7, 95% CI 1.2%–2.3%), but

  8. 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.

  9. Functional Connectivity Associated with Acoustic Stability During Vowel Production: Implications for Vocal-Motor Control

    PubMed Central

    2015-01-01

    Abstract 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

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  11. 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

  12. 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.

  13. 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

  14. Re-Os isotope studies of Mindanao adakites: Implications for sources of metals and melts

    NASA Astrophysics Data System (ADS)

    Dreher, Scott T.; MacPherson, Colin G.; Pearson, D. Graham; Davidson, Jon P.

    2005-12-01

    Whether the downgoing slab in modern subduction zones is able to melt is an important unresolved aspect of plate tectonics. Rare arc lavas with high Sr/Y ratios and low Y and heavy rare earth element concentrations, called adakites, are often attributed to melting of young subducted crust in subduction zones. Osmium isotopic data obtained for 13 adakite samples from Mindanao, Philippines, conflict with the slab-melting model. Ten of the samples have unradiogenic 187Os/188Os ratios inconsistent with partial melting of the ca. 50 Ma Philippine Sea lithosphere subducting beneath Mindanao. The Os isotope signatures are similar to those of young mid-oceanic-ridge basalts and normal arc rocks, consistent with a mantle source. In addition to implications for mass transfer in subduction zones, the apparent association of adakites with Cu-Au deposits makes understanding their origin, and that of the associated metals, economically interesting. This study suggests that a reevaluation is required of the slab-melting hypothesis in general, and that the metals associated with the Mindanao adakites come from the mantle.

  15. RESEARCH: Perceptions of Risk Associated with Use of Farm Chemicals: Implications for Conservation Initiatives

    PubMed

    Tucker; Napier

    1998-07-01

    / Data were collected from 245 farmers within the Darby Creek hydrologic unit in central Ohio to assess perceptions of risk associated with use of farm chemicals. Farmers were asked to evaluate the level of risk associated with use of agricultural chemicals for water quality, food safety, food quality, health of applicator, health of farm animals, wildlife, beneficial plants, beneficial insects, and human health. Study findings revealed that respondents perceived use of farm chemicals posed little or no threat to any of the assessed items. A composite index was formulated from the responses to the nine items and was titled Perceived Risk. Variance in the Perceived Risk index was regressed against social learning variables. The findings revealed that approximately 32% of the variance was explained by the predictive variables included in the model. It was concluded that the theoretical perspective was somewhat useful for understanding perceptions held about agricultural chemical use at the farm level. The findings are discussed in the context of future conservation and educational-information programs within the study region.KEY WORDS: Risk perception; Risk assessment; Groundwater; Pesticide contamination; Food safety; Environmental quality

  16. Studying Associations in Health Care Research.

    PubMed

    Flannelly, Kevin J; Flannelly, Laura T; Jankowski, Katherine R B

    2016-01-01

    This article discusses some of the types of relationships observed in healthcare research and depicts them in graphic form. The article begins by explaining two basic associations observed in chemistry and physics (Boyles' Law and Charles' Law), and illustrates how these associations are similar to curvilinear and linear associations, respectively, found in healthcare. Graphs of curvilinear associations include morbidity curves and survival and mortality curves. Several examples of linear relationships are given and methods of testing linear relationships with interval and ratio data are introduced (i.e., correlation and ordinary least-squares regression). In addition, 2 × 2 contingency tables for testing the association between categorical (or nominal) data are described. Finally, Sir Austin Bradford Hill's eight criteria for assessing causality from research on associations between variables are presented and explained. Three appendices provide interested readers with opportunities to practice interpreting selected curvilinear and linear relationships.

  17. 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

  18. 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

  19. 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

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

    PubMed

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

    2013-12-01

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

  1. Joint Linkage and Association Analysis with Exome Sequence Data Implicates SLC25A40 in Hypertriglyceridemia

    PubMed Central

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

    2013-01-01

    Hypertriglyceridemia (HTG) is a heritable risk factor for cardiovascular disease. Investigating the genetics of HTG may identify new drug targets. There are ∼35 known single-nucleotide variants (SNVs) that explain only ∼10% of variation in triglyceride (TG) level. Because of the genetic heterogeneity of HTG, a family study design is optimal for identification of rare genetic variants with large effect size because the same mutation can be observed in many relatives and cosegregation with TG can be tested. We considered HTG in a five-generation family of European American descent (n = 121), ascertained for familial combined hyperlipidemia. By using Bayesian Markov chain Monte Carlo joint oligogenic linkage and association analysis, we detected linkage to chromosomes 7 and 17. Whole-exome sequence data revealed shared, highly conserved, private missense SNVs in both SLC25A40 on chr7 and PLD2 on chr17. Jointly, these SNVs explained 49% of the genetic variance in TG; however, only the SLC25A40 SNV was significantly associated with TG (p = 0.0001). This SNV, c.374A>G, causes a highly disruptive p.Tyr125Cys substitution just outside the second helical transmembrane region of the SLC25A40 inner mitochondrial membrane transport protein. Whole-gene testing in subjects from the Exome Sequencing Project confirmed the association between TG and SLC25A40 rare, highly conserved, coding variants (p = 0.03). These results suggest a previously undescribed pathway for HTG and illustrate the power of large pedigrees in the search for rare, causal variants. PMID:24268658

  2. 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

  3. Increased Perceived Stress is Associated with Blunted Hedonic Capacity: Potential Implications for Depression Research

    PubMed Central

    Pizzagalli, Diego A.; Bogdan, Ryan; Ratner, Kyle G.; Jahn, Allison L.

    2007-01-01

    Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity; in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the degree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants' propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n = 88) and Study 2 (n = 80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression. PMID:17854766

  4. Disentangling pooled triad genotypes for association studies.

    PubMed

    Shi, Min; Umbach, David M; Weinberg, Clarice R

    2014-09-01

    Association studies that genotype affected offspring and their parents (triads) offer robustness to genetic population structure while enabling assessments of maternal effects, parent-of-origin effects, and gene-by-environment interaction. We propose case-parents designs that use pooled DNA specimens to make economical use of limited available specimens. One can markedly reduce the number of genotyping assays required by randomly partitioning the case-parent triads into pooling sets of h triads each and creating three pools from every pooling set, one pool each for mothers, fathers, and offspring. Maximum-likelihood estimation of relative risk parameters proceeds via log-linear modeling using the expectation-maximization algorithm. The approach can assess offspring and maternal genetic effects and accommodate genotyping errors and missing genotypes. We compare the power of our proposed analysis for testing offspring and maternal genetic effects to that based on a difference approach and that of the gold standard based on individual genotypes, under a range of allele frequencies, missing parent proportions, and genotyping error rates. Power calculations show that the pooling strategies cause only modest reductions in power if genotyping errors are low, while reducing genotyping costs and conserving limited specimens.

  5. A review of cognitive factors in the etiology of rape: theories, empirical studies, and implications.

    PubMed

    Drieschner, K; Lange, A

    1999-01-01

    In the past decade, research into the etiology of rape has increasingly focused on cognitive variables. The studies reviewed in the present article provide evidence that men with a high proclivity to rape have more rape supportive attitudes, are more likely to consider victims to be responsible for rape, and are less knowledgeable about the negative impact of rape on the victims. These men tend to misperceive cues emitted by women in heterosocial interactions; fail to generate inhibitory self-verbalizations to suppress association of sex and aggression; and have more coercive, sexual fantasies. Furthermore, a high proclivity to rape is associated with a semantic network in which concepts of sex and power are closely linked in such a way that power cues are necessary precursors of sexual feelings. Multivariate studies suggest that rape-supportive attitudes interact with noncognitive factors in the etiology of rape. Implications for rape prevention and treatment of rapists are considered. Finally, methodological issues are discussed, and recommendations for future research are given. PMID:9987584

  6. Admixture in Hispanic Americans: its impact on ITGAM association and implications for admixture mapping in SLE.

    PubMed

    Molineros, J E; Kim-Howard, X; Deshmukh, H; Jacob, C O; Harley, J B; Nath, S K

    2009-07-01

    Systemic Lupus Erythematosus (SLE) disproportionately affects minorities, such as Hispanic Americans (HA). Prevalence of SLE is 3-5 times higher in HA than in European-derived populations and have more active disease at the time of diagnosis, with more serious organ system involvement. HA is an admixed population, it is possible that there is an effect of admixture on the relative risk of the disease. This admixture can create substantial increase of linkage disequilibrium (LD) in both magnitude and range, which can provide a unique opportunity for admixture mapping. The main objectives of this study are to (a) estimate hidden population structure in HA individuals; (b) estimate individual ancestry proportions and its impact on SLE risk; (c) assess impact of admixture on ITGAM association, a recently identified SLE susceptibility gene; and (d) estimate power of admixture mapping in HA. Our dataset contained 1125 individuals, of whom 884 (657 SLE cases and 227 controls) were self-classified as HA. Using 107 unlinked ancestry informative markers (AIMs), we estimated hidden population structure and individual ancestry in HA. Out of 5671 possible pairwise LD, 54% were statistically significant, indicating recent population admixture. The best-fitted model for HA was a four-population model with average ancestry of European (48%), American-Indian (AI) (40%), African (8%) and a fourth population (4%) with unknown ancestry. We also identified significant higher risk associated with AI ancestry (odds ratio (OR)=4.84, P=0.0001, 95% CI (confidence interval)=2.14-10.95) on overall SLE. We showed that ITGAM is associated as a risk factor for SLE (OR=2.06, P=8.74 x 10(-5), 95% CI=1.44-2.97). This association is not affected by population substructure or admixture. We have shown that HA have great potential and are an appropriate population for admixture mapping. As expected, the case-only design is more powerful than case-control design, for any given admixture proportion or

  7. Specific and common genes implicated across major mental disorders: a review of meta-analysis studies.

    PubMed

    Gatt, Justine M; Burton, Karen L O; Williams, Leanne M; Schofield, Peter R

    2015-01-01

    Major efforts have been directed at family-based association and case-control studies to identify the involvement of candidate genes in the major disorders of mental health. What remains unknown is whether candidate genes are associated with multiple disorders via pleiotropic mechanisms, and/or if other genes are specific to susceptibility for individual disorders. Here we undertook a review of genes that have been identified in prior meta-analyses examining specific genes and specific mental disorders that have core disruptions to emotional and cognitive function and contribute most to burden of illness- major depressive disorder (MDD), anxiety disorders (AD, including panic disorder and obsessive compulsive disorder), schizophrenia (SZ) and bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD). A literature review was conducted up to end-March 2013 which included a total of 1519 meta-analyses across 157 studies reporting multiple genes implicated in one or more of the five disorders studied. A total of 134 genes (206 variants) were identified as significantly associated risk variants for MDD, AD, ADHD, SZ or BD. Null genetic effects were also reported for 195 genes (426 variants). 13 genetic variants were shared in common between two or more disorders (APOE e4, ACE Ins/Del, BDNF Val66Met, COMT Val158Met, DAOA G72/G30 rs3918342, DAT1 40-bp, DRD4 48-bp, SLC6A4 5-HTTLPR, HTR1A C1019G, MTHR C677T, MTHR A1298C, SLC6A4 VNTR and TPH1 218A/C) demonstrating evidence for pleiotrophy. Another 12 meta-analyses of GWAS studies of the same disorders were identified, with no overlap in genetic variants reported. This review highlights the progress that is being made in identifying shared and unique genetic mechanisms that contribute to the risk of developing several major psychiatric disorders, and identifies further steps for progress.

  8. Metastasis-associated long noncoding RNAs in gastrointestinal cancer: Implications for novel biomarkers and therapeutic targets

    PubMed Central

    Zhang, Fei-Fei; Luo, Yu-Hao; Wang, Hui; Zhao, Liang

    2016-01-01

    Long non-coding RNAs (lncRNAs), a newly discovered class of ncRNA molecules, have been widely accepted as crucial regulators of various diseases including cancer. Increasing numbers of studies have demonstrated that lncRNAs are involved in diverse physiological and pathophysiological processes, such as cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. Aberrant expression of lncRNAs frequently occurs in gastrointestinal cancer and plays emerging roles in cancer metastasis. In this review, we focus on and outline the regulatory functions of recently identified metastasis-associated lncRNAs, and evaluate the potential roles of lncRNAs as novel diagnostic biomarkers and therapeutic targets in gastrointestinal cancer.

  9. Hedonic and Behavioral Deficits Associated with Apathy in Parkinson’s Disease: Potential Treatment Implications

    PubMed Central

    Jordan, Lizabeth L.; Zahodne, Laura B.; Okun, Michael S.; Bowers, Dawn

    2013-01-01

    Many individuals with Parkinson’s disease (PD) experience apathy independent of depression. In this study we examined hedonic and behavioral deficits related to apathy in 50 PD patients and 42 healthy older adults who completed standardized measures. Regression analyses revealed that apathy was associated with anticipatory, but not consummatory, anhedonia and reduced goal-directed behavior, independent of PD diagnosis, age, education and depressive symptoms. These findings suggest that apathy is characterized by deficits in anticipatory pleasure and behavioral drive rather than consummatory pleasure or reward responsiveness. Therefore, PD patients with apathy would likely benefit from psychotherapeutic treatment that encourages structured, goal-directed plans for pleasurable events and stimulation which provide adaptive hedonic effects. In addition, given the proposed shared mechanism of dopamine depletion within the ventral striatum in apathy and anticipatory anhedonia, future trials of dopamine-eliciting activities (e.g. exercise and other non-pharmacologic methods) appear warranted to improve these symptoms in PD. PMID:23712560

  10. 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

  11. Genome-Wide Association Studies and Hepatitis C: Harvesting the Benefits of the Genomic Revolution.

    PubMed

    Eslam, Mohammed; George, Jacob

    2015-11-01

    Utilizing genome-wide association studies (GWASs) to examine the variation in hepatitis C virus (HCV) phenotypes has led to quantum improvements in our understanding of both the genetic basis and the underlying pathogenesis of HCV infection. In this context, the discovery of interferon lambda polymorphisms is unique with far reaching implications that extend well beyond HCV to various other liver and extrahepatic diseases. In this review, we summarize the data on the impact of GWASs on our understanding of HCV disease.

  12. 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

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

    PubMed Central

    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

  14. Inactivation of PTCH1 is associated with the development of cervical carcinoma: clinical and prognostic implication.

    PubMed

    Chakraborty, Chandraditya; Dutta, Sankhadeep; Mukherjee, Nupur; Samadder, Sudip; Roychowdhury, Anirban; Roy, Anup; Mondal, Ranajit Kumar; Basu, Partha; Roychoudhury, Susanta; Panda, Chinmay Kumar

    2015-02-01

    The aim of this study was to analyze the alterations of PTCH1 (deletion/promoter methylation/mutation/expression) during the development of cervical cancer (CACX). For this purpose, deletion/methylation of PTCH1 were analyzed in HPV16 positive exfoliated asymptomatic cervical swabs (n = 74), cervical intraepithelial neoplasia (CIN) (n = 32), CACX (n = 174) samples, and two CACX cell lines. The deletion of PTCH1 increased significantly from CIN (11.5%) to stage I/II (42%) and comparable in stage III/IV (46%). Low frequency (14-16%) of PTCH1 methylation was seen in the asymptomatic exfoliated cervical cells and in the normal epithelium adjacent to the tumor followed by a significant increase in CIN (31%) to stage I/II (57%) and comparable in stage III/IV (58%). The overall alterations (deletion/methylation) of PTCH1 significantly increased from CIN (34%) to stage I/II (70%) and comparable in stage III/IV (69%). Interestingly, in the normal epithelium, methylation of PTCH1 was high in basal/parabasal layers (83%), followed by decrease in the spinous layer (33 %), and showed significant inverse correlation with its expression. Reduced expression of PTCH1 seen in tumors showed a significant association with its alterations (deletion/methylation). The expression pattern of PTCH1 showed an inverse correlation with the nuclear expression of GLI1 in the normal epithelium as well as in the tumors. High nuclear expression of HPV16, E6, and E7 were seen in basal/parabasal layers of the normal epithelium and also in tumors. The PTCH1 alterations (deletion and/or methylation) in tumors and its methylation in adjacent normal epithelium were associated with poor prognosis of patients. Thus, our data suggests that activation of the Hedgehog pathway due to PTCH1 inactivation along with HPV infection is important in CACX development. PMID:25330948

  15. 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.

  16. Genetic analysis of metabolic polymorphisms in molecular epidemiological studies: social and ethical implications.

    PubMed

    Hainaut, P; Vähäkangas, K

    1999-01-01

    The use of genetic biomarkers in epidemiological studies raises specific social and ethical issues related to the selection of molecular markers and methods of analysis, obtaining participation, the storage of biological samples and their linkage with individual data, the disclosure of information and the publication of results. Several of these issues are similar to those associated with the use of any type of biomarker in epidemiology. Other problems are specifically related to the use of genetic material and the perception that genetic information raises special concerns regarding privacy, risk of abuse and psychosocial impact in this chapter we define how genetic studies performed in the context of molecular epidemiological studies (genetic analysis) differ from genetic screening or genetic testing conducted in a clinical or public health context We then examine the ethical implications of this distinction and describe how general ethical principles may apply to genetic analysis in the area of molecular epidemiology. In particular we discuss specific questions such as those of obtaining participation, working with archival samples and communicating results. We advocate an approach whereby ethical issues are tackled as an intrinsic part of study design; this requires broad discussion with all the parties involved.

  17. 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

  18. 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

  19. Prevalence and Associated Factors of Schistosomiasis among Children in Yemen: Implications for an Effective Control Programme

    PubMed Central

    Sady, Hany; Al-Mekhlafi, Hesham M.; Mahdy, Mohammed A. K.; Lim, Yvonne A. L.; Mahmud, Rohela; Surin, Johari

    2013-01-01

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

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

    PubMed

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

    2013-01-01

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

  1. 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

  2. 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...

  3. 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…

  4. Aberrant Expression of NF-κB in Liver Fluke Associated Cholangiocarcinoma: Implications for Targeted Therapy

    PubMed Central

    Seubwai, Wunchana; Wongkham, Chaisiri; Puapairoj, Anucha; Khuntikeo, Narong; Pugkhem, Ake; Hahnvajanawong, Chariya; Chaiyagool, Jariya; Umezawa, Kazuo; Okada, Seiji; Wongkham, Sopit

    2014-01-01

    Background Up-regulation and association of nuclear factor kappa B (NF-κB) with carcinogenesis and tumor progression has been reported in several malignancies. In the current study, expression of NF-κB in cholangiocarcinoma (CCA) patient tissues and its clinical significance were determined. The possibility of using NF-κB as the therapeutic target of CCA was demonstrated. Methodology Expression of NF-κB in CCA patient tissues was determined using immunohistochemistry. Dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor, was used to inhibit NF-κB action. Cell growth was determined using an MTT assay, and cell apoptosis was shown by DNA fragmentation, flow cytometry and immunocytofluorescent staining. Effects of DHMEQ on growth and apoptosis were demonstrated in CCA cell lines and CCA-inoculated mice. DHMEQ-induced apoptosis in patient tissues using a histoculture drug response assay was quantified by TUNEL assay. Principal Findings Normal bile duct epithelia rarely expressed NF-κB (subunits p50, p52 and p65), whereas all CCA patient tissues (n  =  48) over-expressed all NF-κB subunits. Inhibiting NF-κB action by DHMEQ significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner. DHMEQ increased cell apoptosis by decreasing the anti-apoptotic protein expressions–Bcl-2, XIAP–and activating caspase pathway. DHMEQ effectively reduced tumor size in CCA-inoculated mice and induced cell apoptosis in primary histocultures of CCA patient tissues. Conclusions NF-κB was over-expressed in CCA tissues. Inhibition of NF-κB action significantly reduced cell growth and enhanced cell apoptosis. This study highlights NF-κB as a molecular target for CCA therapy. PMID:25170898

  5. Styles of Lecturing: A Study and Its Implications.

    ERIC Educational Resources Information Center

    Brown, George; Bakhtar, Mali

    1988-01-01

    Investigation of 258 Great Britain college faculty's teaching method preferences indicated that most of the subjects preferred the lecture method, with five different types of lecture identified: oral lecturing; visual information giving; exemplary lecturing; eclectic lecturing; and amorphous talking. Lecturing styles were closely associated with…

  6. Couples, Pairs, and Clusters: Mechanisms and Implications of Centromere Associations in Meiosis

    PubMed Central

    Obeso, David; Pezza, Roberto J; Dawson, Dean

    2013-01-01

    Observations from a wide range of organisms show the centromeres form associations of pairs or small groups at different stages of meiotic prophase. Little is known about the functions or mechanisms of these associations, but in many cases synaptonemal complex elements seem to play a fundamental role. Two main associations are observed: homology-independent associations very early in the meiotic program – sometimes referred to as centromere coupling, and a later association of homologous centromeres, referred to as centromere pairing or tethering. The later centromere pairing initiates during synaptonemal complex assembly, then persists after the dissolution of the synaptonemal complex. While the function of the homology-independent centromere coupling remains a mystery, centromere pairing appears to have a direct impact on the chromosome segregation fidelity of achiasmatic chromosomes. Recent work in yeast, Drosophila, and mice suggest centromere pairing is a previously unappreciated, general meiotic feature that may promote meiotic segregation fidelity of the exchange and non-exchange chromosomes. PMID:24126501

  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. 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

  9. 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

  10. 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

  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).

  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. Comparing apples and oranges: equating the power of case-control and quantitative trait association studies.

    PubMed

    Yang, Jian; Wray, Naomi R; Visscher, Peter M

    2010-04-01

    Genome-wide association studies have achieved unprecedented success in the identification of novel genes and pathways implicated in complex traits. Typically, studies for disease use a case-control (CC) design and studies for quantitative traits (QT) are population based. The question that we address is what is the equivalence between CC and QT association studies in terms of detection power and sample size? We compare the binary and continuous traits by assuming a threshold model for disease and assuming that the effect size on disease liability has similar feature as on QT. We derive the approximate ratio of the non-centrality parameter (NCP) between CC and QT association studies, which is determined by sample size, disease prevalence (K) and the proportion of cases (v) in the CC study. For disease with prevalence <0.1, CC association study with equal numbers of cases and controls (v=0.5) needs smaller sample size than QT association study to achieve equivalent power, e.g. a CC association study of schizophrenia (K=0.01) needs only approximately 55% sample size required for association study of height. So a planned meta-analysis for height on approximately 120,000 individuals has power equivalent to a CC study on 33,100 schizophrenia cases and 33,100 controls, a size not yet achievable for this disease. With equal sample size, when v=K, the power of CC association study is much less than that of QT association study because of the information lost by transforming a quantitative continuous trait to a binary trait. PMID:19918758

  14. Medical association supports studies on marijuana therapy.

    PubMed

    1995-06-16

    The Gay and Lesbian Medical Association (GLMA) issued a statement on May 19, 1995, announcing its support of clinical trials of the therapeutic uses of marijuana. The U.S. Department of Health and Human Services has continued to resist permitting clinical trials of marijuana despite evidence that it can relieve symptoms of cancer, multiple sclerosis, and glaucoma. According to Dr. Alvin Novick, head of GLMA's AIDS Task Force, the Clinton Administration is being asked to not let its political fears blind it to the positive and legitimate scientific research designed to alleviate the suffering of thousands of AIDS patients.

  15. 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…

  16. Experimental studies in explicitly paradoxical interventions: results and implications.

    PubMed

    Strong, S R

    1984-09-01

    A dozen experimental studies have assessed the effectiveness of paradoxical interventions with agoraphobia, depression, insomnia and procrastination. The studies suggest that paradoxical interventions are more effective than no treatment and placebo treatment and are as effective and, in some instances, more effective than other behavioral interventions. Several studies show that the wording of paradoxical interventions affects their impact.

  17. Genome-Wide Association Study of Autistic-Like Traits in a General Population Study of Young Adults

    PubMed Central

    Jones, Rachel Maree; Cadby, Gemma; Melton, Phillip E.; Abraham, Lawrence J.; Whitehouse, Andrew J.; Moses, Eric K.

    2013-01-01

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

  18. A Genome-wide Association Study of Myasthenia Gravis

    PubMed Central

    Renton, Alan E.; Pliner, Hannah A.; Provenzano, Carlo; Evoli, Amelia; Ricciardi, Roberta; Nalls, Michael A.; Marangi, Giuseppe; Abramzon, Yevgeniya; Arepalli, Sampath; Chong, Sean; Hernandez, Dena G.; Johnson, Janel O.; Bartoccioni, Emanuela; Scuderi, Flavia; Maestri, Michelangelo; Raphael Gibbs, J.; Errichiello, Edoardo; Chiò, Adriano; Restagno, Gabriella; Sabatelli, Mario; Macek, Mark; Scholz, Sonja W.; Corse, Andrea; Chaudhry, Vinay; Benatar, Michael; Barohn, Richard J.; McVey, April; Pasnoor, Mamatha; Dimachkie, Mazen M.; Rowin, Julie; Kissel, John; Freimer, Miriam; Kaminski, Henry J.; Sanders, Donald B.; Lipscomb, Bernadette; Massey, Janice M.; Chopra, Manisha; Howard, James F.; Koopman, Wilma J.; Nicolle, Michael W.; Pascuzzi, Robert M.; Pestronk, Alan; Wulf, Charlie; Florence, Julaine; Blackmore, Derrick; Soloway, Aimee; Siddiqi, Zaeem; Muppidi, Srikanth; Wolfe, Gil; Richman, David; Mezei, Michelle M.; Jiwa, Theresa; Oger, Joel; Drachman, Daniel B.; Traynor, Bryan J.

    2016-01-01

    IMPORTANCE Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood. OBJECTIVE To identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study. DESIGN, SETTING, AND PARTICIPANTS DNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody–positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication. MAIN OUTCOMES AND MEASURES We calculated P values for association between 8114394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0 × 10−8 was set for genome-wide significance after Bonferroni correction for multiple testing. RESULTS In the over all case-control cohort, we identified association signals at CTLA4 (rs231770; P = 3.98 × 10−8; odds ratio, 1.37; 95% CI, 1.25–1.49), HLA-DQA1 (rs9271871; P = 1.08 × 10−8; odds ratio, 2.31; 95% CI, 2.02 – 2.60), and TNFRSF11A (rs4263037; P = 1.60 × 10−9; odds ratio, 1.41; 95% CI, 1.29–1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P = 1.32 × 10−12; odds ratio, 1.56; 95% CI, 1.44–1.68) and the other was detected

  19. 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.

  20. A Case Study of Faculty Workload Issues in Arizona: Implications for State Higher Education Policy.

    ERIC Educational Resources Information Center

    Jordan, Stephen M.; Layzell, Daniel T.

    This study examined college faculty workloads within the context of accountability. The report first provides an overview of the current structure of faculty workload; second, presents the findings of one specific faculty teaching and workload study conducted in Arizona; third, discusses the implications for higher education policy derived from…

  1. 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)

  2. 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

  3. Partitioning of sediment-associated organic matter in agricultural watersheds: controlling parameters and water quality implications

    NASA Astrophysics Data System (ADS)

    Journet, S.; Pellerin, B. A.; Bachand, P. A.; Spencer, R.; Bergamaschi, B. A.; Hernes, P. J.

    2009-12-01

    Sediment-associated organic matter (OM) may constitute a significant source of dissolved organic matter (DOM) in agricultural watersheds, but the partitioning of sediment-bound OM is still poorly characterized in such systems. The Willow Slough agricultural watershed in the Central Valley of California, USA, is the focus of a study of DOM dynamics in agricultural watersheds. Weekly surface water samples collected at the watershed outlet since January 2006 show that dissolved organic carbon (DOC) concentrations increase during summer irrigation up to 7 mg/L, and steadily return to winter baseline concentrations (2 mg/L). A similar trend is observed for total suspended sediment concentrations (TSS), which peak about five weeks earlier than DOC (late June) around 200 mg/L, suggesting that sediments may contribute significantly to the delivery of DOM. We investigated the potential impact of sediment-bound OM partitioning on DOM concentration and composition in agricultural surface waters and will present laboratory data related to the equilibrium abiotic release of DOM from suspended, bed, and bank sediments, collected in the Willow Slough watershed over a range of land uses and hydrologic conditions. Desorption isotherms show distinct DOC contributions between sediment types (from 2 to 15% OC desorbed), with suspended sediment from summer irrigation yielding up to 3.4 times more DOC than winter storm suspended sediment, and 4.8 times more than summer bed sediment. In addition, environmental parameters such as water temperature, conductivity, and pH were found to affect OM partitioning differently, pH displaying the most control on DOC release (up to 60% increase from pH 6.5 to pH 9.5). Finally, a detailed biogeochemical characterization of the desorbed DOM quality (including amino acids composition) will serve as a basis for comparing riverine and sediment-derived DOM. By assessing the contribution of DOM from sediments in agricultural watersheds, this research

  4. 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.

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

    USGS Publications Warehouse

    Guangcai, W.; Zuochen, Z.; Min, W.; Cravotta, C.A.; Chenglong, L.

    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 ??18O, ??D, 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??C to 160??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. Copyright ?? 2005 National Ground Water Association.

  6. 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.

  7. Terrestrial case studies of ilmenite exploration and lunar implications

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  8. In Silico Modelling of Novel Drug Ligands Associated with Abnormal Tau Phosphorylation: Implications for Concussion Associated Tauopathy Intervention†

    PubMed Central

    Zhao, Wei; Ho, Lap; Wang, Jun; Bi, Weina; Yemul, Shrishailam; Ward, Libby; Freire, Daniel; Mazzola, Paolo; Brathwaite, Justin; Mezei, Mihaly; Sanchez, Roberto; Elder, Gregory A.; Pasinetti, Giulio Maria

    2016-01-01

    The objective of this study was to develop an in silico screening model for characterization of potential novel ligands from commercial drug libraries able to functionally activate certain olfactory receptors (ORs), which are members of the class A rhodopsin-like family of G protein couple receptors (GPCRs), in the brain of murine models of concussion. We previously found that concussions may significantly influence expression of certain ORs, e.g. OR4M1 in subjects with a history of concussion/traumatic brain injury (TBI). In this study we built a 3-D OR4M1 model and used it in in silico screening of potential novel ligands from commercial drug libraries. We report that in vitro activation of OR4M1 with the commercially available ZINC library compound 10915775 led to a significant attenuation of abnormal tau phosphorylation in embryonic cortico-hippocampal neuronal cultures derived from NSE-OR4M1 transgenic mice, possibly through modulation of the JNK signaling pathway. The attenuation of abnormal tau phosphorylation was rather selective since ZINC10915775 significantly decreased tau phosphorylation on tau Ser202/T205 (AT8 epitope) and tau Thr212/Ser214 (AT100 epitope), but not on tau Ser396/404 (PHF-1 epitope). Moreover, no response of ZINC10915775 was found in control hippocampal neuronal cultures derived from wild type littermates. Our in silico model provides novel means to pharmacologically modulate select ubiquitously expressed ORs in the brain through high affinity ligand activation to prevent and eventually to treat concussion induced down regulation of ORs and subsequent cascade of tau pathology. PMID:26910498

  9. 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…

  10. Implications for Private Educators of Recent Studies on Education.

    ERIC Educational Resources Information Center

    Senese, Donald J.

    The decline in academic achievements among public school students during the past two decades is discussed and several studies that support the evidence on the lack of educational excellence are cited. It is noted that the results of these studies offer a message about Catholic education, since many of the proposals offered to rectify this problem…

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

    PubMed

    Andrews, Arlene Bowers

    2012-04-01

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

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

    PubMed

    Andrews, Arlene Bowers

    2012-04-01

    When a client faces a penalty of death, defense attorneys may call on social workers in many capacities: mitigation specialist, expert witness, consulting specialist, direct witness, or defense-initiated victim outreach worker. The American Bar Association set forth standards for capital defense attorneys, which led an interdisciplinary team to produce the "Supplementary Guidelines for the Mitigation Function of Defense Teams in Death Penalty Cases" to promote the exceptional competence and diligence required when the consequence is life or death. This article summarizes the "Supplementary Guidelines," with implications for social work practice--that is, professional responsibility, competence, interviewing skill, knowledge of behavioral and mental impairment, records review, life history compilation, data interpretation, witness support, law-related knowledge, and testimony. The social work, which is scrutinized in a court of law, requires cultural competence, diverse oral and written communication skills, diligence, and the highest ethical standards. PMID:23038877

  13. 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

  14. 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

  15. 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.

  16. 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

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

    PubMed

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

    2006-08-01

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

  18. Part-set cuing of order information: implications for associative theories of serial order memory.

    PubMed

    Serra, M; Nairne, J S

    2000-07-01

    In three experiments, the effect of cuing, at the point of test, on memory for order and/or position was investigated. Experiment 1 used a partial reconstruction of order task to demonstrate a mnemonic benefit of part-set cuing at the time of test; this result is used to argue that people may commonly use interitem associative information, rather than just position information, to help them remember serial order. Experiment 2 replicated these findings and simultaneously demonstrated the mnemonic detriment that part-set cuing typically produces in free recall. Experiment 3 showed that cues presented at test will either help or hinder reconstruction of order, depending on whether those cues are consistent or inconsistent with the original presentation order. The results of all three experiments are discussed within the framework of position and associative theories of serial order memory.

  19. 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

  20. 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.

  1. 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.

  2. 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'.

  3. 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.

  4. 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

  5. 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

  6. 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

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

    NASA Astrophysics Data System (ADS)

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

    2003-12-01

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

  8. 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

  9. Petrogenesis of the Devonian High-Mg rock association and its tectonic implication for the Chinese Altai orogenic belt, NW China

    NASA Astrophysics Data System (ADS)

    He, Y.

    2014-12-01

    The Chinese Altai is a key region to decipher the accretionary history of the gigantic CAOB, one of the largest accretionary orogenic belts on the earth. However, its Paleozoic tectonothermal events and tectonic implications remain debated. In this study, a suite of igneous rocks, including high Mg dacite of the Kangbutiebao Formation and the associated gneissic granite, have been studied for their petrogenesis and tectonic implication. The high Mg dacite is dated at 400±2Ma, which broadly resembles the emplacement age of the high Mg gneissic granite of 406±9Ma, possibly suggesting that they were generated in a common tectono-magmatic event. Both rocks have zircon inheritances of ~500 Ma, which is consistent with the age of predominant zircon population for in the widespread Habahe sequence, indicating that their precursor magmas were probably mainly derived from the Habahe sediments. The high-Mg rock association has similar REE and trace element patterns to those of the Habahe sediments and they plot close to the field of the Habahe sediments in Th/Ta versus La/Ta diagram. They have high A/CNK ratios (1.33-2.05), supporting their source was sedimentary rocks. In Ba/Th versus (La/Sm)N diagram, these rocks are characterized by high La/Sm ratios which suggests a greater contribution of sediments rather than altered oceanic crust in the magma generation. However, the high Mg# values (~51) of the studied rocks argue against derivation purely from remelting of Habahe sediments. In order to explain the high Mg# values (~51) of these rocks, the participation of mantle-derived melt into the precursor magma is considered. Zircons from this rock association mostly have ɛHf(t) values from +0.85 to +9.71, supporting the involvement of juvenile materials in the magma generation. Samples from the high Mg rock association fall in the same field as the sanukitoids in TiO2 versus Mg# and Sr/Y versus Y diagrams, plot in the fractional crystallization trend of differentiated

  10. 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…

  11. Implications for the Social Studies of Increased State Educational Financing.

    ERIC Educational Resources Information Center

    Poster, John B.

    The contraditions within the systems of school support and school policy-making make it difficult to find a manner of governance of the social studies program which is protected from extraneous influence and yet avoids creating a buffer between the schools and the democratic forces to which they are responsive. State and federal governments…

  12. Critical History: Implications for History/Social Studies Education.

    ERIC Educational Resources Information Center

    Segall, Avner

    1999-01-01

    Examines ways in which history/social studies educators might respond to the challenges posed by the critical literature in and about history in order to reconsider why we learn history, what we do (and could do) with it, and for what (and whose) purposes. (CMK)

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. A Permanency Planning Study: Implications for Child Welfare Curriculum.

    ERIC Educational Resources Information Center

    Sallee, Alvin L.; Marlow, Christine

    The way in which findings from a statewide study on permanency planning were utilized and integrated within an accredited undergraduate social work curriculum is described. The concept of permanency planning (through the provision of in-home services to help the child remain in his/her biological home or the removal of the child and placement in…

  20. 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.

  1. Comparative life-history traits of three phytoseiid mites associated with Tetranychus urticae (Acari: Tetranychidae) colonies in clementine orchards in eastern Spain: implications for biological control.

    PubMed

    Abad-Moyano, Raquel; Pina, Tatiana; Ferragut, Francisco; Urbaneja, Alberto

    2009-02-01

    The management of Tetranychus urticae, a key pest of clementine trees, is mainly based on the use of acaricides. However, more environmentally safe measures, such as biological control, are being encouraged. Life-history traits of the three most abundant phytoseiid mites associated with T. urticae on this crop (Euseius stipulatus, Phytoseiulus persimilis and Neoseiulus californicus) were studied. The experiments were performed under laboratory conditions (25 degrees C, 80 +/- 5% RH and 16:8 h (L:D)) on clementine leaves and T. urticae as prey. Euseius stipulatus could not complete its life cycle, whereas P. persimilis and N. californicus completed it satisfactorily. The estimated intrinsic rate of increase (rm) was significantly higher for P. persimilis (0.344 day(-1)) than for N. californicus (0.244 day(-1)) and both were higher than the rm value of T. urticae on clementine leaves. Implications of these results for the biological control of T. urticae in this crop are discussed.

  2. 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).

  3. 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

  4. Circadian disruption: potential implications in inflammatory and metabolic diseases associated with alcohol.

    PubMed

    Voigt, Robin M; Forsyth, Christopher B; Keshavarzian, Ali

    2013-01-01

    Circadian rhythms are a prominent and critical feature of cells, tissues, organs, and behavior that help an organism function most efficiently and anticipate things such as food availability. Therefore, it is not surprising that disrupted circadian rhythmicity, a prominent feature of modern-day society, promotes the development and/or progression of a wide variety of diseases, including inflammatory, metabolic, and alcohol-associated disorders. This article will discuss the influence of interplay between alcohol consumption and circadian rhythmicity and how circadian rhythm disruption affects immune function and metabolism as well as potential epigenetic mechanisms that may be contributing to this phenomenon. PMID:24313168

  5. Circadian disruption: potential implications in inflammatory and metabolic diseases associated with alcohol.

    PubMed

    Voigt, Robin M; Forsyth, Christopher B; Keshavarzian, Ali

    2013-01-01

    Circadian rhythms are a prominent and critical feature of cells, tissues, organs, and behavior that help an organism function most efficiently and anticipate things such as food availability. Therefore, it is not surprising that disrupted circadian rhythmicity, a prominent feature of modern-day society, promotes the development and/or progression of a wide variety of diseases, including inflammatory, metabolic, and alcohol-associated disorders. This article will discuss the influence of interplay between alcohol consumption and circadian rhythmicity and how circadian rhythm disruption affects immune function and metabolism as well as potential epigenetic mechanisms that may be contributing to this phenomenon.

  6. Implications of the OECD Comparative Study of Performance Standards for Educational Reform in the United States.

    ERIC Educational Resources Information Center

    Baker, Eva L.

    This paper discusses the implications for educational reform in the United States of the Organization for Economic Cooperation and Development (OECD) comparative study of performance standards. To provide some context for the reader, the paper briefly reprises major shifts in the intellectual underpinnings of U.S. educational reform and reports on…

  7. Viewing the Curriculum as a Product: Implications from a Marketing Research Study.

    ERIC Educational Resources Information Center

    Franzak, Frank J.; Cowles, Deborah L.

    1993-01-01

    From a marketing perspective, the curriculum is an important product of the college or university. A study using survey research and target marketing investigated what the business community wants this product to be. Implications for structuring the curriculum as preparation for employment of marketing graduates are examined. (Author/MSE)

  8. 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…

  9. 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…

  10. 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…

  11. Natural analogue studies: present status and performance assessment implications

    NASA Astrophysics Data System (ADS)

    Smellie, John A. T.; Karlsson, Fred; Alexander, W. Russell

    1997-04-01

    Studies of natural geological and archaeological systems as analogues to long-term processes, which are predicted to occur within a radioactive waste repository environment, have become increasingly popular over the last 10 years or so, to the extent that such studies form an integral part of many national programmes for radioactive waste disposal. There is now a common consensus that the natural analogue approach is a very useful scientific methodology to: (a) identify and understand processes and mechanisms analogous to those which could occur in the vicinity of a repository over realistic timescales, (b) derive input data which have been successfully used to test some of the laboratory-based models which form the basis of long-term repository performance assessment, and (c) to produce data which can be input directly to performance assessment models. Increasingly, analogues are playing an important role in public awareness, enabling the layman to understand better the concept of radioactive disposal and demonstrating the reliability of the disposal system over long periods of geological time. The complexity of geological systems means that it is very often difficult and sometimes impossible to quantify precisely the physico-chemical boundary conditions necessary to model a particular geochemical process or mechanism. Consequently, the availability of quantitative analogue data is limited when repository performance assessments are considered. However, this in no way detracts from their value in building confidence by demonstrating that important processes do exist and by showing qualitatively that they behave in a way predicted by models based on laboratory-derived data. The transfer of natural analogue data from the complexity of field studies to simplistic models which, by necessity, are used in performance assessments, is an area of activity which is presently being addressed. Field analogue studies are now being planned to interface with laboratory

  12. The innervated anterolateral thigh flap: anatomical study and clinical implications.

    PubMed

    Ribuffo, Diego; Cigna, Emanuele; Gargano, Francesco; Spalvieri, Cristina; Scuderi, Nicolò

    2005-02-01

    During the past 20 years, the neural anatomy of many flaps has been investigated, although no extensive studies have been reported yet on the anterolateral thigh flap. The goal of this study was to describe the sensory territories of the nerves supplying the anterolateral thigh flap with dissections on fresh cadavers and with local anesthetic injections in living subjects. The sensate anterolateral thigh flap is typically described as innervated by the lateral cutaneous femoral nerve. Two other well-known nerves, the superior perforator nerve and the median perforator nerve, which enter the flap at its medial border, might have a role in anterolateral thigh flap innervation. Twenty-nine anterolateral thigh flaps were elevated in 15 cadavers, and the lateral cutaneous femoral nerve, the superior perforator nerve, and median perforator nerve were dissected. In the injection study, the lateral cutaneous femoral nerve, superior perforator nerve, and median perforator nerve in 16 thighs of eight subjects were sequentially blocked. The resulting sensory deficit from each injection was mapped on the skin and superimposed on the marked anterolateral thigh flap territory. The study shows that the sensate anterolateral thigh flap is basically innervated by all three nerves. The lateral cutaneous femoral nerve was present in 29 of 29 thighs, whereas the superior perforator nerve was present in 25 of 29 and the median perforator nerve in 24 of 29 thighs. Furthermore, in the proximal half of the flap, the lateral cutaneous femoral nerve lies deep, whereas the superior perforator nerve and median perforator nerve lie more superficially. Whereas the lateral cutaneous femoral nerve innervates the entire flap, the superior perforator nerve innervates 25 percent of the flap and the median perforator nerve innervates 60 percent of the flap. Clinically, a small anterolateral thigh flap (7 x 5 cm) can be raised sparing the lateral cutaneous femoral nerve and using only the selective

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Trends and group differences in the association between educational attainment and U.S. adult mortality: implications for understanding education's causal influence.

    PubMed

    Hayward, Mark D; Hummer, Robert A; Sasson, Isaac

    2015-02-01

    Has the shape of the association between educational attainment and U.S. adult mortality changed in recent decades? If so, is it changing consistently across demographic groups? What can changes in the shape of the association tell us about the possible mechanisms in play for improving health and lowering mortality risk over the adult life course? This paper develops the argument that societal technological change may have had profound effects on the importance of educational attainment - particularly advanced education - in the U.S. adult population for garnering health advantages and that these changes should be reflected in changes in the functional form of the association between educational attainment and mortality. We review the historical evidence on the changing functional form of the association, drawing on studies based in the United States, to assess whether these changes are consistent with our argument about the role of technological change. We also provide an updated analysis of these functional form patterns and trends, contrasting data from the early 21st Century with data from the late 20th Century. This updated evidence suggests that the shape of the association between educational attainment and U.S. adult mortality appears to be reflecting lower and lower adult mortality for very highly educated Americans compared to their low-educated counterparts in the 21st Century. We draw on this review and updated evidence to reflect on the question whether education's association with adult mortality has become increasingly causal in recent decades, why, and the potential research, policy, and global implications of these changes. PMID:25440841

  19. Trends and group differences in the association between educational attainment and U.S. adult mortality: implications for understanding education's causal influence.

    PubMed

    Hayward, Mark D; Hummer, Robert A; Sasson, Isaac

    2015-02-01

    Has the shape of the association between educational attainment and U.S. adult mortality changed in recent decades? If so, is it changing consistently across demographic groups? What can changes in the shape of the association tell us about the possible mechanisms in play for improving health and lowering mortality risk over the adult life course? This paper develops the argument that societal technological change may have had profound effects on the importance of educational attainment - particularly advanced education - in the U.S. adult population for garnering health advantages and that these changes should be reflected in changes in the functional form of the association between educational attainment and mortality. We review the historical evidence on the changing functional form of the association, drawing on studies based in the United States, to assess whether these changes are consistent with our argument about the role of technological change. We also provide an updated analysis of these functional form patterns and trends, contrasting data from the early 21st Century with data from the late 20th Century. This updated evidence suggests that the shape of the association between educational attainment and U.S. adult mortality appears to be reflecting lower and lower adult mortality for very highly educated Americans compared to their low-educated counterparts in the 21st Century. We draw on this review and updated evidence to reflect on the question whether education's association with adult mortality has become increasingly causal in recent decades, why, and the potential research, policy, and global implications of these changes.

  20. Surface roughness of minerals and implications for dissolution studies

    NASA Astrophysics Data System (ADS)

    Anbeek, Chris

    1992-04-01

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

  1. 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

  2. Geo hazard studies and their policy implications in Nicaragua

    NASA Astrophysics Data System (ADS)

    Strauch, W.

    2007-05-01

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

  3. 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

  4. 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

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

    USGS Publications Warehouse

    Johnson, James H.; Chalupnicki, Marc A.

    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.

  6. Implications of biofilm-associated waterborne Cryptosporidium oocysts for the water industry.

    PubMed

    Angles, Mark L; Chandy, Joseph P; Cox, Peter T; Fisher, Ian H; Warnecke, Malcolm R

    2007-08-01

    Waterborne Cryptosporidium has been responsible for drinking water-associated disease outbreaks in a number of developed countries. As a result of the resistance of Cryptosporidium to chlorine, which is typically applied as a final barrier to protect the quality of distributed drinking water, current management practices are focused on source-water management and water treatment as ways of preventing Cryptosporidium from entering drinking-water supplies. In the event that treatment barriers fail, surprisingly little is known of the fate of oocysts once they enter a distribution system. To assess properly the risks of waterborne Cryptosporidium, a more thorough understanding of the fate of oocysts in water distribution systems, with emphasis on Cryptosporidium-biofilm interactions, is required.

  7. 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

    2015-10-07

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

  8. 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.

  9. Variability in nest survival rates and implications to nesting studies

    USGS Publications Warehouse

    Klett, A.T.; Johnson, D.H.

    1982-01-01

    We used four reasonably large samples (83-213) of Mallard (Anas platyrhynchos) and Blue-winged Teal (A. discors) nests on an interstate highway right-of-way in southcentral North Dakota to evaluate potential biases in hatch-rate estimates. Twelve consecutive, weekly searches for nests were conducted with a cable-chain drag in 1976 and 1977. Nests were revisited at weekly intervals. Four methods were used to estimate hatch rates for the four data sets: the Traditional Method, the Mayfield Method, and two modifications of the Mayfield Method that are sometimes appropriate when daily mortality rates of nests are not constant. Hatch rates and the average age of nests at discovery declined as the interval between searches decreased, suggesting that mortality rates were not constant in our samples. An analysis of variance indicated that daily mortality rates varied with the age of nests in all four samples. Mortality was generally highest during the early laying period, moderately high during the late laying period, and lowest during incubation. We speculate that this relationship of mortality to nest age might be due to the presence of hens at nests or to differences in the vulnerability of nest sites to predation. A modification of the Mayfield Method that accounts for age-related variation in nest mortality was most appropriate for our samples. We suggest methods for conducting nesting studies and estimating nest success for species possessing similar nesting habits.

  10. Cytochrome c(2) Exit Strategy: Dissociation Studies and Evolutionary Implications.

    PubMed

    Pogorelov, Taras V; Autenrieth, Felix; Roberts, Elijah; Luthey-Schulten, Zaida A

    2007-01-25

    Small, water-soluble, type c cytochromes form a transient network connecting major bioenergetic membrane protein complexes in both photosynthesis and respiration. In the photosynthesis cycle of Rhodobacter sphaeroides, cytochrome c2 (cyt c2) docks to the reaction center (RC), undergoes electron transfer, and exits for the cytochrome bc1 complex. Translations of cyt c2 about the RC-cyt c2 docking interface and surrounding membrane reveal possible exit pathways. A pathway at a minimal elevation allowed by the architecture of the RC is analyzed using both an all-atom steered molecular dynamics simulation of the RC-cyt c2 complex and a bioinformatic analysis of the structures and sequences of cyt c. The structure-based phylogenetic analysis allows for the identification of structural elements that have evolved to satisfy the requirements of having multiple functional partners. The patterns of evolutionary variation obtained from the phylogenetic analysis of both docking partners of cyt c2 reveal conservation of key residues involved in the interaction interfaces that would be candidates for further experimental studies. Additionally, using the molecular mechanics Poisson-Boltzmann surface area method we calculate that the binding free energy of reduced cyt c2 to the RC is nearly 6 kcal/mol more favorable than with oxidized cyt c2. The redox-dependent variations lead to changes in structural flexibility, behavior of the interfacial water molecules, and eventually changes in the binding free energy of the complex. PMID:17228920

  11. 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.

  12. Ethical implications of using the minipig in regulatory toxicology studies.

    PubMed

    Webster, John; Bollen, Peter; Grimm, Herwig; Jennings, Maggy

    2010-01-01

    Two key questions are addressed in this article. What are the potential harms to minipigs relative to the harms for dogs and non-human primates and can these harms be reduced more easily in minipigs than in other species? Are there potential benefits resulting from the use of minipigs relative to dogs and non-human primates? In considering the answers to these questions, we present an ethical framework which was developed taking into account the viewpoint of all concerned parties. This ethical matrix provides a framework upon which to identify and explore issues raised by the moral imperative to seek a fair compromise between the differing needs of different interest groups, which includes both the moral agents and the moral patients. The moral agents are the different groups of human stakeholders including society at large, regulatory bodies, industrialists and animal care staff. The moral patients are the laboratory animals, both breeding stock held by the animal supplier, and experimental animals in laboratories. In considering these animals it cannot be assumed that dogs, monkeys and minipigs differ with regard to the pain and suffering that they may experience and undergo when treated in studies designed for safety assessment. On this basis we rejected the argument that minipigs are more acceptable experimental animals than dogs or monkeys despite the fact that their use may prove less offensive to some groups within society at large. Species selection must be made on a case-by-case basis where the benefits are assessed by weighing the scientific evidence relating to the predictivity of the animal model, against the harm that may accrue to the animals both from the test procedures and their lifetime experience within the laboratory environment.

  13. 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

  14. 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

  15. 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.

  16. Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality

    PubMed Central

    Smith, G. D.; Hart, C.; Upton, M.; Hole, D.; Gillis, C.; Watt, G.; Hawthorne, V.

    2000-01-01

    OBJECTIVES—Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland.
DESIGN—Prospective observational study.
SETTING—Renfrew and Paisley, in the West of Scotland.
SUBJECTS—7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline.
MAIN OUTCOME MEASURES—Deaths during 20 years of follow up classified into specific causes.
RESULTS—Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations.
CONCLUSION—Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the

  17. 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

  18. A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia

    PubMed Central

    Bechstedt, S.; Albert, J.T.; Kreil, D.P.; Müller-Reichert, T.; Göpfert, M.C.; Howard, J.

    2010-01-01

    Mechanoreceptors are sensory cells that transduce mechanical stimuli into electrical signals and mediate the perception of sound, touch and acceleration. Ciliated mechanoreceptors possess an elaborate microtubule cytoskeleton that facilitates the coupling of external forces to the transduction apparatus. In a screen for genes preferentially expressed in Drosophila campaniform mechanoreceptors, we identified DCX-EMAP, a unique member of the EMAP family (echinoderm–microtubule-associated proteins) that contains two doublecortin domains. DCX-EMAP localizes to the tubular body in campaniform receptors and to the ciliary dilation in chordotonal mechanoreceptors in Johnston's organ, the fly's auditory organ. Adult flies carrying a piggyBac insertion in the DCX-EMAP gene are uncoordinated and deaf and display loss of mechanosensory transduction and amplification. Electron microscopy of mutant sensilla reveals loss of electron-dense materials within the microtubule cytoskeleton in the tubular body and ciliary dilation. Our results establish a catalogue of candidate genes for Drosophila mechanosensation and show that one candidate, DCX-EMAP, is likely to be required for mechanosensory transduction and amplification. PMID:20975667

  19. 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

  20. 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

  1. Association of Arsenic and Phosphorus with Iron Nanoparticles between Streams and Aquifers: Implications for Arsenic Mobility.

    PubMed

    Hartland, Adam; Larsen, Joshua R; Andersen, Martin S; Baalousha, Mohammed; O'Carroll, Denis

    2015-12-15

    The microbial oxidation of organic matter coupled to reductive iron oxide dissolution is widely recognized as the dominant mechanism driving elevated arsenic (As) concentrations in aquifers. This paper considers the potential of nanoparticles to increase the mobility of As in aquifers, thereby accounting for discrepancies between predicted and observed As transport reported elsewhere. Arsenic, phosphorus, and iron size distributions and natural organic matter association were examined along a flow path from surface water via the hyporheic zone to shallow groundwater. Our analysis demonstrates that the colloidal Fe concentration (>1 kDa) correlates with both colloidal P and colloidal As concentrations. Importantly, increases in the concentration of colloidal P (>1 kDa) were positively correlated with increases in the concentration of nominally dissolved As (<1 kDa), but no correlation was observed between colloidal As and nominally dissolved P. This suggests that P actively competes for adsorption sites on Fe nanoparticles, displacing adsorbed As, thus mirroring their interaction with Fe oxides in the aquifer matrix. Dynamic redox fronts at the interface between streams and aquifers may therefore provide globally widespread conditions for the generation of Fe nanoparticles, a mobile phase for As adsorption currently not a part of reactive transport models.

  2. 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.

  3. Interaction of adeno-associated virus Rep78 with p53: implications in growth inhibition.

    PubMed

    Batchu, R B; Shammas, M A; Wang, J Y; Munshi, N C

    1999-08-01

    Adeno-associated virus (AAV) is a nonpathogenic, single-stranded DNA virus belonging to the parvoviridae family. Onco-suppressive properties of AAV against adenovirus, a DNA tumor virus, have been well documented. Rep78, a major regulatory protein of AAV, is believed to be responsible for its antioncogenic properties. Most DNA tumor viruses disturb the cell cycle pathways by essentially abrogating the functions of p53. Here we present evidence that AAV acts as an antiproliferative agent against adenovirus by protecting the adenoviral-mediated degradation of p53 as confirmed by both Western blot analysis and immunoprecipitation analysis with anti-p53 antibody. Coimmunoprecipitation experiments revealed that the AAV Rep78 is physically bound to p53 in vivo. Furthermore, the binding of purified p53 to the AAV Rep78 affinity column confirms their interaction. These results document for the first time that the antiproliferative effects of AAV against adenovirus are mediated, at least in part, by the interaction of AAV Rep78 with p53.

  4. PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.

    PubMed

    Chen, Chiung-Mei; Hou, Yi-Ting; Liu, Ju-Yun; Wu, Yih-Ru; Lin, Chih-Hsin; Fung, Hon-Chung; Hsu, Wen-Chuin; Hsu, Yuying; Lee, Shen-Hung; Hsieh-Li, Hsiu-Mei; Su, Ming-Tsan; Chen, Shui-Tein; Lane, Hsien-Yuan; Lee-Chen, Guey-Jen

    2009-01-01

    PPP2R2B, a protein widely expressed in neurons throughout the brain, regulates the protein phosphatase 2A (PP2A) activity for the microtubule-associated protein tau and other substrates. Altered PP2A activity has been implicated in spinocerebellar ataxia 12, Alzheimer's disease (AD), and other tauopathies. Through a case-control study and a reporter assay, we investigated the association of PPP2R2B CAG repeat polymorphism with Taiwanese AD, essential tremor (ET), Parkinson's disease (PD), and schizophrenia and clarified the functional implication of this polymorphism. The distribution of the alleles was not significantly different between patients and controls, with 68.6-76.1% alleles at lengths of 10, 13, and 16 triplets. No expanded alleles were detected in either group. However, the frequency of the individuals carrying the short 5-, 6-, and 7-triplet alleles was notably higher in patients with AD (5/180 [2.8%], Fisher's exact test, P = 0.003; including 2 homozygotes) and ET (4/132 [3.0%], Fisher's exact test, P < 0.001) than in the controls (1/625 [0.2%]). The PPP2R2B transcriptional activity was significantly lower in the luciferase reporter constructs containing the (CAG)(5-7) allele than in those containing the common 10-, 13-, and 16-triplet alleles in both neuroblastoma and embryonic kidney cells. Therefore, our preliminary results suggest that the PPP2R2B gene CAG repeat polymorphism may be functional and may, in part, play a role in conferring susceptibility to AD and ET in Taiwan.

  5. A genome-wide association study of testicular germ cell tumor.

    PubMed

    Rapley, Elizabeth A; Turnbull, Clare; Al Olama, Ali Amin; Dermitzakis, Emmanouil T; Linger, Rachel; Huddart, Robert A; Renwick, Anthony; Hughes, Deborah; Hines, Sarah; Seal, Sheila; Morrison, Jonathan; Nsengimana, Jeremie; Deloukas, Panagiotis; Rahman, Nazneen; Bishop, D Timothy; Easton, Douglas F; Stratton, Michael R

    2009-07-01

    We conducted a genome-wide association study for testicular germ cell tumor (TGCT), genotyping 307,666 SNPs in 730 cases and 1,435 controls from the UK and replicating associations in a further 571 cases and 1,806 controls. We found strong evidence for susceptibility loci on chromosome 5 (per allele OR = 1.37 (95% CI = 1.19-1.58), P = 3 x 10(-13)), chromosome 6 (OR = 1.50 (95% CI = 1.28-1.75), P = 10(-13)) and chromosome 12 (OR = 2.55 (95% CI = 2.05-3.19), P = 10(-31)). KITLG, encoding the ligand for the receptor tyrosine kinase KIT, which has previously been implicated in the pathogenesis of TGCT and the biology of germ cells, may explain the association on chromosome 12. PMID:19483681

  6. Recent Progress in the Understanding of Obesity: Contributions of Genome-Wide Association Studies.

    PubMed

    Andersen, Mette Korre; Sandholt, Camilla Helene

    2015-12-01

    Since 2007, discovery of genetic variants associated with general obesity and fat distribution has advanced tremendously through genome-wide association studies (GWAS). Currently, the number of robustly associated loci is 190. Even though these loci explain <3 % of the variance, they have provided us a still emerging picture of genomic localization, frequency and effect size spectra, and hints of functional implications. The translation into biological knowledge has turned out to be an immense task. However, in silico enrichment analyses of genes involved in specific pathways or expressed in specific tissues have the power to suggest biological mechanisms underlying obesity. Inspired by this, we highlight genes in five loci potentially mechanistically linked to leptin-receptor trafficking and signaling in primary cilia. The clinical application of genetic knowledge as prediction, prevention, or treatment strategies is unfortunately still far from reality. Thus, despite major advances, further research is warranted to solve one of the greatest health problems in modern society.

  7. 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.

  8. Estimating Variations of H2O in Andesitic Magmas - Implications to Eruption Variability and Associated Hazards

    NASA Astrophysics Data System (ADS)

    Turner, M. B.; Turner, S.; Adam, J.; O'Neill, H. S.

    2011-12-01

    The transition between explosive and effusive eruptions at andesitic volcanoes is linked to the ability of the magma to degas through exsolution, vesicle growth and coalescence. Water makes up the majority of volatiles within andesitic magmas and therefore knowledge of initial magmatic water contents and subsequent variation during magma ascent will help define the location and the timescales associated with degassing events. Olivine melt inclusion analysis is the traditional method to acquire the water contents of pre-erupted magma. However, olivine phenocrysts with sufficiently large melt inclusions for analysis (>30μm) are not common in erupted rocks from andesitic volcanoes. Therefore using the method of Wade et al. (2008) we aim to calculate magmatic water contents of andesitic rocks from direct measurements of water in clinopyroxene phenocrysts. This technique is based on the findings of Hauri et al. (2006) that demonstrated the partitioning of water between pyroxene and melt is proportional to the tetrahedral site occupied by AlIV/(IV)T. However, the site localities of water in clinopyroxenes are not well constrained and other minor and trace element substitutions may affect this correlation. Therefore, in the first instance we have acquired rocks from a number of volcanic settings to test the feasibility of the clinopyroxene method on volcanic rocks and to help better constrain pyroxene/melt water partitioning. Clinopyroxene is found in most andesitic settings and can crystallise over a large range of temperatures and pressures. This allows the greatest potential to record magmatic water contents over a large range of magmatic conditions, not only for initial stages of magma formation, but also for later stages of magma ascent.

  9. 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…

  10. 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…

  11. 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

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2016-10-01

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

  14. Etiological significance of associations between childhood trauma and borderline personality disorder: conceptual and clinical implications.

    PubMed

    Sabo, A N

    1997-01-01

    Numerous studies over the past decade have pointed to the frequent occurrence of trauma and neglect in the childhood experience of patients with Borderline Personality Disorder (BPD). Advancing research on Posttraumatic Stress Disorder (PTSD) and Dissociative Disorders offers further insight into understanding shared clinical phenomena with BPD. Drawing upon attachment theory, models of learned helplessness, and early primate deprivation, empirical, theoretical and clinical data are integrated to conceptualize the role of trauma and neglect in the etiology of BPD. PMID:9113822

  15. 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

  16. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention.

    PubMed

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P

    2013-01-15

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that

  17. Identification of molecular targets associated with ethanol toxicity and implications in drug development.

    PubMed

    Wang, Lin-Lin; Yang, An-Kui; He, Shu-Ming; Liang, Jun; Zhou, Zhi-Wei; Li, Yong; Zhou, Shu-Feng

    2010-01-01

    Alcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the molecular targets of ethanol-induced toxicity in humans based on a systematic review of literature data and then discussed current and potential therapeutic targets for alcohol abuse and dependence. Using human samples with ethanol exposure, microarray analyses of gene expression have shown that numerous genes are up- and/or down-regulated by alcohol exposure. The ethanol-responsive genes mainly encode functional proteins such as proteins involved in nucleic acid binding, transcription factors, selected regulatory molecules, and receptors. These genes are also correlated with important biological pathways, such as angiogenesis, integrin signalling pathway, inflammation, wnt signaling pathway, platelet-derived growth factor signaling pathway, p53 pathway, epidermal growth factor receptor signaling pathway and apoptosis signaling pathway. Currently, only three medications were approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol abuse and alcohol dependence, including the aldehyde dehydrogenase inhibitor disulfiram, the micro-opioid receptor antagonist naltrexone, and the N-methyl-D-aspartate (NMDA) receptor inhibitor acamprosate (oral and injectable extended-release formulations). In addition, a number of agents are being investigated as novel treatments for alcohol abuse and dependence. These include selective 5-HT reuptake inhibitors (e.g. fluoxetine), 5-HT(1) receptor agonists (e.g. buspirone), 5-HT(2) receptor antagonists (e.g. ritanserin), 5-HT(3) receptor antagonists (e.g. ondansetron), dopamine receptor antagonists (e.g. aripiprazole and quetiapine), dopamine receptor agonists (e.g. bromocriptine), GABA(B) receptor agonists (e.g. baclofen), and cannabinoid-1 (CB(1)) receptor antagonists. Some of these agents have shown promising efficacy in initial clinical studies

  18. 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.

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

    PubMed

    Daly, Ann K; Day, Chris P

    2009-11-01

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

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

    PubMed

    Gazendam, Femke J; Kindt, Merel

    2012-01-01

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

  1. 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

  2. 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.

  3. Taxonomic implications of three prospective studies on the course and outcome of personality disorders.

    PubMed

    Verheul, Roel

    2005-10-01

    The Children in the Community (CIC) Study (Cohen, Crawford, Johnson, & Kasen, this issue), the McLean Study of Adult Development (MSAD; Zanarini, Frankenburg, Hennen, Reich, & Silk, this issue), and the Collaborative Longitudinal Personality Disorders Study (CLPS; Skodol et al., this issue) are three large prospective studies on the course and outcome of psychiatric disorders, borderline personality disorder, and personality disorders, respectively. These studies, involving approximately 2,000 subjects, have yielded an enormous amount of scientifically and clinically relevant information. In this commentary, I primarily aim to discuss the implications for future revisions to the DSM classification of personality disorders.

  4. 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.

  5. Association of intron loss with high mutation rate in Arabidopsis: implications for genome size evolution.

    PubMed

    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.

  6. 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.

  7. 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.

  8. 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

  9. Structural Details of Ufd1 Binding to p97 and Their Functional Implications in ER-Associated Degradation

    PubMed Central

    Le, Oanh Thi Tu; Lee, Sang Yoon; Yang, Jin Kuk

    2016-01-01

    The hexameric ATPase p97 has been implicated in diverse cellular processes through interactions with many different adaptor proteins at its N-terminal domain. Among these, the Ufd1-Npl4 heterodimer is a major adaptor, and the p97-Ufd1-Npl4 complex plays an essential role in endoplasmic reticulum-associated degradation (ERAD), acting as a segregase that translocates the ubiquitinated client protein from the ER membrane into the cytosol for proteasomal degradation. We determined the crystal structure of the complex of the N-terminal domain of p97 and the SHP box of Ufd1 at a resolution of 1.55 Å. The 11-residue-long SHP box of Ufd1 binds at the far-most side of the Nc lobe of the p97 N domain primarily through hydrophobic interactions, such that F225, F228, N233 and L235 of the SHP box contact hydrophobic residues on the surface of the p97 Nc lobe. Mutating these key interface residues abolished the interactions in two different binding experiments, isothermal titration calorimetry and co-immunoprecipitation. Furthermore, cycloheximide chase assays showed that these same mutations caused accumulation of tyrosinase-C89R, a well-known ERAD substrate, thus implying decreased rate of protein degradation due to their defects in ERAD function. Together, these results provide structural and biochemical insights into the interaction between p97 N domain and Ufd1 SHP box. PMID:27684549

  10. Redox-implications associated with the formation of complexes between copper ions and reduced or oxidized glutathione.

    PubMed

    Aliaga, Margarita E; López-Alarcón, Camilo; Bridi, Raquel; Speisky, Hernán

    2016-01-01

    Binding of copper by reduced glutathione (GSH) is generally seen as a mechanism to lower, if not abolish, the otherwise high electrophilicity and redox activity of its free ions. In recent years, however, this concept has been contradicted by new evidence revealing that, rather than stabilizing free copper ions, its binding to GSH leads to the formation of a Cu(I)-[GSH]2 complex capable of reducing molecular oxygen into superoxide. It is now understood that, under conditions leading to the removal of such radicals, the Cu(I)-[GSH]2 complex is readily oxidized into Cu(II)-GSSG. Interestingly, in the presence of a GSH excess, the latter complex is able to regenerate the superoxide-generating capacity of the complex it originated from, opening the possibility that a GSH-dependent interplay exists between the reduced and the oxidized glutathione forms of these copper-complexes. Furthermore, recent evidence obtained from experiments conducted in non-cellular systems and intact mitochondria indicates that the Cu(II)-GSSG complex is also able to function in a catalytic manner as an efficient superoxide dismutating- and catalase-like molecule. Here we review and discuss the most relevant chemical and biological evidence on the formation of the Cu(I)-[GSH]2 and Cu(II)-GSSG complexes and on the potential redox implications associated with their intracellular occurrence.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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…

  17. 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.

  18. 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

  19. 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

  20. Cause versus association in observational studies in psychopharmacology.

    PubMed

    Andrade, Chittaranjan

    2014-08-01

    Hypotheses may be generated (and conclusions drawn) from observational studies in areas where information from randomized controlled trials (RCTs) is unavailable. However, observational studies can only establish that significant associations exist between predictor and outcome variables. Observational studies cannot establish that the associations identified represent cause-and-effect relationships. This article discusses examples of associations that were identified in observational studies and that were subsequently refuted in RCTs. Examples are also provided of associations that have yet to be confirmed or refuted but that are nevertheless influential in psychopharmacologic practice. Explanations are offered about how confounding might explain significant relationships between variables that are not related by cause and effect. As a conclusion of this exercise, clinicians are cautioned against placing too much reliance on the findings of observational research.

  1. 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

  2. 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

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

    PubMed

    Zhou, Li; He, Meian; Mo, Zengnan; Wu, Chen; Yang, Handong; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue; Zhu, Jingwen; Li, Huaixing; Lin, Xu; Zhu, Jiang; Min, Xinwen; Lang, Mingjian; Li, Dongfeng; Zhai, Kan; Chang, Jiang; Tan, Wen; Yuan, Jing; Chen, Weihong; Wang, Youjie; Wei, Sheng; Miao, Xiaoping; Wang, Feng; Fang, Weimin; Liang, Yuan; Deng, Qifei; Dai, Xiayun; Lin, Dafeng; Huang, Suli; Guo, Huan; Lilly Zheng, S; Xu, Jianfeng; Lin, Dongxin; Hu, Frank B; Wu, Tangchun

    2013-01-01

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

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

    PubMed Central

    Munroe, Patricia B.

    2015-01-01

    The study of family pedigrees with rare monogenic cardiovascular disorders has revealed new molecular players in physiological processes. Genome-wide association studies of complex traits with a heritable component may afford a similar and potentially intellectually richer opportunity. In this review we focus on the interpretation of genetic associations and the issue of causality in relation to known and potentially new physiology. We mainly discuss cardiometabolic traits as it reflects our personal interests, but the issues pertain broadly in many other disciplines. We also describe some of the resources that are now available that may expedite follow up of genetic association signals into observations on causal mechanisms and pathophysiology. PMID:26106147

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

    PubMed

    Munroe, Patricia B; Tinker, Andrew

    2015-09-01

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

  6. 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.

  7. 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.

  8. 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

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

    PubMed

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

    2009-10-01

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

  10. Sequential Use of Transcriptional Profiling, Expression Quantitative Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney Aging

    PubMed Central

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

    2009-01-01

    Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6×10−5, empirical p = 0.01) that explains 1%–2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans. PMID:19834535

  11. Genetic Association Studies in Lumbar Disc Degeneration: A Systematic Review

    PubMed Central

    Eskola, Pasi J.; Lemmelä, Susanna; Kjaer, Per; Solovieva, Svetlana; Männikkö, Minna; Tommerup, Niels; Lind-Thomsen, Allan; Husgafvel-Pursiainen, Kirsti; Cheung, Kenneth M. C.; Chan, Danny

    2012-01-01

    Objective Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans. Methods A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990–2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. Results Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328) and MMP9 (rs17576). Conclusions Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration. PMID:23185509

  12. A Comprehensive Genetic Association Study of Alzheimer Disease in African Americans

    PubMed Central

    Logue, Mark W.; Schu, Matthew; Vardarajan, Badri N.; Buros, Jacki; Green, Robert C.; Go, Rodney C. P.; Griffith, Patrick; Obisesan, Thomas O.; Shatz, Rhonna; Borenstein, Amy; Cupples, L. Adrienne; Lunetta, Kathryn L.; Fallin, M. Daniele; Baldwin, Clinton T.; Farrer, Lindsay A.

    2012-01-01

    Objectives To evaluate the association of genetic variation with late-onset Alzheimer disease (AD) in African Americans, including genes implicated in recent genome-wide association studies of whites. Design We analyzed a genome-wide set of 2.5 million imputed markers to evaluate the genetic basis of AD in an African American population. Subjects Five hundred thirteen well-characterized African American AD cases and 496 cognitively normal African American control subjects. Setting Data were collected from multiple sites as part of the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and the Henry Ford Health System as part of the Genetic and Environmental Risk Factors for Alzheimer Disease Among African Americans (GenerAAtions) Study. Results Several significant single-nucleotide polymorphisms (SNPs) were observed in the region of the apolipoprotein E gene (APOE). After adjusting for the confounding effects of APOE genotype, one of these SNPs, rs6859 in PVRL2, remained significantly associated with AD (P=.0087). Association was also observed with SNPs in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, although the effect direction for some SNPs and the most significant SNPs differed from findings in data sets consisting of whites. Finally, using the African American genome-wide association study data set as a discovery sample, we obtained suggestive evidence of association with SNPs for several novel candidate genes. Conclusions Some genes contribute to AD pathogenesis in both white and African American cohorts, although it is unclear whether the causal variants are the same. A larger African American sample will be needed to confirm novel gene associations, which may be population specific. PMID:22159054

  13. 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

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

    PubMed

    Bentham, James; Morris, David L; Cunninghame Graham, Deborah S; 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

    2015-12-01

    Systemic lupus erythematosus (SLE) 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, constituting a new GWAS, a meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including ten new 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 finding 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

  15. HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation

    PubMed Central

    2012-01-01

    Background The pathogenesis of allergic airway inflammation in asthmatic patients is complex and characterized by cellular infiltrates and activity of many cytokines and chemokines. Both the transcription factor hypoxia inducible factor-1 (HIF-1) and chemokine CCL2 have been shown to play pivotal roles in allergic airway inflammation. The interrelationship between these two factors is not known. We hypothesized that the expression of HIF-1 and CCL2 may be correlated and that the expression of CCL2 may be under the regulation of HIF-1. Several lines of evidence are presented to support this hypothesis. Methods The effects of treating wild-type OVA (ovalbumin)-sensitized/challenged mice with ethyl-3,4-dihydroxybenzoate (EDHB), which upregulate HIF, on CCL2 expression, were determined. Mice conditionally knocked out for HIF-1β was examined for their ability to mount an allergic inflammatory response and CCL2 expression in the lung after intratracheal exposure to ovalbumin. The association of HIF-1α and CCL2 levels was also measured in endobronchial biopsies and bronchial fluid of asthma patients after challenge. Results We show that both HIF-1α and CCL2 were upregulated during an OVA (ovalbumin)-induced allergic response in mice. The levels of HIF-1α and CCL2 were significantly increased following treatment with a pharmacological agent which upregulates HIF-1α, ethyl-3,4-dihydroxybenzoate (EDHB). In contrast, the expression levels of HIF-1α and CCL2 were decreased in the lungs of mice that have been conditionally knocked out for ARNT (HIF-1β) following sensitization with OVA when compared to levels in wild type mice. In asthma patients, the levels of HIF-1α and CCL2 increased after challenge with the allergen. Conclusions These data suggest that CCL2 expression is regulated, in part, by HIF-1 in the lung. These findings also demonstrate that both CCL2 and HIF-1 are implicated in the pathogenesis of allergic airway inflammation. PMID:22823210

  16. 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%.

  17. 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

  18. 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

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

    PubMed

    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

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

    PubMed

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

    2016-01-01

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

  1. 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. 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

  3. 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.

  4. 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

  5. A Genome-Wide Association Study Identifies Multiple Regions Associated with Head Size in Catfish

    PubMed Central

    Geng, Xin; Liu, Shikai; Yao, Jun; Bao, Lisui; Zhang, Jiaren; Li, Chao; Wang, Ruijia; Sha, Jin; Zeng, Peng; Zhi, Degui; Liu, Zhanjiang

    2016-01-01

    Skull morphology is fundamental to evolution and the biological adaptation of species to their environments. With aquaculture fish species, head size is also important for economic reasons because it has a direct impact on fillet yield. However, little is known about the underlying genetic basis of head size. Catfish is the primary aquaculture species in the United States. In this study, we performed a genome-wide association study using the catfish 250K SNP array with backcross hybrid catfish to map the QTL for head size (head length, head width, and head depth). One significantly associated region on linkage group (LG) 7 was identified for head length. In addition, LGs 7, 9, and 16 contain suggestively associated regions for head length. For head width, significantly associated regions were found on LG9, and additional suggestively associated regions were identified on LGs 5 and 7. No region was found associated with head depth. Head size genetic loci were mapped in catfish to genomic regions with candidate genes involved in bone development. Comparative analysis indicated that homologs of several candidate genes are also involved in skull morphology in various other species ranging from amphibian to mammalian species, suggesting possible evolutionary conservation of those genes in the control of skull morphologies. PMID:27558670

  6. Immaturity associated antigens are lost during induction for T cell lymphoblastic leukemia: implications for minimal residual disease detection

    PubMed Central

    Roshal, Mikhail; Fromm, Jonathan R; Winter, Stuart; Dunsmore, Kimberly; Wood, Brent

    2011-01-01

    Background Induction chemotherapy for acute leukemia often leads to antigenic shifts in residual abnormal blast populations. Studies in precursor B cell ALL (B-ALL) and AML have demonstrated that chemotherapy commonly results in the loss of antigens associated with immaturity, limiting their utility for minimal residual disease (MRD) detection. Little information is available about the stability of these antigens in precursor T cell ALL (T-ALL) though it is presumed that CD99 and TdT are highly informative based on limited studies. Methods In a longitudinal investigation, we explored patterns of lineage specific and immaturity associated antigens in T-ALL in a large cohort of patients treated under the multicenter Children's Oncology Group (COG) protocol. All samples were analyzed using multicolor flow cytometry in a standardized fashion at a single institution. Results We report that markers of immaturity particularly, TdT and CD99 dramatically decline on leukemic blasts during therapy. CD34 and CD10 expression is confined to a minority of pre-treatment samples and is also not stable. In contrast, lineage associated markers including CD2, CD3, CD4, CD5, CD7 and CD8 failed to show significant trends. Conclusions Our study strongly argues for expansion of immunophenotyping panels for T-ALL MRD to decrease reliance on immature antigens. This study represents the first demonstration of consistent immunophenotypic shifts in T-ALL. PMID:20155852

  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. 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.

  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. Clinical End-Points Associated with Mycobacterium tuberculosis and Lung Cancer: Implications into Host-Pathogen Interaction and Coevolution

    PubMed Central

    Tian, Yansheng; Hao, Tong; Cao, Bin; Zhang, Wei; Ma, Yan; Lin, Qiang; Li, Xiaomin

    2015-01-01

    There is a recent emerging theory that suggests a cross-link between pathogens and cancer. In this context, we examined the association between the Mycobacterium tuberculosis (MTB) with its L-forms (MTB-L) and lung cancer. In the present study, we have optimized and applied a highly sensitive assay to detect the presence of MTB and MTB-L in 187 lung cancer samples and 39 samples of other cancer origins. By carefully controlling confounding factors, we have found that 62% of the lung cancer samples are MTB-L positive, while only 5.1% of the other cancer samples are MTB-L positive. Through generalized linear models and random forest models, we have further identified a set of clinical end-points that are strongly associated with MTB-L presence. Our finding provides the basis for future studies to investigate the underlying mechanism linking MTB-L infection to lung cancer development. PMID:26583138

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

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

    PubMed

    Bleck, Jennifer; DeBate, Rita

    2016-10-01

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

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

    PubMed

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

    2016-10-01

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

  20. Recommendations for using standardised phenotypes in genetic association studies.

    PubMed

    Naylor, Melissa G; Weiss, Scott T; Lange, Christoph

    2009-07-01

    Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity). These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  1. 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

  2. Concurrent outbreaks of Shigella sonnei and enterotoxigenic Escherichia coli infections associated with parsley: implications for surveillance and control of foodborne illness.

    PubMed

    Naimi, Timothy S; Wicklund, Julie H; Olsen, Sonja J; Krause, Gerard; Wells, Joy G; Bartkus, Joanne M; Boxrud, David J; Sullivan, Maureen; Kassenborg, Heidi; Besser, John M; Mintz, Eric D; Osterholm, Michael T; Hedberg, Craig W

    2003-04-01

    In recent years, the globalization of the food supply and the development of extensive food distribution networks have increased the risk of foodborne disease outbreaks involving multiple states or countries. In particular, outbreaks associated with fresh produce have emerged as an important public health concern. During July and August 1998, eight restaurant-associated outbreaks of shigellosis caused by a common strain of Shigella sonnei occurred in the United States and Canada. The outbreak strain was characterized by unique pulsed-field gel electrophoresis patterns. Epidemiologic investigation determined that the illness was associated with the ingestion of parsley at four restaurants; at the other four restaurants, the majority of the people who contracted the illness ate parsley. Isolates from patrons in two unrelated restaurant-associated enterotoxigenic Escherichia coli (ETEC) outbreaks in Minnesota shared a common serotype and pulsed-field gel electrophoresis (PFGE) pattern. Parsley was the implicated or suspected source of both ETEC outbreaks. In each of the outbreak-associated restaurants, parsley was chopped, held at room temperature, and used as an ingredient or garnish for multiple dishes. Infected food workers at several restaurants may also have contributed to the propagation of the outbreak. The sources of parsley served in outbreak-associated restaurants were traced, and a 1,600-acre farm in Baja California, Mexico, was identified as a likely source of the parsley implicated in six of the seven Shigella outbreaks and as a possible source of the parsley implicated in the two ETEC outbreaks. Global food supplies and large distribution networks demand strengthened laboratory and epidemiologic capacity to enable state and local public health agencies to conduct foodborne disease surveillance and to promote effective responses to multistate outbreaks.

  3. Tissue-Specific Genetic Control of Splicing: Implications for the Study of Complex Traits

    PubMed Central

    Cronin, Kenneth D; Maia, Jessica M; Shianna, Kevin V; Gabriel, Willow N; Welsh-Bohmer, Kathleen A; Hulette, Christine M; Denny, Thomas N; Goldstein, David B

    2008-01-01

    Numerous genome-wide screens for polymorphisms that influence gene expression have provided key insights into the genetic control of transcription. Despite this work, the relevance of specific polymorphisms to in vivo expression and splicing remains unclear. We carried out the first genome-wide screen, to our knowledge, for SNPs that associate with alternative splicing and gene expression in human primary cells, evaluating 93 autopsy-collected cortical brain tissue samples with no defined neuropsychiatric condition and 80 peripheral blood mononucleated cell samples collected from living healthy donors. We identified 23 high confidence associations with total expression and 80 with alternative splicing as reflected by expression levels of specific exons. Fewer than 50% of the implicated SNPs however show effects in both tissue types, reflecting strong evidence for distinct genetic control of splicing and expression in the two tissue types. The data generated here also suggest the possibility that splicing effects may be responsible for up to 13 out of 84 reported genome-wide significant associations with human traits. These results emphasize the importance of establishing a database of polymorphisms affecting splicing and expression in primary tissue types and suggest that splicing effects may be of more phenotypic significance than overall gene expression changes. PMID:19222302

  4. 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.

  5. 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

  6. 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.

  7. Association of Genetic Variation in Genes Implicated in the β–Catenin Destruction Complex with Risk of Breast Cancer

    PubMed Central

    Wang, Xianshu; Goode, Ellen L.; Fredericksen, Zachary S.; Vierkant, Robert A.; Pankratz, V. Shane; Rider, David N.; Vachon, Celine M.; Cerhan, James R.; Olson, Janet E.; Couch, Fergus J.

    2009-01-01

    Aberrant Wnt/β-catenin signaling leading to nuclear accumulation of the oncogene product β-catenin is observed in a wide spectrum of human malignancies. The destruction complex in the Wnt/β-catenin pathway is critical for regulating the level of β-catenin in the cytoplasm and in the nucleus. Here we report a comprehensive study of the contribution of genetic variation in six genes encoding the β-catenin destruction complex (APC, AXIN1, AXIN2, CSNK1D, CSNK1E and GSK3B) to breast cancer using a Mayo Clinic Breast Cancer Case-Control Study. A total of 79 candidate functional and tagSNPs were genotyped in 798 invasive cases and 843 unaffected controls. Of these, rs454886 in the APC tumor suppressor gene was associated with increased breast cancer risk (per-allele odds ratio (OR) = 1.23; 95% CI, 1.05–1.43; Ptrend = 0.01). In addition, five SNPs in AXIN2 were associated with increased risk of breast cancer (Ptrend < 0.05). Haplotype-based tests identified significant associations between specific haplotypes in APC (P ≤ 0.03) and AXIN2 (P = 0.03) and breast cancer risk. Further characterization of the APC and AXIN2 variants suggested that AXIN2 rs4791171 was significantly associated with risk in premenopausal (Ptrend = 0.0002; q = 0.02) but not in postmenopausal women. The combination of our findings and numerous genetic and functional studies showing that APC and AXIN2 perform crucial tumor suppressor functions suggest that further investigation of the contribution of AXIN2 and APC SNPs to breast cancer risk are needed. PMID:18708403

  8. Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases.

    PubMed

    Lee, Wen-Chung

    2016-06-09

    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.

  9. 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

  10. Allostatic load is associated with chronic conditions in the Boston Puerto Rican Health Study.

    PubMed

    Mattei, Josiemer; Demissie, Serkalem; Falcon, Luis M; Ordovas, Jose M; Tucker, Katherine

    2010-06-01

    Puerto Ricans living in the United States mainland present multiple disparities in prevalence of chronic diseases, relative to other racial and ethnic groups. Allostatic load (AL), or the cumulative wear and tear of physiological responses to stressors such as major life events, social and environmental burden, has been proposed as a possible mechanism for the inequalities observed in minority groups, but has not been studied in Puerto Ricans. The aim of this study was to determine the association of AL to six chronic diseases (abdominal obesity, hypertension, diabetes, and self-reported cardiovascular disease (CVD), arthritis and cancer) in Puerto Ricans, and to contrast AL to metabolic syndrome (MetS). Participants of the Boston Puerto Rican Health Study (n=1116, ages 45-75 years) underwent a home-based interview, where questionnaires were completed and biological samples collected. A summary definition of AL was constructed using clinically-defined cutoffs and medication use for 10 physiological parameters in different body systems. Logistic regression models were run to determine associations between AL score and disease status, controlling for age, sex, smoking, alcohol use, physical activity, total fat intake and energy intake. Parallel models were also run with MetS score replacing AL. We found that increasing categories of AL score were significantly associated with abdominal obesity, hypertension, diabetes and self-reported cardiovascular disease (CVD) and arthritis, but not with self-reported cancer. The strength of associations of AL with all conditions, except diabetes and cancer, was similar to or larger than those of MetS score. In conclusion, Puerto Rican older adults experienced physiological dysregulation that was associated with increased odds of chronic conditions. AL was more strongly associated with most conditions, compared to MetS, suggesting that this cumulative measure may be a better predictor of disease. These results have prospective

  11. Genome-wide Association Studies of Maximum Number of Drinks

    PubMed Central

    Pan, Yue; Luo, Xingguang; Liu, Xuefeng; Wu, Long-Yang; Zhang, Qunyuan; Wang, Liang; Wang, Weize; Zuo, Lingjun; Wang, Ke-Sheng

    2014-01-01

    Maximum number of drinks (MaxDrinks) defined as “Maximum number of alcoholic drinks consumed in a 24-hour period” is an intermediate phenotype that is closely related to alcohol dependence (AD). Family, twin and adoption studies have shown that the heritability of MaxDrinks is approximately 0.5. We conducted the first genome-wide association (GWA) study and meta-analysis of MaxDrinks as a continuous phenotype. 1059 individuals were from the Collaborative Study on the Genetics of Alcoholism (COGA) sample and 1628 individuals were from the Study of Addiction – Genetics and Environment (SAGE) sample. Family sample with 3137 individuals was from the Australian twin-family study of alcohol use disorder (OZALC). Two population-based Caucasian samples (COGA and SAGE) with 1 million single-nucleotide polymorphisms (SNPs) were used for gene discovery and one family-based Caucasian sample was used for replication. Through meta-analysis we identified 162 SNPs associated with MaxDirnks (p < 10−4). The most significant association with MaxDrinks was observed with SNP rs11128951 (p = 4.27×10−8) near SGOL1 gene at 3p24.3. Furthermore, several SNPs (rs17144687 near DTWD2, rs12108602 near NDST4, and rs2128158 in KCNB2) showed significant associations with MaxDrinks (p < 5×10−7) in the meta-analysis. Especially, 8 SNPs in DDC gene showed significant associations with MaxDrinks (p< 5×10−7) in the SAGE sample. Several flanking SNPs in above genes/regions were confirmed in the OZALC family sample. In conclusions, we identified several genes/regions associated with MaxDrinks. These findings can improve the understanding about the pathogenesis of alcohol consumption phenotypes and alcohol-related disorders. PMID:23953852

  12. 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

  13. 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.

  14. 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

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

    PubMed Central

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

    2014-01-01

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

  16. 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…

  17. 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

  18. 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

  19. 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.

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

    PubMed

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

    2015-02-01

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

  1. Genome-Wide Association Studies in Nephrology: Using Known Associations for Data Checks

    PubMed Central

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

    2014-01-01

    Prior to conducting genome-wide association studies (GWAS) of renal traits and diseases, systematic checks to ensure data integrity and analytical workflow should be conducted. Using positive controls (ie, known associations between a single-nucleotide polymorphism [SNP] and a corresponding trait) allows for identifying errors that are not apparent solely from global evaluation of summary statistics. Strong genetic control associations of chronic kidney disease (CKD), as derived from GWAS, are lacking in the non-African CKD population; thus, in this perspective we provide examples of and considerations for using positive controls among patients with CKD. Using data from individuals with CKD who participated in the CRIC (Chronic Renal Insufficiency Cohort) Study or PediGFR (Pediatric Investigation for Genetic Factors Linked to Renal Progression) Consortium, we evaluated 2 kinds of positive control traits: traits unrelated to kidney function (bilirubin, body height) and those related to kidney function (cystatin C, urate). For the former, the proportion of variance in the control trait that is explained by the control SNP is the main determinant of the strength of the observable association, irrespective of adjustment for kidney function. For the latter, adjustment for kidney function can be effective in uncovering known associations among patients with CKD. For instance, in 1,092 participants of the PediGFR Consortium, the p-value for association of cystatin C concentrations and rs911119 in the CST3 gene decreased from 2.7*10-3 to 2.4*10-8 upon adjustment for serum creatinine–based estimated glomerular filtration rate. In this perspective, we give recommendations for the appropriate selection of control traits and SNPs that can be used for data checks prior to conducting GWAS among patients with CKD. PMID:25465167

  2. Genetics of human stature: Lessons from genome-wide association studies.

    PubMed

    Perola, Markus

    2011-01-01

    Over the past 2 to 3 years, linkage disequilibrium mapping methods, or genome-wide association studies (GWAS), have made a seminal turn in the molecular genetic studies of complex human traits such as height, i.e., stature. Human stature is a highly heritable trait across populations and the phenotype for stature is easily measured and related to many other traits; therefore, it is available in most studies evaluating any phenotype. For this reason, it has become a beacon for large consortium genetic studies, during both the pre-GWAS and GWAS eras. Tens of thousands of genome-scanned individuals have been analysed together against their genome. Several loci have been implicated in association with stature (54 of these have been published), and most chromosomes have a locus linked to the trait in family studies. However, the prediction power of loci indentified by molecular genetic methods still remains inferior to clinical assessment of offspring stature using midparental height as a guide. Although the genomic methods provide important insights into heritability of stature, it will be a major challenge for molecular genetic studies to provide information that surpasses that of midparental height.

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

    PubMed

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

    2011-05-10

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

  4. 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…

  5. 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...

  6. 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.

  7. 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; Koellinger, Philipp D; Cesarini, David; Benjamin, Daniel J

    2016-05-26

    Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases. PMID:27225129

  8. 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; Koellinger, Philipp D; Cesarini, David; Benjamin, Daniel J

    2016-05-11

    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.

  9. 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

  10. Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal Defects.

    PubMed

    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

    2015-07-20

    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.

  11. 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.

  12. Water resources in the twenty-first century; a study of the implications of climate uncertainty

    USGS Publications Warehouse

    Moss, Marshall E.; Lins, Harry F.

    1989-01-01

    The interactions of the water resources on and within the surface of the Earth with the atmosphere that surrounds it are exceedingly complex. Increased uncertainty can be attached to the availability of water of usable quality in the 21st century, therefore, because of potential anthropogenic changes in the global climate system. For the U.S. Geological Survey to continue to fulfill its mission with respect to assessing the Nation's water resources, an expanded program to study the hydrologic implications of climate uncertainty will be required. The goal for this program is to develop knowledge and information concerning the potential water-resources implications for the United States of uncertainties in climate that may result from both anthropogenic and natural changes of the Earth's atmosphere. Like most past and current water-resources programs of the Geological Survey, the climate-uncertainty program should be composed of three elements: (1) research, (2) data collection, and (3) interpretive studies. However, unlike most other programs, the climate-uncertainty program necessarily will be dominated by its research component during its early years. Critical new concerns to be addressed by the research component are (1) areal estimates of evapotranspiration, (2) hydrologic resolution within atmospheric (climatic) models at the global scale and at mesoscales, (3) linkages between hydrology and climatology, and (4) methodology for the design of data networks that will help to track the impacts of climate change on water resources. Other ongoing activities in U.S. Geological Survey research programs will be enhanced to make them more compatible with climate-uncertainty research needs. The existing hydrologic data base of the Geological Survey serves as a key element in assessing hydrologic and climatologic change. However, this data base has evolved in response to other needs for hydrologic information and probably is not as sensitive to climate change as is

  13. Genome-wide association study of antisocial personality disorder.

    PubMed

    Rautiainen, M-R; Paunio, T; Repo-Tiihonen, E; Virkkunen, M; Ollila, H M; Sulkava, S; Jolanki, O; Palotie, A; Tiihonen, J

    2016-01-01

    The pathophysiology of antisocial personality disorder (ASPD) remains unclear. Although the most consistent biological finding is reduced grey matter volume in the frontal cortex, about 50% of the total liability to developing ASPD has been attributed to genetic factors. The contributing genes remain largely unknown. Therefore, we sought to study the genetic background of ASPD. We conducted a genome-wide association study (GWAS) and a replication analysis of Finnish criminal offenders fulfilling DSM-IV criteria for ASPD (N=370, N=5850 for controls, GWAS; N=173, N=3766 for controls and replication sample). The GWAS resulted in suggestive associations of two clusters of single-nucleotide polymorphisms at 6p21.2 and at 6p21.32 at the human leukocyte antigen (HLA) region. Imputation of HLA alleles revealed an independent association with DRB1*01:01 (odds ratio (OR)=2.19 (1.53-3.14), P=1.9 × 10(-5)). Two polymorphisms at 6p21.2 LINC00951-LRFN2 gene region were replicated in a separate data set, and rs4714329 reached genome-wide significance (OR=1.59 (1.37-1.85), P=1.6 × 10(-9)) in the meta-analysis. The risk allele also associated with antisocial features in the general population conditioned for severe problems in childhood family (β=0.68, P=0.012). Functional analysis in brain tissue in open access GTEx and Braineac databases revealed eQTL associations of rs4714329 with LINC00951 and LRFN2 in cerebellum. In humans, LINC00951 and LRFN2 are both expressed in the brain, especially in the frontal cortex, which is intriguing considering the role of the frontal cortex in behavior and the neuroanatomical findings of reduced gray matter volume in ASPD. To our knowledge, this is the first study showing genome-wide significant and replicable findings on genetic variants associated with any personality disorder.

  14. Pharmacogenetic Association Study of Warfarin Safety Endpoints in Puerto Ricans

    PubMed Central

    Valentín, Isa I.; Rivera, Giselle; Nieves-Plaza, Mariely; Cruz, Iadelisse; Renta, Jessica Y.; Cadilla, Carmen L.; Feliu, Juan F.; Seip, Richard L.; Ruaño, Gualberto; Duconge, Jorge

    2014-01-01

    Objective This study was intended to determine the incidence rate of warfarin-related adverse events (e.g., bleeding) in Puerto Ricans and whether a genetic association between warfarin pharmacogenes and any of these adverse events was observed over the initiation period (i.e., the first 90 days of therapy). Methods We conducted an observational, retrospective cohort study of pharmacogenetic association in 122 warfarin-treated, male, Puerto Rican patients (69.9 ±9.6 years) from the Veterans Affair Caribbean Healthcare System (VACHS) who consented to participate. Genotyping was performed using the CYP2C9 and VKORC 1 assays by Luminex. Event-free survival curves were estimated using the Kaplan–Meier method and analyzed by log-rank test. Cox regression models were constructed and hazard ratios (HR) calculated. Results Carriers of functional CYP2C9 and VKORC1 polymorphisms demonstrated a higher incidence rate of multiple adverse events (i.e., 5.2 vs. 1.0 cases per 100 patient-months; RR = 4.8, p = 0.12) than did wild types. A significant association was observed between multiple adverse events and carrier status (HR = 2.5; 95% CI : 1.0–6.3, p = 0.04). However, no significant associations between genotypes and individual outcomes over the first 90 days of therapy were found. Conclusion The association of CYP2C9 and VKORC1 genotypes and risks for adverse events due to exposure to warfarin was examined for the first time in Puerto Ricans. Despite a lack of association with individual events in this study population, our findings revealed a potential utility of genotyping for the prevention of multiple adverse events during warfarin therapy. PMID:25244877

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Equivalence of concentration-response relationships in aquatic toxicology studies: Testing and implications for potency estimation

    SciTech Connect

    Oris, J.T.

    1997-10-01

    The purpose of this study was to describe statistical procedures to test the equivalence of concentration-response relationships in acute toxicology studies and to illustrate the implications of nonequivalence on potency endpoints such as LC10, LC50, or LC90. A logistic regression model for binary response endpoints such as mortality that allowed for the examination of equivalence of slopes and intercepts of the responses between populations is described. Test statistics were derived from comparing nested regression models. This procedure was used to test the equivalence of concentration versus acute mortality response relationships between two nonpolar, narcotic chemicals in a single population of fish and between two populations of fish with different exposure histories to a polycyclic aromatic hydrocarbon. These case studies illustrate different outcomes in the comparison of concentration-response relationships and demonstrate the need to consider more than a single endpoint (e.g., LC50) in a risk assessment context when nonparallel concentration-responses are observed.

  20. 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

  1. Genetics, Genome-Wide Association Studies, and Menarche.

    PubMed

    Witchel, Selma Feldman

    2016-07-01

    Puberty is characterized by maturation of the hypothalamic-pituitary-gonadal axis, development of secondary sexual features, increased linear growth velocity, maturation of the epiphyses limiting additional growth, and achievement of menarche. The age at menarche appears to have a significant genetic component. With the advent of genome-wide association studies (GWASs), the genome has been interrogated to find associations between specific loci and age at menarche. It is apparent that multiple genetic loci, epigenetic mechanisms, and environmental factors modulate this biological event crucial for reproductive competence.

  2. Genetics, Genome-Wide Association Studies, and Menarche.

    PubMed

    Witchel, Selma Feldman

    2016-07-01

    Puberty is characterized by maturation of the hypothalamic-pituitary-gonadal axis, development of secondary sexual features, increased linear growth velocity, maturation of the epiphyses limiting additional growth, and achievement of menarche. The age at menarche appears to have a significant genetic component. With the advent of genome-wide association studies (GWASs), the genome has been interrogated to find associations between specific loci and age at menarche. It is apparent that multiple genetic loci, epigenetic mechanisms, and environmental factors modulate this biological event crucial for reproductive competence. PMID:27513021

  3. Genome-Wide Association Study of Periodontal Health Measured by Probing Depth in Adults Ages 18−49 years

    PubMed Central

    Shaffer, John R.; Polk, Deborah E.; Wang, Xiaojing; Feingold, Eleanor; Weeks, Daniel E.; Lee, Myoung-Keun; Cuenco, Karen T.; Weyant, Robert J.; Crout, Richard J.; McNeil, Daniel W.; Marazita, Mary L.

    2013-01-01

    The etiology of chronic periodontitis clearly includes a heritable component. Our purpose was to perform a small exploratory genome-wide association study in adults ages 18–49 years to nominate genes associated with periodontal disease−related phenotypes for future consideration. Full-mouth periodontal pocket depth probing was performed on participants (N = 673), with affected status defined as two or more sextants with probing depths of 5.5 mm or greater. Two variations of this phenotype that differed in how missing teeth were treated were used in analysis. More than 1.2 million genetic markers across the genome were genotyped or imputed and tested for genetic association. We identified ten suggestive loci (p-value ≤ 1E-5), including genes/loci that have been previously implicated in chronic periodontitis: LAMA2, HAS2, CDH2, ESR1, and the genomic region on chromosome 14q21-22 between SOS2 and NIN. Moreover, we nominated novel loci not previously implicated in chronic periodontitis or related pathways, including the regions 3p22 near OSBPL10 (a lipid receptor implicated in hyperlipidemia), 4p15 near HSP90AB2P (a heat shock pseudogene), 11p15 near GVINP1 (a GTPase pseudogene), 14q31 near SEL1L (an intracellular transporter), and 18q12 in FHOD3 (an actin cytoskeleton regulator). Replication of these results in additional samples is needed. This is one of the first research efforts to identify genetic polymorphisms associated with chronic periodontitis-related phenotypes by the genome-wide association study approach. Though small, efforts such this are needed in order to nominate novel genes and generate new hypotheses for exploration and testing in future studies. PMID:24347629

  4. 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

  5. Voxelwise genome-wide association study (vGWAS).

    PubMed

    Stein, Jason L; Hua, Xue; Lee, Suh; Ho, April J; Leow, Alex D; Toga, Arthur W; Saykin, Andrew J; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J; Craig, David W; Gerber, Jill D; Allen, April N; Corneveaux, Jason J; Dechairo, Bryan M; Potkin, Steven G; Weiner, Michael W; Thompson, Paul

    2010-11-15

    The structure of the human brain is highly heritable, and is thought to be influenced by many common genetic variants, many of which are currently unknown. Recent advances in neuroimaging and genetics have allowed collection of both highly detailed structural brain scans and genome-wide genotype information. This wealth of information presents a new opportunity to find the genes influencing brain structure. Here we explore the relation between 448,293 single nucleotide polymorphisms in each of 31,622 voxels of the entire brain across 740 elderly subjects (mean age+/-s.d.: 75.52+/-6.82 years; 438 male) including subjects with Alzheimer's disease, Mild Cognitive Impairment, and healthy elderly controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We used tensor-based morphometry to measure individual differences in brain structure at the voxel level relative to a study-specific template based on healthy elderly subjects. We then conducted a genome-wide association at each voxel to identify genetic variants of interest. By studying only the most associated variant at each voxel, we developed a novel method to address the multiple comparisons problem and computational burden associated with the unprecedented amount of data. No variant survived the strict significance criterion, but several genes worthy of further exploration were identified, including CSMD2 and CADPS2. These genes have high relevance to brain structure. This is the first voxelwise genome wide association study to our knowledge, and offers a novel method to discover genetic influences on brain structure.

  6. Sunitinib-associated Pancreatic Atrophy in Patients with Gastrointestinal Stromal Tumor: A Toxicity with Prognostic Implications Detected at Imaging.

    PubMed

    Shinagare, Atul B; Steele, Erin; Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Ramaiya, Nikhil H

    2016-10-01

    Purpose To evaluate the effect and clinical importance of sunitinib on pancreatic volume in patients with gastrointestinal stromal tumor (GIST). Materials and Methods This retrospective study was approved by the institutional review board and compliant with HIPAA. The requirement to obtain informed consent was waived. The authors evaluated 65 patients with GIST treated with oral sunitinib and a control group of 30 patients with GIST who did not receive any therapy (mean age: 56 years [range, 29-75 years] vs 60 years [range, 27-78 years], respectively; P = .11) seen at their institution from January 2002 through December 2008. Segmented pancreatic volumes of study and control groups were measured with computed tomography by using commercial software by two independent readers who were blinded to study group and the timing of the scan at a median of 6.2 and 6.1 months, respectively. Pre- and posttreatment volumes (Wilcoxon signed rank test) and rate of volume change per month (Wilcoxon rank sum test) were compared. Interobserver agreement was calculated. Associations and prognostic importance of pancreatic atrophy were studied by using multivariate linear regression and Cox proportional analysis, respectively. Results Both readers recorded significant pancreatic volume loss in the study group (respective median pre- and posttreatment volume: 76.1 cm(3) and 58.4 cm(3) for reader 1 and 67.7 cm(3) and 59.0 cm(3) for reader 2; P < .0001 for both) but not in the control group (respective median pre- and posttreatment volume: 79.9 cm(3) and 83.8 cm(3) for reader 1 [P = .43] and 79.9 cm(3) and 84.8 cm(3) for reader 2 [P = .50]). The rate of volume loss per month was greater in the study group than in the control group (reader 1: -2.1% vs -0.1%, respectively, P = .003; reader 2: -2.0% vs -0.3%, P < .0001). Twenty-three of the 65 patients who received sunitinib (35%) showed at least 3% pancreatic volume loss per month, compared with only one of the 30 patients in the control

  7. The neural correlates of person familiarity. A functional magnetic resonance imaging study with clinical implications.

    PubMed

    Shah, N J; Marshall, J C; Zafiris, O; Schwab, A; Zilles, K; Markowitsch, H J; Fink, G R

    2001-04-01

    Neural activity was measured in 10 healthy volunteers by functional MRI while they viewed familiar and unfamiliar faces and listened to familiar and unfamiliar voices. The familiar faces and voices were those of people personally known to the subjects; they were not people who are more widely famous in the media. Changes in neural activity associated with stimulus modality irrespective of familiarity were observed in modules previously demonstrated to be activated by faces (fusiform gyrus bilaterally) and voices (superior temporal gyrus bilaterally). Irrespective of stimulus modality, familiarity of faces and voices (relative to unfamiliar faces and voices) was associated with increased neural activity in the posterior cingulate cortex, including the retrosplenial cortex. Our results suggest that recognizing a person involves information flow from modality-specific modules in the temporal cortex to the retrosplenial cortex. The latter area has recently been implicated in episodic memory and emotional salience, and now seems to be a key area involved in assessing the familiarity of a person. We propose that disturbances in the information flow described may underlie neurological and psychiatric disorders of the recognition of familiar faces, voices and persons (prosopagnosia, phonagnosia and Capgras delusion, respectively). PMID:11287379

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Retrospective study of necropsy-associated coagulase-positive staphylococci in horses.

    PubMed

    Haenni, Marisa; Targant, Hayette; Forest, Karine; Sévin, Corinne; Tapprest, Jackie; Laugier, Claire; Madec, Jean-Yves

    2010-11-01

    Coagulase-positive staphylococci (CoPS) are potential causative agents of equine infections, but they are rarely responsible for the death of the animal. In the current study, staphylococci implicated in the death or euthanasia of horses were retrospectively studied in 3,457 necropsies performed over a decade (1995-2006). Morbidity associated with CoPS was 1.7%, representing 60 isolates of CoPS, which were identified as Staphylococcus aureus (59) and Staphylococcus pseudintermedius (1). Coagulase-positive staphylococci (alone or in association with another bacterial species) were associated with the death or euthanasia of 90% of the cases (54/60). Proportions of antibiotic resistance to penicillin G and tetracycline reached 62.7% and 23.7%, respectively. Virulence genes were detected in 91.7% of the strains, with a majority of seh or sei enterotoxin genes. Finally, 3 methicillin-resistant Staphylococcus aureus (MRSA) isolates belonging to the t064 spa-type were identified. One strain was isolated in 2003 and might thus be one of the first cases of equine MRSA in France. PMID:21088182

  13. 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.

  14. A genome-wide association study of attempted suicide

    PubMed Central

    Willour, Virginia L.; Seifuddin, Fayaz; Mahon, Pamela B.; Jancic, Dubravka; Pirooznia, Mehdi; Steele, Jo; Schweizer, Barbara; Goes, Fernando S.; Mondimore, Francis M.; MacKinnon, Dean F.; Perlis, Roy H.; Lee, Phil Hyoun; Huang, Jie; Kelsoe, John R.; Shilling, Paul D.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Purcell, Shaun; Smoller, Jordan W.; Craddock, Nicholas; DePaulo, J. Raymond; Schulze, Thomas G.; McMahon, Francis J.; Zandi, Peter P.; Potash, James B.

    2011-01-01

    The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. While attempted suicide linkage regions have been identified on 2p11–12 and 6q25–26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single nucleotide polymorphism (SNP) genotypes of 1,201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1,497 BP subjects without a history of suicide attempts. 2,507 SNPs with evidence for association at p<0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (p= 5.07 × 10−8). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. PMID:21423239

  15. A genome-wide association study of attempted suicide.

    PubMed

    Willour, V L; Seifuddin, F; Mahon, P B; Jancic, D; Pirooznia, M; Steele, J; Schweizer, B; Goes, F S; Mondimore, F M; Mackinnon, D F; Perlis, R H; Lee, P H; Huang, J; Kelsoe, J R; Shilling, P D; Rietschel, M; Nöthen, M; Cichon, S; Gurling, H; Purcell, S; Smoller, J W; Craddock, N; DePaulo, J R; Schulze, T G; McMahon, F J; Zandi, P P; Potash, J B

    2012-04-01

    The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. Although attempted suicide linkage regions have been identified on 2p11-12 and 6q25-26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single-nucleotide polymorphism (SNP) genotypes of 1201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1497 BP subjects without a history of suicide attempts. In all, 2507 SNPs with evidence for association at P<0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (P=5.07 × 10(-8)). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. PMID:21423239

  16. 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

  17. Set-based tests for genetic association in longitudinal studies.

    PubMed

    He, Zihuai; Zhang, Min; Lee, Seunggeun; Smith, Jennifer A; Guo, Xiuqing; Palmas, Walter; Kardia, Sharon L R; Diez Roux, Ana V; Mukherjee, Bhramar

    2015-09-01

    Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set of genetic variants. Generalized score type tests are developed, which we show are robust to misspecification of within-subject correlation, a feature that is desirable for longitudinal analysis. In addition, a joint test incorporating gene-time interaction is further proposed. Computational advancement is made for scalable implementation of the proposed methods in large-scale genome-wide association studies (GWAS). The proposed methods are evaluated through extensive simulation studies and illustrated using data from the Multi-Ethnic Study of Atherosclerosis (MESA). Our simulation results indicate substantial gain in power using LGRF when compared with two commonly used existing alternatives: (i) single marker tests using longitudinal outcome and (ii) existing gene-based tests using the average value of repeated measurements as the outcome.

  18. Common Mental Disorders Associated with Tuberculosis: A Matched Case-Control Study

    PubMed Central

    de Araújo, Gleide Santos; Pereira, Susan Martins; dos Santos, Darci Neves; Marinho, Jamocyr Moura; Rodrigues, Laura Cunha; Barreto, Mauricio Lima

    2014-01-01

    Introduction Despite the availability of treatment and a vaccine, tuberculosis continues to be a public health problem worldwide. Mental disorders might contribute to the burden of the disease. Objective The objective of this study was to investigate the association between common mental disorders and tuberculosis. Methods A matched case-control study was conducted. The study population included symptomatic respiratory patients who attended three referral hospitals and six community clinics in the city of Salvador, Brazil. A doctor’s diagnosis defined potential cases and controls