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Sample records for association scan reveals

  1. Genome-Wide Scan Reveals Mutation Associated with Melanoma

    Science.gov (United States)

    ... 1999 Spotlight on Research 2012 July 2012 (historical) Genome-Wide Scan Reveals Mutation Associated with Melanoma A ... out to see if a technology called whole genome sequencing would help them find other genetic risk ...

  2. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption.

    Science.gov (United States)

    Pirastu, Nicola; Kooyman, Maarten; Robino, Antonietta; van der Spek, Ashley; Navarini, Luciano; Amin, Najaf; Karssen, Lennart C; Van Duijn, Cornelia M; Gasparini, Paolo

    2016-01-01

    Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption. PMID:27561104

  3. A genome-wide linkage and association scan reveals novel loci for hypertension and blood pressure traits.

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    Youling Guo

    Full Text Available Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9 × 10(-8 for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5 × 10(-4 and 2.9 × 10(-5 in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7 × 10(-5 for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening.

  4. A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation.

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    Silvia Naitza

    2012-01-01

    Full Text Available Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS for the key inflammatory biomarkers Interleukin-6 (IL-6, the general measure of inflammation erythrocyte sedimentation rate (ESR, monocyte chemotactic protein-1 (MCP-1, and high-sensitivity C-reactive protein (hsCRP in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals-5 of which were identified only with the custom arrays-and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10(-29; for ESR, at the HBB (rs4910472, p = 2.31×10(-11 and UCN119B/SPPL3 (rs11829037, p = 8.91×10(-10 loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10(-13 and in CADM3 (rs3026968, p = 7.63×10(-13; for hsCRP, within the CRP gene (rs3093077, p = 5.73×10(-21, near DARC (rs3845624, p = 1.43×10(-10, UNC119B/SPPL3 (rs11829037, p = 1.50×10(-14, and ICOSLG/AIRE (rs113459440, p = 1.54×10(-08 loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267; for ESR at CR1 (rs12567990 and TMEM57 (rs10903129; for MCP-1 at DARC (rs12075; and for hsCRP at CRP (rs1205, HNF1A (rs225918, and APOC-I (rs4420638. Our

  5. A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation

    Science.gov (United States)

    Naitza, Silvia; Porcu, Eleonora; Steri, Maristella; Taub, Dennis D.; Mulas, Antonella; Xiao, Xiang; Strait, James; Dei, Mariano; Lai, Sandra; Busonero, Fabio; Maschio, Andrea; Usala, Gianluca; Zoledziewska, Magdalena; Sidore, Carlo; Zara, Ilenia; Pitzalis, Maristella; Loi, Alessia; Virdis, Francesca; Piras, Roberta; Deidda, Francesca; Whalen, Michael B.; Crisponi, Laura; Concas, Antonio; Podda, Carlo; Uzzau, Sergio; Scheet, Paul; Longo, Dan L.; Lakatta, Edward; Abecasis, Gonçalo R.; Cao, Antonio; Schlessinger, David; Uda, Manuela

    2012-01-01

    Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals—5 of which were identified only with the custom arrays—and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10−29); for ESR, at the HBB (rs4910472, p = 2.31×10−11) and UCN119B/SPPL3 (rs11829037, p = 8.91×10−10) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10−13) and in CADM3 (rs3026968, p = 7.63×10−13); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10−21), near DARC (rs3845624, p = 1.43×10−10), UNC119B/SPPL3 (rs11829037, p = 1.50×10−14), and ICOSLG/AIRE (rs113459440, p = 1.54×10−08) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs

  6. Ancient Pb and Ti mobilization revealed by Scanning Ion Imaging

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    Kusiak, Monika A.; Whitehouse, Martin J.; Wilde, Simon A.

    2014-05-01

    Zircons from strongly layered early Archean ortho- and paragneisses in ultra-high temperature (UHT) metamorphic rocks of the Napier Complex, Enderby Land, East Antarctica are characterized by complex U-Th-Pb systematics [1,2,3]. A large number of zircons from three samples, Gage Ridge, Mount Sones and Dallwitz Nunatak, are reversely discordant (U/Pb ages older than 207Pb/206Pb ages) with the oldest date of 3.9 Ga [4] (for the grain from Gage Ridge orthogneiss). To further investigate this process, we utilized a novel high spatial resolution Scanning Ion Imaging technique on the CAMECA IMS 1280 at the Natural History Museum in Stockholm. Areas of 70 μm x 70 μm were selected for imaging in mono- and multicollection modes using a ~2 μm rastered primary beam to map out the distribution of 48Ti, 89Y, 180Hf, 232Th, 238U, 204Pb, 206Pb and 207Pb. The ion maps reveal variable distribution of certain elements within analysed grains that can be compared to their CL response. Yttrium, together with U and Th, exhibits zonation visible on the CL images, Hf shows expected minimal variation. Unusual patchiness is visible in the map for Ti and Pb distribution. The bright patches with enhanced signal do not correspond to any zones or to crystal imperfections (e.g. cracks). The presence of patchy titanium is likely to affect Ti-in-zircon thermometry, and patchy Pb affecting 207Pb/206Pb ages, usually considered as more robust for Archean zircons. Using the WinImage program, we produced 207Pb/206Pb ratio maps that allow calculation of 207Pb/206Pb ages for spots of any size within the frame of the picture and at any time after data collection. This provides a new and unique method for obtaining age information from zircon. These maps show areas of enhanced brightness where the 207Pb/206Pb ratio is higher and demonstrate that within these small areas (μm scale) the apparent 207Pb/206Pb age is older, in some of these patches even > 4 Ga. These data are a result of ancient Pb

  7. Family-based association tests for genomewide association scans.

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    Chen, Wei-Min; Abecasis, Goncalo R

    2007-11-01

    With millions of single-nucleotide polymorphisms (SNPs) identified and characterized, genomewide association studies have begun to identify susceptibility genes for complex traits and diseases. These studies involve the characterization and analysis of very-high-resolution SNP genotype data for hundreds or thousands of individuals. We describe a computationally efficient approach to testing association between SNPs and quantitative phenotypes, which can be applied to whole-genome association scans. In addition to observed genotypes, our approach allows estimation of missing genotypes, resulting in substantial increases in power when genotyping resources are limited. We estimate missing genotypes probabilistically using the Lander-Green or Elston-Stewart algorithms and combine high-resolution SNP genotypes for a subset of individuals in each pedigree with sparser marker data for the remaining individuals. We show that power is increased whenever phenotype information for ungenotyped individuals is included in analyses and that high-density genotyping of just three carefully selected individuals in a nuclear family can recover >90% of the information available if every individual were genotyped, for a fraction of the cost and experimental effort. To aid in study design, we evaluate the power of strategies that genotype different subsets of individuals in each pedigree and make recommendations about which individuals should be genotyped at a high density. To illustrate our method, we performed genomewide association analysis for 27 gene-expression phenotypes in 3-generation families (Centre d'Etude du Polymorphisme Humain pedigrees), in which genotypes for ~860,000 SNPs in 90 grandparents and parents are complemented by genotypes for ~6,700 SNPs in a total of 168 individuals. In addition to increasing the evidence of association at 15 previously identified cis-acting associated alleles, our genotype-inference algorithm allowed us to identify associated alleles at 4

  8. MIBG scans in patients with stage 4 neuroblastoma reveal two metastatic patterns, one is associated with MYCN amplification and in MYCN-amplified tumours correlates with a better prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Bleeker, Gitta [Academic Medical Centre/Emma Children' s Hospital, Department of Paediatric Oncology, Amsterdam (Netherlands); Academic Medical Centre, Department of Oncogenomics, Amsterdam (Netherlands); Eck-Smit, Berthe L. van [Academic Medical Centre, Department of Nuclear Medicine, Amsterdam (Netherlands); Zwinderman, Koos H. [Academic Medical Centre, Department of Biostatistics, Amsterdam (Netherlands); Versteeg, Rogier [Academic Medical Centre, Department of Oncogenomics, Amsterdam (Netherlands); Noesel, Max M. van [Erasmus Medical Centre/Sophia Children' s Hospital, Department of Paediatric Oncology/Haematology, Rotterdam (Netherlands); Kam, Boen L. [Erasmus Medical Centre, Department of Nuclear Medicine, Rotterdam (Netherlands); Kaspers, Gertjan J. [VU University Medical Centre, Department of Paediatric Oncology, Amsterdam (Netherlands); Schie, Annelies van [VU University Medical Centre, Department of Nuclear Medicine, Amsterdam (Netherlands); Kreissman, Susan G. [Duke University Medical Centre, Durham, NC (United States); University of Florida, Children' s Oncology Group (COG), Gainesville, FL (United States); Yanik, Gregory [University of Florida, Children' s Oncology Group (COG), Gainesville, FL (United States); University of Michigan, Department of Paediatrics, Division of Haematology and Oncology, Ann Arbor, MI (United States); Hero, Barbara [University Hospital of Cologne, Children' s Hospital, Cologne (Germany); Schmidt, Matthias [University Hospital of Cologne, Department of Nuclear Medicine, Cologne (Germany); Laureys, Genevieve [Ghent University Hospital, Department of Paediatric Haematology and Oncology, Ghent (Belgium); Lambert, Bieke [Ghent University Hospital, Department of Nuclear Medicine, Ghent (Belgium); Oera, Ingrid [Academic Medical Centre, Department of Oncogenomics, Amsterdam (Netherlands); Lund University Hospital, Department of Paediatric Oncology, Lund (Sweden); Schulte, Johannes H. [University Children' s Hospital Essen, Essen (Germany); Caron, Huib N.; Tytgat, Godelieve A. [Academic Medical Centre/Emma Children' s Hospital, Department of Paediatric Oncology, Amsterdam (Netherlands); Dutch Childhood Oncology Group (DCOG), The Hague (Netherlands)

    2014-09-30

    The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma. Diagnostic {sup 123}I-MIBG scans from 249 patients (123 from a European and 126 from the COG cohort) were assessed for metastatic spread in 14 body segments and the form of the lesions: ''focal'' (clear margins distinguishable from adjacent background) or ''diffuse'' (indistinct margins, dispersed throughout the body segment). The total numbers of diffuse and focal lesions were recorded. Patients were then categorized as having lesions exclusively focal, lesions more focal than diffuse, lesions more diffuse than focal, or lesions exclusively diffuse. Diffuse lesions affected a median of seven body segments and focal lesions a median of two body segments (P < 0.001, both cohorts). Patients with a focal pattern had a median of 2 affected body segments and those with a diffuse pattern a median of 11 affected body segments (P < 0.001, both cohorts). Thus, two MIBG-avid metastatic patterns emerged: ''limited-focal'' and ''extensive-diffuse''. The median numbers of affected body segments in MYCN-amplified (MNA) tumours were 5 (European cohort) and 4 (COG cohort) compared to 9 and 11, respectively, in single-copy MYCN (MYCNsc) tumours (P < 0.001). Patients with exclusively focal metastases were more likely to have a MNA tumour (60 % and 70 %, respectively) than patients with the other types of metastases (23 % and 28 %, respectively; P < 0.001). In a multivariate Cox regression analysis, focal metastases were associated with a better event-free and overall survival than the other types of metastases in patients with MNA tumours in the COG cohort (P < 0.01). Two metastatic patterns were found: a ''limited and focal'' pattern found mainly in patients with MNA neuroblastoma that correlated with prognosis, and an ''extensive and

  9. Revealing the 1 nm/s Extensibility of Nanoscale Amorphous Carbon in a Scanning Electron Microscope

    DEFF Research Database (Denmark)

    Zhang, Wei

    2013-01-01

    In an ultra-high vacuum scanning electron microscope, the edged branches of amorphous carbon film (∼10 nm thickness) can be continuously extended with an eye-identifying speed (on the order of ∼1 nm/s) under electron beam. Such unusual mobility of amorphous carbon may be associated with deformation...

  10. Color-shape associations revealed with implicit association tests.

    Science.gov (United States)

    Chen, Na; Tanaka, Kanji; Watanabe, Katsumi

    2015-01-01

    Kandinsky proposed a correspondence theory that suggests associations between specific colors and shapes (i.e., circle-blue, square-red, triangle-yellow). Makin and Wuerger tested the theory using the Implicit Association Test (IAT) and did not find clear evidence for Kandinsky's color-shape associations among British participants. In the present study, we first replicated the previous study among Japanese participants and found similar results to those of Makin and Wuerger, showing little support for Kandinsky's theory. In the subsequent experiment, we tested another set of color-shape associations that had been revealed by using an explicit matching method (circle-red, square-blue, triangle-yellow) in Japanese participants. The IAT tests showed that response times were significantly faster when circle-red, square-blue, and triangle-yellow combinations were mapped onto the same response key, rather than different key combinations, indicating that these color-shape combinations were encoded. These results provide the first empirical evidence that color-shape associations can be measured by indirect behavioral methods, and in particular, Japanese people's color-shape associations (circle-red, square-blue, triangle-yellow) can be observed by both direct and indirect experimental methods.

  11. Color-shape associations revealed with implicit association tests.

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    Na Chen

    Full Text Available Kandinsky proposed a correspondence theory that suggests associations between specific colors and shapes (i.e., circle-blue, square-red, triangle-yellow. Makin and Wuerger tested the theory using the Implicit Association Test (IAT and did not find clear evidence for Kandinsky's color-shape associations among British participants. In the present study, we first replicated the previous study among Japanese participants and found similar results to those of Makin and Wuerger, showing little support for Kandinsky's theory. In the subsequent experiment, we tested another set of color-shape associations that had been revealed by using an explicit matching method (circle-red, square-blue, triangle-yellow in Japanese participants. The IAT tests showed that response times were significantly faster when circle-red, square-blue, and triangle-yellow combinations were mapped onto the same response key, rather than different key combinations, indicating that these color-shape combinations were encoded. These results provide the first empirical evidence that color-shape associations can be measured by indirect behavioral methods, and in particular, Japanese people's color-shape associations (circle-red, square-blue, triangle-yellow can be observed by both direct and indirect experimental methods.

  12. Dissociable modulation of overt visual attention in valence and arousal revealed by topology of scan path.

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    Jianguang Ni

    Full Text Available Emotional stimuli have evolutionary significance for the survival of organisms; therefore, they are attention-grabbing and are processed preferentially. The neural underpinnings of two principle emotional dimensions in affective space, valence (degree of pleasantness and arousal (intensity of evoked emotion, have been shown to be dissociable in the olfactory, gustatory and memory systems. However, the separable roles of valence and arousal in scene perception are poorly understood. In this study, we asked how these two emotional dimensions modulate overt visual attention. Twenty-two healthy volunteers freely viewed images from the International Affective Picture System (IAPS that were graded for affective levels of valence and arousal (high, medium, and low. Subjects' heads were immobilized and eye movements were recorded by camera to track overt shifts of visual attention. Algebraic graph-based approaches were introduced to model scan paths as weighted undirected path graphs, generating global topology metrics that characterize the algebraic connectivity of scan paths. Our data suggest that human subjects show different scanning patterns to stimuli with different affective ratings. Valence salient stimuli (with neutral arousal elicited faster and larger shifts of attention, while arousal salient stimuli (with neutral valence elicited local scanning, dense attention allocation and deep processing. Furthermore, our model revealed that the modulatory effect of valence was linearly related to the valence level, whereas the relation between the modulatory effect and the level of arousal was nonlinear. Hence, visual attention seems to be modulated by mechanisms that are separate for valence and arousal.

  13. The structure of a model pulmonary surfactant as revealed by scanning force microscopy.

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    von Nahmen, A; Schenk, M.; Sieber, M; Amrein, M

    1997-01-01

    The structures formed by a pulmonary surfactant model system of dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), and recombinant surfactant-associated protein C (SP-C) were studied using scanning force microscopy (SFM) on Langmuir-Blodgett films. The films appeared to be phase separated, in agreement with earlier investigations by fluorescence light microscopy. There were smooth polygonal patches of mostly lipid, surrounded by a corrugated rim rich in SP-C. When ...

  14. Time factors associated with CT scan usage in trauma patients

    NARCIS (Netherlands)

    P.H.P. Fung Kon Jin; A.R. van Geene; K.F. Linnau; G.J. Jurkovich; K.J. Ponsen; J.C. Goslings

    2009-01-01

    INTRODUCTION: While computed tomography (CT) scan usage in acute trauma patients is currently part of the standard complete diagnostic workup, little is known regarding the time factors involved when CT scanning is added to the standard workup. An analysis of the current time factors and intervals i

  15. X-ray CT Scanning Reveals Long-Term Copper Pollution Effects on Functional Soil Structure

    DEFF Research Database (Denmark)

    Naveed, Muhammad; Møldrup, Per; Homstrup, Martin;

    factors such as soil type, land use, and soil contamination. In this study, we quantified the soil structure using X-ray CT scanning and revealed the effect of a long history of Copper (Cu) pollution on it. A fallow field at Hygum Denmark provides this opportunity as it had a long history of Copper......Soil structure plays the main role in the ability of the soil to fulfill essential soil functions such as the root growth, rate of water infiltration and retention, transport of gaseous and chemicals/pollutants through the soil. Soil structure is a dynamic soil property and affected by various...... sulphate contamination in a gradient with Cu content varies from 21 mg kg-1 to 3837 mg kg-1. Total 20 intact soil columns (diameter of 10 cm and height of 8 cm) were sampled at five locations along the Cu-gradient from a depth of 5 to 15 cm below surface level. The soil columns were scanned at a voxel...

  16. Genome scan for nonadditive heterotic trait loci reveals mainly underdominant effects in Saccharomyces cerevisiae.

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    Laiba, Efrat; Glikaite, Ilana; Levy, Yael; Pasternak, Zohar; Fridman, Eyal

    2016-04-01

    The overdominant model of heterosis explains the superior phenotype of hybrids by synergistic allelic interaction within heterozygous loci. To map such genetic variation in yeast, we used a population doubling time dataset of Saccharomyces cerevisiae 16 × 16 diallel and searched for major contributing heterotic trait loci (HTL). Heterosis was observed for the majority of hybrids, as they surpassed their best parent growth rate. However, most of the local heterozygous loci identified by genome scan were surprisingly underdominant, i.e., reduced growth. We speculated that in these loci adverse effects on growth resulted from incompatible allelic interactions. To test this assumption, we eliminated these allelic interactions by creating hybrids with local hemizygosity for the underdominant HTLs, as well as for control random loci. Growth of hybrids was indeed elevated for most hemizygous to HTL genes but not for control genes, hence validating the results of our genome scan. Assessing the consequences of local heterozygosity by reciprocal hemizygosity and allele replacement assays revealed the influence of genetic background on the underdominant effects of HTLs. Overall, this genome-wide study on a multi-parental hybrid population provides a strong argument against single gene overdominance as a major contributor to heterosis, and favors the dominance complementation model.

  17. Dynamics of ribosome scanning and recycling revealed by translation complex profiling.

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    Archer, Stuart K; Shirokikh, Nikolay E; Beilharz, Traude H; Preiss, Thomas

    2016-07-28

    Regulation of messenger RNA translation is central to eukaryotic gene expression control. Regulatory inputs are specified by them RNA untranslated regions (UTRs) and often target translation initiation. Initiation involves binding of the 40S ribosomal small subunit (SSU) and associated eukaryotic initiation factors (eIFs)near the mRNA 5′ cap; the SSU then scans in the 3′ direction until it detects the start codon and is joined by the 60S ribosomal large subunit (LSU) to form the 80S ribosome. Scanning and other dynamic aspects of the initiation model have remained as conjectures because methods to trap early intermediates were lacking. Here we uncover the dynamics of the complete translation cycle in live yeast cells using translation complex profile sequencing (TCP-seq), a method developed from the ribosome profiling approach. We document scanning by observing SSU footprints along 5′ UTRs. Scanning SSU have 5′-extended footprints (up to~75 nucleotides), indicative of additional interactions with mRNA emerging from the exit channel, promoting forward movement. We visualized changes in initiation complex conformation as SSU footprints coalesced into three major sizes at start codons (19, 29 and 37 nucleotides). These share the same 5′ start site but differ at the 3′ end, reflecting successive changes at the entry channel from an open to a closed state following start codon recognition. We also observe SSU 'lingering' at stop codons after LSU departure. Our results underpin mechanistic models of translation initiation and termination, built on decades of biochemical and structural investigation, with direct genome-wide in vivo evidence. Our approach captures ribosomal complexes at all phases of translation and will aid in studying translation dynamics in diverse cellular contexts. Dysregulation of translation is common in disease and, for example, SSU scanning is a target of anti-cancer drug development. TCP-seq will prove useful in discerning differences

  18. Sedimentary processes in Zenisu deep-sea channel revealed by side-scan imagery

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    Wu, Shiguo; Guo, Junhua; Hidekazu, Tokuyama

    2005-12-01

    Side-scan sonar data collected by Cruises 99-09 Leg 2 and 00-06 Leg 1 of R/V Yokosuka were used to reveal the sedimentary processes in Zenisu deep-sea channel. The middle and lower segments of the channel are rich in turbidite and other debrite deposits. By high-resolution imaging, three sedimentary processes were distinguished with distinct acoustic features. 1. Slumps and slides occur with contrasting backscatter, rough surface textures, blockings, and acoustic shadows at head walls. They are very extensive and often in lobate form downslope. 2. Debris flow has uniform, general medium backscatter, sometimes showing marbling/lineation in lobate form. 3. Turbidity current is characterized by low backscatter confined to the channel as acoustic signal is attenuated. Regional tectonics must be the dominating factor that controls deposition pattern in this area.

  19. Evolutionary change driven by metal exposure as revealed by coding SNP genome scan in wild yellow perch (Perca flavescens).

    Science.gov (United States)

    Bélanger-Deschênes, Sébastien; Couture, Patrice; Campbell, Peter G C; Bernatchez, Louis

    2013-07-01

    Pollution can drive rapid evolutionary change in wild populations. This study targets functional polymorphisms of chronically metal-contaminated wild yellow perch (Perca flavescens). A de novo transcriptome scan contrasted subsets of individuals from clean (n = 16) and contaminated (n = 16) lakes to identify 87 candidate annotated coding SNPs. Candidate genotypes and liver [metal] were obtained in 10 populations (n = 1,052) and a genome scan distinguished outliers: one nuclear (cyclin G1 gene) and two mitochondrial (cytochrome b and NADH dehydrogenase subunit 2 genes) also displaying allelic correlation to mean population [cadmium]. Whole mtDNA and 17 kb surrounding cyclin G1 were characterised through 454 sequencing thus revealing two non-synonymous substitutions involving dissimilar amino acids. Based on associated functions and inter-population differentiation, contaminated perch may have been selected for fast life cycle completion (p53 pathway) and memorization impairment mitigation (long-term potentiation pathway). In accordance with predicted evolutionary trajectory for stressed and energy deprived organisms, adapted perch would not compensate for repair mechanism inhibition, instead reallocating energy towards growth and favouring inexpensive impairment mitigation adaptations over costly detoxification. Overall, 85 years of selection could have driven rapid, potentially adaptive evolution by selecting alleles increasing perch fitness in polluted environments. PMID:23722603

  20. Scanning a microhabitat: plant-microbe interactions revealed by confocal laser microscopy

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    Massimiliano eCardinale

    2014-03-01

    Full Text Available No plant or cryptogam exists in nature without microorganisms associated with its tissues. Plants as microbial hosts are puzzles of different microhabitats, each of them colonized by specifically adapted microbiomes. The interactions with such microorganisms have drastic effects on the host fitness. Since the last 20 years, the combination of microscopic tools and molecular approaches contributed to new insights into microbe-host interactions. Particularly, confocal laser scanning microscopy (CLSM facilitated the exploration of microbial habitats and allowed the observation of host-associated microorganisms in situ with an unprecedented accuracy. Here I present an overview of the progresses made in the study of the interactions between microorganisms and plants or plant-like organisms, focusing on the role of CLSM for the understanding of their significance. I critically discuss risks of misinterpretation when procedures of CLSM are not properly optimized. I also review approaches for quantitative and statistical analyses of CLSM images, the combination with other molecular and microscopic methods, and suggest the re-evaluation of natural autofluorescence. In this review, technical aspects were coupled with scientific outcomes, to facilitate the readers in identifying possible CLSM applications in their research or to expand their existing potential. The scope of this review is to highlight the importance of confocal microscopy in the study of plant-microbe interactions and also to be an inspiration for integrating microscopy with molecular techniques in future researches of microbial ecology.

  1. Revealing the Secrets of Stonehenge Through the Application of Laser Scanning, Photogrammetry and Visualisation Techniques

    Science.gov (United States)

    Bryan, P. G.; Abbott, M.; Dodson, A. J.

    2013-07-01

    Stonehenge is perhaps the most famous prehistoric monument in the world. Begun as a simple earthwork enclosure, it was built in several stages with the unique lintelled stone circle being erected in the Neolithic period in around 2,500 BC. Today Stonehenge, together with Avebury and other associated sites, form the heart of a World Heritage Site (WHS) with a unique and dense concentration of outstanding prehistoric monuments. In 2011 English Heritage (EH) embarked on a new survey of the monument. Undertaken by the Greenhatch Group, a commercial survey company based near Derby, a combination of laser scanning and photogrammetric approaches were used to generate the required scale and detailed level of output required by English Heritage. This paper will describe the background to this project and its context within previous survey activities at this World Heritage Site. It will explain the data acquisition technology and processes undertaken on site, the datasets derived from post-processing and their filtering and analysis within both subsequent research projects. Alongside a description of how the data is currently being exploited and proposed future applications within the conservation and management of the site, it will finish by considering the impact of developing geospatial imaging technologies.

  2. Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery.

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    Robert Kalescky

    2016-04-01

    Full Text Available Intra-protein information is transmitted over distances via allosteric processes. This ubiquitous protein process allows for protein function changes due to ligand binding events. Understanding protein allostery is essential to understanding protein functions. In this study, allostery in the second PDZ domain (PDZ2 in the human PTP1E protein is examined as model system to advance a recently developed rigid residue scan method combining with configurational entropy calculation and principal component analysis. The contributions from individual residues to whole-protein dynamics and allostery were systematically assessed via rigid body simulations of both unbound and ligand-bound states of the protein. The entropic contributions of individual residues to whole-protein dynamics were evaluated based on covariance-based correlation analysis of all simulations. The changes of overall protein entropy when individual residues being held rigid support that the rigidity/flexibility equilibrium in protein structure is governed by the La Châtelier's principle of chemical equilibrium. Key residues of PDZ2 allostery were identified with good agreement with NMR studies of the same protein bound to the same peptide. On the other hand, the change of entropic contribution from each residue upon perturbation revealed intrinsic differences among all the residues. The quasi-harmonic and principal component analyses of simulations without rigid residue perturbation showed a coherent allosteric mode from unbound and bound states, respectively. The projection of simulations with rigid residue perturbation onto coherent allosteric modes demonstrated the intrinsic shifting of ensemble distributions supporting the population-shift theory of protein allostery. Overall, the study presented here provides a robust and systematic approach to estimate the contribution of individual residue internal motion to overall protein dynamics and allostery.

  3. Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery.

    Science.gov (United States)

    Kalescky, Robert; Zhou, Hongyu; Liu, Jin; Tao, Peng

    2016-04-01

    Intra-protein information is transmitted over distances via allosteric processes. This ubiquitous protein process allows for protein function changes due to ligand binding events. Understanding protein allostery is essential to understanding protein functions. In this study, allostery in the second PDZ domain (PDZ2) in the human PTP1E protein is examined as model system to advance a recently developed rigid residue scan method combining with configurational entropy calculation and principal component analysis. The contributions from individual residues to whole-protein dynamics and allostery were systematically assessed via rigid body simulations of both unbound and ligand-bound states of the protein. The entropic contributions of individual residues to whole-protein dynamics were evaluated based on covariance-based correlation analysis of all simulations. The changes of overall protein entropy when individual residues being held rigid support that the rigidity/flexibility equilibrium in protein structure is governed by the La Châtelier's principle of chemical equilibrium. Key residues of PDZ2 allostery were identified with good agreement with NMR studies of the same protein bound to the same peptide. On the other hand, the change of entropic contribution from each residue upon perturbation revealed intrinsic differences among all the residues. The quasi-harmonic and principal component analyses of simulations without rigid residue perturbation showed a coherent allosteric mode from unbound and bound states, respectively. The projection of simulations with rigid residue perturbation onto coherent allosteric modes demonstrated the intrinsic shifting of ensemble distributions supporting the population-shift theory of protein allostery. Overall, the study presented here provides a robust and systematic approach to estimate the contribution of individual residue internal motion to overall protein dynamics and allostery. PMID:27115535

  4. Species-scanning mutagenesis of the serotonin transporter reveals residues essential in selective, high-affinity recognition of antidepressants

    DEFF Research Database (Denmark)

    Mortensen, O V; Kristensen, A S; Wiborg, O

    2001-01-01

    )tropane, or for 3,4-methylenedioxymethamphetamine (MDMA). Analysis of six hSERT/bSERT chimeras and subsequent species-scanning mutagenesis of each isoform revealed methionine-180, tyrosine-495, and phenylalanine-513 to be responsible for the increase in citalopram and paroxetine potencies at hSERT and methionine...

  5. Tension zones of deep-seated rockslides revealed by thermal anomalies and airborne laser scan data

    Science.gov (United States)

    Baroň, Ivo; Bečkovský, David; Gajdošík, Juraj; Opálka, Filip; Plan, Lukas; Winkler, Gerhard

    2015-04-01

    Open cracks, tension fractures and crevice caves are important diagnostic features of gravitationally deformed slopes. When the cracks on the upper part of the slope open to the ground surface, they transfer relatively warm and buoyant air from the underground in cold seasons and thus could be detected by the infrared thermography (IRT) as warmer anomalies. Here we present two IRT surveys of deep-seated rockslides in Austria and the Czech Republic. We used thermal imaging cameras Flir and Optris, manipulated manually from the ground surface and also from unmanned aerial vehicle and piloted ultralight-plane platforms. The surveys were conducted during cold days of winter 2014/2015 and early in the morning to avoid the negative effect of direct sunshine. The first study site is the Bad Fischau rockslide in the southern part of the Vienna Basin (Austria). It was firstly identified by the morphostructural analysis of 1-m digital terrain model from the airborne laser scan data. The rockslide is superimposed on, and closely related to the active marginal faults of the Vienna basin, which is a pull apart structure. There is the 80-m-deep Eisenstein Show Cave situated in the southern lateral margin of the rockslide. The cave was originally considered to be purely of hydrothermal (hypogene) karstification; however its specific morphology and position within the detachment zone of the rockslide suggests its relation to gravitational slope-failure. The IRT survey revealed the Eisenstein Cave at the ground surface and also several other open cracks and possible cleft caves along the margins, headscarp, and also within the body of the rockslide. The second surveyed site was the Kněhyně rockslide in the flysch belt of the Outer Western Carpathians in the eastern Czech Republic. This deep-seated translational rockslide formed about eight known pseudokarst crevice caves, which reach up to 57 m in depth. The IRT survey recognized several warm anomalies indicating very deep

  6. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits. PMID:27490364

  7. Timelapse scanning reveals spatial variation in tomato (Solanum lycopersicum L.) root elongation rates during partial waterlogging

    DEFF Research Database (Denmark)

    Dresbøll, Dorte Bodin; Thorup-Kristensen, Kristian; McKenzie, Blair M.;

    2013-01-01

    by increasing elongation rates. Methods Tomato plants (Solanum lycopersicum L.) were grown in peat in root chambers (300 × 215 × 6 mm) with a transparent front. Root chambers were maintained in flatbed scanners tilted at 30° to vertical and scanned every 3 h before, during and after waterlogging the lower layer...

  8. Variables associated with environmental scanning among clinicians at substance abuse treatment clinics

    OpenAIRE

    Koch, Alison L; Arfken, Cynthia L.; Dickson, Marcus W.; Elizabeth Agius; Mitchelson, Jacqueline K.

    2005-01-01

    Introduction. Environmental scanning, as a component of absorptive capacity, has been shown to be associated with increased use of innovative treatment techniques at substance abuse treatment programmes. As the transfer of innovative, evidence-based treatment techniques from research to practice is gaining attention, we aimed to identify variables associated with higher levels of environmental scanning among substance abuse treatment clinicians. Method. A cross-sectional survey was administ...

  9. Use of Bone Scan During Initial Prostate Cancer Workup, Downstream Procedures, and Associated Medicare Costs

    Energy Technology Data Exchange (ETDEWEB)

    Falchook, Aaron D. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Salloum, Ramzi G. [Department of Health Services Policy and Management, University of South Carolina, Columbia, South Carolina (United States); Hendrix, Laura H. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Chen, Ronald C., E-mail: ronald_chen@med.unc.edu [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States)

    2014-06-01

    Purpose: For patients with a high likelihood of having metastatic disease (high-risk prostate cancer), bone scan is the standard, guideline-recommended test to look for bony metastasis. We quantified the use of bone scans and downstream procedures, along with associated costs, in patients with high-risk prostate cancer, and their use in low- and intermediate-risk patients for whom these tests are not recommended. Methods and Materials: Patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason score, and clinical T stage were used to define D'Amico risk categories. We report use of bone scans from the date of diagnosis to the earlier of treatment or 6 months. In patients who underwent bone scans, we report use of bone-specific x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and bone biopsy within 3 months after bone scan. Costs were estimated using 2012 Medicare reimbursement rates. Results: In all, 31% and 48% of patients with apparent low- and intermediate-risk prostate cancer underwent a bone scan; of these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone biopsies were uncommon. Overall, <1% of low- and intermediate-risk patients were found to have metastatic disease. The annual estimated Medicare cost for bone scans and downstream procedures was $11,300,000 for low- and intermediate-risk patients. For patients with apparent high-risk disease, only 62% received a bone scan, of whom 14% were found to have metastasis. Conclusions: There is overuse of bone scans in patients with low- and intermediate-risk prostate cancers, which is unlikely to yield clinically actionable information and results in a potential Medicare waste. However, there is underuse of bone scans in high-risk patients for whom metastasis is likely.

  10. Wigner and Kondo physics in quantum point contacts revealed by scanning gate microscopy

    OpenAIRE

    Brun, B; Martins, F.; Faniel, S.; Hackens, B.; Bachelier, G.; Cavanna, A.; Ulysse, C.; Ouerghi, A.; Gennser, U.; Mailly, D.; S. Huant; Bayot, V.; Sanquer, M.; Sellier, H.

    2013-01-01

    Quantum point contacts exhibit mysterious conductance anomalies in addition to well known conductance plateaus at multiples of 2e^2/h. These 0.7 and zero-bias anomalies have been intensively studied, but their microscopic origin in terms of many-body effects is still highly debated. Here we use the charged tip of a scanning gate microscope to tune in situ the electrostatic potential of the point contact. While sweeping the tip distance, we observe repetitive splittings of the zero-bias anomal...

  11. Roller Coaster Scanning reveals spontaneous triggering of dendritic spikes in CA1 interneurons.

    Science.gov (United States)

    Katona, Gergely; Kaszás, Attila; Turi, Gergely F; Hájos, Norbert; Tamás, Gábor; Vizi, E Sylvester; Rózsa, Balázs

    2011-02-01

    Inhibitory interneurons are considered to be the controlling units of neural networks, despite their sparse number and unique morphological characteristics compared with excitatory pyramidal cells. Although pyramidal cell dendrites have been shown to display local regenerative events--dendritic spikes (dSpikes)--evoked by artificially patterned stimulation of synaptic inputs, no such studies exist for interneurons or for spontaneous events. In addition, imaging techniques have yet to attain the required spatial and temporal resolution for the detection of spontaneously occurring events that trigger dSpikes. Here we describe a high-resolution 3D two-photon laser scanning method (Roller Coaster Scanning) capable of imaging long dendritic segments resolving individual spines and inputs with a temporal resolution of a few milliseconds. By using this technique, we found that local, NMDA receptor-dependent dSpikes can be observed in hippocampal CA1 stratum radiatum interneurons during spontaneous network activities in vitro. These NMDA spikes appear when approximately 10 spatially clustered inputs arrive synchronously and trigger supralinear integration in dynamic interaction zones. In contrast to the one-to-one relationship between computational subunits and dendritic branches described in pyramidal cells, here we show that interneurons have relatively small (∼14 μm) sliding interaction zones. Our data suggest a unique principle as to how interneurons integrate synaptic information by local dSpikes. PMID:21224413

  12. Variables associated with environmental scanning among clinicians at substance abuse treatment clinics

    Directory of Open Access Journals (Sweden)

    Alison L. Koch

    2005-01-01

    Full Text Available Introduction. Environmental scanning, as a component of absorptive capacity, has been shown to be associated with increased use of innovative treatment techniques at substance abuse treatment programmes. As the transfer of innovative, evidence-based treatment techniques from research to practice is gaining attention, we aimed to identify variables associated with higher levels of environmental scanning among substance abuse treatment clinicians. Method. A cross-sectional survey was administered to 162 clinicians at 15 substance abuse treatment clinics in Michigan. Measures: Environmental scanning was measured by frequency of use of the Internet, journals, seminars or conferences, and people at other treatment clinics for new substance abuse treatment information. Clinicians were asked for their perceptions of their clinic’s openness to new treatment techniques and support for acquiring new information, access to and satisfaction with information sources at work, as well as if they feel it is their job to keep up to date with current treatment research. Additional measures included whether they intended to quit their jobs and whether they were emotionally drained from work. Findings: We found positive associations between environmental scanning and perceived clinic support for acquiring new information, perceived clinic openness to new treatment techniques, access to e-mail and Internet at work, and satisfaction with resources. Turnover intention and being emotionally drained were negatively associated with environmental scanning. Conclusion. : Individual and organizational level variables were found to be associated with higher levels of environmental scanning activity. Although the causal directions of these associations are not known, the findings suggest ways to increase environmental scanning among clinicians.

  13. Magnetoelectric coupling in supercoducting Sr2 VO3 FeAs revealed by scanning tunneling microscopy

    Science.gov (United States)

    Choi, Seokhwan; Choi, Hyunwoo; Lee, Hyun-Jung; Jung, Jin-Oh; Son, Donghyun; Kim, Jun Sung; Ok, Jong Mok; Lee, Jhinhwan

    2015-03-01

    Sr2VO3FeAs is known to exhibit high Tc (~ 37K) superconductivity with no magnetic ordering in the FeAs layer but weak magnetic moment in the V sublattice. An angle resolved photo emission spectroscopy also shows the non-trivial Fermi surface due to the V 3d orbitals. We have studied on Sr2VO3FeAs single crystal using spectroscopic imaging scanning tunneling microscopy (SI-STM) with variable temperature from 4.6K to 100K, and magnetic field up to 7T. Our results show that Sr2VO3FeAs has charge density wave (CDW) modulation in the V sublattice with the same wave vector observed in the neutron scattering experiment. The modulation strength is reduced with applying magnetic field. An electronic Fermi surface with largest V 3d character shows suppressed superconductivity possibly due to strong V-site correlation. However the multi-orbital nature of FeAs allows overall unsuppressed superconductivity at high Tc.

  14. Wigner and Kondo physics in quantum point contacts revealed by scanning gate microscopy

    Science.gov (United States)

    Brun, B.; Martins, F.; Faniel, S.; Hackens, B.; Bachelier, G.; Cavanna, A.; Ulysse, C.; Ouerghi, A.; Gennser, U.; Mailly, D.; Huant, S.; Bayot, V.; Sanquer, M.; Sellier, H.

    2014-06-01

    Quantum point contacts exhibit mysterious conductance anomalies in addition to well-known conductance plateaus at multiples of 2e2/h. These 0.7 and zero-bias anomalies have been intensively studied, but their microscopic origin in terms of many-body effects is still highly debated. Here we use the charged tip of a scanning gate microscope to tune in situ the electrostatic potential of the point contact. While sweeping the tip distance, we observe repetitive splittings of the zero-bias anomaly, correlated with simultaneous appearances of the 0.7 anomaly. We interpret this behaviour in terms of alternating equilibrium and non-equilibrium Kondo screenings of different spin states localized in the channel. These alternating Kondo effects point towards the presence of a Wigner crystal containing several charges with different parities. Indeed, simulations show that the electron density in the channel is low enough to reach one-dimensional Wigner crystallization over a size controlled by the tip position.

  15. Cysteine scanning reveals minor local rearrangements of the horizontal helix of respiratory complex I.

    Science.gov (United States)

    Steimle, Stefan; Schnick, Christian; Burger, Eva-Maria; Nuber, Franziska; Krämer, Dorothée; Dawitz, Hannah; Brander, Sofia; Matlosz, Bartlomiej; Schäfer, Jacob; Maurer, Katharina; Glessner, Udo; Friedrich, Thorsten

    2015-10-01

    The NADH:ubiquinone oxidoreductase, respiratory complex I, couples electron transfer from NADH to ubiquinone with the translocation of protons across the membrane. The complex consists of a peripheral arm catalyzing the redox reaction and a membrane arm catalyzing proton translocation. The membrane arm is almost completely aligned by a 110 Å unique horizontal helix that is discussed to transmit conformational changes induced by the redox reaction in a piston-like movement to the membrane arm driving proton translocation. Here, we analyzed such a proposed movement by cysteine-scanning of the helix of the Escherichia coli complex I. The accessibility of engineered cysteine residues and the flexibility of individual positions were determined by labeling the preparations with a fluorescent marker and a spin-probe, respectively, in the oxidized and reduced states. The differences in fluorescence labeling and the rotational flexibility of the spin probe between both redox states indicate only slight conformational changes at distinct positions of the helix but not a large movement. PMID:26115017

  16. Clinical study on eating disorders. Brain atrophy revealed by cranial computed tomography scans

    Energy Technology Data Exchange (ETDEWEB)

    Nishiwaki, Shinichi

    1988-06-01

    Cranial computed tomography (CT) scans were reviewed in 34 patients with anorexia nervosa (Group I) and 22 with bulimia (Group II) to elucidate the cause and pathological significance of morphological brain alterations. The findings were compared with those from 47 normal women. The incidence of brain atrophy was significantly higher in Group I (17/34, 50%) and Group II (11/22, 50%) than the control group (3/47, 6%). In Group I, there was a significant increase in the left septum-caudate distance, the maximum width of interhemispheric fissure, the width of the both-side Sylvian fissures adjacent to the skull, and the maximum width of the third ventricle. A significant increase in the maximum width of interhemispheric fissure and the width of the left-side Sylvian fissure adjacent to the skull were noted as well in Group II. Ventricular brain ratios were significantly higher in Groups I and II than the control group (6.76 and 7.29 vs 4.55). Brain atrophy did not correlate with age, body weight, malnutrition, eating behavior, depression, thyroid function, EEG findings, or intelligence scale. In Group I, serum cortisol levels after the administration of dexamethasone were correlated with ventricular brain ratio. (Namekawa, K) 51 refs.

  17. Chromosome 21 Scan in Down Syndrome Reveals DSCAM as a Predisposing Locus in Hirschsprung Disease

    NARCIS (Netherlands)

    A-S. Jannot (Anne-Sophie); A. Pelet (Anna); A. Henrion-Caude (Alexandra); A. Chaoui (Asma); M. Masse-Morel (Marine); S. Arnold (Stacey); D. Sanlaville (Damien); I. Ceccherini (Isabella); S. Borrego (Salud); R.M.W. Hofstra (Robert); A. Munnich (Arnold); N. Bondurand (Nadège); A. Chakravarti (Aravinda); F. Clerget-Darpoux (Françoise); J. Amiel (Jeanne); S. Lyonnet (Stanislas)

    2013-01-01

    textabstractHirschsprung disease (HSCR) genetics is a paradigm for the study and understanding of multigenic disorders. Association between Down syndrome and HSCR suggests that genetic factors that predispose to HSCR map to chromosome 21. To identify these additional factors, we performed a dose-dep

  18. Myelin organization in the nodal, paranodal, and juxtaparanodal regions revealed by scanning x-ray microdiffraction.

    Science.gov (United States)

    Inouye, Hideyo; Liu, Jiliang; Makowski, Lee; Palmisano, Marilena; Burghammer, Manfred; Riekel, Christian; Kirschner, Daniel A

    2014-01-01

    X-ray diffraction has provided extensive information about the arrangement of lipids and proteins in multilamellar myelin. This information has been limited to the abundant inter-nodal regions of the sheath because these regions dominate the scattering when x-ray beams of 100 µm diameter or more are used. Here, we used a 1 µm beam, raster-scanned across a single nerve fiber, to obtain detailed information about the molecular architecture in the nodal, paranodal, and juxtaparanodal regions. Orientation of the lamellar membrane stacks and membrane periodicity varied spatially. In the juxtaparanode-internode, 198-202 Å-period membrane arrays oriented normal to the nerve fiber axis predominated, whereas in the paranode-node, 205-208 Å-period arrays oriented along the fiber direction predominated. In parts of the sheath distal to the node, multiple sets of lamellar reflections were observed at angles to one another, suggesting that the myelin multilayers are deformed at the Schmidt-Lanterman incisures. The calculated electron density of myelin in the different regions exhibited membrane bilayer profiles with varied electron densities at the polar head groups, likely due to different amounts of major myelin proteins (P0 glycoprotein and myelin basic protein). Scattering from the center of the nerve fibers, where the x-rays are incident en face (perpendicular) to the membrane planes, provided information about the lateral distribution of protein. By underscoring the heterogeneity of membrane packing, microdiffraction analysis suggests a powerful new strategy for understanding the underlying molecular foundation of a broad spectrum of myelinopathies dependent on local specializations of myelin structure in both the PNS and CNS.

  19. Scanning electron microscopy reveals severe external root resorption in the large periapical lesion.

    Science.gov (United States)

    Ookubo, Kensuke; Ookubo, Atsushi; Tsujimoto, Masaki; Sugimoto, Kouji; Yamada, Shizuka; Hayashi, Yoshihiko

    2016-06-01

    The present study was designed to investigate the relationships between clinicopathological findings and the resorptive conditions of root apices of teeth with periodontitis. The samples included 21 root apices with large periapical radiolucent lesions. The preoperative computed tomography (CT) and intraoperative findings were correlated with the presence, extension, and the progression pattern of periapical resorption using a scanning electron microscope. The subjects' age, gender, chief complaint, type of tooth, percussion test results, size of periapical lesion using CT, and intraoperative findings were recorded. All apicoectomies were performed under an operative microscope for endodontic microsurgery. A significant large size was observed in cystic lesions compared with granulomatous lesions. The cementum surface at the periphery of the lesion was covered with globular structures (2-3 μm in diameter). Cementum resorption started as small defect formations at the surface. As the defect formation progressed, a lamellar structure appeared at the resorption area, and the size of globular structures became smaller than that of globules at the surface. Further resorption produced typical lacuna formation, which was particularly observed in fracture cases. The most morphologically severe destructive pattern of dentin resorption was observed in large cystic lesions. This study is the first report to elucidate the relationships between three clinical types of undesirable periapical lesions: (1) undertreatment, (2) periapical fracture, (3) macro-level resorption, and the microstructure of external root resorption including from small defects at the cementum surface to a significant destructive pattern inside the dentin. Microsc. Res. Tech. 79:495-500, 2016. © 2016 Wiley Periodicals, Inc. PMID:26957368

  20. ACCURATE 3D SCANNING OF DAMAGED ANCIENT GREEK INSCRIPTIONS FOR REVEALING WEATHERED LETTERS

    Directory of Open Access Journals (Sweden)

    A. I. Papadaki

    2015-02-01

    Full Text Available In this paper two non-invasive non-destructive alternative techniques to the traditional and invasive technique of squeezes are presented alongside with specialized developed processing methods, aiming to help the epigraphists to reveal and analyse weathered letters in ancient Greek inscriptions carved in masonry or marble. The resulting 3D model would serve as a detailed basis for the epigraphists to try to decipher the inscription. The data were collected by using a Structured Light scanner. The creation of the final accurate three dimensional model is a complicated procedure requiring large computation cost and human effort. It includes the collection of geometric data in limited space and time, the creation of the surface, the noise filtering and the merging of individual surfaces. The use of structured light scanners is time consuming and requires costly hardware and software. Therefore an alternative methodology for collecting 3D data of the inscriptions was also implemented for reasons of comparison. Hence, image sequences from varying distances were collected using a calibrated DSLR camera aiming to reconstruct the 3D scene through SfM techniques in order to evaluate the efficiency and the level of precision and detail of the obtained reconstructed inscriptions. Problems in the acquisition processes as well as difficulties in the alignment step and mesh optimization are also encountered. A meta-processing framework is proposed and analysed. Finally, the results of processing and analysis and the different 3D models are critically inspected and then evaluated by a specialist in terms of accuracy, quality and detail of the model and the capability of revealing damaged and ”hidden” letters.

  1. Genome-wide association scan for five major dimensions of personality

    OpenAIRE

    Terracciano, Antonio; Sanna, Serena; Uda, Manuela; Deiana, Barbara; Usala, Gianluca; Busonero, Fabio; Maschio, Andrea; Scally, Matthew; Patriciu, Nicholas; Chen, Wei-Min; Distel, Marijn A.; Slagboom, Eline P.; Boomsma, Dorret I.; Villafuerte, Sandra; Śliwerska, Elżbieta

    2008-01-01

    Personality traits are summarized by five broad dimensions with pervasive influences on major life outcomes, strong links to psychiatric disorders, and clear heritable components. To identify genetic variants associated with each of the five dimensions of personality we performed a genome wide association (GWA) scan of 3,972 individuals from a genetically isolated population within Sardinia, Italy. Based on analyses of 362,129 single nucleotide polymorphisms (SNPs) we found several strong sig...

  2. Progressive Dyspnea Associated with a Crazy-Paving Appearance on a Chest Computed Tomography Scan

    Directory of Open Access Journals (Sweden)

    Nimrod Maimon

    2006-01-01

    Full Text Available A ‘crazy-paving’ appearance of the lungs on computed tomography scanning of the chest was first described nearly 20 years ago in patients with pulmonary alveolar proteinosis, and was thought to be characteristic of this condition. However, this pattern has subsequently been reported in a variety of pulmonary diseases and is now considered to be nonspecific. The present report describes a case of a 74-year-old man in whom congestive heart failure presented with a crazy-paving appearance of the lungs on a chest computed tomography scan. This uncommon association illustrates the importance of the correlation of clinical and radiographic information.

  3. Scanning STED-FCS reveals spatiotemporal heterogeneity of lipid interaction in the plasma membrane of living cells

    Science.gov (United States)

    Honigmann, Alf; Mueller, Veronika; Ta, Haisen; Schoenle, Andreas; Sezgin, Erdinc; Hell, Stefan W.; Eggeling, Christian

    2014-11-01

    The interaction of lipids and proteins plays an important role in plasma membrane bioactivity, and much can be learned from their diffusion characteristics. Here we present the combination of super-resolution STED microscopy with scanning fluorescence correlation spectroscopy (scanning STED-FCS, sSTED-FCS) to characterize the spatial and temporal heterogeneity of lipid interactions. sSTED-FCS reveals transient molecular interaction hotspots for a fluorescent sphingolipid analogue. The interaction sites are smaller than 80 nm in diameter and lipids are transiently trapped for several milliseconds in these areas. In comparison, newly developed fluorescent phospholipid and cholesterol analogues with improved phase-partitioning properties show more homogenous diffusion, independent of the preference for liquid-ordered or disordered membrane environments. Our results do not support the presence of nanodomains based on lipid-phase separation in the basal membrane of our cultured nonstimulated cells, and show that alternative interactions are responsible for the strong local trapping of our sphingolipid analogue.

  4. Dental silver tooth fillings: A source of mercury exposure revealed by whole-body image scan and tissue analysis

    International Nuclear Information System (INIS)

    Mercury (Hg) vapor is released from dental silver tooth fillings into human mouth air after chewing, but its possible uptake routes and distribution among body tissues are unknown. This investigation demonstrates that when radioactive 203Hg is mixed with dental Hg/silver fillings (amalgam) and placed in teeth of adult sheep, the isotope will appear in various organs and tissues within 29 days. Evidence of Hg uptake, as determined by whole-body scanning and measurement of isotope in specific tissues, revealed three uptake sites: lung, gastrointestinal, and jaw tissue absorption. Once absorbed, high concentrations of dental amalgam Hg rapidly localize in kidneys and liver. Results are discussed in view of potential health consequences from long-term exposure to Hg from this dental material

  5. Dental silver tooth fillings: A source of mercury exposure revealed by whole-body image scan and tissue analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, L.J.; Kloiber, R.; Vimy, M.J.; Takahashi, Y.; Lorscheider, F.L. (Univ. of Calgary, Alberta (Canada))

    1989-12-01

    Mercury (Hg) vapor is released from dental silver tooth fillings into human mouth air after chewing, but its possible uptake routes and distribution among body tissues are unknown. This investigation demonstrates that when radioactive 203Hg is mixed with dental Hg/silver fillings (amalgam) and placed in teeth of adult sheep, the isotope will appear in various organs and tissues within 29 days. Evidence of Hg uptake, as determined by whole-body scanning and measurement of isotope in specific tissues, revealed three uptake sites: lung, gastrointestinal, and jaw tissue absorption. Once absorbed, high concentrations of dental amalgam Hg rapidly localize in kidneys and liver. Results are discussed in view of potential health consequences from long-term exposure to Hg from this dental material.

  6. BDNFVal66Met and 5-HTTLPR genotype are each associated with visual scanning patterns of faces in young children

    Directory of Open Access Journals (Sweden)

    Antonios I. Christou

    2015-07-01

    Full Text Available Previous studies have documented both neuroplasticity-related BDNF Val66Met and emotion regulation-related 5-HTTLPR polymorphisms as genetic variants that contribute to the processing of emotions from faces. More specifically, research has shown the BDNF Met allele and the 5-HTTLPR Short allele to be associated with mechanisms of negative affectivity that relate to susceptibility for psychopathology. We examined visual scanning pathways in response to angry, happy, and neutral faces in relation to BDNF Val66Met and 5-HTTLPR genotyping in 49 children aged 4- to 7-years. Analyses revealed that variations in the visual processing of facial expressions of anger interacted with BDNF Val66Met genotype, such that children who carried at least one low neuroplasticity Met allele exhibited a vigilance-avoidance pattern of visual scanning compared to homozygotes for the high neuroplasticity Val allele. In a separate investigation of eye gaze towards the eye versus mouth regions of neutral faces, we observed that short allele 5-HTTLPR carriers exhibited reduced looking at the eye region compared with those with the higher serotonin uptake Long allele. Together, these findings suggest that genetic mechanisms early in life may influence the establishment of patterns of visual scanning of environmental stressors, which in conjunction with other factors such as negative life events may lead to psychological difficulties and disorders in the later adolescent and adult years.

  7. Potential cancer risk associated to CT scan. State of the art of epidemiological studies

    Energy Technology Data Exchange (ETDEWEB)

    Bernier, Marie-Odile; Baysson, Neige Joumy Helene; Jacob, Sophie; Laurier, Dominique [Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses (France). Lab. of Epidemiology

    2013-07-01

    Introduction: The increasing use of computed tomography (CT) scans in paediatric population raises the question of a possible health impact of ionizing radiation exposure associated with CT scans. Material and methods: Two large cohort studies have been recently published that assessed the risk of cancer related to CT examinations of children and young adults. Methodology and results of these studies are presented. Results: The UK cohort included over 176,000 young people, who underwent one or more CT scans between 1985 and 2002. The Australian study compared the risk of cancer and leukaemia in a population of 680,000 young people exposed to CT scans between 1985 and 2005 to non-exposed similar age people. Both studies showed a significant dose-response relation between exposure to CT and leukaemia or brain tumour risks. These results are consistent with predictions from A-bomb survivors' data. However, uncertainties in dosimetric estimation and potential bias linked to underlying medical conditions should be considered. Conclusion and perspectives: Further studies with more accurate dosimetry and assessment of potential bias and uncertainties are needed. Ongoing national studies and the European collaborative EPI-CT study will help to better understand the relation between low level radiation exposure and cancer and to support recommendations for patients'' radiation protection. (orig.)

  8. Potential cancer risk associated to CT scan. State of the art of epidemiological studies

    International Nuclear Information System (INIS)

    Introduction: The increasing use of computed tomography (CT) scans in paediatric population raises the question of a possible health impact of ionizing radiation exposure associated with CT scans. Material and methods: Two large cohort studies have been recently published that assessed the risk of cancer related to CT examinations of children and young adults. Methodology and results of these studies are presented. Results: The UK cohort included over 176,000 young people, who underwent one or more CT scans between 1985 and 2002. The Australian study compared the risk of cancer and leukaemia in a population of 680,000 young people exposed to CT scans between 1985 and 2005 to non-exposed similar age people. Both studies showed a significant dose-response relation between exposure to CT and leukaemia or brain tumour risks. These results are consistent with predictions from A-bomb survivors' data. However, uncertainties in dosimetric estimation and potential bias linked to underlying medical conditions should be considered. Conclusion and perspectives: Further studies with more accurate dosimetry and assessment of potential bias and uncertainties are needed. Ongoing national studies and the European collaborative EPI-CT study will help to better understand the relation between low level radiation exposure and cancer and to support recommendations for patients'' radiation protection. (orig.)

  9. A Unique Case of Pulmonary Hyalinizing Granuloma Associated With FDG-avid PET Scan and Deep Venous Thrombosis.

    Science.gov (United States)

    Khalid, Imran; Stone, Chad; Kvale, Paul

    2009-04-01

    An 83-year-old obese woman with a 60-pack-year smoking history was referred for evaluation of an abnormal chest radiograph [chest x-ray (CXR)]. Her past medical history was significant for recurrent deep venous thrombosis without any predisposing factors. CXR showed a large mass in the right mid lung and another nodule at the right apex, highly suspicious for a neoplastic process. These were not present on a CXR from 2 years earlier. An fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scan revealed that all lesions were strongly FDG-avid. Six CT-guided core-needle lung biopsy specimens were obtained from the lung mass and all contained dense, lamellar, or "ropy" keloid-like collagen bundles arranged in a haphazard pattern. The biopsy specimens lacked significant necrosis and granulomas. Congo red stain with polarization was also negative for amyloid. The diagnosis of pulmonary hyalinizing granuloma (PHG) was made. A complete hypercoagulable workup was performed but no underlying abnormalities were found, including a negative lupus anticoagulant and malignancy workup. The patient was maintained on warfarin and followed with serial CT scans for 1 year, with spontaneous regression in the lung mass. The case is unique as it is the first case that reports an association of PHG with recurrent deep venous thrombosis in the absence of autoimmune or procoagulant factors and emphasizes the need for life-long anticoagulation in such scenarios. Also, we report the FDG-avid PET scan findings here that are novel for this disease in adults and add PHG to the list of diseases causing false-positive PET scans when malignancy is suspected. PMID:23168510

  10. Structure, mechanics, and binding mode heterogeneity of LEDGF/p75-DNA nucleoprotein complexes revealed by scanning force microscopy

    Science.gov (United States)

    Vanderlinden, Willem; Lipfert, Jan; Demeulemeester, Jonas; Debyser, Zeger; de Feyter, Steven

    2014-04-01

    LEDGF/p75 is a transcriptional coactivator implicated in the pathogenesis of AIDS and leukemia. In these contexts, LEDGF/p75 acts as a cofactor by tethering protein cargo to transcriptionally active regions in the human genome. Our study - based on scanning force microscopy (SFM) imaging - is the first to provide structural information on the interaction of LEDGF/p75 with DNA. Two novel approaches that allow obtaining insights into the DNA conformation inside nucleoprotein complexes revealed (1) that LEDGF/p75 can bind at least in three different binding modes, (2) how DNA topology and protein dimerization affect these binding modes, and (3) geometrical and mechanical aspects of the nucleoprotein complexes. These structural and mechanical details will help us to better understand the cellular mechanisms of LEDGF/p75 as a transcriptional coactivator and as a cofactor in disease.LEDGF/p75 is a transcriptional coactivator implicated in the pathogenesis of AIDS and leukemia. In these contexts, LEDGF/p75 acts as a cofactor by tethering protein cargo to transcriptionally active regions in the human genome. Our study - based on scanning force microscopy (SFM) imaging - is the first to provide structural information on the interaction of LEDGF/p75 with DNA. Two novel approaches that allow obtaining insights into the DNA conformation inside nucleoprotein complexes revealed (1) that LEDGF/p75 can bind at least in three different binding modes, (2) how DNA topology and protein dimerization affect these binding modes, and (3) geometrical and mechanical aspects of the nucleoprotein complexes. These structural and mechanical details will help us to better understand the cellular mechanisms of LEDGF/p75 as a transcriptional coactivator and as a cofactor in disease. Electronic supplementary information (ESI) available: SFM topographs of phage lambda DNA in situ, in the absence and presence of LEDGF/p75; model-independent tests for DNA chain equilibration in 2D; SFM topographs of

  11. Function of cancer associated genes revealed by modern univariate and multivariate association tests.

    Directory of Open Access Journals (Sweden)

    Malka Gorfine

    Full Text Available Copy number variation (CNV plays a role in pathogenesis of many human diseases, especially cancer. Several whole genome CNV association studies have been performed for the purpose of identifying cancer associated CNVs. Here we undertook a novel approach to whole genome CNV analysis, with the goal being identification of associations between CNV of different genes (CNV-CNV across 60 human cancer cell lines. We hypothesize that these associations point to the roles of the associated genes in cancer, and can be indicators of their position in gene networks of cancer-driving processes. Recent studies show that gene associations are often non-linear and non-monotone. In order to obtain a more complete picture of all CNV associations, we performed omnibus univariate analysis by utilizing dCov, MIC, and HHG association tests, which are capable of detecting any type of association, including non-monotone relationships. For comparison we used Spearman and Pearson association tests, which detect only linear or monotone relationships. Application of dCov, MIC and HHG tests resulted in identification of twice as many associations compared to those found by Spearman and Pearson alone. Interestingly, most of the new associations were detected by the HHG test. Next, we utilized dCov's and HHG's ability to perform multivariate analysis. We tested for association between genes of unknown function and known cancer-related pathways. Our results indicate that multivariate analysis is much more effective than univariate analysis for the purpose of ascribing biological roles to genes of unknown function. We conclude that a combination of multivariate and univariate omnibus association tests can reveal significant information about gene networks of disease-driving processes. These methods can be applied to any large gene or pathway dataset, allowing more comprehensive analysis of biological processes.

  12. Nuclear lamina—like filaments and nuclear matrix in allium cepa as revealed by scanning electron microscopy

    Institute of Scientific and Technical Information of China (English)

    HAOSHUI

    1992-01-01

    In this study,freeze-fractured specimens of allium cepa root tip meristems were examined under the scanning electron microscope(SEM),This technique permitted the visualization of the outer membrane of the nuclear envelope with nuclear pore complexes and polyribosomes.Some of the cell nuclei prepared with this procedure had fissures of various widths on their nuclear envelopes through which the nuclear lamina-like filaments(LLF) undernearth the nucleoplasmic side of the envelopes were clearly visible.The diameters of these filaments veried between 25 and 125nm.Many of the LLFs showed granular thickenings at places,and were attached to the inner surface of nuclear envelope in some regions .Similar LLFs were also seen at the peripheries of the freeze-fractured faces of nuclei.Meanwhile,the spatial relation between the nuclear matrix filaments(NMF) and other nuclear structures(nucleoli,chromation and peripheral lamina-like filaments) was revealed in these fractured preparations.In addition,the methods and techniques in studying the nuclear lamina morphology and the roles played by NMFs in activities of various nuclear sturctures were discessed in brief.

  13. Correlations between Photovoltaic Characteristics, Adsorption Number, and Regeneration Kinetics in Dye-Sensitized Solar Cells Revealed by Scanning Photocurrent Microscopy.

    Science.gov (United States)

    Mitsui, Masaaki; Kawano, Yuya; Mori, Kyosuke; Wakabayashi, Naoto

    2015-06-30

    Newly developed simultaneous scanning photocurrent and luminescence microscopy was applied to ruthenium-based dye-sensitized solar cells (DSCs) comprising a cover glass photoanode with a 100 nm thick TiO2 layer. Using this, we have investigated the lateral variations of several parameters of these DSCs under short-circuit conditions. Simultaneous measurement of photocurrent and luminescence images for the same area of the DSC demonstrated submicrometric lateral resolution of our photocurrent microscopy, which is approximately 10 times better than the resolution of photocurrent microscopy used in past studies. The photovoltaic parameters, such as short-circuit current density, open-circuit voltage, and charge-collection efficiency, were thus evaluated for local (or submicrometric) regions of the DSCs. Furthermore, the photocurrent saturation behavior of the DSCs was examined as a function of the excitation rate and analyzed on the basis of a three-state kinetic model. This protocol allowed for quantification of the dye-adsorption number and dye-regeneration rate constant for any local area of the DSCs. Consequently, the correlations between the dye adsorption number, photovoltaic parameters, and regeneration rate constant, which are difficult to address through examination of the entire cell, were revealed by the "zoom-in" approach utilizing this high-resolution photocurrent microscopy.

  14. Genome-Wide Scan for Adaptive Divergence and Association with Population-Specific Covariates.

    Science.gov (United States)

    Gautier, Mathieu

    2015-12-01

    In population genomics studies, accounting for the neutral covariance structure across population allele frequencies is critical to improve the robustness of genome-wide scan approaches. Elaborating on the BayEnv model, this study investigates several modeling extensions (i) to improve the estimation accuracy of the population covariance matrix and all the related measures, (ii) to identify significantly overly differentiated SNPs based on a calibration procedure of the XtX statistics, and (iii) to consider alternative covariate models for analyses of association with population-specific covariables. In particular, the auxiliary variable model allows one to deal with multiple testing issues and, providing the relative marker positions are available, to capture some linkage disequilibrium information. A comprehensive simulation study was carried out to evaluate the performances of these different models. Also, when compared in terms of power, robustness, and computational efficiency to five other state-of-the-art genome-scan methods (BayEnv2, BayScEnv, BayScan, flk, and lfmm), the proposed approaches proved highly effective. For illustration purposes, genotyping data on 18 French cattle breeds were analyzed, leading to the identification of 13 strong signatures of selection. Among these, four (surrounding the KITLG, KIT, EDN3, and ALB genes) contained SNPs strongly associated with the piebald coloration pattern while a fifth (surrounding PLAG1) could be associated to morphological differences across the populations. Finally, analysis of Pool-Seq data from 12 populations of Littorina saxatilis living in two different ecotypes illustrates how the proposed framework might help in addressing relevant ecological issues in nonmodel species. Overall, the proposed methods define a robust Bayesian framework to characterize adaptive genetic differentiation across populations. The BayPass program implementing the different models is available at http://www1.montpellier.inra.fr/CBGP/software/baypass/.

  15. Genome-Wide Scan for Adaptive Divergence and Association with Population-Specific Covariates.

    Science.gov (United States)

    Gautier, Mathieu

    2015-12-01

    In population genomics studies, accounting for the neutral covariance structure across population allele frequencies is critical to improve the robustness of genome-wide scan approaches. Elaborating on the BayEnv model, this study investigates several modeling extensions (i) to improve the estimation accuracy of the population covariance matrix and all the related measures, (ii) to identify significantly overly differentiated SNPs based on a calibration procedure of the XtX statistics, and (iii) to consider alternative covariate models for analyses of association with population-specific covariables. In particular, the auxiliary variable model allows one to deal with multiple testing issues and, providing the relative marker positions are available, to capture some linkage disequilibrium information. A comprehensive simulation study was carried out to evaluate the performances of these different models. Also, when compared in terms of power, robustness, and computational efficiency to five other state-of-the-art genome-scan methods (BayEnv2, BayScEnv, BayScan, flk, and lfmm), the proposed approaches proved highly effective. For illustration purposes, genotyping data on 18 French cattle breeds were analyzed, leading to the identification of 13 strong signatures of selection. Among these, four (surrounding the KITLG, KIT, EDN3, and ALB genes) contained SNPs strongly associated with the piebald coloration pattern while a fifth (surrounding PLAG1) could be associated to morphological differences across the populations. Finally, analysis of Pool-Seq data from 12 populations of Littorina saxatilis living in two different ecotypes illustrates how the proposed framework might help in addressing relevant ecological issues in nonmodel species. Overall, the proposed methods define a robust Bayesian framework to characterize adaptive genetic differentiation across populations. The BayPass program implementing the different models is available at http://www1.montpellier

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

    Science.gov (United States)

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

    2011-01-01

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

  17. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits.

    Directory of Open Access Journals (Sweden)

    Angelo Scuteri

    2007-07-01

    Full Text Available The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x10(-7, hip circumference (p = 3.4 x 10(-8, and weight (p = 9.1 x 10(-7. In Sardinia, homozygotes for the rare "G" allele of this SNP (minor allele frequency = 0.46 were 1.3 BMI units heavier than homozygotes for the common "A" allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6. Homozygotes for the rare "A" allele of this SNP (minor allele frequency = 0.12 were 1.8 BMI units heavier than homozygotes for the common "G" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496 and in Hispanic Americans (N = 839, we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001, weight (p = 0.001, and hip circumference (p = 0.0005. We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for

  18. The ultrastructure of pollen grain surface in allotetraploid petunia (Petunia hybrida hort. superbissima as revealed by scanning electron microscopy

    Directory of Open Access Journals (Sweden)

    S. Muszyński

    2015-05-01

    Full Text Available The ultrastructure of pollen grain surface in allotetraploid petunias was analyzed by scanning electron microscopy. The pollen grain wall is developed into characteristic pattern of convulations.

  19. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  20. Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression

    DEFF Research Database (Denmark)

    Tuikue Ndam, Nicaise; Bischoff, Emmanuel; Proux, Caroline;

    2008-01-01

    BACKGROUND: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances on ...

  1. Genomewide association scan of suicidal thoughts and behaviour in major depression.

    Directory of Open Access Journals (Sweden)

    Alexandra Schosser

    Full Text Available BACKGROUND: Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06. For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality. CONCLUSIONS/SIGNIFICANCE: This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further.

  2. The intrinsic defect structure of exfoliated MoS2 single layers revealed by Scanning Tunneling Microscopy

    Science.gov (United States)

    Vancsó, Péter; Magda, Gábor Zsolt; Pető, János; Noh, Ji-Young; Kim, Yong-Sung; Hwang, Chanyong; Biró, László P.; Tapasztó, Levente

    2016-01-01

    MoS2 single layers have recently emerged as strong competitors of graphene in electronic and optoelectronic device applications due to their intrinsic direct bandgap. However, transport measurements reveal the crucial role of defect-induced electronic states, pointing out the fundamental importance of characterizing their intrinsic defect structure. Transmission Electron Microscopy (TEM) is able to image atomic scale defects in MoS2 single layers, but the imaged defect structure is far from the one probed in the electronic devices, as the defect density and distribution are substantially altered during the TEM imaging. Here, we report that under special imaging conditions, STM measurements can fully resolve the native atomic scale defect structure of MoS2 single layers. Our STM investigations clearly resolve a high intrinsic concentration of individual sulfur atom vacancies, and experimentally identify the nature of the defect induced electronic mid-gap states, by combining topographic STM images with ab intio calculations. Experimental data on the intrinsic defect structure and the associated defect-bound electronic states that can be directly used for the interpretation of transport measurements are essential to fully understand the operation, reliability and performance limitations of realistic electronic devices based on MoS2 single layers. PMID:27445217

  3. Combinatorial Mismatch Scan (CMS for loci associated with dementia in the Amish

    Directory of Open Access Journals (Sweden)

    Vance Jeffery M

    2006-03-01

    Full Text Available Abstract Background Population heterogeneity may be a significant confounding factor hampering detection and verification of late onset Alzheimer's disease (LOAD susceptibility genes. The Amish communities located in Indiana and Ohio are relatively isolated populations that may have increased power to detect disease susceptibility genes. Methods We recently performed a genome scan of dementia in this population that detected several potential loci. However, analyses of these data are complicated by the highly consanguineous nature of these Amish pedigrees. Therefore we applied the Combinatorial Mismatch Scanning (CMS method that compares identity by state (IBS (under the presumption of identity by descent (IBD sharing in distantly related individuals from such populations where standard linkage and association analyses are difficult to implement. CMS compares allele sharing between individuals in affected and unaffected groups from founder populations. Comparisons between cases and controls were done using two Fisher's exact tests, one testing for excess in IBS allele frequency and the other testing for excess in IBS genotype frequency for 407 microsatellite markers. Results In all, 13 dementia cases and 14 normal controls were identified who were not related at least through the grandparental generation. The examination of allele frequencies identified 24 markers (6% nominally (p ≤ 0.05 associated with dementia; the most interesting (empiric p ≤ 0.005 markers were D3S1262, D5S211, and D19S1165. The examination of genotype frequencies identified 21 markers (5% nominally (p ≤ 0.05 associated with dementia; the most significant markers were both located on chromosome 5 (D5S1480 and D5S211. Notably, one of these markers (D5S211 demonstrated differences (empiric p ≤ 0.005 under both tests. Conclusion Our results provide the initial groundwork for identifying genes involved in late-onset Alzheimer's disease within the Amish community. Genes

  4. Environmental scanning electron microscopic study of macrophages associated with the tunica vasculosa lentis in the developing rat eye

    OpenAIRE

    Djano, J; Griffin, B; van Bruggen, I; McMenamin, P

    1999-01-01

    AIMS—To demonstrate the value of environmental scanning electron microscopy (ESEM) when used in combination with immunogold/silver enhancement methods as a valuable tool in ocular research, and to determine the phenotype of macrophages associated with the tunica vasculosa lentis while maintaining a topographical view of the lens surface.
METHODS—Prenatal and postnatal rat eyes were investigated by conventional scanning electron microscopy and ESEM. In the latter case tissues were prestained w...

  5. Leukemia surfaceome analysis reveals new disease-associated features.

    Science.gov (United States)

    Mirkowska, Paulina; Hofmann, Andreas; Sedek, Lukasz; Slamova, Lucie; Mejstrikova, Ester; Szczepanski, Tomasz; Schmitz, Maike; Cario, Gunnar; Stanulla, Martin; Schrappe, Martin; van der Velden, Vincent H J; Bornhauser, Beat C; Wollscheid, Bernd; Bourquin, Jean-Pierre

    2013-06-20

    A better description of the leukemia cell surface proteome (surfaceome) is a prerequisite for the development of diagnostic and therapeutic tools. Insights into the complexity of the surfaceome have been limited by the lack of suitable methodologies. We combined a leukemia xenograft model with the discovery-driven chemoproteomic Cell Surface Capture technology to explore the B-cell precursor acute lymphoblastic leukemia (BCP-ALL) surfaceome; 713 cell surface proteins, including 181 CD proteins, were detected through combined analysis of 19 BCP-ALL cases. Diagnostic immunophenotypes were recapitulated in each case, and subtype specific markers were detected. To identify new leukemia-associated markers, we filtered the surfaceome data set against gene expression information from sorted, normal hematopoietic cells. Nine candidate markers (CD18, CD63, CD31, CD97, CD102, CD157, CD217, CD305, and CD317) were validated by flow cytometry in patient samples at diagnosis and during chemotherapy. CD97, CD157, CD63, and CD305 accounted for the most informative differences between normal and malignant cells. The ALL surfaceome constitutes a valuable resource to assist the functional exploration of surface markers in normal and malignant lymphopoiesis. This unbiased approach will also contribute to the development of strategies that rely on complex information for multidimensional flow cytometry data analysis to improve its diagnostic applications. PMID:23649467

  6. Comparative Transcriptomics Reveals Jasmonic Acid-Associated Metabolism Related to Cotton Fiber Initiation.

    Directory of Open Access Journals (Sweden)

    Liman Wang

    Full Text Available Analysis of mutants and gene expression patterns provides a powerful approach for investigating genes involved in key stages of plant fiber development. In this study, lintless-fuzzless XinWX and linted-fuzzless XinFLM with a single genetic locus difference for lint were used to identify differentially expressed genes. Scanning electron microscopy showed fiber initiation in XinFLM at 0 days post anthesis (DPA. Fiber transcriptional profiling of the lines at three initiation developmental stages (-1, 0, 1 DPA was performed using an oligonucleotide microarray. Loop comparisons of the differentially expressed genes within and between the lines was carried out, and functional classification and enrichment analysis showed that gene expression patterns during fiber initiation were heavily associated with hormone metabolism, transcription factor regulation, lipid transport, and asparagine biosynthetic processes, as previously reported. Further, four members of the allene-oxide cyclase (AOC family that function in jasmonate biosynthesis were parallel up-regulation in fiber initiation, especially at -1 DPA, compared to other tissues and organs in linted-fuzzed TM-1. Real time-quantitative PCR (RT-qPCR analysis in different fiber mutant lines revealed that AOCs were up-regulated higher at -1 DPA in lintless-fuzzless than that in linted-fuzzless and linted-fuzzed materials, and transcription of the AOCs was increased under jasmonic acid (JA treatment. Expression analysis of JA biosynthesis-associated genes between XinWX and XinFLM showed that they were up-regulated during fiber initiation in the fuzzless-lintless mutant. Taken together, jasmonic acid-associated metabolism was related to cotton fiber initiation. Parallel up-regulation of AOCs expression may be important for normal fiber initiation development, while overproduction of AOCs might disrupt normal fiber development.

  7. Standing-wave-excited multiplanar fluorescence in a laser scanning microscope reveals 3D information on red blood cells

    CERN Document Server

    Amor, Rumelo; Amos, William Bradshaw; McConnell, Gail

    2014-01-01

    Standing-wave excitation of fluorescence is highly desirable in optical microscopy because it improves the axial resolution. We demonstrate here that multiplanar excitation of fluorescence by a standing wave can be produced in a single-spot laser scanning microscope by placing a plane reflector close to the specimen. We report that the relative intensities in each plane of excitation depend on the Stokes shift of the fluorochrome. We show by the use of dyes specific for the cell membrane how standing-wave excitation can be exploited to generate precise contour maps of the surface membrane of red blood cells, with an axial resolution of ~90 nm. The method, which requires only the addition of a plane mirror to an existing confocal laser scanning microscope, may well prove useful in studying diseases which involve the red cell membrane, such as malaria.

  8. Associations between the developmental trajectories of visual scanning and disengagement of attention in infants

    NARCIS (Netherlands)

    Hunnius, S.; Geuze, R.H.; Van Geert, P. L. C.

    2006-01-01

    The relation between the developmental trajectories of visual scanning and disengagement of attention and gaze were examined throughout early infancy. A sample of 10 infants carried out a scanning and a disengagement task with the same visual stimuli six times between 6 and 26 weeks of age. Frequenc

  9. Genome-wide association scan suggests basis for microtia in Awassi sheep.

    Science.gov (United States)

    Jawasreh, K; Boettcher, P J; Stella, A

    2016-08-01

    Hereditary underdevelopment of the ear, a condition also known as microtia, has been observed in several sheep breeds as well as in humans and other species. Its genetic basis in sheep is unknown. The Awassi sheep, a breed native to southwest Asia, carries this phenotype and was targeted for molecular characterization via a genome-wide association study. DNA samples were collected from sheep in Jordan. Eight affected and 12 normal individuals were genotyped with the Illumina OvineSNP50(®) chip. Multilocus analyses failed to identify any genotypic association. In contrast, a single-locus analysis revealed a statistically significant association (P = 0.012, genome-wide) with a SNP at basepair 34 647 499 on OAR23. This marker is adjacent to the gene encoding transcription factor GATA-6, which has been shown to play a role in many developmental processes, including chondrogenesis. The lack of extended homozygosity in this region suggests a fairly ancient mutation, and the time of occurrence was estimated to be approximately 3000 years ago. Many of the earless sheep breeds may thus share the causative mutation, especially within the subgroup of fat-tailed, wool sheep. PMID:26990958

  10. Genome-wide association scan suggests basis for microtia in Awassi sheep.

    Science.gov (United States)

    Jawasreh, K; Boettcher, P J; Stella, A

    2016-08-01

    Hereditary underdevelopment of the ear, a condition also known as microtia, has been observed in several sheep breeds as well as in humans and other species. Its genetic basis in sheep is unknown. The Awassi sheep, a breed native to southwest Asia, carries this phenotype and was targeted for molecular characterization via a genome-wide association study. DNA samples were collected from sheep in Jordan. Eight affected and 12 normal individuals were genotyped with the Illumina OvineSNP50(®) chip. Multilocus analyses failed to identify any genotypic association. In contrast, a single-locus analysis revealed a statistically significant association (P = 0.012, genome-wide) with a SNP at basepair 34 647 499 on OAR23. This marker is adjacent to the gene encoding transcription factor GATA-6, which has been shown to play a role in many developmental processes, including chondrogenesis. The lack of extended homozygosity in this region suggests a fairly ancient mutation, and the time of occurrence was estimated to be approximately 3000 years ago. Many of the earless sheep breeds may thus share the causative mutation, especially within the subgroup of fat-tailed, wool sheep.

  11. Estimating the lifetime risk of cancer associated with multiple CT scans

    International Nuclear Information System (INIS)

    Multiple CT scans are often done on the same patient resulting in an increased risk of cancer. Prior publications have estimated risks on a population basis and often using an effective dose. Simply adding up the risks from single scans does not correctly account for the survival function. A methodology for estimating personal radiation risks attributed to multiple CT imaging using organ doses is presented in this article. The estimated magnitude of the attributable risk fraction for the possible development of radiation-induced cancer indicates the necessity for strong clinical justification when ordering multiple CT scans. (paper)

  12. High-Resolution Imaging by Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Two Morphologically Distinct Types of Retinal Hard Exudates.

    Science.gov (United States)

    Yamaguchi, Muneo; Nakao, Shintaro; Kaizu, Yoshihiro; Kobayashi, Yoshiyuki; Nakama, Takahito; Arima, Mitsuru; Yoshida, Shigeo; Oshima, Yuji; Takeda, Atsunobu; Ikeda, Yasuhiro; Mukai, Shizuo; Ishibashi, Tatsuro; Sonoda, Koh-Hei

    2016-01-01

    Histological studies from autopsy specimens have characterized hard exudates as a composition of lipid-laden macrophages or noncellular materials including lipid and proteinaceous substances (hyaline substances). However, the characteristics of hard exudates in living patients have not been examined due to insufficient resolution of existing equipment. In this study, we used adaptive optics scanning laser ophthalmoscopy (AO-SLO) to examine the characteristics of hard exudates in patients with retinal vascular diseases. High resolution imaging using AO-SLO enables morphological classification of retinal hard exudates into two types, which could not be distinguished either on fundus examination or by spectral domain optical coherence tomography (SD-OCT). One, termed a round type, consisted of an accumulation of spherical particles (average diameter of particles: 26.9 ± 4.4 μm). The other, termed an irregular type, comprised an irregularly shaped hyper-reflective deposition. The retinal thickness in regions with round hard exudates was significantly greater than the thickness in regions with irregular hard exudates (P = 0.01 →0.02). This differentiation of retinal hard exudates in patients by AO-SLO may help in understanding the pathogenesis and clinical prognosis of retinal vascular diseases. PMID:27641223

  13. High-Resolution Imaging by Adaptive Optics Scanning Laser Ophthalmoscopy Reveals Two Morphologically Distinct Types of Retinal Hard Exudates

    Science.gov (United States)

    Yamaguchi, Muneo; Nakao, Shintaro; Kaizu, Yoshihiro; Kobayashi, Yoshiyuki; Nakama, Takahito; Arima, Mitsuru; Yoshida, Shigeo; Oshima, Yuji; Takeda, Atsunobu; Ikeda, Yasuhiro; Mukai, Shizuo; Ishibashi, Tatsuro; Sonoda, Koh-hei

    2016-01-01

    Histological studies from autopsy specimens have characterized hard exudates as a composition of lipid-laden macrophages or noncellular materials including lipid and proteinaceous substances (hyaline substances). However, the characteristics of hard exudates in living patients have not been examined due to insufficient resolution of existing equipment. In this study, we used adaptive optics scanning laser ophthalmoscopy (AO-SLO) to examine the characteristics of hard exudates in patients with retinal vascular diseases. High resolution imaging using AO-SLO enables morphological classification of retinal hard exudates into two types, which could not be distinguished either on fundus examination or by spectral domain optical coherence tomography (SD-OCT). One, termed a round type, consisted of an accumulation of spherical particles (average diameter of particles: 26.9 ± 4.4 μm). The other, termed an irregular type, comprised an irregularly shaped hyper-reflective deposition. The retinal thickness in regions with round hard exudates was significantly greater than the thickness in regions with irregular hard exudates (P = 0.01 →0.02). This differentiation of retinal hard exudates in patients by AO-SLO may help in understanding the pathogenesis and clinical prognosis of retinal vascular diseases. PMID:27641223

  14. Time-resolved step-scan Fourier transform infrared spectroscopy reveals differences between early and late M intermediates of bacteriorhodopsin.

    Science.gov (United States)

    Rödig, C; Chizhov, I; Weidlich, O; Siebert, F

    1999-05-01

    In this report, from time-resolved step-scan Fourier transform infrared investigations from 15 ns to 160 ms, we provide evidence for the subsequent rise of three different M states that differ in their structures. The first state rises with approximately 3 microseconds to only a small percentage. Its structure as judged from amide I/II bands differs in small but well-defined aspects from the L state. The next M state, which appears in approximately 40 microseconds, has almost all of the characteristics of the "late" M state, i.e., it differs considerably from the first one. Here, the L left arrow over right arrow M equilibrium is shifted toward M, although some percentage of L still persists. In the last M state (rise time approximately 130 microseconds), the equilibrium is shifted toward full deprotonation of the Schiff base, and only small additional structural changes take place. In addition to these results obtained for unbuffered conditions or at pH 7, experiments performed at lower and higher pH are presented. These results are discussed in terms of the molecular changes postulated to occur in the M intermediate to allow the shift of the L/M equilibrium toward M and possibly to regulate the change of the accessibility of the Schiff base necessary for effective proton pumping. PMID:10233083

  15. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

    OpenAIRE

    Adhikari, Kaustubh; Fontanil, Tania; Cal, Santiago; Mendoza-Revilla, Javier; Fuentes-Guajardo, Macarena; Chacón-Duque, Juan-Camilo; Al-Saadi, Farah; Johansson, Jeanette A.; Quinto-Sanchez, Mirsha; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Barquera Lozano, Rodrigo; Macín Pérez, Gastón; Gómez-Valdés, Jorge

    2016-01-01

    We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identifi...

  16. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

    OpenAIRE

    Adhikari, Kaustubh; Fontanil, Tania; Cal, Santiago; Mendoza-Revilla, Javier; Fuentes-Guajardo, Macarena; Chacón-Duque, Juan-Camilo; Al-Saadi, Farah; Johansson, Jeanette A.; Quinto-Sanchez, Mirsha; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Barquera Lozano, Rodrigo; Macín Pérez, Gastón; Gómez-Valdés, Jorge

    2016-01-01

    We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified l...

  17. Associative symmetry of the memory for object-location associations as revealed by the testing effect.

    Science.gov (United States)

    Sommer, Tobias; Schoell, Eszter; Büchel, Christian

    2008-06-01

    The nature of episodic associations has been subject to a long standing debate, where the two opposing positions postulate associations as either a holistic representation of the constituent elements or as independently modifiable pointers between them. In spite of a history of inconsistent findings, evidence in favour of the theory of symmetric associations has accumulated, yet only for verbal memory [Caplan, J. B., Glaholt, M. G., & McIntosh, A. R. (2006). Linking associative and serial list memory: Pairs versus triples. Journal of Experimental Psychology: Learning, Memory, and Cognition, 32(6), 1244-1265; Kahana, M. J. (2002). Associative symmetry and memory theory. Memory and Cognition, 30(6), 823-840]. Although object-location associations differ in several fundamental characteristics from verbal paired-associates, we recently found associative symmetry in the memory for this class of associations as well [Sommer, T., Rose, M., & Büchel, C. (2007). Associative symmetry vs. independent associations in the memory for object-location associations. Journal of Experimental Psychology: Learning, Memory, and Cognition, 33(1), 90-106]. Due to the inconsistencies in the verbal literature, we felt it to be pertinent to confirm this finding using another experimental approach. Based on recent advances in understanding the effects of successive testing, we were able to make use of this knowledge and introduce this effect as an experimental manipulation in the study of associative symmetry. In particular, we investigated whether the influence of a prior memory test on a subsequent memory test differs when the same or opposite constituent element of an object-location paired-associate cues the retrieval on each test. We observed an identical testing effect for both conditions, which was exclusively driven by reminiscence, the recovery of previously inaccessible information. This finding lends strong support in favour of holistically or symmetrically represented object

  18. Correction of step artefact associated with MRI scanning of long bones.

    Science.gov (United States)

    Rathnayaka, Kanchana; Cowin, Gary; Schuetz, Michael A; Sahama, Tony; Schmutz, Beat

    2013-07-01

    3D models of long bones are being utilised for a number of fields including orthopaedic implant design. Accurate reconstruction of 3D models is of utmost importance to design accurate implants to allow achieving a good alignment between two bone fragments. Thus for this purpose, CT scanners are employed to acquire accurate bone data exposing an individual to a high amount of ionising radiation. Magnetic resonance imaging (MRI) has been shown to be a potential alternative to computed tomography (CT) for scanning of volunteers for 3D reconstruction of long bones, essentially avoiding the high radiation dose from CT. In MRI imaging of long bones, the artefacts due to random movements of the skeletal system create challenges for researchers as they generate inaccuracies in the 3D models generated by using data sets containing such artefacts. One of the defects that have been observed during an initial study is the lateral shift artefact occurring in the reconstructed 3D models. This artefact is believed to result from volunteers moving the leg during two successive scanning stages (the lower limb has to be scanned in at least five stages due to the limited scanning length of the scanner). As this artefact creates inaccuracies in the implants designed using these models, it needs to be corrected before the application of 3D models to implant design. Therefore, this study aimed to correct the lateral shift artefact using 3D modelling techniques. The femora of five ovine hind limbs were scanned with a 3T MRI scanner using a 3D vibe based protocol. The scanning was conducted in two halves, while maintaining a good overlap between them. A lateral shift was generated by moving the limb several millimetres between two scanning stages. The 3D models were reconstructed using a multi threshold segmentation method. The correction of the artefact was achieved by aligning the two halves using the robust iterative closest point (ICP) algorithm, with the help of the overlapping

  19. Chronic osteomyelitis: bone and gallium scan patterns associated with active disease

    International Nuclear Information System (INIS)

    Bone and gallium scans are used to assess osteomyelitis patients with prior bone disease. To refine the criteria for interpreting these scans, the data from 136 consecutive patients with clinically suspected osteomyelitis were reviewed. Active osteomyelitis was diagnosed with surgery or biopsy and culture in 49 patients, excluded with the same criteria in 16, and excluded by clinical follow-up for at least 6 months in 71. Five different scintigraphic patterns were found. The true-positive and false-positive ratios, the likelihood ratios, and posterior probabilities for active osteomyelitis in each pattern were calculated. Only one pattern (gallium uptake exceeding bone-seeking radiopharmaceutical uptake) was indicative of active disease. Other patterns slightly raised or decreased the probability of disease. The extent of these changes varies directly with the prior probability of disease, determined from patient-specific factors (e.g., clinical data, laboratory data, findings on plain films) known best by the referring clinician

  20. BDNF Val66Met and 5-HTTLPR Genotype are Each Associated with Visual Scanning Patterns of Faces in Young Children

    OpenAIRE

    Christou, Antonios I.; Wallis, Yvonne; Bair, Hayley; Crawford, Hayley; Frisson, Steven; Zeegers, Maurice P; McCleery, Joseph P.

    2015-01-01

    Previous studies have documented both neuroplasticity-related BDNF Val66Met and emotion regulation-related 5-HTTLPR polymorphisms as genetic variants that contribute to the processing of emotions from faces. More specifically, research has shown the BDNF Met allele and the 5-HTTLPR Short allele to be associated with mechanisms of negative affectivity that relate to susceptibility for psychopathology. We examined visual scanning pathways in response to angry, happy, and neutral faces in relati...

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

    Directory of Open Access Journals (Sweden)

    Curtis David

    2007-06-01

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

  2. Association analyses of 249,796 individuals reveal eighteen new loci associated with body mass index

    Science.gov (United States)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian’an; Mägi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segré, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F.; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Åsa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R.B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I.F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N.M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J.C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Gräßler, Jürgen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; König, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J.; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N.; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W.; Morken, Mario A.; Morris, Andrew P.; Mulic, Rosanda; Ngwa, Julius S.; Nelis, Mari; Neville, Matt J.; Nyholt, Dale R.; O’Donnell, Christopher J.; O’Rahilly, Stephen; Ong, Ken K.; Oostra, Ben; Paré, Guillaume; Parker, Alex N.; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H.; Platou, Carl G.P.; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W.; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R.; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R.; Sandhu, Manjinder S.; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J.; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S.; Smit, Jan H.; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J.; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M.; Thompson, John R.; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B.J.; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I. G.; Voight, Benjamin F.; Waite, Lindsay L.; Wallaschofski, Henri; Walters, G. Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H.; Willemsen, Gonneke; Witte, Daniel R.; Witteman, Jacqueline C.; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P.; Farooqi, I. Sadaf; Hebebrand, Johannes; Huikuri, Heikki V.; James, Alan L.; Kähönen, Mika; Levinson, Douglas F.; Macciardi, Fabio; Nieminen, Markku S.; Ohlsson, Claes; Palmer, Lyle J.; Ridker, Paul M.; Stumvoll, Michael; Beckmann, Jacques S.; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Collins, Francis S.; Cupples, L. Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Grönberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B.; Hattersley, Andrew T.; Hayes, Richard B.; Heinrich, Joachim; Hu, Frank B.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A.; Metspalu, Andres; Munroe, Patricia B.; Ouwehand, Willem H.; Pedersen, Oluf; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J.; Schwarz, Peter E.H.; Shuldiner, Alan R.; Spector, Timothy D.; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, André; Valle, Timo T.; Wabitsch, Martin; Waeber, Gérard; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Wright, Alan F.; Zillikens, M. Carola; Chatterjee, Nilanjan; McCarroll, Steven A.; Purcell, Shaun; Schadt, Eric E.; Visscher, Peter M.; Assimes, Themistocles L.; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Haritunians, Talin; Hunter, David J.; Kaplan, Robert C.; Mohlke, Karen L.; O’Connell, Jeffrey R.; Peltonen, Leena; Schlessinger, David; Strachan, David P.; van Duijn, Cornelia M.; Wichmann, H.-Erich; Frayling, Timothy M.; Thorsteinsdottir, Unnur; Abecasis, Gonçalo R.; Barroso, Inês; Boehnke, Michael; Stefansson, Kari; North, Kari E.; McCarthy, Mark I.; Hirschhorn, Joel N.; Ingelsson, Erik; Loos, Ruth J.F.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but the underlying genetic factors remain largely elusive. To identify genetic loci for obesity-susceptibility, we examined associations between body mass index (BMI) and ~2.8 million SNPs in up to 123,865 individuals, with targeted follow-up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity-susceptibility loci and identified 18 new loci associated with BMI (P<5×10−8), one of which includes a copy number variant near GPRC5B. Some loci (MC4R, POMC, SH2B1, BDNF) map near key hypothalamic regulators of energy balance, and one is near GIPR, an incretin receptor. Furthermore, genes in other newly-associated loci may provide novel insights into human body weight regulation. PMID:20935630

  3. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

    Science.gov (United States)

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I; Monda, Keri L; Thorleifsson, Gudmar; Jackson, Anne U; Lango Allen, Hana; Lindgren, Cecilia M; Luan, Jian'an; Mägi, Reedik; Randall, Joshua C; Vedantam, Sailaja; Winkler, Thomas W; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Weedon, Michael N; Wheeler, Eleanor; Wood, Andrew R; Ferreira, Teresa; Weyant, Robert J; Segrè, Ayellet V; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K; Absher, Devin M; Amin, Najaf; Dixon, Anna L; Fisher, Eva; Glazer, Nicole L; Goddard, Michael E; Heard-Costa, Nancy L; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F; Myers, Richard H; Narisu, Narisu; Perry, John R B; Peters, Marjolein J; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J; Timpson, Nicholas J; Tyrer, Jonathan P; van Wingerden, Sophie; Watanabe, Richard M; White, Charles C; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I; Cooper, Matthew N; Jansson, John-Olov; Lawrence, Robert W; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T S; Almgren, Peter; Arnold, Alice M; Aspelund, Thor; Atwood, Larry D; Balkau, Beverley; Balmforth, Anthony J; Bennett, Amanda J; Ben-Shlomo, Yoav; Bergman, Richard N; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I F; Boes, Tanja; Bonnycastle, Lori L; Bornstein, Stefan R; Brown, Morris J; Buchanan, Thomas A; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N M; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Facheris, Maurizio F; Felix, Stephan B; Fischer-Posovszky, Pamela; Folsom, Aaron R; Friedrich, Nele; Freimer, Nelson B; Fu, Mao; Gaget, Stefan; Gejman, Pablo V; Geus, Eco J C; Gieger, Christian; Gjesing, Anette P; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Grässler, Jürgen; Greenawalt, Danielle M; Groves, Christopher J; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S; Havulinna, Aki S; Hayward, Caroline; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W; Kolcic, Ivana; König, Inke R; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G; McArdle, Wendy L; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W; Morken, Mario A; Morris, Andrew P; Mulic, Rosanda; Ngwa, Julius S; Nelis, Mari; Neville, Matt J; Nyholt, Dale R; O'Donnell, Christopher J; O'Rahilly, Stephen; Ong, Ken K; Oostra, Ben; Paré, Guillaume; Parker, Alex N; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H; Platou, Carl G P; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R; Sandhu, Manjinder S; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S; Smit, Jan H; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M; Thompson, John R; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B J; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie

    2010-11-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

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

    NARCIS (Netherlands)

    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.; Maloney, Cliona M.; 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; de Boer, Anthonius; Drenos, Fotios; Elbers, Clara C.; Fang, James C.; Fox, Caroline S.; Frackelton, Edward C.; Fuchs, Barry; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Goe, 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; Marshal, Vanessa; Melander, Olle; Mentch, Frank D.; Meyer, Nuala J.; Monda, Keri L.; Montpetit, Alexandre; Murugesan, Gurunathan; Nakayama, Karen; Nondah, 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.; Christie, Jason D.; 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.; Maerz, 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.; Watkins, Hugh; 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.; Kumari, Meena; 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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  7. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I;

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SN...

  8. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    NARCIS (Netherlands)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian'an; Maegi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segre, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpelaenen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tonu; Feitosa, Mary F.; Kutalik, Zoltan; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R. B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I. F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proenca, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N. M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J. C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Graessler, Juergen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jorgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; Koenig, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaloy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J.; Lecoeur, Cecile; Lehtimaeki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N.; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W.; Morken, Mario A.; Morris, Andrew P.; Mulic, Rosanda; Ngwa, Julius S.; Nelis, Mari; Neville, Matt J.; Nyholt, Dale R.; O'Donnell, Christopher J.; O'Rahilly, Stephen; Ong, Ken K.; Oostra, Ben; Pare, Guillaume; Parker, Alex N.; Perola, Markus; Pichler, Irene; Pietilaeinen, Kirsi H.; Platou, Carl G. P.; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W.; Ridderstrale, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R.; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R.; Sandhu, Manjinder S.; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J.; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S.; Smit, Jan H.; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J.; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M.; Thompson, John R.; Thomson, Brian; Toenjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B. J.; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I. G.; Voight, Benjamin F.; Waite, Lindsay L.; Wallaschofski, Henri; Walters, G. Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H.; Willemsen, Gonneke; Witte, Daniel R.; Witteman, Jacqueline C.; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P.; Farooqi, I. Sadaf; Hebebrand, Johannes; Huikuri, Heikki V.; James, Alan L.; Kaehoenen, Mika; Levinson, Douglas F.; Macciardi, Fabio; Nieminen, Markku S.; Ohlsson, Claes; Palmer, Lyle J.; Ridker, Paul M.; Stumvoll, Michael; Beckmann, Jacques S.; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Collins, Francis S.; Cupples, L. Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Greonberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B.; Hattersley, Andrew T.; Hayes, Richard B.; Heinrich, Joachim; Hu, Frank B.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A.; Metspalu, Andres; Munroe, Patricia B.; Ouwehand, Willem H.; Pedersen, Oluf; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J.; Schwarz, Peter E. H.; Shuldiner, Alan R.; Spector, Timothy D.; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, Andre; Valle, Timo T.; Wabitsch, Martin; Waeber, Gerard; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Wright, Alan F.; Zillikens, M. Carola; Chatterjee, Nilanjan; McCarroll, Steven A.; Purcell, Shaun; Schadt, Eric E.; Visscher, Peter M.; Assimes, Themistocles L.; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Haritunians, Talin; Hunter, David J.; Kaplan, Robert C.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Peltonen, Leena; Schlessinger, David; Strachan, David P.; van Duijn, Cornelia M.; Wichmann, H-Erich; Frayling, Timothy M.; Thorsteinsdottir, Unnur; Abecasis, Goncalo R.; Barroso, Ines; Boehnke, Michael; Stefansson, Kari; North, Kari E.; McCarthy, Mark I.; Hirschhorn, Joel N.; Ingelsson, Erik; Loos, Ruth J. F.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of

  9. CT head-scan dosimetry in an anthropomorphic phantom and associated measurement of ACR accreditation-phantom imaging metrics under clinically representative scan conditions

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Claudia C.; Stern, Stanley H.; Chakrabarti, Kish [U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993 (United States); Minniti, Ronaldo [National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, Maryland 20899 (United States); Parry, Marie I. [Walter Reed National Military Medical Center, 8901 Rockville Pike, Bethesda, Maryland 20889 (United States); Skopec, Marlene [National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892 (United States)

    2013-08-15

    Gy, respectively. The GE Discovery delivers about the same amount of dose (43.7 mGy) when run under similar operating and image-reconstruction conditions, i.e., without tube current modulation and ASIR. The image-metrics analysis likewise showed that the MTF, NPS, and CNR associated with the reconstructed images are mutually comparable when the three scanners are run with similar settings, and differences can be attributed to different edge-enhancement properties of the applied reconstruction filters. Moreover, when the GE scanner was operated with the facility's scanner settings for routine head exams, which apply 50% ASIR and use only approximately half of the 100%-FBP dose, the CNR of the images showed no significant change. Even though the CNR alone is not sufficient to characterize the image quality and justify any dose reduction claims, it can be useful as a constancy test metric.Conclusions: This work presents a straightforward method to connect direct measurements of CT dose with objective image metrics such as high-contrast resolution, noise, and CNR. It demonstrates that OSLD measurements in an anthropomorphic head phantom allow a realistic and locally precise estimation of magnitude and spatial distribution of dose in tissue delivered during a typical CT head scan. Additional objective analysis of the images of the ACR accreditation phantom can be used to relate the measured doses to high contrast resolution, noise, and CNR.

  10. Environmental scanning electron microscope (ESEM) evaluation of crystal and plaque formation associated with biocorrosion.

    Science.gov (United States)

    Geiger, S L; Ross, T J; Barton, L L

    1993-08-01

    The biofilm attributed to Desulfovibrio vulgaris growing in the presence of ferrous metals was examined with an environmental scanning electron microscope. This novel microscope produced images of iron sulfide colloids and other iron containing structures that had not been reported previously. A plaque composed of iron sulfide enveloped the surface of the corroding metal while crystals containing magnesium, iron, sulfur, and phosphorus were present in the culture where corrosion was in progress. A structure resembling the tubercule found in aerobic corrosion was observed on stainless steel undergoing biocorrosion and the elements present in this structure included sulfur, iron, chloride, calcium, potassium, and chromium.

  11. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features.

    Science.gov (United States)

    Adhikari, Kaustubh; Fontanil, Tania; Cal, Santiago; Mendoza-Revilla, Javier; Fuentes-Guajardo, Macarena; Chacón-Duque, Juan-Camilo; Al-Saadi, Farah; Johansson, Jeanette A; Quinto-Sanchez, Mirsha; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Barquera Lozano, Rodrigo; Macín Pérez, Gastón; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Gonzalez-José, Rolando; Headon, Denis; López-Otín, Carlos; Tobin, Desmond J; Balding, David; Ruiz-Linares, Andrés

    2016-01-01

    We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair. PMID:26926045

  12. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features.

    Science.gov (United States)

    Adhikari, Kaustubh; Fontanil, Tania; Cal, Santiago; Mendoza-Revilla, Javier; Fuentes-Guajardo, Macarena; Chacón-Duque, Juan-Camilo; Al-Saadi, Farah; Johansson, Jeanette A; Quinto-Sanchez, Mirsha; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Barquera Lozano, Rodrigo; Macín Pérez, Gastón; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Gonzalez-José, Rolando; Headon, Denis; López-Otín, Carlos; Tobin, Desmond J; Balding, David; Ruiz-Linares, Andrés

    2016-03-01

    We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.

  13. Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy

    OpenAIRE

    Pillas, D.; Hoggart, C. J.; Evans, D. M.; O'Reilly, P. F.; Sipila, K.; Lahdesmaki, R.; Millwood, I. Y.; Kaakinen, M; Netuveli, G.; Blane, D; Charoen, P.; Sovio, U; Pouta, A.; Freimer, N; Hartikainen, A. L.

    2010-01-01

    Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,...

  14. The Use of Scan Statistics and Control Charts in Assessing Ventilator-Associated Pneumonia Quality Control Programs

    Directory of Open Access Journals (Sweden)

    Brian H. Nathanson

    2010-01-01

    Full Text Available Scan statistics are concerned with clusters of events over time. In the realm of critical care medicine, such clusters might include the occurrence of ventilator-associated pneumonia (VAP. Given N patients over time, the number of observations in a “moving window” of fixed length can be counted and the maximum cluster value becomes a scan statistic for which both parametric and exact methods exist to calculate its rarity. A statistically unusual cluster may indicate a breakdown in quality. Another approach to monitoring rare events is a g-type statistical process control chart where prospectively observing unusually long periods of time between events can indicate a significant improvement in quality. Both methods are presented in detail and applied to a 24-bed medical/surgical ICU's experience with VAP during a 27-month period.

  15. Identification of Promising Mutants Associated with Egg Production Traits Revealed by Genome-Wide Association Study.

    Directory of Open Access Journals (Sweden)

    Jingwei Yuan

    Full Text Available Egg number (EN, egg laying rate (LR and age at first egg (AFE are important production traits related to egg production in poultry industry. To better understand the knowledge of genetic architecture of dynamic EN during the whole laying cycle and provide the precise positions of associated variants for EN, LR and AFE, laying records from 21 to 72 weeks of age were collected individually for 1,534 F2 hens produced by reciprocal crosses between White Leghorn and Dongxiang Blue-shelled chicken, and their genotypes were assayed by chicken 600 K Affymetrix high density genotyping arrays. Subsequently, pedigree and SNP-based genetic parameters were estimated and a genome-wide association study (GWAS was conducted on EN, LR and AFE. The heritability estimates were similar between pedigree and SNP-based estimates varying from 0.17 to 0.36. In the GWA analysis, we identified nine genome-wide significant loci associated with EN of the laying periods from 21 to 26 weeks, 27 to 36 weeks and 37 to 72 weeks. Analysis of GTF2A1 and CLSPN suggested that they influenced the function of ovary and uterus, and may be considered as relevant candidates. The identified SNP rs314448799 for accumulative EN from 21 to 40 weeks on chromosome 5 created phenotypic differences of 6.86 eggs between two homozygous genotypes, which could be potentially applied to the molecular breeding for EN selection. Moreover, our finding showed that LR was a moderate polygenic trait. The suggestive significant region on chromosome 16 for AFE suggested the relationship between sex maturity and immune in the current population. The present study comprehensively evaluates the role of genetic variants in the development of egg laying. The findings will be helpful to investigation of causative genes function and future marker-assisted selection and genomic selection in chickens.

  16. Additive and epistatic genome-wide association for growth and ultrasound scan measures of carcass-related traits in Brahman cattle.

    Science.gov (United States)

    Ali, A A; Khatkar, M S; Kadarmideen, H N; Thomson, P C

    2015-04-01

    Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems.

  17. Additive and epistatic genome-wide association for growth and ultrasound scan measures of carcass-related traits in Brahman cattle.

    Science.gov (United States)

    Ali, A A; Khatkar, M S; Kadarmideen, H N; Thomson, P C

    2015-04-01

    Genome-wide association studies are routinely used to identify genomic regions associated with traits of interest. However, this ignores an important class of genomic associations, that of epistatic interactions. A genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) using highly dense markers can detect epistatic interactions, but is a difficult task due to multiple testing and computational demand. However, It is important for revealing complex trait heredity. This study considers analytical methods that detect statistical interactions between pairs of loci. We investigated a three-stage modelling procedure: (i) a model without the SNP to estimate the variance components; (ii) a model with the SNP using variance component estimates from (i), thus avoiding iteration; and (iii) using the significant SNPs from (ii) for genome-wide epistasis analysis. We fitted these three-stage models to field data for growth and ultrasound measures for subcutaneous fat thickness in Brahman cattle. The study demonstrated the usefulness of modelling epistasis in the analysis of complex traits as it revealed extra sources of genetic variation and identified potential candidate genes affecting the concentration of insulin-like growth factor-1 and ultrasound scan measure of fat depth traits. Information about epistasis can add to our understanding of the complex genetic networks that form the fundamental basis of biological systems. PMID:25754883

  18. Family-Based Genome-Wide Association Scan of Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Mick, Eric; Todorov, Alexandre; Smalley, Susan; Hu, Xiaolan; Loo, Sandra; Todd, Richard D.; Biederman, Joseph; Byrne, Deirdre; Dechairo, Bryan; Guiney, Allan; McCracken, James; McGough, James; Nelson, Stanley F.; Reiersen, Angela M.; Wilens, Timothy E.; Wozniak, Janet; Neale, Benjamin M.; Faraone, Stephen V.

    2010-01-01

    Objective: Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of…

  19. Three-cohort targeted gene screening reveals a non-synonymous TRKA polymorphism associated with schizophrenia

    DEFF Research Database (Denmark)

    van Schijndel, Jessica E; van Loo, Karen M J; van Zweeden, Martine;

    2009-01-01

    selected non-synonymous single-nucleotide polymorphisms (SNPs) in three independent Caucasian schizophrenia case-control cohorts (USA, Denmark and Norway). A meta-analysis revealed ten non-synonymous SNPs that were nominally associated with schizophrenia, nine of which have not been previously linked...

  20. Eye Tracking Reveals Impaired Attentional Disengagement Associated with Sensory Response Patterns in Children with Autism

    Science.gov (United States)

    Sabatos-DeVito, Maura; Schipul, Sarah E.; Bulluck, John C.; Belger, Aysenil; Baranek, Grace T.

    2016-01-01

    This study used a gap-overlap paradigm to examine the impact of distractor salience and temporal overlap on the ability to disengage and orient attention in 50 children (4-13 years) with ASD, DD and TD, and associations between attention and sensory response patterns. Results revealed impaired disengagement and orienting accuracy in ASD.…

  1. An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas

    DEFF Research Database (Denmark)

    Cirilo, Priscila Daniele Ramos; Marchi, Fábio Albuquerque; Barros Filho, Mateus de Camargo;

    2013-01-01

    integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell...... transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs....

  2. 3D Body Scanning Measurement System Associated with RF Imaging, Zero-padding and Parallel Processing

    Directory of Open Access Journals (Sweden)

    Kim Hyung Tae

    2016-04-01

    Full Text Available This work presents a novel signal processing method for high-speed 3D body measurements using millimeter waves with a general processing unit (GPU and zero-padding fast Fourier transform (ZPFFT. The proposed measurement system consists of a radio-frequency (RF antenna array for a penetrable measurement, a high-speed analog-to-digital converter (ADC for significant data acquisition, and a general processing unit for fast signal processing. The RF waves of the transmitter and the receiver are converted to real and imaginary signals that are sampled by a high-speed ADC and synchronized with the kinematic positions of the scanner. Because the distance between the surface and the antenna is related to the peak frequency of the conjugate signals, a fast Fourier transform (FFT is applied to the signal processing after the sampling. The sampling time is finite owing to a short scanning time, and the physical resolution needs to be increased; further, zero-padding is applied to interpolate the spectra of the sampled signals to consider a 1/m floating point frequency. The GPU and parallel algorithm are applied to accelerate the speed of the ZPFFT because of the large number of additional mathematical operations of the ZPFFT. 3D body images are finally obtained by spectrograms that are the arrangement of the ZPFFT in a 3D space.

  3. Opisthorchiasis-associated biliary stones:Light and scanning electron microscopic study

    Institute of Scientific and Technical Information of China (English)

    Banchob Sripa; Pipatphong Kanla; Poonsiri Sinawat; Melissa R. Haswell-Elkins

    2004-01-01

    AIM: Biliary stones are frequentty encountered in areas endemic for opisthorchiasis in Thailand. The present study was to describe the prevalence and pathogenesis of these stones.METHODS: Gallstones and/or common bile duct stones and bile specimens from 113 consecutive cholecystectomies were included. Bile samples, including sludge and/or microcalculi, were examined for Opisthorchis viverrini eggs,calcium and bilirubin. The stones were also processed for scanning electron microscopic (SEM) study.RESULTS: Of the 113 cases, 82 had pigment stones, while one had cholesterol stones. The other 30 cases had no stones. Most of the stone cases (76%, 63/83) had multiple stones, while the remainder had a single stone. Stones were more frequently observed in females. Bile examination was positive for O. viverrini eggs in 50% of the cases studied. Aggregates of calcium bilirubinate precipitates were observed in all cases with sludge. Deposition of calcium bilirubinate on the eggshell was visualized by special staining. A SEM study demonstrated the presence of the parasite eggs in the stones. Numerous crystals,morphologically consistent with calcium derivatives and cholesterol precipitates, were seen.CONCLUSION: Northeast Thailand has a high prevalence of pigment stones, as observed at the cholecystectomy, and liver fluke infestation seems involved in the pathogenesis of stone formation.

  4. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lindgren

    2009-06-01

    Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  5. A genome-wide association scan (GWAS) for mean telomere length within the COGS project

    DEFF Research Database (Denmark)

    Pooley, Karen A; Bojesen, Stig E; Weischer, Maren;

    2013-01-01

    Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All ∼...

  6. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.R. Jarvelin; A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evid

  7. Two cases of multiple sclerosis associated with multiple enhancements of lesions on CT scan

    International Nuclear Information System (INIS)

    Computed tomographic (CT) examination revealed well-circumscribed enhanced lesions during the period of clinical exacerbation in two cases of clinically definite multiple sclerosis. One patient underwent CT-controlled stereotaxic needle biopsy of a lesion. Luxol fast blue stain revealed marked demyelination of the specimen, and hematoxylin eosin stain showed marked perivascular focal infiltrations of lymphocytes and macrophages, and the existence of increased numbers of microglia and oligoglia. These histological findings demonstrated characteristics typical of multiple-sclerosis lesions and also suggested destruction of the blood-brain barrier, which may enhance the contrast of the lesion in the CT image. Serial and repeated CT examination showed three types of lesions : low-density lesions that disappeared after showing enhancement, type 1; low-density lesions that had disappeared without showing enhancement, type 2; and isodensity lesions that disappeared after showing enhancement, type 3. We postulate that type 1 lesions were accompanied by destruction of the blood-brain barrier, and that type 2 were not. Type 3 lesions may be too small to appear enhanced in the CT image. Lesions that appeared markedly enhanced in the CT cuts responded to steroid therapy and soon disappeared, possibly suggesting that remyelination may occur in the tissue of the central nervous system, indicating remission of the clinical features of these lesions. (author)

  8. Rapid Mutation Scanning of Genes Associated with Familial Cancer Syndromes Using Denaturing High-Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Deborah J. Marsh

    2001-01-01

    Full Text Available Germline mutations in tumor suppressor genes, or less frequently oncogenes, have been identified in up to 19 familial cancer syndromes including Li-Fraumeni syndrome, familial paraganglioma, familial adenomatous polyposis coli and breast and ovarian cancers. Multiple genes have been associated with some syndromes as approximately 26 genes have been linked to the development of these familial cancers. With this increased knowledge of the molecular determinants of familial cancer comes an equal expectation for efficient genetic screening programs. We have trialled denaturing highperformance liquid chromatography (dHPLC as a tool for rapid germline mutation scanning of genes implicated in three familial cancer syndromes - Cowden syndrome (PTEN mutation, multiple endocrine neoplasia type 2 (RET mutation and von Hippel-Lindau disease (VHL mutation. Thirty-two mutations, including 21 in PTEN, 9 in RET plus a polymorphism, and 2 in VHL, were analyzed using the WAVE DNA fragment analysis system with 100% detection efficiency. In the case of the tumor suppressor gene PTEN, mutations were scattered along most of the gene. However, mutations in the RET proto-oncogene associated with multiple endocrine neoplasia type 2 were limited to specific clusters or “hot spots”. The use of GC-clamped primers to scan for mutations scattered along PTEN exons was shown to greatly enhance the sensitivity of detection of mutant hetero- and homoduplex peaks at a single denaturation temperature compared to fragments generated using non-GC-clamped primers. Thus, when scanning tumor suppressor genes for germline mutation using dHPLC, the incorporation of appropriate GCclamped primers will likely increase the efficiency of mutation detection.

  9. Application of pooled genotyping to scan candidate regions for association with HDL cholesterol levels

    Directory of Open Access Journals (Sweden)

    Hinds David A

    2004-11-01

    Full Text Available Abstract Association studies are used to identify genetic determinants of complex human traits of medical interest. With the large number of validated single nucleotide polymorphisms (SNPs currently available, two limiting factors in association studies are genotyping capability and costs. Pooled DNA genotyping has been proposed as an efficient means of screening SNPs for allele frequency differences in case-control studies and for prioritising them for subsequent individual genotyping analysis. Here, we apply quantitative pooled genotyping followed by individual genotyping and replication to identify associations with human serum high-density lipoprotein (HDL cholesterol levels. The DNA from individuals with low and high HDL cholesterol levels was pooled separately, each pool was amplified by polymerase chain reaction in triplicate and each amplified product was separately hybridised to a high-density oligonucleotide array. Allele frequency differences between case and control groups with low and high HDL cholesterol levels were estimated for 7,283 SNPs distributed across 71 candidate gene regions spanning a total of 17.1 megabases. A novel method was developed to take advantage of independently derived haplotype map information to improve the pooled estimates of allele frequency differences. A subset of SNPs with the largest estimated allele frequency differences between low and high HDL cholesterol groups was chosen for individual genotyping in the study population, as well as in a separate replication population. Four SNPs in a single haplotype block within the cholesteryl ester transfer protein (CETP gene interval were significantly associated with HDL cholesterol levels in both populations. Our study is among the first to demonstrate the application of pooled genotyping followed by confirmation with individual genotyping to identify genetic determinants of a complex trait.

  10. Univariate/multivariate genome-wide association scans using data from families and unrelated samples.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    Full Text Available As genome-wide association studies (GWAS are becoming more popular, two approaches, among others, could be considered in order to improve statistical power for identifying genes contributing subtle to moderate effects to human diseases. The first approach is to increase sample size, which could be achieved by combining both unrelated and familial subjects together. The second approach is to jointly analyze multiple correlated traits. In this study, by extending generalized estimating equations (GEEs, we propose a simple approach for performing univariate or multivariate association tests for the combined data of unrelated subjects and nuclear families. In particular, we correct for population stratification by integrating principal component analysis and transmission disequilibrium test strategies. The proposed method allows for multiple siblings as well as missing parental information. Simulation studies show that the proposed test has improved power compared to two popular methods, EIGENSTRAT and FBAT, by analyzing the combined data, while correcting for population stratification. In addition, joint analysis of bivariate traits has improved power over univariate analysis when pleiotropic effects are present. Application to the Genetic Analysis Workshop 16 (GAW16 data sets attests to the feasibility and applicability of the proposed method.

  11. [Acute intestinal obstruction revealing enteropathy associated t-cell lymphoma, about a case].

    Science.gov (United States)

    Garba, Abdoul Aziz; Adamou, Harissou; Magagi, Ibrahim Amadou; Brah, Souleymane; Habou, Oumarou

    2016-01-01

    Enteropathy associated T-cell lymphoma (EATL) is a rare complication of celiac disease (CD). We report a case of EATL associated with CD revealed by acute intestinal obstruction. A North African woman of 38 years old with a history of infertility and chronic abdominal pain was admitted in emergency with acute intestinal obstruction. During the surgery, we found a tumor on the small intestine with mesenteric lymphadenopathy. Histology and immunohistochemistry of the specimen objectified a digestive T lymphoma CD3+ and immunological assessment of celiac disease was positive. The diagnosis of EATL was thus retained. Chemotherapy (CHOEP protocol) was established as well as gluten-free diet with a complete response to treatment. The EATL is a rare complication of CD that can be revealed by intestinal obstruction. The prognosis can be improved by early treatment involving surgery and chemotherapy. Its prevention requires early diagnosis of celiac and gluten-free diets. PMID:27217874

  12. CLINICOPATHOLOGICAL FACTORS ASSOCIATED WITH POSITIVE PREOPERATIVE AXILLARY ULTRASOUND SCANNING IN BREAST CANCER PATIENTS

    Directory of Open Access Journals (Sweden)

    Lona Jalini

    2016-01-01

    Full Text Available Background: Axillary lymph node status is the most important breast cancer prognostic factor. Preoperative axillary ultrasound examination (PAUS is used to triage patients for sentinel lymph node biopsy (SLNB or axillary lymph node dissection (ALND. We assessed the detection rate of lymph node metastases by PAUS in a screening unit and evaluated associations between clinicopathological factors and PAUS positivity. Patients and Methods: This was a single-centre retrospective analysis of data extracted from a hospital breast cancer database and clinical records. Clinical, radiological, and pathological and prognostic indices were compared between PAUS-positive and PAUS-negative patients subsequently found to have lymph node metastases on histopathological analysis. Results: Two hundred and two patients were eligible for analysis. 50.5% of lymph node-positive patients were correctly identified as PAUS positive. Patients with PAUS-positive lymph nodes had less favorable disease characteristics, namely clinically palpable lymph nodes, higher Nottingham prognostic (NPI index, high lymph node burden according to the European Society of Medical Oncology (ESMO group classification, and larger, grade 3 tumors with lymphovascular invasion and extranodal spread. Moreover, PAUS-positive patients had more macrometastases and lymph node involvement than PAUS-negative patients. Conclusion: PAUS-positive patients and PAUS-negative (SLNB-positive patients have different clinicopathological characteristics. The presence of LVI, extranodal spread, grade 3 histology, or large tumors with poor prognostic indices in PAUS-negative patients should be regarded with caution and perhaps prompt second-look ultrasound examination.

  13. The Hidden Diversity of Zanclea Associated with Scleractinians Revealed by Molecular Data

    KAUST Repository

    Montano, Simone

    2015-07-24

    Scleractinian reef corals have recently been acknowledged as the most numerous host group found in association with hydroids belonging to the Zanclea genus. However, knowledge of the molecular phylogenetic relationships among Zanclea species associated with scleractinians is just beginning. This study, using the nuclear 28S rDNA region and the fast-evolving mitochondrial 16S rRNA and COI genes, provides the most comprehensive phylogenetic reconstruction of the genus Zanclea with a particular focus on the genetic diversity among Zanclea specimens associated with 13 scleractinian genera. The monophyly of Zanclea associated with scleractinians was strongly supported in all nuclear and mitochondrial phylogenetic reconstructions. Furthermore, a combined mitochondrial 16S and COI phylogenetic tree revealed a multitude of hidden molecular lineages within this group (Clades I, II, III, V, VI, VII, and VIII), suggesting the existence of both host-generalist and genus-specific lineages of Zanclea associated with scleractinians. In addition to Z. gallii living in association with the genus Acropora, we discovered four well-supported lineages (Clades I, II, III, and VII), each one forming a strict association with a single scleractinian genus, including sequences of Zanclea associated with Montipora from two geographically separated areas (Maldives and Taiwan). Two host-generalist Zanclea lineages were also observed, and one of them was formed by Zanclea specimens symbiotic with seven scleractinian genera (Clade VIII). We also found that the COI gene allows the recognition of separated hidden lineages in agreement with the commonly recommended mitochondrial 16S as a DNA barcoding gene for Hydrozoa and shows reasonable potential for phylogenetic and evolutionary analyses in the genus Zanclea. Finally, as no DNA sequences are available for the majority of the nominal Zanclea species known, we note that they will be necessary to elucidate the diversity of the Zanclea

  14. Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders.

    Science.gov (United States)

    Gómez-Marín, Carlos; Tena, Juan J; Acemel, Rafael D; López-Mayorga, Macarena; Naranjo, Silvia; de la Calle-Mustienes, Elisa; Maeso, Ignacio; Beccari, Leonardo; Aneas, Ivy; Vielmas, Erika; Bovolenta, Paola; Nobrega, Marcelo A; Carvajal, Jaime; Gómez-Skarmeta, José Luis

    2015-06-16

    Increasing evidence in the last years indicates that the vast amount of regulatory information contained in mammalian genomes is organized in precise 3D chromatin structures. However, the impact of this spatial chromatin organization on gene expression and its degree of evolutionary conservation is still poorly understood. The Six homeobox genes are essential developmental regulators organized in gene clusters conserved during evolution. Here, we reveal that the Six clusters share a deeply evolutionarily conserved 3D chromatin organization that predates the Cambrian explosion. This chromatin architecture generates two largely independent regulatory landscapes (RLs) contained in two adjacent topological associating domains (TADs). By disrupting the conserved TAD border in one of the zebrafish Six clusters, we demonstrate that this border is critical for preventing competition between promoters and enhancers located in separated RLs, thereby generating different expression patterns in genes located in close genomic proximity. Moreover, evolutionary comparison of Six-associated TAD borders reveals the presence of CCCTC-binding factor (CTCF) sites with diverging orientations in all studied deuterostomes. Genome-wide examination of mammalian HiC data reveals that this conserved CTCF configuration is a general signature of TAD borders, underscoring that common organizational principles underlie TAD compartmentalization in deuterostome evolution. PMID:26034287

  15. Whole genome PCR scanning reveals the syntenic genome structure of toxigenic Vibrio cholerae strains in the O1/O139 population.

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    Bo Pang

    Full Text Available Vibrio cholerae is commonly found in estuarine water systems. Toxigenic O1 and O139 V. cholerae strains have caused cholera epidemics and pandemics, whereas the nontoxigenic strains within these serogroups only occasionally lead to disease. To understand the differences in the genome and clonality between the toxigenic and nontoxigenic strains of V. cholerae serogroups O1 and O139, we employed a whole genome PCR scanning (WGPScanning method, an rrn operon-mediated fragment rearrangement analysis and comparative genomic hybridization (CGH to analyze the genome structure of different strains. WGPScanning in conjunction with CGH revealed that the genomic contents of the toxigenic strains were conservative, except for a few indels located mainly in mobile elements. Minor nucleotide variation in orthologous genes appeared to be the major difference between the toxigenic strains. rrn operon-mediated rearrangements were infrequent in El Tor toxigenic strains tested using I-CeuI digested pulsed-field gel electrophoresis (PFGE analysis and PCR analysis based on flanking sequence of rrn operons. Using these methods, we found that the genomic structures of toxigenic El Tor and O139 strains were syntenic. The nontoxigenic strains exhibited more extensive sequence variations, but toxin coregulated pilus positive (TCP+ strains had a similar structure. TCP+ nontoxigenic strains could be subdivided into multiple lineages according to the TCP type, suggesting the existence of complex intermediates in the evolution of toxigenic strains. The data indicate that toxigenic O1 El Tor and O139 strains were derived from a single lineage of intermediates from complex clones in the environment. The nontoxigenic strains with non-El Tor type TCP may yet evolve into new epidemic clones after attaining toxigenic attributes.

  16. A comprehensive alanine-scanning mutagenesis study reveals roles for salt bridges in the structure and activity of Pseudomonas aeruginosa elastase.

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    Bian, Fei; Yue, Shousong; Peng, Zhenying; Zhang, Xiaowei; Chen, Gao; Yu, Jinhui; Xuan, Ning; Bi, Yuping

    2015-01-01

    The relationship between salt bridges and stability/enzymatic activity is unclear. We studied this relationship by systematic alanine-scanning mutation analysis using the typical M4 family metalloprotease Pseudomonas aeruginosa elastase (PAE, also known as pseudolysin) as a model. Structural analysis revealed seven salt bridges in the PAE structure. We constructed ten mutants for six salt bridges. Among these mutants, six (Asp189Ala, Arg179Ala, Asp201Ala, Arg205Ala, Arg245Ala and Glu249Ala) were active and four (Asp168Ala, Arg198Ala, Arg253Ala, and Arg279Ala) were inactive. Five mutants were purified, and their catalytic efficiencies (kcat/Km), half-lives (t1/2) and thermal unfolding curves were compared with those of PAE. Mutants Asp189Ala and Arg179Ala both showed decreased thermal stabilities and increased activities, suggesting that the salt bridge Asp189-Arg179 stabilizes the protein at the expense of catalytic efficiency. In contrast, mutants Asp201Ala and Arg205Ala both showed slightly increased thermal stability and slightly decreased activity, suggesting that the salt bridge Asp201-Arg205 destabilizes the protein. Mutant Glu249Ala is related to a C-terminal salt bridge network and showed both decreased thermal stability and decreased activity. Furthermore, Glu249Ala showed a thermal unfolding curve with three discernable states [the native state (N), the partially unfolded state (I) and the unfolded state (U)]. In comparison, there were only two discernable states (N and U) in the thermal unfolding curve of PAE. These results suggest that Glu249 is important for catalytic efficiency, stability and unfolding cooperativity. This study represents a systematic mutational analyses of salt bridges in the model metalloprotease PAE and provides important insights into the structure-function relationship of enzymes. PMID:25815820

  17. Genomic regions underlying agronomic traits in linseed (Linum usitatissimum L.) as revealed by association mapping

    Institute of Scientific and Technical Information of China (English)

    Braulio J. Soto-Cerda; Scott Duguid; Helen Booker; Gordon Rowland; Axel Diederichsen; Sylvie Cloutier

    2014-01-01

    The extreme climate of the Canadian Prairies poses a major chal enge to improve yield. Although it is possible to breed for yield per se, focusing on yield-related traits could be advantageous because of their simpler genetic architecture. The Canadian flax core col ection of 390 accessions was genotyped with 464 simple sequence repeat markers, and phenotypic data for nine agronomic traits including yield, bol s per area, 1,000 seed weight, seeds per bol , start of flowering, end of flowering, plant height, plant branching, and lodging col ected from up to eight environments was used for association mapping. Based on a mixed model (principal component analysis (PCA) þ kinship matrix (K)), 12 significant marker-trait associations for six agronomic traits were identi-fied. Most of the associations were stable across environments as revealed by multivariate analyses. Statistical simulation for five markers associated with 1000 seed weight indicated that the favorable al eles have additive effects. None of the modern cultivars carried the five favorable al eles and the maximum number of four observed in any accessions was mostly in breeding lines. Our results confirmed the complex genetic architecture of yield-related traits and the inherent difficulties associated with their identification while il ustrating the potential for improvement through marker-assisted selection.

  18. Genomic regions underlying agronomic traits in linseed (Linum usitatissimum L.) as revealed by association mapping.

    Science.gov (United States)

    Soto-Cerda, Braulio J; Duguid, Scott; Booker, Helen; Rowland, Gordon; Diederichsen, Axel; Cloutier, Sylvie

    2014-01-01

    The extreme climate of the Canadian Prairies poses a major challenge to improve yield. Although it is possible to breed for yield per se, focusing on yield-related traits could be advantageous because of their simpler genetic architecture. The Canadian flax core collection of 390 accessions was genotyped with 464 simple sequence repeat markers, and phenotypic data for nine agronomic traits including yield, bolls per area, 1,000 seed weight, seeds per boll, start of flowering, end of flowering, plant height, plant branching, and lodging collected from up to eight environments was used for association mapping. Based on a mixed model (principal component analysis (PCA) + kinship matrix (K)), 12 significant marker-trait associations for six agronomic traits were identified. Most of the associations were stable across environments as revealed by multivariate analyses. Statistical simulation for five markers associated with 1000 seed weight indicated that the favorable alleles have additive effects. None of the modern cultivars carried the five favorable alleles and the maximum number of four observed in any accessions was mostly in breeding lines. Our results confirmed the complex genetic architecture of yield-related traits and the inherent difficulties associated with their identification while illustrating the potential for improvement through marker-assisted selection. PMID:24138336

  19. Revealing genes associated with vitellogenesis in the liver of the zebrafish (Danio rerio by transcriptome profiling

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    Hyslop Terry

    2009-03-01

    Full Text Available Abstract Background In oviparous vertebrates, including fish, vitellogenesis consists of highly regulated pathways involving 17β-estradiol (E2. Previous studies focused on a relatively small number of hepatic expressed genes during vitellogenesis. This study aims to identify hepatic genes involved in vitellogenesis and regulated by E2, by using zebrafish microarray gene expression profiling, and to provide information on functional distinctive genes expressed in the liver of a vitellogenic female, using zebrafish as a model fish. Results Genes associated with vitellogenesis were revealed by the following paired t-tests (SAM comparisons: a two-month old vitellogenic (Vit2 females were compared with non-vitellogenic (NV females, showing 825 differentially expressed transcripts during early stages of vitellogenesis, b four-month old vitellogenic (Vit4 females were compared with NV females, showing 1,046 differentially expressed transcripts during vitellogenesis and c E2-treated males were compared with control males, showing 1,828 differentially expressed transcripts regulated by E2. A Venn diagram revealed 822 common transcripts in the three groups, indicating that these transcripts were involved in vitellogenesis and putatively regulated by E2. In addition, 431 transcripts were differentially expressed in Vit2 and Vit4 females but not in E2-treated males, indicating that they were putatively not up-regulated by E2. Correspondence analysis showed high similarity in expression profiles of Vit2 with Vit4 and of NV females with control males. The E2-treated males differed from the other groups. The repertoire of genes putatively regulated by E2 in vitellogenic females included genes associated with protein synthesis and reproduction. Genes associated with the immune system processes and biological adhesion, were among the genes that were putatively not regulated by E2. E2-treated males expressed a large array of transcripts that were not associated

  20. Genome-wide association and functional follow-up reveals new loci for kidney function.

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    Cristian Pattaro

    Full Text Available Chronic kidney disease (CKD is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR, the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

  1. Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes

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    Wainstein Julio

    2009-06-01

    Full Text Available Abstract Background Although mitochondrial dysfunction is consistently manifested in patients with Type 2 Diabetes mellitus (T2DM, the association of mitochondrial DNA (mtDNA sequence variants with T2DM varies among populations. These differences might stem from differing environmental influences among populations. However, other potentially important considerations emanate from the very nature of mitochondrial genetics, namely the notable high degree of partitioning in the distribution of human mtDNA variants among populations, as well as the interaction of mtDNA and nuclear DNA-encoded factors working in concert to govern mitochondrial function. We hypothesized that association of mtDNA genetic variants with T2DM could be revealed while controlling for the effect of additional inherited factors, reflected in family history information. Methods To test this hypothesis we set out to investigate whether mtDNA genetic variants will be differentially associated with T2DM depending on the diabetes status of the parents. To this end, association of mtDNA genetic backgrounds (haplogroups with T2DM was assessed in 1055 Jewish patients with and without T2DM parents ('DP' and 'HP', respectively. Results Haplogroup J1 was found to be 2.4 fold under-represented in the 'HP' patients (p = 0.0035. These results are consistent with a previous observation made in Finnish T2DM patients. Moreover, assessing the haplogroup distribution in 'DP' versus 'HP' patients having diabetic siblings revealed that haplogroup J1 was virtually absent in the 'HP' group. Conclusion These results imply the involvement of inherited factors, which modulate the susceptibility of haplogroup J1 to T2DM.

  2. Genome scans reveal candidate domestication and improvement genes in cultivated sunflower, as well as post-domestication introgression with wild relatives.

    Science.gov (United States)

    Baute, Gregory J; Kane, Nolan C; Grassa, Christopher J; Lai, Zhao; Rieseberg, Loren H

    2015-04-01

    The development of modern crops typically involves both selection and hybridization, but to date most studies have focused on the former. In the present study, we explore how both processes, and their interactions, have molded the genome of the cultivated sunflower (Helianthus annuus), a globally important oilseed. To identify genes targeted by selection during the domestication and improvement of sunflower, and to detect post-domestication hybridization with wild species, we analyzed transcriptome sequences of 80 genotypes, including wild, landrace, and modern lines of H. annuus, as well as two cross-compatible wild relatives, Helianthus argophyllus and Helianthus petiolaris. Outlier analyses identified 122 and 15 candidate genes associated with domestication and improvement, respectively. As in several previous studies, genes putatively involved in oil biosynthesis were the most extreme outliers. Additionally, several promising associations were observed with previously mapped quantitative trait loci (QTLs), such as branching. Admixture analyses revealed that all the modern cultivar genomes we examined contained one or more introgressions from wild populations, with every chromosome having evidence of introgression in at least one modern line. Cumulatively, introgressions cover c. 10% of the cultivated sunflower genome. Surprisingly, introgressions do not avoid candidate domestication genes, probably because of the reintroduction of branching.

  3. Genome scans reveal candidate domestication and improvement genes in cultivated sunflower, as well as post-domestication introgression with wild relatives.

    Science.gov (United States)

    Baute, Gregory J; Kane, Nolan C; Grassa, Christopher J; Lai, Zhao; Rieseberg, Loren H

    2015-04-01

    The development of modern crops typically involves both selection and hybridization, but to date most studies have focused on the former. In the present study, we explore how both processes, and their interactions, have molded the genome of the cultivated sunflower (Helianthus annuus), a globally important oilseed. To identify genes targeted by selection during the domestication and improvement of sunflower, and to detect post-domestication hybridization with wild species, we analyzed transcriptome sequences of 80 genotypes, including wild, landrace, and modern lines of H. annuus, as well as two cross-compatible wild relatives, Helianthus argophyllus and Helianthus petiolaris. Outlier analyses identified 122 and 15 candidate genes associated with domestication and improvement, respectively. As in several previous studies, genes putatively involved in oil biosynthesis were the most extreme outliers. Additionally, several promising associations were observed with previously mapped quantitative trait loci (QTLs), such as branching. Admixture analyses revealed that all the modern cultivar genomes we examined contained one or more introgressions from wild populations, with every chromosome having evidence of introgression in at least one modern line. Cumulatively, introgressions cover c. 10% of the cultivated sunflower genome. Surprisingly, introgressions do not avoid candidate domestication genes, probably because of the reintroduction of branching. PMID:25641359

  4. Genomic scan of selective sweeps in thin and fat tail sheep breeds for identifying of candidate regions associated with fat deposition

    Directory of Open Access Journals (Sweden)

    Moradi Mohammad Hossein

    2012-02-01

    Full Text Available Abstract Background Identification of genomic regions that have been targets of selection for phenotypic traits is one of the most important and challenging areas of research in animal genetics. However, currently there are relatively few genomic regions identified that have been subject to positive selection. In this study, a genome-wide scan using ~50,000 Single Nucleotide Polymorphisms (SNPs was performed in an attempt to identify genomic regions associated with fat deposition in fat-tail breeds. This trait and its modification are very important in those countries grazing these breeds. Results Two independent experiments using either Iranian or Ovine HapMap genotyping data contrasted thin and fat tail breeds. Population differentiation using FST in Iranian thin and fat tail breeds revealed seven genomic regions. Almost all of these regions overlapped with QTLs that had previously been identified as affecting fat and carcass yield traits in beef and dairy cattle. Study of selection sweep signatures using FST in thin and fat tail breeds sampled from the Ovine HapMap project confirmed three of these regions located on Chromosomes 5, 7 and X. We found increased homozygosity in these regions in favour of fat tail breeds on chromosome 5 and X and in favour of thin tail breeds on chromosome 7. Conclusions In this study, we were able to identify three novel regions associated with fat deposition in thin and fat tail sheep breeds. Two of these were associated with an increase of homozygosity in the fat tail breeds which would be consistent with selection for mutations affecting fat tail size several thousand years after domestication.

  5. Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer's disease.

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    Masataka Kikuchi

    Full Text Available Alzheimer's disease (AD, the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs, we identified the PINs expressed in three brain regions: the entorhinal cortex (EC, hippocampus (HIP and superior frontal gyrus (SFG. Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system.

  6. Nuclear Scans

    Science.gov (United States)

    Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

  7. Results from a horizon scan on risks associated with transplantation of human organs, tissues and cells: from donor to patient.

    Science.gov (United States)

    Herberts, C A; Park, M V D Z; Pot, J W G A; de Vries, C G J C A

    2015-03-01

    The successful transplantation of human materials such as organs, tissues and cells into patients does not only depend on the benefits, but also on the mitigation of risks. To gain insight into recent publications on risks associated with the process of transferring human materials from donor to recipient we performed a horizon scan by reviewing scientific literature and news websites of 2011 on this subject. We found there is ample information on how extended donor criteria, such as donor age, affect the survival rates of organs or patients. Interestingly, gender mismatch does not appear to be a major risk factor in organ rejection. Data on risks of donor tumor transmission was very scarce; however, risk categories for various tumor types have been suggested. In order to avoid rejection, a lot of research is directed towards engineering tissues from a patient's own tissues and cells. Some but not all of these developments have reached the clinic. Developments in the field of stem cell therapy are rapid. However, many hurdles are yet to be overcome before these cells can be applied on a large scale in the clinic. The processes leading to genetic abnormalities in cells differentiated from stem cells need to be identified in order to avoid transplantation of aberrant cells. New insights have been obtained on storage and preservation of human materials, a critical step for success of their clinical use. Likewise, quality management systems have been shown to improve the quality and safety of human materials used for transplantation.

  8. Comorbid Analysis of Genes Associated with Autism Spectrum Disorders Reveals Differential Evolutionary Constraints

    Science.gov (United States)

    David, Maude M.; Enard, David; Ozturk, Alp; Daniels, Jena; Jung, Jae-Yoon; Diaz-Beltran, Leticia; Wall, Dennis. P.

    2016-01-01

    The burden of comorbidity in Autism Spectrum Disorder (ASD) is substantial. The symptoms of autism overlap with many other human conditions, reflecting common molecular pathologies suggesting that cross-disorder analysis will help prioritize autism gene candidates. Genes in the intersection between autism and related conditions may represent nonspecific indicators of dysregulation while genes unique to autism may play a more causal role. Thorough literature review allowed us to extract 125 ICD-9 codes comorbid to ASD that we mapped to 30 specific human disorders. In the present work, we performed an automated extraction of genes associated with ASD and its comorbid disorders, and found 1031 genes involved in ASD, among which 262 are involved in ASD only, with the remaining 779 involved in ASD and at least one comorbid disorder. A pathway analysis revealed 13 pathways not involved in any other comorbid disorders and therefore unique to ASD, all associated with basal cellular functions. These pathways differ from the pathways associated with both ASD and its comorbid conditions, with the latter being more specific to neural function. To determine whether the sequence of these genes have been subjected to differential evolutionary constraints, we studied long term constraints by looking into Genomic Evolutionary Rate Profiling, and showed that genes involved in several comorbid disorders seem to have undergone more purifying selection than the genes involved in ASD only. This result was corroborated by a higher dN/dS ratio for genes unique to ASD as compare to those that are shared between ASD and its comorbid disorders. Short-term evolutionary constraints showed the same trend as the pN/pS ratio indicates that genes unique to ASD were under significantly less evolutionary constraint than the genes associated with all other disorders. PMID:27414027

  9. Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.

    Science.gov (United States)

    Phasukkijwatana, Nopasak; Kunhapan, Bussaraporn; Stankovich, Jim; Chuenkongkaew, Wanicha L; Thomson, Russell; Thornton, Timothy; Bahlo, Melanie; Mushiroda, Taisei; Nakamura, Yusuke; Mahasirimongkol, Surakameth; Tun, Aung Win; Srisawat, Chatchawan; Limwongse, Chanin; Peerapittayamongkol, Chayanon; Sura, Thanyachai; Suthammarak, Wichit; Lertrit, Patcharee

    2010-07-01

    Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.

  10. Correlation of spicule sign on computed tomography scans with peripheral lung cancers associated with interstitial lung disease and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Chen, L; Gao, L; Wu, W L

    2015-03-27

    The objective of this study was to investigate the correlation between spicular signs on computed tomography (CT) scans and peripheral lung cancer (PLC) that is associated with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). We analyzed clinical data from 96 PLC cases and grouped patients based on whether they had interstitial pneumonia into either ILD/COPD group or non-ILD/COPD group. The occurrence rate of spicule sign was 90.3% in the ILD/COPD group and 61.8% in the non-ILD/COPD group, respectively. There was a significant difference between these groups (P < 0.05). There were no significant differences in the occurrence rate of spicular signs among patients with different pathological types of PLC. The severity of ILD affected the spicular morphology on CT scans directly. There was a significant correlation between the appearance of spicule sign on CT scans and PLC that was associated with ILD/COPD.

  11. Functional Coding Variation in Recombinant Inbred Mouse Lines Reveals Novel Serotonin Transporter-Associated Phenotypes

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro, Ana [Vanderbilt University; Airey, David [University of Tennessee Health Science Center, Memphis; Thompson, Brent [Vanderbilt University; Zhu, C [Vanderbilt University; Rinchik, Eugene M [ORNL; Lu, Lu [University of Tennessee Health Science Center, Memphis; Chesler, Elissa J [ORNL; Erikson, Keith [University of North Carolina; Blakely, Randy [Vanderbilt University

    2009-01-01

    The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology or treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism and obsessive-compulsive disorder (OCD). Here we utilize naturally occurring polymorphisms in recombinant inbred (RI) lines to identify novel phenotypes associated with altered SERT function. The widely used mouse strain C57BL/6J, harbors a SERT haplotype defined by two nonsynonymous coding variants (Gly39 and Lys152 (GK)). At these positions, many other mouse lines, including DBA/2J, encode Glu39 and Arg152 (ER haplotype), assignments found also in hSERT. Synaptosomal 5-HT transport studies revealed reduced uptake associated with the GK variant. Heterologous expression studies confirmed a reduced SERT turnover rate for the GK variant. Experimental and in silico approaches using RI lines (C57Bl/6J X DBA/2J=BXD) identifies multiple anatomical, biochemical and behavioral phenotypes specifically impacted by GK/ER variation. Among our findings are multiple traits associated with anxiety and alcohol consumption, as well as of the control of dopamine (DA) signaling. Further bioinformatic analysis of BXD phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis that, in turn, dictates ironregulated DA phenotypes. Our studies provide a novel example of the power of coordinated in vitro, in vivo and in silico approaches using murine RI lines to elucidate and quantify the system-level impact of gene variation.

  12. A comparative scanning electron microscopy evaluation of smear layer removal with apple vinegar and sodium hypochlorite associated with EDTA

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    George Táccio de Miranda Candeiro

    2011-12-01

    Full Text Available OBJECTIVE: The purpose of this study was to evaluate by scanning electron microscopy (SEM the removal of smear layer from the middle and apical root thirds after use of different irrigating solutions. MATERIAL AND METHODS: Forty roots of permanent human teeth had their canals instrumented and were randomly assigned to 4 groups (n=10, according to the irrigating solution: apple vinegar (group A, apple vinegar finished with 17% ethylenediaminetetraacetic acid (EDTA (group B, 1% sodium hypochlorite (NaOCl finished with 17% EDTA (group C and saline (group D - control. After chemomechanical preparation, the roots were cleaved longitudinally and their middle and apical thirds were examined by SEM at ×1,000 magnification. Two calibrated examiners (kappa=0.92 analyzed the SEM micrographs qualitatively attributing scores that indicated the efficacy of the solutions in removing the smear layer from the surface of the dentin tubules (1 - poor, 2 - good and 3 - excellent. Data from the control and experimental groups were analyzed by the Kruskal-Wallis and Dunn's test, while the Wilcoxon test was used to compare the middle and apical thirds of the canals within the same group (a=0.05. RESULTS: The middle third presented less amount of smear layer than the apical third, regardless of the irrigant. There was statistically significant difference (p=0.0402 among the groups in the middle third. In the apical third, the apple vinegar/EDTA group showed the greatest removal of smear layer (p=0.0373. CONCLUSION: Apple vinegar associated or not with EDTA was effective in removing smear layer when used as an endodontic irrigant.

  13. Metagenomic Sequencing of the Chronic Obstructive Pulmonary Disease Upper Bronchial Tract Microbiome Reveals Functional Changes Associated with Disease Severity

    OpenAIRE

    Cameron, Simon J S; Keir E Lewis; Huws, Sharon A.; Wanchang Lin; Hegarty, Matthew J.; Lewis, Paul D.; Mur, Luis A. J.; Pachebat, Justin A

    2016-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide. The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results. Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associate...

  14. Autonomous gliders reveal features of the water column associated with foraging by adelie penguins.

    Science.gov (United States)

    Kahl, L Alex; Schofield, Oscar; Fraser, William R

    2010-12-01

    Despite their strong dependence on the pelagic environment, seabirds and other top predators in polar marine ecosystems are generally studied during their reproductive phases in terrestrial environments. As a result, a significant portion of their life history is understudied which in turn has led to limited understanding. Recent advances in autonomous underwater vehicle (AUV) technologies have allowed satellite-tagged Adélie penguins to guide AUV surveys of the marine environment at the Palmer Long-Term Ecological Research (LTER) site on the western Antarctic Peninsula. Near real-time data sent via Iridium satellites from the AUVs to a centralized control center thousands of miles away allowed scientists to adapt AUV sampling strategies to meet the changing conditions of the subsurface. Such AUV data revealed the water masses and fine-scale features associated with Adélie penguin foraging trips. During this study, the maximum concentration of chlorophyll was between 30 and 50 m deep. Encompassing this peak in the chlorophyll concentration, within the water-column, was a mixture of nutrient-laden Upper Circumpolar Deep (UCDW) and western Antarctic Peninsula winter water (WW). Together, data from the AUV survey and penguin dives reveal that 54% of foraging by Adélie penguins occurs immediately below the chlorophyll maximum. These data demonstrate how bringing together emerging technologies, such as AUVs, with established methods such as the radio-tagging of penguins can provide powerful tools for monitoring and hypothesis testing of previously inaccessible ecological processes. Ocean and atmosphere temperatures are expected to continue increasing along the western Antarctic Peninsula, which will undoubtedly affect regional marine ecosystems. New and emerging technologies such as unmanned underwater vehicles and individually mounted satellite tracking devices will provide the tools critical to documenting and understanding the widespread ecological change

  15. Mineral Compositions and Micro-Structural of Epoxy-Repaired Rock Revealed by X-ray Diffraction and Scanning Electron Microscopy

    OpenAIRE

    Wei Hu; Xu Wu; Jiawen Zhou; Minghui Hao; Xingguo Yang

    2013-01-01

    In order to improve the mechanical properties of rock with lots of cracks, this study adopts electronic methods (X-ray diffraction and scanning electron microscopy) to determine the mineral compositions and micro structural characteristics of epoxy-repaired rock. Fractured rocks with low strength or high permeability may not be appropriate for dam foundation. The strength and durability of fractured rock are increased after chemical grouting. Test results show that, some of the cracks and voi...

  16. Quantitative weaknesses of the Marcus-Hush theory of electrode kinetics revealed by Reverse Scan Square Wave Voltammetry: The reduction of 2-methyl-2-nitropropane at mercury microelectrodes

    Science.gov (United States)

    Laborda, Eduardo; Wang, Yijun; Henstridge, Martin C.; Martínez-Ortiz, Francisco; Molina, Angela; Compton, Richard G.

    2011-08-01

    The Marcus-Hush and Butler-Volmer kinetic electrode models are compared experimentally by studying the reduction of 2-methyl-2-nitropropane in acetonitrile at mercury microelectrodes using Reverse Scan Square Wave Voltammetry. This technique is found to be very sensitive to the electrode kinetics and to permit critical comparison of the two models. The Butler-Volmer model satisfactorily fits the experimental data whereas Marcus-Hush does not quantitatively describe this redox system.

  17. Laterality of brain areas associated with arithmetic calculations revealed by functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; ZHANG Quan; ZHANG Jing; LI Wei

    2005-01-01

    Background Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions: arithmetic calculation may be one of these phenomena. In this study, first, laterality of brain areas associated with arithmetic calculations was revealed by functional magnetic resonance imaging (fMRI). Second, the relationship among laterality, handedness, and types of arithmetic task was assessed. Third, we postulate possible reasons for laterality.Methods Using a block-designed experiment, twenty-five right-handed and seven left-handed healthy volunteers carried out simple calculations, complex calculations and proximity judgments. T1WI and GRE-EPI fMRI were performed with a GE 1.5T whole body MRI scanner. Statistical parametric mapping (SPM99) was used to process data and localize functional areas. Numbers of activated voxels were recorded to calculate laterality index for evaluating the laterality of functional brain areas.Results For both groups, the activation of functional areas in the frontal lobe showed a tendency towards the nonpredominant hand side, but the functional areas in the inferior parietal lobule had left laterality. During simple and complex calculations, the laterality indices of the prefrontal cortex and premotor area were higher in the right-handed group than that in the left-handed group, whereas the laterality of the inferior parietal lobule had no such significant difference. In both groups, when the difficulty of the task increased, the laterality of the prefrontal cortex, premotor area, and inferior parietal lobule decreased, but the laterality of posterior part of the inferior frontal gyrus increased.Conclusions The laterality of the functional brain areas associated with arithmetic calculations can be detected with fMRI. The laterality of the functional areas was related to handedness and task difficulty.

  18. Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics.

    Science.gov (United States)

    Sinha, Sudhir; Kosalai, K; Arora, Shalini; Namane, Abdelkader; Sharma, Pawan; Gaikwad, Anil N; Brodin, Priscille; Cole, Stewart T

    2005-07-01

    Membrane-associated proteins of Mycobacterium tuberculosis offer a challenge, as well as an opportunity, in the quest for better therapeutic and prophylactic interventions against tuberculosis. The authors have previously reported that extraction with the detergent Triton X-114 (TX-114) is a useful step in proteomic analysis of mycobacterial cell membranes, and detergent-soluble membrane proteins of mycobacteria are potent stimulators of human T cells. In this study 1-D and 2-D gel electrophoresis-based protocols were used for the analysis of proteins in the TX-114 extract of M. tuberculosis membranes. Peptide mass mapping (using MALDI-TOF-MS, matrix assisted laser desorption/ionization time of flight mass spectrometry) of 116 samples led to the identification of 105 proteins, 9 of which were new to the M. tuberculosis proteome. Functional orthologues of 73 of these proteins were also present in Mycobacterium leprae, suggesting their relative importance. Bioinformatics predicted that as many as 73% of the proteins had a hydrophobic disposition. 1-D gel electrophoresis revealed more hydrophobic/transmembrane and basic proteins than 2-D gel electrophoresis. Identified proteins fell into the following major categories: protein synthesis, cell wall biogenesis/architecture and conserved hypotheticals/unknowns. To identify immunodominant proteins of the detergent phase (DP), 14 low-molecular-mass fractions prepared by continuous-elution gel electrophoresis were subjected to T cell activation assays using blood samples from BCG-vaccinated healthy donors from a tuberculosis endemic area. Analysis of the responses (cell proliferation and IFN-gamma production) showed that the immunodominance of certain DP fractions was most probably due to ribosomal proteins, which is consistent with both their specificity for mycobacteria and their abundance. Other membrane-associated proteins, including transmembrane proteins/lipoproteins and ESAT-6, did not appear to contribute

  19. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  20. Conserved S-Layer-Associated Proteins Revealed by Exoproteomic Survey of S-Layer-Forming Lactobacilli.

    Science.gov (United States)

    Johnson, Brant R; Hymes, Jeffrey; Sanozky-Dawes, Rosemary; Henriksen, Emily DeCrescenzo; Barrangou, Rodolphe; Klaenhammer, Todd R

    2015-10-16

    The Lactobacillus acidophilus homology group comprises Gram-positive species that include L. acidophilus, L. helveticus, L. crispatus, L. amylovorus, L. gallinarum, L. delbrueckii subsp. bulgaricus, L. gasseri, and L. johnsonii. While these bacteria are closely related, they have varied ecological lifestyles as dairy and food fermenters, allochthonous probiotics, or autochthonous commensals of the host gastrointestinal tract. Bacterial cell surface components play a critical role in the molecular dialogue between bacteria and interaction signaling with the intestinal mucosa. Notably, the L. acidophilus complex is distinguished in two clades by the presence or absence of S-layers, which are semiporous crystalline arrays of self-assembling proteinaceous subunits found as the outermost layer of the bacterial cell wall. In this study, S-layer-associated proteins (SLAPs) in the exoproteomes of various S-layer-forming Lactobacillus species were proteomically identified, genomically compared, and transcriptionally analyzed. Four gene regions encoding six putative SLAPs were conserved in the S-layer-forming Lactobacillus species but not identified in the extracts of the closely related progenitor, L. delbrueckii subsp. bulgaricus, which does not produce an S-layer. Therefore, the presence or absence of an S-layer has a clear impact on the exoproteomic composition of Lactobacillus species. This proteomic complexity and differences in the cell surface properties between S-layer- and non-S-layer-forming lactobacilli reveal the potential for SLAPs to mediate intimate probiotic interactions and signaling with the host intestinal mucosa.

  1. Conserved S-Layer-Associated Proteins Revealed by Exoproteomic Survey of S-Layer-Forming Lactobacilli.

    Science.gov (United States)

    Johnson, Brant R; Hymes, Jeffrey; Sanozky-Dawes, Rosemary; Henriksen, Emily DeCrescenzo; Barrangou, Rodolphe; Klaenhammer, Todd R

    2016-01-01

    The Lactobacillus acidophilus homology group comprises Gram-positive species that include L. acidophilus, L. helveticus, L. crispatus, L. amylovorus, L. gallinarum, L. delbrueckii subsp. bulgaricus, L. gasseri, and L. johnsonii. While these bacteria are closely related, they have varied ecological lifestyles as dairy and food fermenters, allochthonous probiotics, or autochthonous commensals of the host gastrointestinal tract. Bacterial cell surface components play a critical role in the molecular dialogue between bacteria and interaction signaling with the intestinal mucosa. Notably, the L. acidophilus complex is distinguished in two clades by the presence or absence of S-layers, which are semiporous crystalline arrays of self-assembling proteinaceous subunits found as the outermost layer of the bacterial cell wall. In this study, S-layer-associated proteins (SLAPs) in the exoproteomes of various S-layer-forming Lactobacillus species were proteomically identified, genomically compared, and transcriptionally analyzed. Four gene regions encoding six putative SLAPs were conserved in the S-layer-forming Lactobacillus species but not identified in the extracts of the closely related progenitor, L. delbrueckii subsp. bulgaricus, which does not produce an S-layer. Therefore, the presence or absence of an S-layer has a clear impact on the exoproteomic composition of Lactobacillus species. This proteomic complexity and differences in the cell surface properties between S-layer- and non-S-layer-forming lactobacilli reveal the potential for SLAPs to mediate intimate probiotic interactions and signaling with the host intestinal mucosa. PMID:26475115

  2. Genome-wide SNP scan of pooled DNA reveals nonsense mutation in FGF20 in the scaleless line of featherless chickens

    Directory of Open Access Journals (Sweden)

    Wells Kirsty L

    2012-06-01

    Full Text Available Abstract Background Scaleless (sc/sc chickens carry a single recessive mutation that causes a lack of almost all body feathers, as well as foot scales and spurs, due to a failure of skin patterning during embryogenesis. This spontaneous mutant line, first described in the 1950s, has been used extensively to explore the tissue interactions involved in ectodermal appendage formation in embryonic skin. Moreover, the trait is potentially useful in tropical agriculture due to the ability of featherless chickens to tolerate heat, which is at present a major constraint to efficient poultry meat production in hot climates. In the interests of enhancing our understanding of feather placode development, and to provide the poultry industry with a strategy to breed heat-tolerant meat-type chickens (broilers, we mapped and identified the sc mutation. Results Through a cost-effective and labour-efficient SNP array mapping approach using DNA from sc/sc and sc/+ blood sample pools, we map the sc trait to chromosome 4 and show that a nonsense mutation in FGF20 is completely associated with the sc/sc phenotype. This mutation, common to all sc/sc individuals and absent from wild type, is predicted to lead to loss of a highly conserved region of the FGF20 protein important for FGF signalling. In situ hybridisation and quantitative RT-PCR studies reveal that FGF20 is epidermally expressed during the early stages of feather placode patterning. In addition, we describe a dCAPS genotyping assay based on the mutation, developed to facilitate discrimination between wild type and sc alleles. Conclusions This work represents the first loss of function genetic evidence supporting a role for FGF ligand signalling in feather development, and suggests FGF20 as a novel central player in the development of vertebrate skin appendages, including hair follicles and exocrine glands. In addition, this is to our knowledge the first report describing the use of the chicken SNP array to

  3. CT Scans

    Science.gov (United States)

    ... cross-sectional pictures of your body. Doctors use CT scans to look for Broken bones Cancers Blood clots Signs of heart disease Internal bleeding During a CT scan, you lie still on a table. The table ...

  4. Thyroid scan

    Science.gov (United States)

    ... PET scan Skin nodules Thyroid cancer Thyroid cancer - medullary carcinoma Thyroid cancer - papillary carcinoma Toxic nodular goiter ... Topics Hyperthyroidism Hypothyroidism Nuclear Scans Thyroid Cancer Thyroid Diseases Thyroid Tests Browse the Encyclopedia A.D.A. ...

  5. Association between Y haplogroups and autosomal AIMs reveals intra-population substructure in Bolivian populations.

    Science.gov (United States)

    Vullo, Carlos; Gomes, Verónica; Romanini, Carola; Oliveira, Andréa M; Rocabado, Omar; Aquino, Juliana; Amorim, António; Gusmão, Leonor

    2015-07-01

    For the correct evaluation of the weight of genetic evidence in a forensic context, databases must reflect the structure of the population, with all possible groups being represented. Countries with a recent history of admixture between strongly differentiated populations are usually highly heterogeneous and sub-structured. Bolivia is one of these countries, with a high diversity of ethnic groups and different levels of admixture (among Native Americans, Europeans and Africans) across the territory. For a better characterization of the male lineages in Bolivia, 17 Y-STR and 42 Y-SNP loci were genotyped in samples from La Paz and Chuquisaca. Only European and Native American Y-haplogroups were detected, and no sub-Saharan African chromosomes were found. Significant differences were observed between the two samples, with a higher frequency of European lineages in Chuquisaca than in La Paz. A sample belonging to haplogroup Q1a3a1a1-M19 was detected in La Paz, in a haplotype background different from those previously found in Argentina. This result supports an old M19 North-south dispersion in South America, possibly via two routes. When comparing the ancestry of each individual assessed through his Y chromosome with the one estimated using autosomal AIMs, (a) increased European ancestry in individuals with European Y chromosomes and (b) higher Native American ancestry in the carriers of Native American Y-haplogroups were observed, revealing an association between autosomal and Y-chromosomal markers. The results of this study demonstrate that a sub-structure does exist in Bolivia at both inter- and intrapopulation levels, a fact which must be taken into account in the evaluation of forensic genetic evidence.

  6. Quantitative protein localization signatures reveal an association between spatial and functional divergences of proteins.

    Science.gov (United States)

    Loo, Lit-Hsin; Laksameethanasan, Danai; Tung, Yi-Ling

    2014-03-01

    Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST), an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to elucidate protein

  7. Quantitative protein localization signatures reveal an association between spatial and functional divergences of proteins.

    Directory of Open Access Journals (Sweden)

    Lit-Hsin Loo

    2014-03-01

    Full Text Available Protein subcellular localization is a major determinant of protein function. However, this important protein feature is often described in terms of discrete and qualitative categories of subcellular compartments, and therefore it has limited applications in quantitative protein function analyses. Here, we present Protein Localization Analysis and Search Tools (PLAST, an automated analysis framework for constructing and comparing quantitative signatures of protein subcellular localization patterns based on microscopy images. PLAST produces human-interpretable protein localization maps that quantitatively describe the similarities in the localization patterns of proteins and major subcellular compartments, without requiring manual assignment or supervised learning of these compartments. Using the budding yeast Saccharomyces cerevisiae as a model system, we show that PLAST is more accurate than existing, qualitative protein localization annotations in identifying known co-localized proteins. Furthermore, we demonstrate that PLAST can reveal protein localization-function relationships that are not obvious from these annotations. First, we identified proteins that have similar localization patterns and participate in closely-related biological processes, but do not necessarily form stable complexes with each other or localize at the same organelles. Second, we found an association between spatial and functional divergences of proteins during evolution. Surprisingly, as proteins with common ancestors evolve, they tend to develop more diverged subcellular localization patterns, but still occupy similar numbers of compartments. This suggests that divergence of protein localization might be more frequently due to the development of more specific localization patterns over ancestral compartments than the occupation of new compartments. PLAST enables systematic and quantitative analyses of protein localization-function relationships, and will be useful to

  8. Scanning electron-microscopic and X-ray-microanalytic observation of diesel-emission particles associated with mutagenicity

    International Nuclear Information System (INIS)

    The particles formed by diesel combustion, which may contain various mutagenic chemicals like polycyclic aromatic hydrocarbons (PAH), are analyzed in their morphology by scanning electron microscopy; their sulfur content is detected by X-ray microanalysis, and mutagenicity is tested with a Salmonella typhimurium bioassay. The authors find a close correlation between sulfur content and mutagenicity of PAH. (Auth.)

  9. Association genetics in Populus reveals the interactions between Pt-miR397a and its target genes

    Science.gov (United States)

    Chen, Jinhui; Chen, Beibei; Yang, Xiaohui; Tian, Jiaxing; Du, Qingzhang; Zhang, Deqiang

    2015-01-01

    Recent studies have revealed associations between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes and diseases. However, association studies to decipher the interactions between miRNAs and their target genes remain to be conducted. Here, we investigated the association of growth and wood traits with SNPs in Pt-miR397a and its targets, in 261 individuals from a natural population of Populus tomentosa. Of the 57 SNPs identified in Pt-miR397a, three strongly affect its secondary stability, and SNPs in target sites in Pt-LAC20 and Pt-HSP40 changed the binding affinity of Pt-miR397a. Single-SNP association analysis revealed that SNPs in Pt-miR397a significantly associated with α-cellulose content and stem volume, and SNPs in target genes also associated with growth and wood-property traits. Multi-SNP association analysis with additive and dominant models found that SNPs in six potential target genes associated with at least one trait in common with Pt-miR397a, revealing a possible genetic interaction between Pt-miR397a and its targets. Furthermore, epistasis analysis revealed epistatic interactions between SNPs in Pt-miR397a and its target genes. Thus, our study indicated that SNPs in Pt-miR397a and six target genes affect wood formation and that association studies can reveal the interactions between miRNAs and their target genes. PMID:26115173

  10. SHEsisEpi, a GPU-enhanced genome-wide SNP-SNP interaction scanning algorithm, efficiently reveals the risk genetic epistasis in bipolar disorder

    Institute of Scientific and Technical Information of China (English)

    Xiaohan Hu; Qiang Liu; Zhao Zhang; Zhiqiang Li; Shilin Wang; Lin He; Yongyong Shi

    2010-01-01

    @@ Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study (GWAS) of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium's (WTCCC)GWAS data of bipolar disorder (BPD) with 500K SNPs.

  11. Mineral Compositions and Micro-Structural of Epoxy-Repaired Rock Revealed by X-ray Diffraction and Scanning Electron Microscopy

    Directory of Open Access Journals (Sweden)

    Wei Hu

    2013-09-01

    Full Text Available In order to improve the mechanical properties of rock with lots of cracks, this study adopts electronic methods (X-ray diffraction and scanning electron microscopy to determine the mineral compositions and micro structural characteristics of epoxy-repaired rock. Fractured rocks with low strength or high permeability may not be appropriate for dam foundation. The strength and durability of fractured rock are increased after chemical grouting. Test results show that, some of the cracks and voids are repaired by epoxy particles, resulted in the decreasing rock porosity. The proportion of epoxy resins is about 3.5%-5.5%, showing a discrete distribution and can not connect with each other.

  12. Mineralogical composition and phase-to-phase relationships in natural hydraulic lime and/or natural cement - raw materials and burnt products revealed by scanning electron microscopy

    Science.gov (United States)

    Kozlovcev, Petr; Přikryl, Richard; Racek, Martin; Přikrylová, Jiřina

    2016-04-01

    In contrast to modern process of production of cement clinker, traditional burning of natural hydraulic lime below sintering temperature relied on the formation of new phases from ion migration between neighbouring mineral grains composing raw material. The importance of the mineralogical composition and spatial distribution of rock-forming minerals in impure limestones used as a raw material for natural hydraulic lime presents not well explored issue in the scientific literature. To fill this gap, the recent study focuses in detailed analysis of experimentally burnt impure limestones (mostly from Barrandian area, Bohemian Massif). The phase changes were documented by optical microscopy, X-ray diffraction, and scanning electron microscopy with an energy dispersive spectrometer (SEM-EDS) coupled with x-ray elemental mapping. The latest allowed for visualization of distribution of elements within raw materials and burnt products. SEM/EDS study brought valuable data on the presence of transitional and/or minor phases, which were poorly detectable by other methods.

  13. Local optical absorption spectra of h-BN–MoS2 van der Waals heterostructure revealed by scanning near-field optical microscopy

    Science.gov (United States)

    Nozaki, Junji; Kobayashi, Yu; Miyata, Yasumitsu; Maniwa, Yutaka; Watanabe, Kenji; Taniguchi, Takashi; Yanagi, Kazuhiro

    2016-06-01

    Van der Waals (vdW) heterostructures, in which different two-dimensional layered materials are stacked, can exhibit unprecedented optical properties. Development of a technique to clarify local optical properties of vdW heterostructures is of great importance for the correct understanding of their backgrounds. Here, we examined local optical absorption spectra of h-BN–MoS2 vdW heterostructures by scanning near-field microscopy measurements with a spatial resolution of 100 nm. In an as-grown sample, there was almost no site dependence of their optical absorption spectra. However, in a degraded sample where defects and deformations were artificially induced, a significant site-dependence of optical absorption spectra was observed.

  14. Laser-scanning astrocyte mapping reveals increased glutamate-responsive domain size and disrupted maturation of glutamate uptake following neonatal cortical freeze-lesion

    Directory of Open Access Journals (Sweden)

    Mortiz eArmbruster

    2014-09-01

    Full Text Available Astrocytic uptake of glutamate shapes extracellular neurotransmitter dynamics, receptor activation, and synaptogenesis. During development, glutamate transport becomes more robust. How neonatal brain insult affects the functional maturation of glutamate transport remains unanswered. Neonatal brain insult can lead to developmental delays, cognitive losses, and epilepsy; the disruption of glutamate transport is known to cause changes in synaptogenesis, receptor activation, and seizure. Using the neonatal freeze-lesion (FL model, we have investigated how insult affects the maturation of astrocytic glutamate transport. As lesioning occurs on the day of birth, a time when astrocytes are still functionally immature, this model is ideal for identifying changes in astrocyte maturation following insult. Reactive astrocytosis, astrocyte proliferation, and in vitro hyperexcitability are known to occur in this model. To probe astrocyte glutamate transport with better spatial precision we have developed a novel technique, Laser Scanning Astrocyte Mapping (LSAM, which combines glutamate transport current (TC recording from astrocytes with laser scanning glutamate photolysis. LSAM allows us to identify the area from which a single astrocyte can transport glutamate and to quantify spatial heterogeneity in the rate of glutamate clearance kinetics within that domain. Using LSAM, we report that cortical astrocytes have an increased glutamate-responsive area following FL and that TCs have faster decay times in distal, as compared to proximal processes. Furthermore, the developmental shift from GLAST- to GLT-1-dominated clearance is disrupted following FL. These findings introduce a novel method to probe astrocyte glutamate uptake and show that neonatal cortical FL disrupts the functional maturation of cortical astrocytes.

  15. Revealing the synergetic effects in Ni nanoparticle-carbon nanotube hybrids by scanning transmission X-ray microscopy and their application in the hydrolysis of ammonia borane

    Science.gov (United States)

    Zhao, Guanqi; Zhong, Jun; Wang, Jian; Sham, Tsun-Kong; Sun, Xuhui; Lee, Shuit-Tong

    2015-05-01

    The hybrids of carbon nanotubes (CNTs) and the supported Ni nanoparticles (NPs) have been studied by scanning transmission X-ray microscopy (STXM) and tested by the hydrolysis reaction of ammonia borane (AB, NH3BH3). Data clearly showed the existence of a strong interaction between Ni NPs and thin CNTs (C-O-Ni bonds), which favored the tunable (buffer) electronic structure of Ni NPs facilitating the catalytic process. The hydrolysis process of AB confirmed the hypothesis that the hybrids with a strong interfacial interaction would show superior catalytic performance, while the hybrids with a weak interfacial interaction show poor performance. Our results provide a wealth of detailed information regarding the electronic structure of the NP-CNT hybrids and provide guidance towards the rational design of high-performance catalysts for energy applications.The hybrids of carbon nanotubes (CNTs) and the supported Ni nanoparticles (NPs) have been studied by scanning transmission X-ray microscopy (STXM) and tested by the hydrolysis reaction of ammonia borane (AB, NH3BH3). Data clearly showed the existence of a strong interaction between Ni NPs and thin CNTs (C-O-Ni bonds), which favored the tunable (buffer) electronic structure of Ni NPs facilitating the catalytic process. The hydrolysis process of AB confirmed the hypothesis that the hybrids with a strong interfacial interaction would show superior catalytic performance, while the hybrids with a weak interfacial interaction show poor performance. Our results provide a wealth of detailed information regarding the electronic structure of the NP-CNT hybrids and provide guidance towards the rational design of high-performance catalysts for energy applications. Electronic supplementary information (ESI) available: Magnified TEM images, high resolution TEM images and the particle size distributions of the samples, the STXM results of a thick tube at different positions, XPS results, stability test. See DOI: 10.1039/c5nr01168j

  16. Mobile gamma-ray scanning system for detecting radiation anomalies associated with 226Ra-bearing materials

    International Nuclear Information System (INIS)

    A mobile gamma-ray scanning system has been developed by Oak Ridge National Laboratory for use in the Department of Energy's remedial action survey programs. The unit consists of a NaI(T1) detection system housed in a specially-equipped van. The system is operator controlled through an on-board mini-computer, with data output provided on the computer video screen, strip chart recorders, and an on-line printer. Data storage is provided by a floppy disk system. Multichannel analysis capabilities are included for qualitative radionuclide identification. A 226Ra-specific algorithm is employed to identify locations containing residual radium-bearing materials. This report presents the details of the system description, software development, and scanning methods utilized with the ORNL system. Laboratory calibration and field testing have established the system sensitivity, field of view, and other performance characteristics, the results of which are also presented. Documentation of the instrumentation and computer programs are included

  17. Historical data reveal 30-year persistence of benthic fauna associations in heavily modified waterbody

    Directory of Open Access Journals (Sweden)

    Ruth Callaway

    2016-08-01

    Full Text Available Baseline surveys form the cornerstone of coastal impact studies where altered conditions, for example through new infrastructure development, are assessed against a temporal reference state. They are snapshots taken before construction. Due to scarcity of relevant data prior to baseline surveys long-term trends can often not be taken into account. Particularly in heavily modified waterbodies this would however be desirable to control for changes in anthropogenic use over time as well as natural ecological variation. Here, the benthic environment of an industrialized embayment was investigated (Swansea Bay, Wales, UK where it is proposed to build a tidal lagoon that would generate marine renewable energy from the tidal range. Since robust long-term baseline data was not available, the value of unpublished historical benthos information from 1984 by a regional water company was assessed with the aim to improve certainty about the persistence of current benthic community patterns. A survey of 101 positions in 2014 identified spatially discrete benthic communities with areas of high and low diversity. Habitat characteristics including sediment properties and the proximity to a sewage outfall explained 17-35% of the variation in the community structure. Comparing the historical information from 1984 with 2014 revealed striking similarity in the benthic communities between those years, not just in their spatial distribution but also to a large extent in the species composition. The 30-year-old information confirmed spatial boundaries of discrete species associations and pinpointed a similar diversity hotspot. A group of five common species was found to be particularly persistent over time (Nucula nitidosa, Spisula elliptica, Spiophanes bombyx, Nephtys hombergii, Diastylis rathkei. According to the Infauna Quality Index (IQI linked to the EU Water Framework Directive (WFD the average ecological status for 2014 was ‘moderate’, but eleven samples

  18. Local Magnetoelectric Effect in La-Doped BiFeO3 Multiferroic Thin Films Revealed by Magnetic-Field-Assisted Scanning Probe Microscopy.

    Science.gov (United States)

    Pan, Dan-Feng; Zhou, Ming-Xiu; Lu, Zeng-Xing; Zhang, Hao; Liu, Jun-Ming; Wang, Guang-Hou; Wan, Jian-Guo

    2016-12-01

    Multiferroic La-doped BiFeO3 thin films have been prepared by a sol-gel plus spin-coating process, and the local magnetoelectric coupling effect has been investigated by the magnetic-field-assisted scanning probe microscopy connected with a ferroelectric analyzer. The local ferroelectric polarization response to external magnetic fields is observed and a so-called optimized magnetic field of ~40 Oe is obtained, at which the ferroelectric polarization reaches the maximum. Moreover, we carry out the magnetic-field-dependent surface conductivity measurements and illustrate the origin of local magnetoresistance in the La-doped BiFeO3 thin films, which is closely related to the local ferroelectric polarization response to external magnetic fields. This work not only provides a useful technique to characterize the local magnetoelectric coupling for a wide range of multiferroic materials but also is significant for deeply understanding the local multiferroic behaviors in the BiFeO3-based systems. PMID:27356565

  19. Cardiac Myocyte Diversity and a Fibroblast Network in the Junctional Region of the Zebrafish Heart Revealed by Transmission and Serial Block-Face Scanning Electron Microscopy

    KAUST Repository

    Lafontant, Pascal J.

    2013-08-23

    The zebrafish has emerged as an important model of heart development and regeneration. While the structural characteristics of the developing and adult zebrafish ventricle have been previously studied, little attention has been paid to the nature of the interface between the compact and spongy myocardium. Here we describe how these two distinct layers are structurally and functionally integrated. We demonstrate by transmission electron microscopy that this interface is complex and composed primarily of a junctional region occupied by collagen, as well as a population of fibroblasts that form a highly complex network. We also describe a continuum of uniquely flattened transitional cardiac myocytes that form a circumferential plate upon which the radially-oriented luminal trabeculae are anchored. In addition, we have uncovered within the transitional ring a subpopulation of markedly electron dense cardiac myocytes. At discrete intervals the transitional cardiac myocytes form contact bridges across the junctional space that are stabilized through localized desmosomes and fascia adherentes junctions with adjacent compact cardiac myocytes. Finally using serial block-face scanning electron microscopy, segmentation and volume reconstruction, we confirm the three-dimensional nature of the junctional region as well as the presence of the sheet-like fibroblast network. These ultrastructural studies demonstrate the previously unrecognized complexity with which the compact and spongy layers are structurally integrated, and provide a new basis for understanding development and regeneration in the zebrafish heart. © 2013 Lafontant et al.

  20. Self-assembly of [Et,Et]-bacteriochlorophyll cF on highly oriented pyrolytic graphite revealed by scanning tunneling microscopy.

    Science.gov (United States)

    Möltgen, H; Kleinermanns, K; Jesorka, A; Schaffner, K; Holzwarth, A R

    2002-06-01

    The chlorosomal light-harvesting antennae of green phototrophic bacteria consist of large supramolecular aggregates of bacteriochlorophyll c (BChl c). The supramolecular structure of (3(1)-R/S)-BChl c on highly oriented pyrolytic graphite (HOPG) and molybdenum disulfide (MoS2) has been investigated by scanning tunneling microscopy (STM). On MoS2, we observed single BChl c molecules, dimers or tetramers, depending on the polarity of the solvent. On HOPG, we observed extensive self-assembly of the dimers and tetramers. We propose C=O...H-O...Mg bonding networks for the observed dimer chains, in agreement with former ultraviolet-visible and infrared spectroscopic work. The BChl c moieties in the tetramers are probably linked by four C=O...H-O hydrogen bonds to form a circle and further stabilized by Mg...O-H bondings to underlying BChl c layers. The tetramers form highly ordered, distinct chains and extended two-dimensional networks. We investigated semisynthetic chlorins for comparison by STM but observed that only BChl c self-assembles to well-structured large aggregates on HOPG. The results on the synthetic chlorins support our structure proposition. PMID:12081324

  1. Comparative Genome Sequence Analysis Reveals the Extent of Diversity and Conservation for Glycan-Associated Proteins in Burkholderia spp.

    OpenAIRE

    Ong, Hui San; Mohamed, Rahmah; Firdaus-Raih, Mohd

    2012-01-01

    Members of the Burkholderia family occupy diverse ecological niches. In pathogenic family members, glycan-associated proteins are often linked to functions that include virulence, protein conformation maintenance, surface recognition, cell adhesion, and immune system evasion. Comparative analysis of available Burkholderia genomes has revealed a core set of 178 glycan-associated proteins shared by all Burkholderia of which 68 are homologous to known essential genes. The genome sequence compari...

  2. Whole-genome scan to detect quantitative trait loci associated with milk protein composition in 3 French dairy cattle breeds.

    Science.gov (United States)

    Sanchez, M P; Govignon-Gion, A; Ferrand, M; Gelé, M; Pourchet, D; Amigues, Y; Fritz, S; Boussaha, M; Capitan, A; Rocha, D; Miranda, G; Martin, P; Brochard, M; Boichard, D

    2016-10-01

    In the context of the PhénoFinLait project, a genome-wide analysis was performed to detect quantitative trait loci (QTL) that affect milk protein composition estimated using mid-infrared spectrometry in the Montbéliarde (MO), Normande (NO), and Holstein (HO) French dairy cattle breeds. The 6 main milk proteins (α-lactalbumin, β-lactoglobulin, and αS1-, αS2-, β-, and κ-caseins) expressed as grams per 100g of milk (% of milk) or as grams per 100g of protein (% of protein) were estimated in 848,068 test-day milk samples from 156,660 cows. Genotyping was performed for 2,773 MO, 2,673 NO, and 2,208 HO cows using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). Individual test-day records were adjusted for environmental effects and then averaged per cow to define the phenotypes analyzed. Quantitative trait loci detection was performed within each breed using a linkage disequilibrium and linkage analysis approach. A total of 39 genomic regions distributed on 20 of the 29 Bos taurus autosomes (BTA) were significantly associated with milk protein composition at a genome-wide level of significance in at least 1 of the 3 breeds. The 9 most significant QTL were located on BTA2 (133 Mbp), BTA6 (38, 47, and 87 Mbp), BTA11 (103 Mbp), BTA14 (1.8 Mbp), BTA20 (32 and 58 Mbp), and BTA29 (8 Mbp). The BTA6 (87 Mbp), BTA11, and BTA20 (58 Mbp) QTL were found in all 3 breeds, and they had highly significant effects on κ-casein, β-lactoglobulin, and α-lactalbumin, expressed as a percentage of protein, respectively. Each of these QTL explained between 13% (BTA14) and 51% (BTA11) of the genetic variance of the trait. Many other QTL regions were also identified in at least one breed. They were located on 14 additional chromosomes (1, 3, 4, 5, 7, 15, 17, 19, 21, 22, 24, 25, 26, and 27), and they explained 2 to 8% of the genetic variance of 1 or more protein composition traits. Concordance analyses, performed between QTL status and sequence-derived polymorphisms from

  3. Z-Scan Analysis: a New Method to Determine the Oxidative State of Low-Density Lipoprotein and Its Association with Multiple Cardiometabolic Biomarkers

    Science.gov (United States)

    de Freitas, Maria Camila Pruper; Figueiredo Neto, Antonio Martins; Giampaoli, Viviane; da Conceição Quintaneiro Aubin, Elisete; de Araújo Lima Barbosa, Milena Maria; Damasceno, Nágila Raquel Teixeira

    2016-04-01

    The great atherogenic potential of oxidized low-density lipoprotein has been widely described in the literature. The objective of this study was to investigate whether the state of oxidized low-density lipoprotein in human plasma measured by the Z-scan technique has an association with different cardiometabolic biomarkers. Total cholesterol, high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A-I and apolipoprotein B, paraoxonase-1, and glucose were analyzed using standard commercial kits, and low-density lipoprotein cholesterol was estimated using the Friedewald equation. A sandwich enzyme-linked immunosorbent assay was used to detect electronegative low-density lipoprotein. Low-density lipoprotein and high-density lipoprotein sizes were determined by Lipoprint® system. The Z-scan technique was used to measure the non-linear optical response of low-density lipoprotein solution. Principal component analysis and correlations were used respectively to resize the data from the sample and test association between the θ parameter, measured with the Z-scan technique, and the principal component. A total of 63 individuals, from both sexes, with mean age 52 years (±11), being overweight and having high levels of total cholesterol and low levels of high-density lipoprotein cholesterol, were enrolled in this study. A positive correlation between the θ parameter and more anti-atherogenic pattern for cardiometabolic biomarkers together with a negative correlation for an atherogenic pattern was found. Regarding the parameters related with an atherogenic low-density lipoprotein profile, the θ parameter was negatively correlated with a more atherogenic pattern. By using Z-scan measurements, we were able to find an association between oxidized low-density lipoprotein state and multiple cardiometabolic biomarkers in samples from individuals with different cardiovascular risk factors.

  4. Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs

    DEFF Research Database (Denmark)

    Croft, Laurence J; Szklarczyk, Damian; Jensen, Lars J;

    2012-01-01

    reveal statistically significant associations between miRNAs and both TFs and signal transduction gene classes. Secondly, prediction of miRNA targets in human and mouse 3'UTRs show enrichment only for TFs but not consistently across prediction methods for signal transduction or other gene classes...

  5. Genome-wide association and functional follow-up reveals new loci for kidney function

    NARCIS (Netherlands)

    C. Pattaro (Cristian); A. Köttgen (Anna); A. Teumer (Alexander); C.A. Böger (Carsten); C. Fuchsberger (Christian); M. Olden (Matthias); M-H. Chen (Ming-Huei); M. Li (Man); X. Gao (Xiaoyi); M. Gorski (Mathias); Q. Yang (Qiong Fang); C.M. O'Seaghdha (Conall); N.L. Glazer (Nicole); A.J. Isaacs (Aaron); C.-T. Liu (Ching-Ti); A.V. Smith (Albert Vernon); J.R. O´Connell; M.V. Struchalin (Maksim); T. Tanaka (Toshiko); A.D. Johnson (Andrew); M.F. Feitosa (Mary Furlan); S.J. Hwang; K. Lohman (Kurt); M. Cornelis (Marilyn); A. Johansson (Åsa); A. Tönjes (Anke); A. Dehghan (Abbas); V. Chouraki (Vincent); E.G. Holliday (Elizabeth); R. Sorice; Z. Kutalik (Zoltán); T. Lehtimäki (Terho); T. Esko (Tõnu); S. Ulivi (Shelia); S. Trompet (Stella); M. Imboden (Medea); B. Kollerits (Barbara); G. Pistis (Giorgio); T.B. Harris (Tamara); L.J. Launer (Lenore); T. Aspelund (Thor); G. Eiriksdottir (Gudny); B.D. Mitchell (Braxton); E.A. Boerwinkle (Eric); R. Schmidt (Reinhold); M. Cavalieri (Margherita); F.B. Hu (Frank); A. Demirkan (Ayşe); B.A. Oostra (Ben); M. de Andrade (Mariza); J.S. Andrews (Jeanette S.); W. Koenig (Wolfgang); T. Illig (Thomas); A. Döring (Angela); H.E. Wichmann (Erich); I. Kolcic (Ivana); T. Zemunik (Tatijana); M. Boban (Mladen); W. Igl (Wilmar); G. Zaboli (Ghazal); S.H. Wild (Sarah); A.F. Wright (Alan); H. Campbell (Harry); R. Biffar (Reiner); F.D.J. Ernst (Florian); G. Homuth (Georg); H.K. Kroemer (Heyo); M. Nauck (Matthias); P. Kovacs (Peter); M. Stumvoll (Michael); R. Mägi (Reedik); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); Y.S. Aulchenko (Yurii); O. Polasek (Ozren); N. Hastie (Nick); V. Vitart (Veronique); J.J. Wang (Jie Jin); S.M. Bergmann (Sven); M. Kähönen (Mika); J. Viikari (Jorma); M.A. Province (Mike); S. Ketkar (Shamika); A.S.F. Doney (Alex); I. Ford (Ian); B.M. Buckley (Brendan M.); B. Paulweber (Bernhard); M. Haun (Margot); C. Sala (Cinzia); M. Ciullo; P. Vollenweider (Peter); O. Raitakari (Olli); A. Metspalu (Andres); C.N.A. Palmer (Colin); P. Gasparini (Paolo); J.W. Jukema (Jan Wouter); F. Kronenberg (Florian); D. Toniolo (Daniela); V. Gudnason (Vilmundur); A.R. Shuldiner (Alan); J. Coresh (Josef); L. Ferrucci (Luigi); D.S. Siscovick (David); P. Tikka-Kleemola (Päivi); I.B. Borecki (Ingrid); S.L.R. Kardia (Sharon); G.C. Curhan (Gary); I. Rudan (Igor); U. Gyllensten (Ulf); J.F. Wilson (James); A. Franke (Andre); P.P. Pramstaller (Peter Paul); R. Rettig (Rainer); I. Prokopenko (Inga); J.C.M. Witteman (Jacqueline); C. Hayward (Caroline); P.M. Ridker (Paul); A. Parsa (Afshin); M. Bochud (Murielle); I.M. Heid (Iris); W. Goessling (Wolfram); D.I. Chasman (Daniel); W.H.L. Kao (Wen); C.S. Fox (Caroline)

    2012-01-01

    textabstractChronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimate

  6. Involvement of surfactant protein D in emphysema revealed by genetic association study

    OpenAIRE

    Ishii, Takeo; Hagiwara, Koichi; Kamio, Koichiro; Ikeda, Shinobu; Arai, Tomio; Mieno, Makiko Naka; Kumasaka, Toshio; Muramatsu, Masaaki; Sawabe, Motoji; Gemma, Akihiko; Kida, Kozui

    2011-01-01

    Surfactant protein D (SFTPD) induces emphysema in knockout mice, but the association of SFTPD with chronic obstructive pulmonary disease (COPD) and emphysema in humans is unclear. Therefore, we aimed to determine the association between genetic variations in SFTPD and susceptibility to COPD and emphysema.

  7. Green LED associated to 20% hydrogen peroxide for dental bleaching: nanomorfologic study of enamel by scanning electron microscopy

    Science.gov (United States)

    Oliveira, Susana C. P. S.; Santos, Gustavo M. P.; Monteiro, Juliana S. C.; Sampaio, Fernando J. P.; Gesteira, Maria F. M.; Zanin, Fátima A. A.; Santos, Marcos A. V.; Pinheiro, Antônio L. B.

    2013-03-01

    Dental bleaching is a much requested procedure in clinical dental practice and widely related to dental esthetics. The literature is contradictory regarding the effects of bleaching agents on the morphology and demineralization of enamel after bleaching. The aim of this study was to analyze in vitro by scanning electron microscopy (SEM) the effect of hydrogen peroxide at 20% at neutral pH, cured by the green LED, to evaluate the action of these substances on dental enamel. We selected 15 pre-molars, lingual surfaces were sectioned and previously marked with a central groove to take the experimental and control groups on the same specimen. The groups were divided as follows. The mesial hemi-faces were the experimental group and distal ones as controls. For morphological analysis were performed 75 electron micrographs SEM with an increase of X 43, X 220 and X 1000 and its images were evaluated by tree observers. Was also performed quantitative analysis of the determination of the surface atomic composition of the samples through microanalysis with the aid of scanning electron microscopy. The use of hydrogen peroxide at a concentration of 20% at photoactivated green LED showed no significant changes in mineral composition of the samples or the dental morphological structure of the same when compared to their controls, according to the study protocol.

  8. Associations between common intestinal parasites and bacteria in humans as revealed by qPCR

    DEFF Research Database (Denmark)

    O'Brien Andersen, L.; Karim, A. B.; Roager, Henrik Munch;

    2016-01-01

    Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we...... set out to investigate potential associations between common single-celled parasites such as Blastocystis spp. and Dientamoeba fragilis and intestinal bacteria. Stool DNA from patients with intestinal symptoms were selected based on being Blastocystis spp.-positive (B+)/negative (B-) and D. fragilis...

  9. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    NARCIS (Netherlands)

    Rooijers, K.; Loayza-Puch, F.; Nijtmans, L.G.J.; Agami, R.

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations oft

  10. Opening the climate envelope reveals no macroscale associations with climate in European birds

    OpenAIRE

    Beale, Colin M.; Lennon, Jack J.; Gimona, Alessandro

    2008-01-01

    Predicting how species distributions might shift as global climate changes is fundamental to the successful adaptation of conservation policy. An increasing number of studies have responded to this challenge by using climate envelopes, modeling the association between climate variables and species distributions. However, it is difficult to quantify how well species actually match climate. Here, we use null models to show that species–climate associations found by climate envelope methods are ...

  11. Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders

    OpenAIRE

    Gómez-Marín, Carlos; Tena, Juan J.; Acemel, Rafael D.; López-Mayorga, Macarena; Naranjo, Silvia; de la Calle-Mustienes, Elisa; Maeso, Ignacio; Beccari, Leonardo; Aneas, Ivy; Vielmas, Erika; Bovolenta, Paola; Nobrega, Marcelo A.; Carvajal, Jaime; Gómez-Skarmeta, José Luis

    2015-01-01

    Increasing evidence in the last years indicates that the vast amount of regulatory information contained in mammalian genomes is organized in precise 3D chromatin structures. However, the impact of this spatial chromatin organization on gene expression and its degree of evolutionary conservation is still poorly understood. The Six homeobox genes are essential developmental regulators organized in gene clusters conserved during evolution. Here, we reveal that the Six clusters share a deeply ev...

  12. A genome-wide association study reveals variants in ARL15 that influence adiponectin levels.

    Directory of Open Access Journals (Sweden)

    J Brent Richards

    2009-12-01

    Full Text Available The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D and coronary heart disease (CHD. We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531 and sought validation of the lead single nucleotide polymorphisms (SNPs in 5 additional cohorts (n = 6,202. Five SNPs were genome-wide significant in their relationship with adiponectin (P< or =5x10(-8. We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19 for lead SNP, rs266717, n = 14,733. A novel variant in the ARL15 (ADP-ribosylation factor-like 15 gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8, n = 14,733. This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6, n = 22,421 more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3, n = 10,128, and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.

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

    Directory of Open Access Journals (Sweden)

    Rico Rueedi

    2014-02-01

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

  14. Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

    Science.gov (United States)

    Shaffer, John R; Orlova, Ekaterina; Lee, Myoung Keun; Leslie, Elizabeth J; Raffensperger, Zachary D; Heike, Carrie L; Cunningham, Michael L; Hecht, Jacqueline T; Kau, Chung How; Nidey, Nichole L; Moreno, Lina M; Wehby, George L; Murray, Jeffrey C; Laurie, Cecelia A; Laurie, Cathy C; Cole, Joanne; Ferrara, Tracey; Santorico, Stephanie; Klein, Ophir; Mio, Washington; Feingold, Eleanor; Hallgrimsson, Benedikt; Spritz, Richard A; Marazita, Mary L; Weinberg, Seth M

    2016-08-01

    Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p mechanisms controlling normal and abnormal facial morphogenesis. PMID:27560520

  15. MRI Scans

    Science.gov (United States)

    Magnetic resonance imaging (MRI) uses a large magnet and radio waves to look at organs and structures inside your body. Health care professionals use MRI scans to diagnose a variety of conditions, from ...

  16. CT scan

    Science.gov (United States)

    ... come from a CT scan. Some people have allergies to contrast dye. Let your doctor know if you have ... vein contains iodine. If you have an iodine allergy, a type of contrast may cause nausea or vomiting , sneezing , itching , or ...

  17. Genotype × Environment Interactions for Agronomic Traits of Rice Revealed by Association Mapping

    Institute of Scientific and Technical Information of China (English)

    XU Fei-fei; TANG Fu-fu; SHAO Ya-fang; CHEN Ya-ling; TONG Chuan; BAO Jin-song

    2014-01-01

    Agronomic traits are important determinants to rice yield, which are controlled by complex genetic factors as well as genotype by environment (G × E) interaction effects. The G × E effects for agronomic traits of rice have been dissected with various approaches, but not with the current available approach, the association studies. In this study, a total of 32 655 single nucleotide polymorphisms were used to carry out associations with 14 agronomic traits among 20 rice accessions in two environments. The G × E interaction effects for all the agronomic traits were at highly significant levels (P<0.01), accounting for 3.4%-22.3% of the total sum of squares except for the length of brown rice. Twenty three putative quantitative trait loci (QTLs), including five previously known and several new promising associations, were identified for 10 of 14 traits. Analysis of the relationships between the traits for which QTLs and the genotype effects could be identified suggested that the higher the genotypic effect, the higher the possibility to identify QTLs for the given trait. The new QTLs detected in this study will facilitate dissection of the complex agronomic traits and may give insight into the G × E effects with association mapping.

  18. Associations between common intestinal parasites and bacteria in humans as revealed by qPCR.

    Science.gov (United States)

    O'Brien Andersen, L; Karim, A B; Roager, H M; Vigsnæs, L K; Krogfelt, K A; Licht, T R; Stensvold, C R

    2016-09-01

    Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we set out to investigate potential associations between common single-celled parasites such as Blastocystis spp. and Dientamoeba fragilis and intestinal bacteria. Stool DNA from patients with intestinal symptoms were selected based on being Blastocystis spp.-positive (B+)/negative (B-) and D. fragilis-positive (D+)/negative (D-), and split into four groups of 21 samples (B+ D+, B+ D-, B- D+, and B- D-). Quantitative PCR targeting the six bacterial taxa Bacteroides, Prevotella, the butyrate-producing clostridial clusters IV and XIVa, the mucin-degrading Akkermansia muciniphila, and the indigenous group of Bifidobacterium was subsequently performed, and the relative abundance of these bacteria across the four groups was compared. The relative abundance of Bacteroides in B- D- samples was significantly higher compared with B+ D- and B+ D+ samples (P Blastocystis alone or combined with D. fragilis is associated with gut microbiota characterized by low relative abundances of Bacteroides and Clostridial cluster XIVa and high levels of Prevotella. PMID:27230509

  19. Swollen eyelid reveals multiple intracranial hydatid cysts associated with a palpebral cyst.

    Science.gov (United States)

    Tzili, N; Ahbeddou, S; Ahmimech, J; Abboud, H; Boutarbouch, M; El Hassan, A; Berraho, A

    2016-02-01

    We report a case of a hydatid cyst of the eyelid in a 12-year-old boy associated with cerebral involvement. The patient was initially treated by neurosurgeons for brain cysts. The course after an interval of two months was marked by regression of the palpebral cyst on albendazole.

  20. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation.

    Science.gov (United States)

    Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Quinto-Sánchez, Mirsha; Mendoza-Revilla, Javier; Camilo Chacón-Duque, Juan; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Lozano, Rodrigo Barquera; Pérez, Gastón Macín; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Cheeseman, Michael; Rosique, Javier; Bedoya, Gabriel; Rothhammer, Francisco; Headon, Denis; González-José, Rolando; Balding, David; Ruiz-Linares, Andrés

    2016-01-01

    We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion. PMID:27193062

  1. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

    Science.gov (United States)

    Adhikari, Kaustubh; Fuentes-Guajardo, Macarena; Quinto-Sánchez, Mirsha; Mendoza-Revilla, Javier; Camilo Chacón-Duque, Juan; Acuña-Alonzo, Victor; Jaramillo, Claudia; Arias, William; Lozano, Rodrigo Barquera; Pérez, Gastón Macín; Gómez-Valdés, Jorge; Villamil-Ramírez, Hugo; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Hurtado, Malena; Villegas, Valeria; Granja, Vanessa; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria- Cátira; Canizales-Quinteros, Samuel; Cheeseman, Michael; Rosique, Javier; Bedoya, Gabriel; Rothhammer, Francisco; Headon, Denis; González-José, Rolando; Balding, David; Ruiz-Linares, Andrés

    2016-01-01

    We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion. PMID:27193062

  2. Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology

    Science.gov (United States)

    Raffensperger, Zachary D.; Heike, Carrie L.; Cunningham, Michael L.; Hecht, Jacqueline T.; Kau, Chung How; Moreno, Lina M.; Wehby, George L.; Murray, Jeffrey C.; Laurie, Cecelia A.; Laurie, Cathy C.; Santorico, Stephanie; Klein, Ophir; Feingold, Eleanor; Hallgrimsson, Benedikt; Spritz, Richard A.; Marazita, Mary L.; Weinberg, Seth M.

    2016-01-01

    Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10−8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis. PMID:27560520

  3. Global metabolomic profiling reveals an association of metal fume exposure and plasma unsaturated fatty acids.

    Directory of Open Access Journals (Sweden)

    Yongyue Wei

    Full Text Available BACKGROUND: Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans. OBJECTIVES: To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure. METHODS: The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry. RESULTS: Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5 exposure (p<0.05. The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [β(95% CI = -0.013(-0.022 ≈ -0.004; p = 0.005], docosapentaenoic acid n3 [β(95% CI = -0.010(-0.018 ≈ -0.002; p = 0.017], and docosapentaenoic acid n6 [β(95% CI = -0.007(-0.013 ≈ -0.001; p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p Study-2011 = 0.025; p Study-2012 = 0.021; p Combined = 0.009. The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders. CONCLUSIONS: High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders.

  4. Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

    Directory of Open Access Journals (Sweden)

    John R Shaffer

    2016-08-01

    Full Text Available Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array imputed to the 1000 Genomes reference panel (Phase 3. We observed genome-wide significant associations (p < 5 x 10-8 for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

  5. Association studies and legume synteny reveal haplotypes determining seed size in Vigna unguiculata

    Directory of Open Access Journals (Sweden)

    Mitchell R Lucas

    2013-04-01

    Full Text Available Highly specific seed market classes for cowpea and other grain legumes exists because grain is most commonly cooked and consumed whole. Size, shape, color, and texture are critical features of these market classes and breeders target development of cultivars for market acceptance. Resistance to biotic and abiotic stresses that are absent from elite breeding material are often introgressed through crosses to landraces or wild relatives. When crosses are made between parents with different grain quality characteristics, recovery of progeny with acceptable or enhanced grain quality is problematic. Thus genetic markers for grain quality traits can help in pyramiding genes needed for specific market classes. Allelic variation dictating the inheritance of seed size can be tagged and used to assist the selection of large-seeded lines. In this work we applied SNP genotyping and knowledge of legume synteny to characterize regions of the cowpea genome associated with seed size. These marker-trait associations will enable breeders to use marker based selection approaches to increase the frequency of progeny with large seed. For ~800 samples derived from eight bi-parental populations, QTL analysis was used to identify markers linked to ten trait determinants. In addition, the population structure of 171 samples from the USDA core collection was identified and incorporated into a genome-wide association study which supported more than half of the trait-associated regions important in the bi-parental populations. Seven of the total ten QTL were supported based on synteny to seed size associated regions identified in the related legume soybean. In addition to delivering markers linked to major trait determinants in the context of modern breeding, we provide an analysis of the diversity of the USDA core collection of cowpea to identify genepools, migrants, admixture, and duplicates.

  6. Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

    Science.gov (United States)

    Shaffer, John R; Orlova, Ekaterina; Lee, Myoung Keun; Leslie, Elizabeth J; Raffensperger, Zachary D; Heike, Carrie L; Cunningham, Michael L; Hecht, Jacqueline T; Kau, Chung How; Nidey, Nichole L; Moreno, Lina M; Wehby, George L; Murray, Jeffrey C; Laurie, Cecelia A; Laurie, Cathy C; Cole, Joanne; Ferrara, Tracey; Santorico, Stephanie; Klein, Ophir; Mio, Washington; Feingold, Eleanor; Hallgrimsson, Benedikt; Spritz, Richard A; Marazita, Mary L; Weinberg, Seth M

    2016-08-01

    Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3). We observed genome-wide significant associations (p < 5 x 10-8) for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

  7. A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes.

    Directory of Open Access Journals (Sweden)

    Fu-Hui Xiao

    Full Text Available It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer's disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity.

  8. Scanning the cell surface proteome of cancer cells and identification of metastasis-associated proteins using a subtractive immunization strategy

    DEFF Research Database (Denmark)

    Rasmussen, Nicolaj; Ditzel, Henrik J

    2009-01-01

    and technologically challenging, and no ideal method is currently available. Here, we describe a strategy that allows scanning of the entire cell surface and identification of molecules that exhibit altered expression between two cell types. Concurrently, this method gives rise to valuable reagents for further...... characterization of the identified proteins. The strategy is based on subtractive immunization of mice, and we used the two isogenic cell lines, NM-2C5 and M-4A4, derived from the MDA-MB-435 cancer cell line, as a model system. Although the two cell lines are equally tumorigenic, only M-4A4 has metastatic...... exhibiting no or very weak reactivity with normal tissues. mAb 15C7 stained a variety of cancers as well as some normal lymphoid organs and was subsequently identified to react with HLA-DR-beta. A third mAb, 31D7, that also specifically recognized HLA-DR-beta was capable of inhibiting the growth of MZ2...

  9. Comprehensive genotyping in two homogeneous Graves' disease samples reveals major and novel HLA association alleles.

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    Pei-Lung Chen

    Full Text Available BACKGROUND: Graves' disease (GD is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families. To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc]  = 1.17 x 10⁻², DPB1*05:01 (OR  = 2.34, P(Bc = 2.58 x 10⁻¹⁰, DQB1*03:02 (OR  = 0.62, P(Bc  = 1.97 x 10⁻², DRB1*15:01 (OR  = 1.68, P(Bc = 1.22 x 10⁻² and DRB1*16:02 (OR  = 2.63, P(Bc  = 1.46 x 10⁻⁵ were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future

  10. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery

    DEFF Research Database (Denmark)

    Poulsen, Michael; Oh, Dong-Chan; Clardy, Jon;

    2011-01-01

    Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social...... of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal...... and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding...

  11. Optical quantal analysis reveals a presynaptic component of LTP at hippocampal Schaffer-associational synapses.

    Science.gov (United States)

    Emptage, Nigel J; Reid, Christopher A; Fine, Alan; Bliss, Timothy V P

    2003-06-01

    The mechanisms by which long-term potentiation (LTP) is expressed are controversial, with evidence for both presynaptic and postsynaptic involvement. We have used confocal microscopy and Ca(2+)-sensitive dyes to study LTP at individual visualized synapses. Synaptically evoked Ca(2+) transients were imaged in distal dendritic spines of pyramidal cells in cultured hippocampal slices, before and after the induction of LTP. At most synapses, from as early as 10 min to at least 60 min after induction, LTP was associated with an increase in the probability of a single stimulus evoking a postsynaptic Ca(2+) response. These observations provide compelling evidence of a presynaptic component to the expression of early LTP at Schaffer-associational synapses. In most cases, the store-dependent evoked Ca(2+) transient in the spine was also increased after induction, a novel postsynaptic aspect of LTP.

  12. An association of vertebral breast cancer metastasis and multiple myeloma, revealed by a spinal cord compression

    OpenAIRE

    Kherfani, Abdelhakim; Amri, Khalil; Hachem, Mahjoub; Abid, Leila; Bouaziz, Mouna; Mestiri, Mondher

    2014-01-01

    Authors describe the case of a patient with breast cancer and multiple myeloma as the second metachronous disease responsible for spinal cord compression. Synchronous occurrence of bone marrow breast cancer disease and multiple myeloma has not been described in the literature, as in this case. By presenting this case, we point to possible association between both diseases and the possible factors involved in the development of second malignant disease.

  13. Genetic association for renal traits among participants of African ancestry reveals new loci for renal function.

    Directory of Open Access Journals (Sweden)

    Ching-Ti Liu

    2011-09-01

    Full Text Available Chronic kidney disease (CKD is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA, and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR, CKD (eGFR 30 mg/g and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B. Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3. In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10(-7 and FNDC1 (p-value = 3.0×10(-7 for UACR, and KCNQ1 with eGFR (p = 3.6×10(-6. Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish.

  14. Liver transcriptomic networks reveal main biological processes associated with feed efficiency in beef cattle

    OpenAIRE

    Alexandre, Pamela A.; Kogelman, Lisette; Santana, Miguel H. A.; Passarelli, Danielle; Pulz, Lidia H.; Fantinato-Neto, Paulo; Silva, Paulo L.; Leme, Paulo R; Strefezzi, Ricardo F.; Coutinho, Luiz L.; Ferraz, José B. S.; Eler, Joanie P.; Kadarmideen, Haja; Fukumasu, Heidge

    2015-01-01

    Background The selection of beef cattle for feed efficiency (FE) traits is very important not only for productive and economic efficiency but also for reduced environmental impact of livestock. Considering that FE is multifactorial and expensive to measure, the aim of this study was to identify biological functions and regulatory genes associated with this phenotype. Results Eight genes were differentially expressed between high and low feed efficient animals (HFE and LFE, respectively). Co-e...

  15. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    OpenAIRE

    Rooijers, Koos; Loayza-Puch, Fabricio; Nijtmans, Leo G.; Agami, Reuven

    2013-01-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson's disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations often affect components of the mitochondrial translation machinery. Here we perform ribosome profiling to measure mitochondrial translation at nucleotide resolution. Using a protocol optimized for the...

  16. Common Trends in Mutualism Revealed by Model Associations Between Invertebrates and Bacteria

    OpenAIRE

    Chaston, John; Goodrich-Blair, Heidi

    2010-01-01

    Mutually beneficial interactions between microbes and animals are a conserved and ubiquitous feature of biotic systems. In many instances animals, including humans, are dependent on their microbial associates for nutrition, defense, or development. To maintain these vital relationships animals have evolved processes that ensure faithful transmission of specific microbial symbionts between generations. Elucidating mechanisms of transmission and symbiont specificity has been aided by the study ...

  17. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

  18. Differences in cardiovascular toxicities associated with cigarette smoking and snuff use revealed using novel zebrafish models

    Directory of Open Access Journals (Sweden)

    Maggie Folkesson

    2016-07-01

    Full Text Available Tobacco use is strongly associated with cardiovascular disease and the only avoidable risk factor associated with development of aortic aneurysm. While smoking is the most common form of tobacco use, snuff and other oral tobacco products are gaining popularity, but research on potentially toxic effects of oral tobacco use has not kept pace with the increase in its use. Here, we demonstrate that cigarette smoke and snuff extracts are highly toxic to developing zebrafish embryos. Exposure to such extracts led to a palette of toxic effects including early embryonic mortality, developmental delay, cerebral hemorrhages, defects in lymphatics development and ventricular function, and aneurysm development. Both cigarette smoke and snuff were more toxic than pure nicotine, indicating that other compounds in these products are also associated with toxicity. While some toxicities were found following exposure to both types of tobacco product, other toxicities, including developmental delay and aneurysm development, were specifically observed in the snuff extract group, whereas cerebral hemorrhages were only found in the group exposed to cigarette smoke extract. These findings deepen our understanding of the pathogenic effects of cigarette smoking and snuff use on the cardiovascular system and illustrate the benefits of using zebrafish to study mechanisms involved in aneurysm development.

  19. Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression

    Directory of Open Access Journals (Sweden)

    Ana Lustig, Arnell Carter, Dorothy Bertak, Divya Enika, Bolormaa Vandanmagsar, William Wood, Kevin G. Becker, Ashani T. Weeraratna, Dennis D. Taub

    2009-01-01

    Full Text Available The decline in adaptive immunity, naïve T-cell output and a contraction in the peripheral T cell receptor (TCR repertoire with age are largely attributable to thymic involution and the loss of critical cytokines and hormones within the thymic microenvironment. To assess the molecular changes associated with this loss of thymic function, we used cDNA microarray analyses to examine the transcriptomes of thymocytes from mice of various ages ranging from very young (1 month to very old (24 months. Genes associated with various biological and molecular processes including oxidative phosphorylation, T- and B- cell receptor signaling and antigen presentation were observed to significantly change with thymocyte age. These include several immunoglobulin chains, chemokine and ribosomal proteins, annexin A2, vav 1 and several S100 signaling proteins. The increased expression of immunoglobulin genes in aged thymocytes could be attributed to the thymic B cells which were found to be actively producing IgG and IgM antibodies. Upon further examination, we found that purified thymic T cells derived from aged but not young thymi also exhibited IgM on their cell surface suggesting the possible presence of auto-antibodies on the surface thymocytes with advancing age. These studies provide valuable insight into the cellular and molecular mechanisms associated with thymic aging.

  20. Phylogenetic Analysis of Staphylococcus aureus CC398 Reveals a Sub-Lineage Epidemiologically Associated with Infections in Horses

    DEFF Research Database (Denmark)

    Abdelbary, Mohamed M. H.; Wittenberg, Anne; Cuny, Christiane;

    2014-01-01

    -allelic polymorphisms, and phylogenetic analyses revealed that an epidemic sub-clone within CC398 (dubbed 'clade (C)') has spread within and between equine hospitals, where it causes nosocomial infections in horses and colonises the personnel. While clade (C) was strongly associated with S. aureus from horses...... in veterinary-care settings (p = 2x10(-7)), it remained extremely rare among S. aureus isolates from human infections....

  1. Metabolomics study of cereal grains reveals the discriminative metabolic markers associated with anatomical compartments

    Directory of Open Access Journals (Sweden)

    A.A. Moazzami

    2015-06-01

    Full Text Available This study used NMR-based metabolomics to compare the metabolic profile of different anatomical compartments of cereal grains i.e. bran and endosperm in order to gain further insightsinto their possible role in the beneficial health effects of whole grain products (WG. Polar watersoluble metabolites in 64 bran and endosperm, samples from rye and wheat were observed using600 MHz NMR. Bran samples had higher contents of 12 metabolites than endosperm samples. A comparative approach revealed higher contents of azelaic acid and sebacic acid in bran than in endosperm. In a pilot study, the consumption of WG rye bread (485 g caused NMR signals in 24h urine corresponding to azelaic acid. The relatively high abundance, anatomical specificity, patternof metabolism, urinary excretion in human, antibacterial, and anticancer activities suggest further studying of azelaic acid when exposure to WG or beneficial effects of WG are investigated.

  2. EDARV370A associated facial characteristics in Uyghur population revealing further pleiotropic effects.

    Science.gov (United States)

    Peng, Qianqian; Li, Jinxi; Tan, Jingze; Yang, Yajun; Zhang, Manfei; Wu, Sijie; Liu, Yu; Zhang, Juan; Qin, Pengfei; Guan, Yaqun; Jiao, Yi; Zhang, Zhaoxia; Sabeti, Pardis C; Tang, Kun; Xu, Shuhua; Jin, Li; Wang, Sijia

    2016-01-01

    An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.

  3. Systematic survey reveals general applicability of "guilt-by-association" within gene coexpression networks

    Directory of Open Access Journals (Sweden)

    Kohane Isaac S

    2005-09-01

    Full Text Available Abstract Background Biological processes are carried out by coordinated modules of interacting molecules. As clustering methods demonstrate that genes with similar expression display increased likelihood of being associated with a common functional module, networks of coexpressed genes provide one framework for assigning gene function. This has informed the guilt-by-association (GBA heuristic, widely invoked in functional genomics. Yet although the idea of GBA is accepted, the breadth of GBA applicability is uncertain. Results We developed methods to systematically explore the breadth of GBA across a large and varied corpus of expression data to answer the following question: To what extent is the GBA heuristic broadly applicable to the transcriptome and conversely how broadly is GBA captured by a priori knowledge represented in the Gene Ontology (GO? Our study provides an investigation of the functional organization of five coexpression networks using data from three mammalian organisms. Our method calculates a probabilistic score between each gene and each Gene Ontology category that reflects coexpression enrichment of a GO module. For each GO category we use Receiver Operating Curves to assess whether these probabilistic scores reflect GBA. This methodology applied to five different coexpression networks demonstrates that the signature of guilt-by-association is ubiquitous and reproducible and that the GBA heuristic is broadly applicable across the population of nine hundred Gene Ontology categories. We also demonstrate the existence of highly reproducible patterns of coexpression between some pairs of GO categories. Conclusion We conclude that GBA has universal value and that transcriptional control may be more modular than previously realized. Our analyses also suggest that methodologies combining coexpression measurements across multiple genes in a biologically-defined module can aid in characterizing gene function or in characterizing

  4. XTACC3-XMAP215 association reveals an asymmetric interaction promoting microtubule elongation

    DEFF Research Database (Denmark)

    Mortuza, Gulnahar B; Cavazza, Tommaso; Garcia-Mayoral, Maria Flor;

    2014-01-01

    215 (chTOG), dissecting the mechanism by which their interaction promotes microtubule elongation during spindle assembly. Using SAXS, we show that the TACC domain (TD) is an elongated structure that mediates the interaction with the C terminus of XMAP215. Our data suggest that one TD and two XMAP215...... molecules associate to form a four-helix coiled-coil complex. A hybrid methods approach was used to define the precise regions of the TACC heptad repeat and the XMAP215 C terminus required for assembly and functioning of the complex. We show that XTACC3 can induce the recruitment of larger amounts of XMAP...

  5. Rare Variants in Neurodegeneration Associated Genes Revealed by Targeted Panel Sequencing in a German ALS Cohort

    Science.gov (United States)

    Krüger, Stefanie; Battke, Florian; Sprecher, Andrea; Munz, Marita; Synofzik, Matthis; Schöls, Ludger; Gasser, Thomas; Grehl, Torsten; Prudlo, Johannes; Biskup, Saskia

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive fatal multisystemic neurodegenerative disorder caused by preferential degeneration of upper and lower motor neurons. To further delineate the genetic architecture of the disease, we used comprehensive panel sequencing in a cohort of 80 German ALS patients. The panel covered 39 confirmed ALS genes and candidate genes, as well as 238 genes associated with other entities of the neurodegenerative disease spectrum. In addition, we performed repeat length analysis for C9orf72. Our aim was to (1) identify potentially disease-causing variants, to (2) assess a proposed model of polygenic inheritance in ALS and to (3) connect ALS with other neurodegenerative entities. We identified 79 rare potentially pathogenic variants in 27 ALS associated genes in familial and sporadic cases. Five patients had pathogenic C9orf72 repeat expansions, a further four patients harbored intermediate length repeat expansions. Our findings demonstrate that a genetic background of the disease can actually be found in a large proportion of seemingly sporadic cases and that it is not limited to putative most frequently affected genes such as C9orf72 or SOD1. Assessing the polygenic nature of ALS, we identified 15 patients carrying at least two rare potentially pathogenic variants in ALS associated genes including pathogenic or intermediate C9orf72 repeat expansions. Multiple variants might influence severity or duration of disease or could account for intrafamilial phenotypic variability or reduced penetrance. However, we could not observe a correlation with age of onset in this study. We further detected potentially pathogenic variants in other neurodegeneration associated genes in 12 patients, supporting the hypothesis of common pathways in neurodegenerative diseases and linking ALS to other entities of the neurodegenerative spectrum. Most interestingly we found variants in GBE1 and SPG7 which might represent differential diagnoses. Based on our

  6. Stable isotopes reveal rail-associated behavior in a threatened carnivore

    OpenAIRE

    Hopkins, John B.; Whittington, Jesse; Anthony P. Clevenger; Michael A. Sawaya; St. Clair, Colleen Cassady

    2014-01-01

    Human–wildlife conflict is a leading cause of adult mortality for large carnivores worldwide. Train collision is the primary cause of mortality for threatened grizzly bears (Ursus arctos) in Banff National Park. We investigated the use of stable isotope analysis as a tool for identifying bears that use the railway in Banff. Rail-associated bears had higher δ15N and δ34S values than bears sampled away from the rail, but similar δ13C values. Because elevated δ15N values are indicative of higher...

  7. Evolutionary Metabolomics Reveals Domestication-Associated Changes in Tetraploid Wheat Kernels.

    Science.gov (United States)

    Beleggia, Romina; Rau, Domenico; Laidò, Giovanni; Platani, Cristiano; Nigro, Franca; Fragasso, Mariagiovanna; De Vita, Pasquale; Scossa, Federico; Fernie, Alisdair R; Nikoloski, Zoran; Papa, Roberto

    2016-07-01

    Domestication and breeding have influenced the genetic structure of plant populations due to selection for adaptation from natural habitats to agro-ecosystems. Here, we investigate the effects of selection on the contents of 51 primary kernel metabolites and their relationships in three Triticum turgidum L. subspecies (i.e., wild emmer, emmer, durum wheat) that represent the major steps of tetraploid wheat domestication. We present a methodological pipeline to identify the signature of selection for molecular phenotypic traits (e.g., metabolites and transcripts). Following the approach, we show that a reduction in unsaturated fatty acids was associated with selection during domestication of emmer (primary domestication). We also show that changes in the amino acid content due to selection mark the domestication of durum wheat (secondary domestication). These effects were found to be partially independent of the associations that unsaturated fatty acids and amino acids have with other domestication-related kernel traits. Changes in contents of metabolites were also highlighted by alterations in the metabolic correlation networks, indicating wide metabolic restructuring due to domestication. Finally, evidence is provided that wild and exotic germplasm can have a relevant role for improvement of wheat quality and nutritional traits.

  8. Stable isotopes reveal rail-associated behavior in a threatened carnivore

    Science.gov (United States)

    Hopkins, John B.; Whittington, Jesse; Clevenger, Anthony P.; Sawaya, Michael A.; St. Clair, Colleen Cassady

    2014-01-01

    Human–wildlife conflict is a leading cause of adult mortality for large carnivores worldwide. Train collision is the primary cause of mortality for threatened grizzly bears (Ursus arctos) in Banff National Park. We investigated the use of stable isotope analysis as a tool for identifying bears that use the railway in Banff. Rail-associated bears had higher δ15N and δ34S values than bears sampled away from the rail, but similar δ13C values. Because elevated δ15N values are indicative of higher animal protein consumption, rail-associated bears likely preyed on ungulates that foraged along the rail or scavenged on train-killed animals. The higher δ34S values in bear hair could have resulted from bears consuming sulfur pellets spilled on the rail or through the uptake of sulfur in the plants bears or animals consumed. Similar δ13C values suggest that the two types of bears had generally similar plant-based diets. Results from this study suggest that stable isotopes analysis could be used as a non-invasive, affordable, and efficient technique to identify and monitor bears that forage on the railway in Banff and potentially other transportation corridors worldwide. PMID:24936982

  9. Revealing disease-associated pathways by network integration of untargeted metabolomics.

    Science.gov (United States)

    Pirhaji, Leila; Milani, Pamela; Leidl, Mathias; Curran, Timothy; Avila-Pacheco, Julian; Clish, Clary B; White, Forest M; Saghatelian, Alan; Fraenkel, Ernest

    2016-09-01

    Uncovering the molecular context of dysregulated metabolites is crucial to understand pathogenic pathways. However, their system-level analysis has been limited owing to challenges in global metabolite identification. Most metabolite features detected by untargeted metabolomics carried out by liquid-chromatography-mass spectrometry cannot be uniquely identified without additional, time-consuming experiments. We report a network-based approach, prize-collecting Steiner forest algorithm for integrative analysis of untargeted metabolomics (PIUMet), that infers molecular pathways and components via integrative analysis of metabolite features, without requiring their identification. We demonstrated PIUMet by analyzing changes in metabolism of sphingolipids, fatty acids and steroids in a Huntington's disease model. Additionally, PIUMet enabled us to elucidate putative identities of altered metabolite features in diseased cells, and infer experimentally undetected, disease-associated metabolites and dysregulated proteins. Finally, we established PIUMet's ability for integrative analysis of untargeted metabolomics data with proteomics data, demonstrating that this approach elicits disease-associated metabolites and proteins that cannot be inferred by individual analysis of these data. PMID:27479327

  10. Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.

    Science.gov (United States)

    Tuch, Brian B; Laborde, Rebecca R; Xu, Xing; Gu, Jian; Chung, Christina B; Monighetti, Cinna K; Stanley, Sarah J; Olsen, Kerry D; Kasperbauer, Jan L; Moore, Eric J; Broomer, Adam J; Tan, Ruoying; Brzoska, Pius M; Muller, Matthew W; Siddiqui, Asim S; Asmann, Yan W; Sun, Yongming; Kuersten, Scott; Barker, Melissa A; De La Vega, Francisco M; Smith, David I

    2010-02-19

    Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.

  11. Stable isotopes reveal rail-associated behavior in a threatened carnivore.

    Science.gov (United States)

    Hopkins, John B; Whittington, Jesse; Clevenger, Anthony P; Sawaya, Michael A; St Clair, Colleen Cassady

    2014-01-01

    Human-wildlife conflict is a leading cause of adult mortality for large carnivores worldwide. Train collision is the primary cause of mortality for threatened grizzly bears (Ursus arctos) in Banff National Park. We investigated the use of stable isotope analysis as a tool for identifying bears that use the railway in Banff. Rail-associated bears had higher δ(15)N and δ(34)S values than bears sampled away from the rail, but similar δ(13)C values. Because elevated δ(15)N values are indicative of higher animal protein consumption, rail-associated bears likely preyed on ungulates that foraged along the rail or scavenged on train-killed animals. The higher δ(34)S values in bear hair could have resulted from bears consuming sulfur pellets spilled on the rail or through the uptake of sulfur in the plants bears or animals consumed. Similar δ(13)C values suggest that the two types of bears had generally similar plant-based diets. Results from this study suggest that stable isotopes analysis could be used as a non-invasive, affordable, and efficient technique to identify and monitor bears that forage on the railway in Banff and potentially other transportation corridors worldwide.

  12. Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

    Science.gov (United States)

    Li, Xu; Wang, Wenqi; Wang, Jiadong; Malovannaya, Anna; Xi, Yuanxin; Li, Wei; Guerra, Rudy; Hawke, David H; Qin, Jun; Chen, Junjie

    2015-01-21

    The current knowledge on how transcription factors (TFs), the ultimate targets and executors of cellular signalling pathways, are regulated by protein-protein interactions remains limited. Here, we performed proteomics analyses of soluble and chromatin-associated complexes of 56 TFs, including the targets of many signalling pathways involved in development and cancer, and 37 members of the Forkhead box (FOX) TF family. Using tandem affinity purification followed by mass spectrometry (TAP/MS), we performed 214 purifications and identified 2,156 high-confident protein-protein interactions. We found that most TFs form very distinct protein complexes on and off chromatin. Using this data set, we categorized the transcription-related or unrelated regulators for general or specific TFs. Our study offers a valuable resource of protein-protein interaction networks for a large number of TFs and underscores the general principle that TFs form distinct location-specific protein complexes that are associated with the different regulation and diverse functions of these TFs.

  13. Stable isotopes reveal rail-associated behavior in a threatened carnivore.

    Science.gov (United States)

    Hopkins, John B; Whittington, Jesse; Clevenger, Anthony P; Sawaya, Michael A; St Clair, Colleen Cassady

    2014-01-01

    Human-wildlife conflict is a leading cause of adult mortality for large carnivores worldwide. Train collision is the primary cause of mortality for threatened grizzly bears (Ursus arctos) in Banff National Park. We investigated the use of stable isotope analysis as a tool for identifying bears that use the railway in Banff. Rail-associated bears had higher δ(15)N and δ(34)S values than bears sampled away from the rail, but similar δ(13)C values. Because elevated δ(15)N values are indicative of higher animal protein consumption, rail-associated bears likely preyed on ungulates that foraged along the rail or scavenged on train-killed animals. The higher δ(34)S values in bear hair could have resulted from bears consuming sulfur pellets spilled on the rail or through the uptake of sulfur in the plants bears or animals consumed. Similar δ(13)C values suggest that the two types of bears had generally similar plant-based diets. Results from this study suggest that stable isotopes analysis could be used as a non-invasive, affordable, and efficient technique to identify and monitor bears that forage on the railway in Banff and potentially other transportation corridors worldwide. PMID:24936982

  14. Microsporidia-nematode associations in methane seeps reveal basal fungal parasitism in the deep sea

    Directory of Open Access Journals (Sweden)

    Amir eSapir

    2014-02-01

    Full Text Available The deep sea is Earth’s largest habitat but little is known about the nature of deep-sea parasitism. In contrast to a few characterized cases of bacterial and protistan parasites, the existence and biological significance of deep-sea parasitic fungi is yet to be understood. Here we report the discovery of a fungus-related parasitic microsporidium, Nematocenator marisprofundi n. gen. n. sp. that infects benthic nematodes at Pacific Ocean methane seeps on the Pacific Ocean floor. This infection is species-specific and has been temporally and spatially stable over two years of sampling, indicating an ecologically consistent host-parasite interaction. A high distribution of spores in the reproductive tracts of infected males and females and their absence from host nematodes’ intestines suggests a sexual transmission strategy in contrast to the fecal-oral transmission of most microsporidia. N. marisprofundi targets the host’s body wall muscles causing cell lysis, and in severe infection even muscle filament degradation. Phylogenetic analyses placed N. marisprofundi in a novel and basal clade not closely related to any described microsporidia clade, suggesting either that microsporidia-nematode parasitism occurred early in microsporidia evolution or that host specialization occurred late in an ancient deep-sea microsporidian lineage. Our findings reveal that methane seeps support complex ecosystems involving interkingdom interactions between bacteria, nematodes, and parasitic fungi and that microsporidia parasitism exists also in the deep sea biosphere.

  15. Structures of ribosome-bound initiation factor 2 reveal the mechanism of subunit association

    Science.gov (United States)

    Sprink, Thiemo; Ramrath, David J. F.; Yamamoto, Hiroshi; Yamamoto, Kaori; Loerke, Justus; Ismer, Jochen; Hildebrand, Peter W.; Scheerer, Patrick; Bürger, Jörg; Mielke, Thorsten; Spahn, Christian M. T.

    2016-01-01

    Throughout the four phases of protein biosynthesis—initiation, elongation, termination, and recycling—the ribosome is controlled and regulated by at least one specified translational guanosine triphosphatase (trGTPase). Although the structural basis for trGTPase interaction with the ribosome has been solved for the last three steps of translation, the high-resolution structure for the key initiation trGTPase, initiation factor 2 (IF2), complexed with the ribosome, remains elusive. We determine the structure of IF2 complexed with a nonhydrolyzable guanosine triphosphate analog and initiator fMet-tRNAiMet in the context of the Escherichia coli ribosome to 3.7-Å resolution using cryo-electron microscopy. The structural analysis reveals previously unseen intrinsic conformational modes of the 70S initiation complex, establishing the mutual interplay of IF2 and initator transfer RNA (tRNA) with the ribsosome and providing the structural foundation for a mechanistic understanding of the final steps of translation initiation. PMID:26973877

  16. Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1.

    Science.gov (United States)

    Strickland, Alleene V; Schabhüttl, Maria; Offenbacher, Hans; Synofzik, Matthis; Hauser, Natalie S; Brunner-Krainz, Michaela; Gruber-Sedlmayr, Ursula; Moore, Steven A; Windhager, Reinhard; Bender, Benjamin; Harms, Matthew; Klebe, Stephan; Young, Peter; Kennerson, Marina; Garcia, Avencia Sanchez Mejias; Gonzalez, Michael A; Züchner, Stephan; Schule, Rebecca; Shy, Michael E; Auer-Grumbach, Michaela

    2015-09-01

    Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) encodes a necessary subunit of the cytoplasmic dynein complex, which traffics cargo along microtubules. Dominant DYNC1H1 mutations are implicated in neural diseases, including spinal muscular atrophy with lower extremity dominance (SMA-LED), intellectual disability with neuronal migration defects, malformations of cortical development, and Charcot-Marie-Tooth disease, type 2O. We hypothesized that additional variants could be found in these and novel motoneuron and related diseases. Therefore, we analyzed our database of 1024 whole exome sequencing samples of motoneuron and related diseases for novel single nucleotide variations. We filtered these results for significant variants, which were further screened using segregation analysis in available family members. Analysis revealed six novel, rare, and highly conserved variants. Three of these are likely pathogenic and encompass a broad phenotypic spectrum with distinct disease clusters. Our findings suggest that DYNC1H1 variants can cause not only lower, but also upper motor neuron disease. It thus adds DYNC1H1 to the growing list of spastic paraplegia related genes in microtubule-dependent motor protein pathways. PMID:26100331

  17. Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma.

    Science.gov (United States)

    Hamsten, C; Häggmark, A; Grundström, J; Mikus, M; Lindskog, C; Konradsen, J R; Eklund, A; Pershagen, G; Wickman, M; Grunewald, J; Melén, E; Hedlin, G; Nilsson, P; van Hage, M

    2016-09-01

    Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma. PMID:27145233

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

    Directory of Open Access Journals (Sweden)

    So Mee Kwon

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

  19. A Voxel-Based Morphometry Study Reveals Local Brain Structural Alterations Associated with Ambient Fine Particles in Older Women

    Science.gov (United States)

    Casanova, Ramon; Wang, Xinhui; Reyes, Jeanette; Akita, Yasuyuki; Serre, Marc L.; Vizuete, William; Chui, Helena C.; Driscoll, Ira; Resnick, Susan M.; Espeland, Mark A.; Chen, Jiu-Chiuan; Wassertheil-Smoller, Sylvia; Goodwin, Mimi; DeNise, Richard; Lipton, Michael; Hannigan, James; Carpini, Anthony; Noble, David; Guzman, Wilton; Kotchen, Jane Morley; Goveas, Joseph; Kerwin, Diana; Ulmer, John; Censky, Steve; Flinton, Troy; Matusewic, Tracy; Prost, Robert; Stefanick, Marcia L.; Swope, Sue; Sawyer-Glover, Anne Marie; Hartley, Susan; Jackson, Rebecca; Hallarn, Rose; Kennedy, Bonnie; Bolognone, Jill; Casimir, Lindsay; Kochis, Amanda; Robbins, John; Zaragoza, Sophia; Carter, Cameron; Ryan, John; Macias, Denise; Sonico, Jerry; Nathan, Lauren; Voigt, Barbara; Villablanca, Pablo; Nyborg, Glen; Godinez, Sergio; Perrymann, Adele; Limacher, Marian; Anderson, Sheila; Toombs, Mary Ellen; Bennett, Jeffrey; Jones, Kevin; Brum, Sandy; Chatfield, Shane; Vantrees, Kevin; Robinson, Jennifer; Wilson, Candy; Koch, Kevin; Hart, Suzette; Carroll, Jennifer; Cherrico, Mary; Ockene, Judith; Churchill, Linda; Fellows, Douglas; Serio, Anthony; Jackson, Sharon; Spavich, Deidre; Margolis, Karen; Bjerk, Cindy; Truwitt, Chip; Peitso, Margaret; Camcrena, Alexa; Grim, Richard; Levin, Julie; Perron, Mary; Brunner, Robert; Golding, Ross; Pansky, Leslie; Arguello, Sandie; Hammons, Jane; Peterson, Nikki; Murphy, Carol; Morgan, Maggie; Castillo, Mauricio; Beckman, Thomas; Huang, Benjamin; Kuller, Lewis; McHugh, Pat; Meltzer, Carolyn; Davis, Denise; Davis, Joyce; Kost, Piera; Lucas, Kim; Potter, Tom; Tarr, Lee; Shumaker, Sally; Espeland, Mark; Coker, Laura; Williamson, Jeff; Felton, Debbie; Gleiser, LeeAnn; Rapp, Steve; Legault, Claudine; Dailey, Maggie; Casanova, Ramon; Robertson, Julia; Hogan, Patricia; Gaussoin, Sarah; Nance, Pam; Summerville, Cheryl; Peral, Ricardo; Tan, Josh; Bryan, Nick; Davatzikos, Christos; Desiderio, Lisa; Buckholtz, Neil; Molchan, Susan; Resnick, Susan; Rossouw, Jacques; Pottern, Linda

    2016-01-01

    Objective: Exposure to ambient fine particulate matter (PM2.5: PM with aerodynamic diameters voxel-wise analyses, we examined whether PM2.5 exposure also affects brain structure. Methods: Brain MRI data were obtained from 1365 women (aged 71–89) in the Women's Health Initiative Memory Study and local brain volumes were estimated using RAVENS (regional analysis of volumes in normalized space). Based on geocoded residential locations and air monitoring data from the U.S. Environmental Protection Agency, we employed a spatiotemporal model to estimate long-term (3-year average) exposure to ambient PM2.5 preceding MRI scans. Voxel-wise linear regression models were fit separately to gray matter (GM) and white matter (WM) maps to analyze associations between brain structure and PM2.5 exposure, with adjustment for potential confounders. Results: Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. No statistically significant associations were observed between PM2.5 exposure and hippocampal volumes. Conclusions: Long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. While our previous work linked smaller WM volumes to PM2.5, this is the first neuroimaging study reporting associations between air pollution exposure and smaller volumes of cortical GM. Our data support the hypothesized synaptic neurotoxicity of airborne particles.

  20. Detection of copy number variants reveals association of cilia genes with neural tube defects.

    Directory of Open Access Journals (Sweden)

    Xiaoli Chen

    Full Text Available BACKGROUND: Neural tube defects (NTDs are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs. METHODS: The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined. RESULTS: Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV. Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05. Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24-5.87. Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05, corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27-8.01. Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways. CONCLUSIONS: Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis.

  1. Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

    Directory of Open Access Journals (Sweden)

    Rao Nagesha AS

    2009-09-01

    Full Text Available Abstract Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST. They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months and long survivors (dogs with better prognosis: surviving 6 months or longer. Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the

  2. Sequence-based Association Analysis Reveals an MGST1 eQTL with Pleiotropic Effects on Bovine Milk Composition

    Science.gov (United States)

    Littlejohn, Mathew D.; Tiplady, Kathryn; Fink, Tania A.; Lehnert, Klaus; Lopdell, Thomas; Johnson, Thomas; Couldrey, Christine; Keehan, Mike; Sherlock, Richard G.; Harland, Chad; Scott, Andrew; Snell, Russell G.; Davis, Stephen R.; Spelman, Richard J.

    2016-01-01

    The mammary gland is a prolific lipogenic organ, synthesising copious amounts of triglycerides for secretion into milk. The fat content of milk varies widely both between and within species, and recent independent genome-wide association studies have highlighted a milk fat percentage quantitative trait locus (QTL) of large effect on bovine chromosome 5. Although both EPS8 and MGST1 have been proposed to underlie these signals, the causative status of these genes has not been functionally confirmed. To investigate this QTL in detail, we report genome sequence-based imputation and association mapping in a population of 64,244 taurine cattle. This analysis reveals a cluster of 17 non-coding variants spanning MGST1 that are highly associated with milk fat percentage, and a range of other milk composition traits. Further, we exploit a high-depth mammary RNA sequence dataset to conduct expression QTL (eQTL) mapping in 375 lactating cows, revealing a strong MGST1 eQTL underpinning these effects. These data demonstrate the utility of DNA and RNA sequence-based association mapping, and implicate MGST1, a gene with no obvious mechanistic relationship to milk composition regulation, as causally involved in these processes. PMID:27146958

  3. Genome-wide association analyses reveal complex genetic architecture underlying natural variation for flowering time in canola.

    Science.gov (United States)

    Raman, H; Raman, R; Coombes, N; Song, J; Prangnell, R; Bandaranayake, C; Tahira, R; Sundaramoorthi, V; Killian, A; Meng, J; Dennis, E S; Balasubramanian, S

    2016-06-01

    Optimum flowering time is the key to maximize canola production in order to meet global demand of vegetable oil, biodiesel and canola-meal. We reveal extensive variation in flowering time across diverse genotypes of canola under field, glasshouse and controlled environmental conditions. We conduct a genome-wide association study and identify 69 single nucleotide polymorphism (SNP) markers associated with flowering time, which are repeatedly detected across experiments. Several associated SNPs occur in clusters across the canola genome; seven of them were detected within 20 Kb regions of a priori candidate genes; FLOWERING LOCUS T, FRUITFUL, FLOWERING LOCUS C, CONSTANS, FRIGIDA, PHYTOCHROME B and an additional five SNPs were localized within 14 Kb of a previously identified quantitative trait loci for flowering time. Expression analyses showed that among FLC paralogs, BnFLC.A2 accounts for ~23% of natural variation in diverse accessions. Genome-wide association analysis for FLC expression levels mapped not only BnFLC.C2 but also other loci that contribute to variation in FLC expression. In addition to revealing the complex genetic architecture of flowering time variation, we demonstrate that the identified SNPs can be modelled to predict flowering time in diverse canola germplasm accurately and hence are suitable for genomic selection of adaptative traits in canola improvement programmes. PMID:26428711

  4. Multifactor dimensionality reduction reveals a three-locus epistatic interaction associated with susceptibility to pulmonary tuberculosis

    DEFF Research Database (Denmark)

    Collins, Ryan L; Hu, Ting; Wejse, Christian;

    2013-01-01

    problem. The goal of the present study was to apply MDR to mining high-order epistatic interactions in a population-based genetic study of tuberculosis (TB). Results The study used a previously published data set consisting of 19 candidate single-nucleotide polymorphisms (SNPs) in 321 pulmonary TB cases......Background Identifying high-order genetics associations with non-additive (i.e. epistatic) effects in population-based studies of common human diseases is a computational challenge. Multifactor dimensionality reduction (MDR) is a machine learning method that was designed specifically for this....... This study highlights the importance of using machine learning methods that are designed to embrace, rather than ignore, the complexity of common diseases such as TB. We recommend future studies of the genetic of TB take into account the possibility that high-order epistatic interactions might play an...

  5. Aflatoxin conducive and non-conducive growth conditions reveal new gene associations with aflatoxin production.

    Science.gov (United States)

    Price, Michael S; Conners, Shannon B; Tachdjian, Sabrina; Kelly, Robert M; Payne, Gary A

    2005-06-01

    Research on aflatoxin (AF) production has traditionally focused on defining the AF biosynthetic pathway with the goal of identifying potential targets for intervention. To understand the effect of nitrogen source, carbon source, temperature, and pH on the regulation of AF biosynthesis, a targeted cDNA microarray consisting of genes associated with AF production over time was employed. Expression profiles for genes involved in AF biosynthesis grouped into five clades. A putative regulon was identified consisting of 20 genes that were induced in the conducive nitrogen and pH treatments and the non-conducive carbon and temperature treatments, as well as four other putative regulons corresponding to each of the four variables studied. Seventeen genes exhibited consistent induction/repression profiles across all the experiments. One of these genes was consistently downregulated with AF production. Overexpression of this gene resulted in repression of AF biosynthesis. The cellular function of this gene is currently unresolved.

  6. Specific and nonspecific interactions in ultraweak protein−protein associations revealed by solvent paramagnetic relaxation enhancements

    DEFF Research Database (Denmark)

    Johansson, Helle; Jensen, Malene Ringkjøbing; Gesmar, Henrik;

    2014-01-01

    Weak and transient protein–protein interactions underlie numerous biological processes. However, the location of the interaction sites of the specific complexes and the effect of transient, non-specific protein–protein interactions often remain elusive. We have investigated the weak selfassociation...... relaxation agent, it is shown that a distinction can be made between residues that are affected only by transient, non-specific protein–protein interactions and residues that are involved in specific protein-protein associations. Thus, the PREs of the former residues increase linearly with the h......GH concentration in the entire concentration range because of a reduction of the diffusion caused by the transient, non-specific protein-protein interactions, while the PREs of the latter residues increase only at the lower hGH concentrations but decrease at the higher concentrations because of specific protein-protein...

  7. Shotgun Metagenomic Sequencing Reveals Functional Genes and Microbiome Associated with Bovine Digital Dermatitis.

    Directory of Open Access Journals (Sweden)

    Martin Zinicola

    Full Text Available Metagenomic methods amplifying 16S ribosomal RNA genes have been used to describe the microbial diversity of healthy skin and lesion stages of bovine digital dermatitis (DD and to detect critical pathogens involved with disease pathogenesis. In this study, we characterized the microbiome and for the first time, the composition of functional genes of healthy skin (HS, active (ADD and inactive (IDD lesion stages using a whole-genome shotgun approach. Metagenomic sequences were annotated using MG-RAST pipeline. Six phyla were identified as the most abundant. Firmicutes and Actinobacteria were the predominant bacterial phyla in the microbiome of HS, while Spirochetes, Bacteroidetes and Proteobacteria were highly abundant in ADD and IDD. T. denticola-like, T. vincentii-like and T. phagedenis-like constituted the most abundant species in ADD and IDD. Recruitment plots comparing sequences from HS, ADD and IDD samples to the genomes of specific Treponema spp., supported the presence of T. denticola and T. vincentii in ADD and IDD. Comparison of the functional composition of HS to ADD and IDD identified a significant difference in genes associated with motility/chemotaxis and iron acquisition/metabolism. We also provide evidence that the microbiome of ADD and IDD compared to that of HS had significantly higher abundance of genes associated with resistance to copper and zinc, which are commonly used in footbaths to prevent and control DD. In conclusion, the results from this study provide new insights into the HS, ADD and IDD microbiomes, improve our understanding of the disease pathogenesis and generate unprecedented knowledge regarding the functional genetic composition of the digital dermatitis microbiome.

  8. Transcriptional changes associated with resistance to inhibitors of epidermal growth factor receptor revealed using metaanalysis

    International Nuclear Information System (INIS)

    EGFR is important in maintaining metabolic homeostasis in healthy cells, but in tumors it activates downstream signaling pathways, causing proliferation, angiogenesis, invasion and metastasis. Consequently, EGFR is targeted in cancers using reversible, irreversible or antibody inhibitors. Unfortunately, tumors develop inhibitor resistance by mutations or overexpressing EGFR, or its ligand, or activating secondary, EGFR-independent pathways. Here we present a global metaanalysis comparing transcriptional profiles from matched pairs of EGFR inhibitor-sensitive vs. -resistant cell lines, using 15 datasets comprising 274 microarrays. We also analyzed separately pairs of cell lines derived using reversible, irreversible or antibody inhibitors. The metaanalysis identifies commonalities in cell lines resistant to EGFR inhibitors: in sensitive cell lines, the ontological categories involving the ErbB receptors pathways, cell adhesion and lipid metabolism are overexpressed; however, resistance to EGFR inhibitors is associated with overexpression of genes for ErbB receptors-independent oncogenic pathways, regulation of cell motility, energy metabolism, immunity especially inflammatory cytokines biosynthesis, cell cycle and responses to exogenous and endogenous stimuli. Specifically in Gefitinib-resistant cell lines, the immunity-associated genes are overexpressed, whereas in Erlotinib-resistant ones so are the mitochondrial genes and processes. Unexpectedly, lines selected using EGFR-targeting antibodies overexpress different gene ontologies from ones selected using kinase inhibitors. Specifically, they have reduced expression of genes for proliferation, chemotaxis, immunity and angiogenesis. This metaanalysis suggests that ‘combination therapies’ can improve cancer treatment outcomes. Potentially, use of mitochondrial blockers with Erlotinib, immunity blockers with Gefitinib, tyrosine kinase inhibitors with antibody inhibitors, may have better chance of avoiding

  9. Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.

    Directory of Open Access Journals (Sweden)

    Brian B Tuch

    Full Text Available Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor.

  10. Structural analysis of coxsackievirus A7 reveals conformational changes associated with uncoating.

    Science.gov (United States)

    Seitsonen, Jani J T; Shakeel, Shabih; Susi, Petri; Pandurangan, Arun P; Sinkovits, Robert S; Hyvönen, Heini; Laurinmäki, Pasi; Ylä-Pelto, Jani; Topf, Maya; Hyypiä, Timo; Butcher, Sarah J

    2012-07-01

    Coxsackievirus A7 (CAV7) is a rarely detected and poorly characterized serotype of the Enterovirus species Human enterovirus A (HEV-A) within the Picornaviridae family. The CAV7-USSR strain has caused polio-like epidemics and was originally thought to represent the fourth poliovirus type, but later evidence linked this strain to the CAV7-Parker prototype. Another isolate, CAV7-275/58, was also serologically similar to Parker but was noninfectious in a mouse model. Sequencing of the genomic region encoding the capsid proteins of the USSR and 275/58 strains and subsequent comparison with the corresponding amino acid sequences of the Parker strain revealed that the Parker and USSR strains are nearly identical, while the 275/58 strain is more distant. Using electron cryomicroscopy and three-dimensional image reconstruction, the structures of the CAV7-USSR virion and empty capsid were resolved to 8.2-Å and 6.1-Å resolutions, respectively. This is one of the first detailed structural analyses of the HEV-A species. Using homology modeling, reconstruction segmentation, and flexible fitting, we constructed a pseudoatomic T = 1 (pseudo T = 3) model incorporating the three major capsid proteins (VP1 to VP3), addressed the conformational changes of the capsid and its constituent viral proteins occurring during RNA release, and mapped the capsid proteins' variable regions to the structure. During uncoating, VP4 and RNA are released analogously to poliovirus 1, the interfaces of VP2 and VP3 are rearranged, and VP1 rotates. Variable regions in the capsid proteins were predicted to map mainly to the surface of VP1 and are thus likely to affect the tropism and pathogenicity of CAV7.

  11. Co-expression network analysis reveals transcription factors associated to cell wall biosynthesis in sugarcane.

    Science.gov (United States)

    Ferreira, Savio Siqueira; Hotta, Carlos Takeshi; Poelking, Viviane Guzzo de Carli; Leite, Debora Chaves Coelho; Buckeridge, Marcos Silveira; Loureiro, Marcelo Ehlers; Barbosa, Marcio Henrique Pereira; Carneiro, Monalisa Sampaio; Souza, Glaucia Mendes

    2016-05-01

    Sugarcane is a hybrid of Saccharum officinarum and Saccharum spontaneum, with minor contributions from other species in Saccharum and other genera. Understanding the molecular basis of cell wall metabolism in sugarcane may allow for rational changes in fiber quality and content when designing new energy crops. This work describes a comparative expression profiling of sugarcane ancestral genotypes: S. officinarum, S. spontaneum and S. robustum and a commercial hybrid: RB867515, linking gene expression to phenotypes to identify genes for sugarcane improvement. Oligoarray experiments of leaves, immature and intermediate internodes, detected 12,621 sense and 995 antisense transcripts. Amino acid metabolism was particularly evident among pathways showing natural antisense transcripts expression. For all tissues sampled, expression analysis revealed 831, 674 and 648 differentially expressed genes in S. officinarum, S. robustum and S. spontaneum, respectively, using RB867515 as reference. Expression of sugar transporters might explain sucrose differences among genotypes, but an unexpected differential expression of histones were also identified between high and low Brix° genotypes. Lignin biosynthetic genes and bioenergetics-related genes were up-regulated in the high lignin genotype, suggesting that these genes are important for S. spontaneum to allocate carbon to lignin, while S. officinarum allocates it to sucrose storage. Co-expression network analysis identified 18 transcription factors possibly related to cell wall biosynthesis while in silico analysis detected cis-elements involved in cell wall biosynthesis in their promoters. Our results provide information to elucidate regulatory networks underlying traits of interest that will allow the improvement of sugarcane for biofuel and chemicals production. PMID:26820137

  12. Unexpected bismuth concentration profiles in metal-organic vapor phase epitaxy-grown Ga(As1−xBix/GaAs superlattices revealed by Z-contrast scanning transmission electron microscopy imaging

    Directory of Open Access Journals (Sweden)

    A. W. Wood

    2015-03-01

    Full Text Available A set of GaAs1−xBix/GaAs multilayer quantum-well structures was deposited by metal-organic vapor phase epitaxy at 390 °C and 420 °C. The precursor fluxes were introduced with the intent of growing discrete and compositionally uniform GaAs1−xBix well and GaAs barrier layers in the epitaxial films. High-resolution high-angle annular-dark-field (or “Z-contrast” scanning transmission electron microscopy imaging revealed concentration profiles that were periodic in the growth direction, but far more complicated in shape than the intended square wave. The observed composition profiles could explain various reports of physical properties measurements that suggest compositional inhomogeneity in GaAs1−xBix alloys as they currently are grown.

  13. Pro-survival role for Parkinson's associated gene DJ-1 revealed in trophically impaired dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Liviu Aron

    Full Text Available The mechanisms underlying the selective death of substantia nigra (SN neurons in Parkinson disease (PD remain elusive. While inactivation of DJ-1, an oxidative stress suppressor, causes PD, animal models lacking DJ-1 show no overt dopaminergic (DA neuron degeneration in the SN. Here, we show that aging mice lacking DJ-1 and the GDNF-receptor Ret in the DA system display an accelerated loss of SN cell bodies, but not axons, compared to mice that only lack Ret signaling. The survival requirement for DJ-1 is specific for the GIRK2-positive subpopulation in the SN which projects exclusively to the striatum and is more vulnerable in PD. Using Drosophila genetics, we show that constitutively active Ret and associated Ras/ERK, but not PI3K/Akt, signaling components interact genetically with DJ-1. Double loss-of-function experiments indicate that DJ-1 interacts with ERK signaling to control eye and wing development. Our study uncovers a conserved interaction between DJ-1 and Ret-mediated signaling and a novel cell survival role for DJ-1 in the mouse. A better understanding of the molecular connections between trophic signaling, cellular stress and aging could uncover new targets for drug development in PD.

  14. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    Science.gov (United States)

    Rooijers, Koos; Loayza-Puch, Fabricio; Nijtmans, Leo G.; Agami, Reuven

    2013-12-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson’s disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations often affect components of the mitochondrial translation machinery. Here we perform ribosome profiling to measure mitochondrial translation at nucleotide resolution. Using a protocol optimized for the retrieval of mitochondrial ribosome protected fragments (RPFs) we show that the size distribution of wild-type mitochondrial RPFs follows a bimodal distribution peaking at 27 and 33 nucleotides, which is distinct from the 30-nucleotide peak of nuclear RPFs. Their cross-correlation suggests generation of mitochondrial RPFs during ribosome progression. In contrast, RPFs from patient-derived mitochondria mutated in tRNA-Tryptophan are centered on tryptophan codons and reduced downstream, indicating ribosome stalling. Intriguingly, long RPFs are enriched in mutated mitochondria, suggesting they characterize stalled ribosomes. Our findings provide the first model for translation in wild-type and disease-triggering mitochondria.

  15. Genome Wide Association Analysis Reveals New Production Trait Genes in a Male Duroc Population.

    Directory of Open Access Journals (Sweden)

    Kejun Wang

    Full Text Available In this study, 796 male Duroc pigs were used to identify genomic regions controlling growth traits. Three production traits were studied: food conversion ratio, days to 100 KG, and average daily gain, using a panel of 39,436 single nucleotide polymorphisms. In total, we detected 11 genome-wide and 162 chromosome-wide single nucleotide polymorphism trait associations. The Gene ontology analysis identified 14 candidate genes close to significant single nucleotide polymorphisms, with growth-related functions: six for days to 100 KG (WT1, FBXO3, DOCK7, PPP3CA, AGPAT9, and NKX6-1, seven for food conversion ratio (MAP2, TBX15, IVL, ARL15, CPS1, VWC2L, and VAV3, and one for average daily gain (COL27A1. Gene ontology analysis indicated that most of the candidate genes are involved in muscle, fat, bone or nervous system development, nutrient absorption, and metabolism, which are all either directly or indirectly related to growth traits in pigs. Additionally, we found four haplotype blocks composed of suggestive single nucleotide polymorphisms located in the growth trait-related quantitative trait loci and further narrowed down the ranges, the largest of which decreased by ~60 Mb. Hence, our results could be used to improve pig production traits by increasing the frequency of favorable alleles via artificial selection.

  16. Scan Statistics

    CERN Document Server

    Glaz, Joseph

    2009-01-01

    Suitable for graduate students and researchers in applied probability and statistics, as well as for scientists in biology, computer science, pharmaceutical science and medicine, this title brings together a collection of chapters illustrating the depth and diversity of theory, methods and applications in the area of scan statistics.

  17. Genetic and genomic dissection of Prolactin revealed potential association with milk production traits in riverine buffalo.

    Science.gov (United States)

    Nadeem, A; Maryam, J

    2016-08-01

    Milk yield and quality has been a major selection criterion for genetic improvement in livestock species. Role of Prolactin gene in determining milk quality in terms of protein profile, lactose, lipids and other imperative macromolecules is very important. In this context, genetic profiling of Prolactin gene in riverine buffalo of Pakistan was performed and potential genetic markers were identified illustrating worth of this gene in marker-assisted selection of superior dairy buffaloes. Series of wet and dry lab experimentation was performed starting with genomic DNA isolation from true to breed representatives of indigenous river buffalo (Nili-Ravi). After amplification of coding regions of Prolactin gene, products were eluted and sequenced by Sanger's chain termination method and aligned to get variations in genomic region. A total of 15 novel variations were identified and analyzed statistically for their significance at population level, haplotypes were constructed, and association was estimated. Phylogenetic analysis was performed to evaluate the rate of evolution for Prolactin gene in various mammalian species. Lastly, biological networking for this molecule was predicted to get the bigger pictorial of its functional machinery. Pathway analysis was performed to find its physiological mode of action in milk synthesis. This is a first report toward complete genetic screening of Prolactin gene in Pakistani buffaloes. Results of this study not only provide an insight for potential role of Prolactin gene in milk-producing abilities of buffalo but also suggest new directions for exploration of more genes that may have promising role to enhance future milk production capabilities of river buffalo breeds of Asian region through marker-assisted selection. PMID:27240674

  18. Gene expression profiling of dendritic cells reveals important mechanisms associated with predisposition to Staphylococcus infections.

    Directory of Open Access Journals (Sweden)

    Mehdi Toufeer

    Full Text Available BACKGROUND: Staphylococcus aureus is a major pathogen of humans and animals and emerging antibiotic-resistant strains have further increased the concern of this health issue. Host genetics influence susceptibility to S. aureus infections, and the genes determining the outcome of infections should be identified to find alternative therapies to treatment with antibiotics. Here, we used outbred animals from a divergent selection based on susceptibility towards Staphylococcus infection to explore host immunogenetics. METHODOLOGY/PRINCIPAL FINDINGS: We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals showing different degrees of susceptibility had distinct gene expression profiles. We measured gene expression levels of in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hrs by using 15 k ovine Agilent microarrays. Furthermore, differential expression of a selected number of genes was confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and showed that genes involved in the inflammatory process and T helper cell polarization were highly up-regulated upon stimulation. Moreover, a set of 204 genes were statistically differentially expressed between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, over-expression of the C1q and Ido1 genes was observed in the resistant line and suggested a role of classical pathway of complement and early regulation of inflammation pathways, respectively. On the contrary, over expression of genes involved in the IL1R pathway was observed in susceptible animals. Furthermore, the leucocyte extravasation pathway was also found to be dominant in the susceptible line. CONCLUSION/SIGNIFICANCE: We successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in an 8-hour kinetics experiment

  19. Gene Expression Profiling of Dendritic Cells Reveals Important Mechanisms Associated with Predisposition to Staphylococcus Infections

    Science.gov (United States)

    Toufeer, Mehdi; Bonnefont, Cécile M. D.; Foulon, Eliane; Caubet, Cécile; Tasca, Christian; Aurel, Marie-Rose; Robert-Granié, Christèle; Rupp, Rachel; Foucras, Gilles

    2011-01-01

    Background Staphylococcus aureus is a major pathogen of humans and animals and emerging antibiotic-resistant strains have further increased the concern of this health issue. Host genetics influence susceptibility to S. aureus infections, and the genes determining the outcome of infections should be identified to find alternative therapies to treatment with antibiotics. Here, we used outbred animals from a divergent selection based on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals showing different degrees of susceptibility had distinct gene expression profiles. We measured gene expression levels of in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hrs) by using 15 k ovine Agilent microarrays. Furthermore, differential expression of a selected number of genes was confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and showed that genes involved in the inflammatory process and T helper cell polarization were highly up-regulated upon stimulation. Moreover, a set of 204 genes were statistically differentially expressed between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, over-expression of the C1q and Ido1 genes was observed in the resistant line and suggested a role of classical pathway of complement and early regulation of inflammation pathways, respectively. On the contrary, over expression of genes involved in the IL1R pathway was observed in susceptible animals. Furthermore, the leucocyte extravasation pathway was also found to be dominant in the susceptible line. Conclusion/Significance We successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in an 8-hour kinetics experiment. The distinct

  20. Whole-genome expression analysis reveals genes associated with treatment response to escitalopram in major depression.

    Science.gov (United States)

    Pettai, Kristi; Milani, Lili; Tammiste, Anu; Võsa, Urmo; Kolde, Raivo; Eller, Triin; Nutt, David; Metspalu, Andres; Maron, Eduard

    2016-09-01

    The reasons for variability in treatment response in major depressive disorder (MDD) are not fully understood, but there is accumulating evidence suggesting that therapeutic outcomes of antidepressants can be influenced by genetic factors. In the present study we applied the microarray Illumina platform for whole genome expression profiling in depressive patients treated with escitalopram medication in order to identify genes underlying response to antidepressant treatment. The initial study sample consisted of 135 outpatients with major depressive disorder (mean age 31.1±11.6 years, 68% females) treated with escitalopram 10-20mg/day for 12 weeks, from which 87 patients (55 females) were included in gene expression analyzing. The gene expression profiles were measured on peripheral blood cells at baseline, at week 4 and at the end of treatment (week 12) using BeadChips Illumina. The fold change was used to demonstrate rate of changes in average gene expressions between studied groups. Statistical analyses were performed using the false discovery rate (FDR). The most interesting gene, which showed the predictive effect on treatment outcome by delineating low dose responders and treatment-resistant patients at the beginning of medication, was NLGN2, belonging to a family of neuronal cell surface proteins and involving in synapse formation. In addition, the several gene clusters, related to immune response, signal transduction and neurotrophin pathway, have distinguished responders from non-responders at the week 4 of treatment. After 4 weeks of escitalopram treatment (10mg/day), the YWHAZ gene has showed the highest transcriptional change in responders as compared with non-responders. Finally, at the end of the treatment we noticed that at least three genes (NR2C2, ZNF641, FKBP1A) have been strongly associated with resistance to escitalopram. Thus the results of this study support that exploration of peripheral gene expression is a useful tool in the further

  1. Metagenomic Analysis Revealed Methylamine and Ureide Utilization of Soybean-Associated Methylobacterium

    Science.gov (United States)

    Minami, Tomoyuki; Anda, Misue; Mitsui, Hisayuki; Sugawara, Masayuki; Kaneko, Takakazu; Sato, Shusei; Ikeda, Seishi; Okubo, Takashi; Tsurumaru, Hirohito; Minamisawa, Kiwamu

    2016-01-01

    Methylobacterium inhabits the phyllosphere of a large number of plants. We herein report the results of comparative metagenome analyses on methylobacterial communities of soybean plants grown in an experimental field in Tohoku University (Kashimadai, Miyagi, Japan). Methylobacterium was identified as the most dominant genus (33%) among bacteria inhabiting soybean stems. We classified plant-derived Methylobacterium species into Groups I, II, and III based on 16S rRNA gene sequences, and found that Group I members (phylogenetically close to M. extorquens) were dominant in soybean-associated Methylobacterium. By comparing 29 genomes, we found that all Group I members possessed a complete set of genes for the N-methylglutamate pathway for methylamine utilization, and genes for urea degradation (urea carboxylase, urea amidolyase, and conventional urease). Only Group I members and soybean methylobacterial isolates grew in a culture supplemented with methylamine as the sole carbon source. They utilized urea or allantoin (a urea-related compound in legumes) as the sole nitrogen source; however, group III also utilized these compounds. The utilization of allantoin may be crucial in soybean-bacterial interactions because allantoin is a transported form of fixed nitrogen in legume plants. Soybean-derived Group I strain AMS5 colonized the model legume Lotus japonicus well. A comparison among the 29 genomes of plant-derived and other strains suggested that several candidate genes are involved in plant colonization such as csgG (curli fimbriae). Genes for the N-methylglutamate pathway and curli fimbriae were more abundant in soybean microbiomes than in rice microbiomes in the field. Based on these results, we discuss the lifestyle of Methylobacterium in the legume phyllosphere. PMID:27431374

  2. Feather corticosterone reveals stress associated with dietary changes in a breeding seabird.

    Science.gov (United States)

    Will, Alexis; Watanuki, Yutaka; Kikuchi, Dale M; Sato, Nobuhiko; Ito, Motohiro; Callahan, Matt; Wynne-Edwards, Katherine; Hatch, Scott; Elliott, Kyle; Slater, Leslie; Takahashi, Akinori; Kitaysky, Alexander

    2015-10-01

    Changes in climate and anthropogenic pressures might affect the composition and abundance of forage fish in the world's oceans. The junk-food hypothesis posits that dietary shifts that affect the quality (e.g., energy content) of food available to marine predators may impact their physiological state and consequently affect their fitness. Previously, we experimentally validated that deposition of the adrenocortical hormone, corticosterone, in feathers is a sensitive measure of nutritional stress in seabirds. Here, we use this method to examine how changes in diet composition and prey quality affect the nutritional status of free-living rhinoceros auklets (Cerorhinca monocerata). Our study sites included the following: Teuri Is. Japan, Middleton Is. central Gulf of Alaska, and St. Lazaria Is. Southeast Alaska. In 2012 and 2013, we collected "bill loads" delivered by parents to feed their chicks (n = 758) to document dietary changes. We deployed time-depth-temperature recorders on breeding adults (n = 47) to evaluate whether changes in prey coincided with changes in foraging behavior. We measured concentrations of corticosterone in fledgling (n = 71) and adult breeders' (n = 82) feathers to determine how birds were affected by foraging conditions. We found that seasonal changes in diet composition occurred on each colony, adults dove deeper and engaged in longer foraging bouts when capturing larger prey and that chicks had higher concentrations of corticosterone in their feathers when adults brought back smaller and/or lower energy prey. Corticosterone levels in feathers of fledglings (grown during the breeding season) and those in feathers of adult breeders (grown during the postbreeding season) were positively correlated, indicating possible carryover effects. These results suggest that seabirds might experience increased levels of nutritional stress associated with moderate dietary changes and that physiological responses to changes in prey composition

  3. Meta-analysis of gene-environment-wide association scans accounting for education level identifies additional loci for refractive error.

    Science.gov (United States)

    Fan, Qiao; Verhoeven, Virginie J M; Wojciechowski, Robert; Barathi, Veluchamy A; Hysi, Pirro G; Guggenheim, Jeremy A; Höhn, René; Vitart, Veronique; Khawaja, Anthony P; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E; Williams, Katie M; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F; Joshi, Peter K; McMahon, George; St Pourcain, Beate; Evans, David M; Simpson, Claire L; Schwantes-An, Tae-Hwi; Igo, Robert P; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M; Amin, Najaf; Uitterlinden, André G; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E H; Lim, Wan'e; Beuerman, Roger W; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N; Foster, Paul J; Klein, Barbara E K; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B; Teo, Yik-Ying; Mackey, David A; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N; Stambolian, Dwight; Wilson, Joan E Bailey; Cheng, Ching-Yu; Hammond, Christopher J; Klaver, Caroline C W; Saw, Seang-Mei; Rahi, Jugnoo S; Korobelnik, Jean-François; Kemp, John P; Timpson, Nicholas J; Smith, George Davey; Craig, Jamie E; Burdon, Kathryn P; Fogarty, Rhys D; Iyengar, Sudha K; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F; Fondran, Jeremy R; Lass, Jonathan H; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O; Jhanji, Vishal; Young, Alvin L; Döring, Angela; Raffel, Leslie J; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K H; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L; Tedja, Milly; Deangelis, Margaret M; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (Pimportant advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.

  4. Metagenomic Sequencing of the Chronic Obstructive Pulmonary Disease Upper Bronchial Tract Microbiome Reveals Functional Changes Associated with Disease Severity.

    Science.gov (United States)

    Cameron, Simon J S; Lewis, Keir E; Huws, Sharon A; Lin, Wanchang; Hegarty, Matthew J; Lewis, Paul D; Mur, Luis A J; Pachebat, Justin A

    2016-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide. The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results. Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease. The bacterial metagenomes within sputum samples from eight COPD patients and ten 'healthy' smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus. The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations. Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism. This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity.

  5. Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking

    Directory of Open Access Journals (Sweden)

    Tan Q

    2013-10-01

    Full Text Available Qiang Tan,1,* Guan Wang,1,* Jia Huang,1 Zhengping Ding,1 Qingquan Luo,1 Tony Mok,2 Qian Tao,2 Shun Lu1 1Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 2Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong *These authors contributed equally to this paper Abstract: The importance of epigenetic regulation has been increasingly recognized in the development of cancer. In this study, we investigated the impact of smoking, a major risk factor of lung cancer, on DNA methylation by comparing the genome-wide DNA methylation patterns between lung adenocarcinoma samples from six smokers and six nonsmokers. We identified that smoking-induced DNA methylations were enriched in the calcium signaling and neuroactive ligand receptor signaling pathways, which are closely related to smoking-induced lung cancers. Interestingly, we discovered that two genes in the mitogen-activated protein kinase signaling pathway (RPS6KA3 and ARAF were hypomethylated in smokers but not in nonsmokers. In addition, we found that the smoking-induced lung cancer-specific DNA methylations were mostly enriched in nuclear activities, including regulation of gene expression and chromatin remodeling. Moreover, the smoking-induced hypermethylation could only be seen in lung adenocarcinoma tissue but not in adjacent normal lung tissue. We also used differentially methylated DNA loci to construct a diagnostic model to distinguish smoking-associated lung cancer from nonsmoking lung cancer with a sensitivity of 88.9% and specificity of 83.2%. Our results provided novel evidence to support that smoking can cause dramatic changes in the DNA methylation landscape of lung cancer, suggesting that epigenetic

  6. Analysis of mitochondrial DNA sequences in childhood encephalomyopathies reveals new disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Aijaz A Wani

    Full Text Available BACKGROUND: Mitochondrial encephalomyopathies are a heterogeneous group of clinical disorders generally caused due to mutations in either mitochondrial DNA (mtDNA or nuclear genes encoding oxidative phosphorylation (OXPHOS. We analyzed the mtDNA sequences from a group of 23 pediatric patients with clinical and morphological features of mitochondrial encephalopathies and tried to establish a relationship of identified variants with the disease. METHODOLOGY/PRINCIPLE FINDINGS: Complete mitochondrial genomes were amplified by PCR and sequenced by automated DNA sequencing. Sequencing data was analyzed by SeqScape software and also confirmed by BLASTn program. Nucleotide sequences were compared with the revised Cambridge reference sequence (CRS and sequences present in mitochondrial databases. The data obtained shows that a number of known and novel mtDNA variants were associated with the disease. Most of the non-synonymous variants were heteroplasmic (A4136G, A9194G and T11916A suggesting their possibility of being pathogenic in nature. Some of the missense variants although homoplasmic were showing changes in highly conserved amino acids (T3394C, T3866C, and G9804A and were previously identified with diseased conditions. Similarly, two other variants found in tRNA genes (G5783A and C8309T could alter the secondary structure of Cys-tRNA and Lys-tRNA. Most of the variants occurred in single cases; however, a few occurred in more than one case (e.g. G5783A and A10149T. CONCLUSIONS AND SIGNIFICANCE: The mtDNA variants identified in this study could be the possible cause of mitochondrial encephalomyopathies with childhood onset in the patient group. Our study further strengthens the pathogenic score of known variants previously reported as provisionally pathogenic in mitochondrial diseases. The novel variants found in the present study can be potential candidates for further investigations to establish the relationship between their incidence and role

  7. Multiple sex-associated regions and a putative sex chromosome in zebrafish revealed by RAD mapping and population genomics.

    Directory of Open Access Journals (Sweden)

    Jennifer L Anderson

    Full Text Available Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio, neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate, the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F(2 offspring of reciprocal crosses between Oregon *AB and Nadia (NA wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome.

  8. Meta-analysis of gene–environment-wide association scans accounting for education level identifies additional loci for refractive error

    Science.gov (United States)

    Fan, Qiao; Verhoeven, Virginie J. M.; Wojciechowski, Robert; Barathi, Veluchamy A.; Hysi, Pirro G.; Guggenheim, Jeremy A.; Höhn, René; Vitart, Veronique; Khawaja, Anthony P.; Yamashiro, Kenji; Hosseini, S Mohsen; Lehtimäki, Terho; Lu, Yi; Haller, Toomas; Xie, Jing; Delcourt, Cécile; Pirastu, Mario; Wedenoja, Juho; Gharahkhani, Puya; Venturini, Cristina; Miyake, Masahiro; Hewitt, Alex W.; Guo, Xiaobo; Mazur, Johanna; Huffman, Jenifer E.; Williams, Katie M.; Polasek, Ozren; Campbell, Harry; Rudan, Igor; Vatavuk, Zoran; Wilson, James F.; Joshi, Peter K.; McMahon, George; St Pourcain, Beate; Evans, David M.; Simpson, Claire L.; Schwantes-An, Tae-Hwi; Igo, Robert P.; Mirshahi, Alireza; Cougnard-Gregoire, Audrey; Bellenguez, Céline; Blettner, Maria; Raitakari, Olli; Kähönen, Mika; Seppala, Ilkka; Zeller, Tanja; Meitinger, Thomas; Ried, Janina S.; Gieger, Christian; Portas, Laura; van Leeuwen, Elisabeth M.; Amin, Najaf; Uitterlinden, André G.; Rivadeneira, Fernando; Hofman, Albert; Vingerling, Johannes R.; Wang, Ya Xing; Wang, Xu; Tai-Hui Boh, Eileen; Ikram, M. Kamran; Sabanayagam, Charumathi; Gupta, Preeti; Tan, Vincent; Zhou, Lei; Ho, Candice E. H.; Lim, Wan'e; Beuerman, Roger W.; Siantar, Rosalynn; Tai, E-Shyong; Vithana, Eranga; Mihailov, Evelin; Khor, Chiea-Chuen; Hayward, Caroline; Luben, Robert N.; Foster, Paul J.; Klein, Barbara E. K.; Klein, Ronald; Wong, Hoi-Suen; Mitchell, Paul; Metspalu, Andres; Aung, Tin; Young, Terri L.; He, Mingguang; Pärssinen, Olavi; van Duijn, Cornelia M.; Jin Wang, Jie; Williams, Cathy; Jonas, Jost B.; Teo, Yik-Ying; Mackey, David A.; Oexle, Konrad; Yoshimura, Nagahisa; Paterson, Andrew D.; Pfeiffer, Norbert; Wong, Tien-Yin; Baird, Paul N.; Stambolian, Dwight; Wilson, Joan E. Bailey; Cheng, Ching-Yu; Hammond, Christopher J.; Klaver, Caroline C. W.; Saw, Seang-Mei; Rahi, Jugnoo S.; Korobelnik, Jean-François; Kemp, John P.; Timpson, Nicholas J.; Smith, George Davey; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Chew, Emily; Janmahasatian, Sarayut; Martin, Nicholas G.; MacGregor, Stuart; Xu, Liang; Schache, Maria; Nangia, Vinay; Panda-Jonas, Songhomitra; Wright, Alan F.; Fondran, Jeremy R.; Lass, Jonathan H.; Feng, Sheng; Zhao, Jing Hua; Khaw, Kay-Tee; Wareham, Nick J.; Rantanen, Taina; Kaprio, Jaakko; Pang, Chi Pui; Chen, Li Jia; Tam, Pancy O.; Jhanji, Vishal; Young, Alvin L.; Döring, Angela; Raffel, Leslie J.; Cotch, Mary-Frances; Li, Xiaohui; Yip, Shea Ping; Yap, Maurice K.H.; Biino, Ginevra; Vaccargiu, Simona; Fossarello, Maurizio; Fleck, Brian; Yazar, Seyhan; Tideman, Jan Willem L.; Tedja, Milly; Deangelis, Margaret M.; Morrison, Margaux; Farrer, Lindsay; Zhou, Xiangtian; Chen, Wei; Mizuki, Nobuhisa; Meguro, Akira; Mäkelä, Kari Matti

    2016-01-01

    Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry individuals, we identify six novel loci (FAM150B-ACP1, LINC00340, FBN1, DIS3L-MAP2K1, ARID2-SNAT1 and SLC14A2) associated with refractive error. In Asian populations, three genome-wide significant loci AREG, GABRR1 and PDE10A also exhibit strong interactions with education (P<8.5 × 10−5), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia. PMID:27020472

  9. Revealing the Large-Scale Structures of Interstellar Gas Associated with the Magellanic SNR N132D

    CERN Document Server

    Sano, H; Yoshiike, S; Fukuda, T; Tachihara, K; Inutsuka, S; Kawamura, A; Fujii, K; Mizuno, N; Inoue, T; Onishi, T; Acero, F; Vink, J

    2015-01-01

    We report preliminary results of large-scale distribution toward the Magellanic supernova remnant N132D using Mopra and Chandra archival datasets. We identified a cavity-like CO structure along the X-ray shell toward the southern half of it. The total mass of associating molecular gas is $\\sim10^4 M_\\odot$, which is smaller than the previous study by an order of magnitude. Further observations using ALMA, ASTE, and Mopra will reveal the detailed spatial structures and its physical conditions.

  10. The Tell-Tale Heart: Population-Based Surveillance Reveals an Association of Rofecoxib and Celecoxib with Myocardial Infarction

    OpenAIRE

    John S Brownstein; Margarita Sordo; Kohane, Isaac S.; Kenneth D Mandl

    2007-01-01

    BACKGROUND: COX-2 selective inhibitors are associated with myocardial infarction (MI). We sought to determine whether population health monitoring would have revealed the effect of COX-2 inhibitors on population-level patterns of MI. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective study of inpatients at two Boston hospitals, from January 1997 to March 2006. There was a population-level rise in the rate of MI that reached 52.0 MI-related hospitalizations per 100,000 (a two standar...

  11. A genome-wide scan study identifies a single nucleotide substitution in ASIP associated with white versus non-white coat-colour variation in sheep (Ovis aries).

    Science.gov (United States)

    Li, M-H; Tiirikka, T; Kantanen, J

    2014-02-01

    In sheep, coat colour (and pattern) is one of the important traits of great biological, economic and social importance. However, the genetics of sheep coat colour has not yet been fully clarified. We conducted a genome-wide association study of sheep coat colours by genotyping 47 303 single-nucleotide polymorphisms (SNPs) in the Finnsheep population in Finland. We identified 35 SNPs associated with all the coat colours studied, which cover genomic regions encompassing three known pigmentation genes (TYRP1, ASIP and MITF) in sheep. Eighteen of these associations were confirmed in further tests between white versus non-white individuals, but none of the 35 associations were significant in the analysis of only non-white colours. Across the tests, the s66432.1 in ASIP showed significant association (P=4.2 × 10(-11) for all the colours; P=2.3 × 10(-11) for white versus non-white colours) with the variation in coat colours and strong linkage disequilibrium with other significant variants surrounding the ASIP gene. The signals detected around the ASIP gene were explained by differences in white versus non-white alleles. Further, a genome scan for selection for white coat pigmentation identified a strong and striking selection signal spanning ASIP. Our study identified the main candidate gene for the coat colour variation between white and non-white as ASIP, an autosomal gene that has been directly implicated in the pathway regulating melanogenesis. Together with ASIP, the two other newly identified genes (TYRP1 and MITF) in the Finnsheep, bordering associated SNPs, represent a new resource for enriching sheep coat-colour genetics and breeding.

  12. Perineal scanning.

    Science.gov (United States)

    Jeanty, P; d'Alton, M; Romero, R; Hobbins, J C

    1986-10-01

    Although various techniques have been described to aid in the ultrasound diagnosis of placenta previa and incompetent cervix, these maneuvers depend on the precise identification of the internal cervical os, a feat which is notoriously difficult to accomplish consistently. In an attempt to get a closer view of the cervix we tried another approach. This simple technique of perineal scanning has the potential to help considerably with these problems. PMID:3530265

  13. SNP analyses of growth factor genes EGF, TGFβ-1, and HGF reveal haplotypic association of EGF with autism

    International Nuclear Information System (INIS)

    Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-β (TGFβ) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGFβ1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGFβ1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism

  14. Fine-scale genetic structure and cryptic associations reveal evidence of kin-based sociality in the African forest elephant.

    Directory of Open Access Journals (Sweden)

    Stephanie G Schuttler

    Full Text Available Spatial patterns of relatedness within animal populations are important in the evolution of mating and social systems, and have the potential to reveal information on species that are difficult to observe in the wild. This study examines the fine-scale genetic structure and connectivity of groups within African forest elephants, Loxodonta cyclotis, which are often difficult to observe due to forest habitat. We tested the hypothesis that genetic similarity will decline with increasing geographic distance, as we expect kin to be in closer proximity, using spatial autocorrelation analyses and Tau K(r tests. Associations between individuals were investigated through a non-invasive genetic capture-recapture approach using network models, and were predicted to be more extensive than the small groups found in observational studies, similar to fission-fusion sociality found in African savanna (Loxodonta africana and Asian (Elephas maximus species. Dung samples were collected in Lopé National Park, Gabon in 2008 and 2010 and genotyped at 10 microsatellite loci, genetically sexed, and sequenced at the mitochondrial DNA control region. We conducted analyses on samples collected at three different temporal scales: a day, within six-day sampling sessions, and within each year. Spatial autocorrelation and Tau K(r tests revealed genetic structure, but results were weak and inconsistent between sampling sessions. Positive spatial autocorrelation was found in distance classes of 0-5 km, and was strongest for the single day session. Despite weak genetic structure, individuals within groups were significantly more related to each other than to individuals between groups. Social networks revealed some components to have large, extensive groups of up to 22 individuals, and most groups were composed of individuals of the same matriline. Although fine-scale population genetic structure was weak, forest elephants are typically found in groups consisting of kin and

  15. Spatial and Species Variations in Bacterial Communities Associated with Corals from the Red Sea as Revealed by Pyrosequencing

    KAUST Repository

    Lee, O. O.

    2012-08-03

    Microbial associations with corals are common and are most likely symbiotic, although their diversity and relationships with environmental factors and host species remain unclear. In this study, we adopted a 16S rRNA gene tag-pyrosequencing technique to investigate the bacterial communities associated with three stony Scleractinea and two soft Octocorallia corals from three locations in the Red Sea. Our results revealed highly diverse bacterial communities in the Red Sea corals, with more than 600 ribotypes detected and up to 1,000 species estimated from a single coral species. Altogether, 21 bacterial phyla were recovered from the corals, of which Gammaproteobacteria was the most dominant group, and Chloroflexi, Chlamydiae, and the candidate phylum WS3 were reported in corals for the first time. The associated bacterial communities varied greatly with location, where environmental conditions differed significantly. Corals from disturbed areas appeared to share more similar bacterial communities, but larger variations in community structures were observed between different coral species from pristine waters. Ordination methods identified salinity and depth as the most influential parameters affecting the abundance of Vibrio, Pseudoalteromonas, Serratia, Stenotrophomonas, Pseudomonas, and Achromobacter in the corals. On the other hand, bacteria such as Chloracidobacterium and Endozoicomonas were more sensitive to the coral species, suggesting that the host species type may be influential in the associated bacterial community, as well. The combined influences of the coral host and environmental factors on the associated microbial communities are discussed. This study represents the first comparative study using tag-pyrosequencing technology to investigate the bacterial communities in Red Sea corals.

  16. Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels.

    Science.gov (United States)

    Arndts, Kathrin; Specht, Sabine; Debrah, Alexander Y; Tamarozzi, Francesca; Klarmann Schulz, Ute; Mand, Sabine; Batsa, Linda; Kwarteng, Alexander; Taylor, Mark; Adjei, Ohene; Martin, Coralie; Layland, Laura E; Hoerauf, Achim

    2014-02-01

    Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF(+) or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community

  17. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

    Directory of Open Access Journals (Sweden)

    Caroline S Fox

    Full Text Available Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT, visceral adipose tissue (VAT, VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09, previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08. Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08, but not men (p = 0.75. Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006 but not men (p = 0.24 for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]. Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI; associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a

  18. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Science.gov (United States)

    Berglin, Lena; Bergquist, Annika; Johansson, Helene; Glaumann, Hans; Jorns, Carl; Lunemann, Sebastian; Wedemeyer, Heiner; Ellis, Ewa C; Björkström, Niklas K

    2014-01-01

    Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC), however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17) and controls (n = 17). We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  19. In situ characterization of intrahepatic non-parenchymal cells in PSC reveals phenotypic patterns associated with disease severity.

    Directory of Open Access Journals (Sweden)

    Lena Berglin

    Full Text Available Liver-infiltrating T cells have been implicated in the pathogenesis of primary sclerosing cholangitis (PSC, however little information is available about changes in other cellular compartments in the liver during PSC. This study aimed to characterize non-parenchymal intrahepatic cells in PSC livers and to find associations between phenotypes and disease severity. Using immunohistochemistry, followed by automated image analysis and quantification and a principal component analysis, we have studied non-parenchymal intrahepatic cells in PSC-patient livers (n = 17 and controls (n = 17. We observed a significant increase of T cells in the PSC patients, localized to the fibrotic areas. MAIT cells, normally present at high numbers in the liver, were not increased to the same extent. PSC patients had lower expression of MHC class I than controls. However, the levels of NKp46+ NK cells were similar between patients and controls, nevertheless, NKp46 was identified as a phenotypic marker that distinguished PSC patients with mild from those with severe fibrosis. Beyond that, a group of PSC patients had lost expression of Caldesmon and this was associated with more extensive bile duct proliferation and higher numbers of T cells. Our data reveals phenotypic patterns in PSC patients associated with disease severity.

  20. Quantitative genetics of CTCF binding reveal local sequence effects and different modes of X-chromosome association.

    Directory of Open Access Journals (Sweden)

    Zhihao Ding

    2014-11-01

    Full Text Available Associating genetic variation with quantitative measures of gene regulation offers a way to bridge the gap between genotype and complex phenotypes. In order to identify quantitative trait loci (QTLs that influence the binding of a transcription factor in humans, we measured binding of the multifunctional transcription and chromatin factor CTCF in 51 HapMap cell lines. We identified thousands of QTLs in which genotype differences were associated with differences in CTCF binding strength, hundreds of them confirmed by directly observable allele-specific binding bias. The majority of QTLs were either within 1 kb of the CTCF binding motif, or in linkage disequilibrium with a variant within 1 kb of the motif. On the X chromosome we observed three classes of binding sites: a minority class bound only to the active copy of the X chromosome, the majority class bound to both the active and inactive X, and a small set of female-specific CTCF sites associated with two non-coding RNA genes. In sum, our data reveal extensive genetic effects on CTCF binding, both direct and indirect, and identify a diversity of patterns of CTCF binding on the X chromosome.

  1. A genome-wide admixture scan identifies MYH9 as a candidate locus associated with non-diabetic end stage renal disease in African Americans

    Science.gov (United States)

    Linda Kao, WH; Klag, Michael J; Meoni, Lucy A; Reich, David; Berthier-Schaad, Yvette; Li, Man; Coresh, Josef; Patterson, Nick; Tandon, Arti; Powe, Neil R; Fink, Nancy E; Sadler, John H; Weir, Matthew R; Abboud, Hanna E; Adler, Sharon; Divers, Jasmin; Iyengar, Sudha K; Freedman, Barry I; Kimmel, Paul L; Knowler, William C; Kohn, Orly F; Kramp, Kristopher; Leehey, David J; Nicholas, Susanne; Pahl, Madeleine; Schelling, Jeffrey R; Sedor, John R; Thornley-Brown, Denyse; Winkler, Cheryl A; Smith, Michael W.; Parekh, Rulan S.

    2008-01-01

    End stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans. This led to the hypothesis that susceptibility alleles for ESRD have a higher frequency in West African than European gene pool. We performed a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and demonstrated a highly significant association between excess African ancestry and non-diabetic ESRD (LOD 5.70) but not diabetic ESRD (LOD 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% credible interval 0.39 – 0.63) compared to African ancestry. Multiple common SNPs (allele frequency ranging from 0.2 to 0.6) in the gene that encodes non-muscle myosin heavy chain type II isoform A (MYH9) were associated with 2-4 times greater risk of non-diabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans. PMID:18794854

  2. Expression Profiling of Glucosinolate Biosynthetic Genes in Brassica oleracea L. var. capitata Inbred Lines Reveals Their Association with Glucosinolate Content

    Directory of Open Access Journals (Sweden)

    Arif Hasan Khan Robin

    2016-06-01

    Full Text Available Glucosinolates are the biochemical compounds that provide defense to plants against pathogens and herbivores. In this study, the relative expression level of 48 glucosinolate biosynthesis genes was explored in four morphologically-different cabbage inbred lines by qPCR analysis. The content of aliphatic and indolic glucosinolate molecules present in those cabbage lines was also estimated by HPLC analysis. The possible association between glucosinolate accumulation and related gene expression level was explored by principal component analysis (PCA. The genotype-dependent variation in the relative expression level of different aliphatic and indolic glucosinolate biosynthesis genes is the novel result of this study. A total of eight different types of glucosinolates, including five aliphatic and three indolic glucosinolates, was detected in four cabbage lines. Three inbred lines BN3383, BN4059 and BN4072 had no glucoraphanin, sinigrin and gluconapin detected, but the inbred line BN3273 had these three aliphatic glucosinolate compounds. PCA revealed that a higher expression level of ST5b genes and lower expression of GSL-OH was associated with the accumulation of these three aliphatic glucosinolate compounds. PCA further revealed that comparatively higher accumulation of neoglucobrassicin in the inbred line, BN4072, was associated with a high level of expression of MYB34 (Bol017062 and CYP81F1 genes. The Dof1 and IQD1 genes probably trans-activated the genes related to biosynthesis of glucoerucin and methoxyglucobrassicin for their comparatively higher accumulation in the BN4059 and BN4072 lines compared to the other two lines, BN3273 and BN3383. A comparatively higher progoitrin level in BN3273 was probably associated with the higher expression level of the GSL-OH gene. The cabbage inbred line BN3383 accounted for the significantly higher relative expression level for the 12 genes out of 48, but this line had comparatively lower total

  3. Expression Profiling of Glucosinolate Biosynthetic Genes in Brassica oleracea L. var. capitata Inbred Lines Reveals Their Association with Glucosinolate Content.

    Science.gov (United States)

    Robin, Arif Hasan Khan; Yi, Go-Eun; Laila, Rawnak; Yang, Kiwoung; Park, Jong-In; Kim, Hye Ran; Nou, Ill-Sup

    2016-01-01

    Glucosinolates are the biochemical compounds that provide defense to plants against pathogens and herbivores. In this study, the relative expression level of 48 glucosinolate biosynthesis genes was explored in four morphologically-different cabbage inbred lines by qPCR analysis. The content of aliphatic and indolic glucosinolate molecules present in those cabbage lines was also estimated by HPLC analysis. The possible association between glucosinolate accumulation and related gene expression level was explored by principal component analysis (PCA). The genotype-dependent variation in the relative expression level of different aliphatic and indolic glucosinolate biosynthesis genes is the novel result of this study. A total of eight different types of glucosinolates, including five aliphatic and three indolic glucosinolates, was detected in four cabbage lines. Three inbred lines BN3383, BN4059 and BN4072 had no glucoraphanin, sinigrin and gluconapin detected, but the inbred line BN3273 had these three aliphatic glucosinolate compounds. PCA revealed that a higher expression level of ST5b genes and lower expression of GSL-OH was associated with the accumulation of these three aliphatic glucosinolate compounds. PCA further revealed that comparatively higher accumulation of neoglucobrassicin in the inbred line, BN4072, was associated with a high level of expression of MYB34 (Bol017062) and CYP81F1 genes. The Dof1 and IQD1 genes probably trans-activated the genes related to biosynthesis of glucoerucin and methoxyglucobrassicin for their comparatively higher accumulation in the BN4059 and BN4072 lines compared to the other two lines, BN3273 and BN3383. A comparatively higher progoitrin level in BN3273 was probably associated with the higher expression level of the GSL-OH gene. The cabbage inbred line BN3383 accounted for the significantly higher relative expression level for the 12 genes out of 48, but this line had comparatively lower total glucosinolates detected

  4. Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Chung Jae

    2009-06-01

    Full Text Available Abstract Background Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition. Methods To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis. Results Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99 between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells. Conclusion Selective epigenetic disruption of distinct biological

  5. A genome-wide association study on androstenone levels in pigs reveals a cluster of candidate genes on chromosome 6

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    Groenen Martien AM

    2010-05-01

    Full Text Available Abstract Background In many countries, male piglets are castrated shortly after birth because a proportion of un-castrated male pigs produce meat with an unpleasant flavour and odour. Main compounds of boar taint are androstenone and skatole. The aim of this high-density genome-wide association study was to identify single nucleotide polymorphisms (SNPs associated with androstenone levels in a commercial sire line of pigs. The identification of major genetic effects causing boar taint would accelerate the reduction of boar taint through breeding to finally eliminate the need for castration. Results The Illumina Porcine 60K+SNP Beadchip was genotyped on 987 pigs divergent for androstenone concentration from a commercial Duroc-based sire line. The association analysis with 47,897 SNPs revealed that androstenone levels in fat tissue were significantly affected by 37 SNPs on pig chromosomes SSC1 and SSC6. Among them, the 5 most significant SNPs explained together 13.7% of the genetic variance in androstenone. On SSC6, a larger region of 10 Mb was shown to be associated with androstenone covering several candidate genes potentially involved in the synthesis and metabolism of androgens. Besides known candidate genes, such as cytochrome P450 A19 (CYP2A19, sulfotransferases SULT2A1, and SULT2B1, also new members of the cytochrome P450 CYP2 gene subfamilies and of the hydroxysteroid-dehydrogenases (HSD17B14 were found. In addition, the gene encoding the ß-chain of the luteinizing hormone (LHB which induces steroid synthesis in the Leydig cells of the testis at onset of puberty maps to this area on SSC6. Interestingly, the gene encoding the α-chain of LH is also located in one of the highly significant areas on SSC1. Conclusions This study reveals several areas of the genome at high resolution responsible for variation of androstenone levels in intact boars. Major genetic factors on SSC1 and SSC6 showing moderate to large effects on androstenone

  6. Characterization of the active microbiotas associated with honey bees reveals healthier and broader communities when colonies are genetically diverse.

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    Heather R Mattila

    Full Text Available Recent losses of honey bee colonies have led to increased interest in the microbial communities that are associated with these important pollinators. A critical function that bacteria perform for their honey bee hosts, but one that is poorly understood, is the transformation of worker-collected pollen into bee bread, a nutritious food product that can be stored for long periods in colonies. We used 16S rRNA pyrosequencing to comprehensively characterize in genetically diverse and genetically uniform colonies the active bacterial communities that are found on honey bees, in their digestive tracts, and in bee bread. This method provided insights that have not been revealed by past studies into the content and benefits of honey bee-associated microbial communities. Colony microbiotas differed substantially between sampling environments and were dominated by several anaerobic bacterial genera never before associated with honey bees, but renowned for their use by humans to ferment food. Colonies with genetically diverse populations of workers, a result of the highly promiscuous mating behavior of queens, benefited from greater microbial diversity, reduced pathogen loads, and increased abundance of putatively helpful bacteria, particularly species from the potentially probiotic genus Bifidobacterium. Across all colonies, Bifidobacterium activity was negatively correlated with the activity of genera that include pathogenic microbes; this relationship suggests a possible target for understanding whether microbes provide protective benefits to honey bees. Within-colony diversity shapes microbiotas associated with honey bees in ways that may have important repercussions for colony function and health. Our findings illuminate the importance of honey bee-bacteria symbioses and examine their intersection with nutrition, pathogen load, and genetic diversity, factors that are considered key to understanding honey bee decline.

  7. Characterization of the active microbiotas associated with honey bees reveals healthier and broader communities when colonies are genetically diverse.

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    Mattila, Heather R; Rios, Daniela; Walker-Sperling, Victoria E; Roeselers, Guus; Newton, Irene L G

    2012-01-01

    Recent losses of honey bee colonies have led to increased interest in the microbial communities that are associated with these important pollinators. A critical function that bacteria perform for their honey bee hosts, but one that is poorly understood, is the transformation of worker-collected pollen into bee bread, a nutritious food product that can be stored for long periods in colonies. We used 16S rRNA pyrosequencing to comprehensively characterize in genetically diverse and genetically uniform colonies the active bacterial communities that are found on honey bees, in their digestive tracts, and in bee bread. This method provided insights that have not been revealed by past studies into the content and benefits of honey bee-associated microbial communities. Colony microbiotas differed substantially between sampling environments and were dominated by several anaerobic bacterial genera never before associated with honey bees, but renowned for their use by humans to ferment food. Colonies with genetically diverse populations of workers, a result of the highly promiscuous mating behavior of queens, benefited from greater microbial diversity, reduced pathogen loads, and increased abundance of putatively helpful bacteria, particularly species from the potentially probiotic genus Bifidobacterium. Across all colonies, Bifidobacterium activity was negatively correlated with the activity of genera that include pathogenic microbes; this relationship suggests a possible target for understanding whether microbes provide protective benefits to honey bees. Within-colony diversity shapes microbiotas associated with honey bees in ways that may have important repercussions for colony function and health. Our findings illuminate the importance of honey bee-bacteria symbioses and examine their intersection with nutrition, pathogen load, and genetic diversity, factors that are considered key to understanding honey bee decline.

  8. A lipidomics study reveals hepatic lipid signatures associating with deficiency of the LDL receptor in a rat model.

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    Wang, Hong Yu; Quan, Chao; Hu, Chunxiu; Xie, Bingxian; Du, Yinan; Chen, Liang; Yang, Wei; Yang, Liu; Chen, Qiaoli; Shen, Bin; Hu, Bian; Zheng, Zhihong; Zhu, Haibo; Huang, Xingxu; Xu, Guowang; Chen, Shuai

    2016-01-01

    The low-density lipoprotein receptor (LDLR) plays a critical role in the liver for the clearance of plasma low-density lipoprotein (LDL). Its deficiency causes hypercholesterolemia in many models. To facilitate the usage of rats as animal models for the discovery of cholesterol-lowering drugs, we took a genetic approach to delete the LDLR in rats aiming to increase plasma LDL cholesterol (LDL-C). An LDLR knockout rat was generated via zinc-finger nuclease technology, which harbors a 19-basepair deletion in the seventh exon of the ldlr gene. As expected, deletion of the LDLR elevated total cholesterol and total triglyceride in the plasma, and caused a tenfold increase of plasma LDL-C and a fourfold increase of plasma very low-density lipoprotein (VLDL-C). A lipidomics analysis revealed that deletion of the LDLR affected hepatic lipid metabolism, particularly lysophosphatidylcholines, free fatty acids and sphingolipids in the liver. Cholesterol ester (CE) 20:4 also displayed a significant increase in the LDLR knockout rats. Taken together, the LDLR knockout rat offers a new model of hypercholesterolemia, and the lipidomics analysis reveals hepatic lipid signatures associating with deficiency of the LDL receptor. PMID:27378433

  9. Morphological and behavioral differences in the gastropod Trophon geversianus associated to distinct environmental conditions, as revealed by a multidisciplinary approach

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    Márquez, Federico; Nieto Vilela, Rocío Aimé; Lozada, Mariana; Bigatti, Gregorio

    2015-01-01

    The gastropod Trophon geversianus exhibits shell polymorphisms along its distribution in subtidal and intertidal habitats. Our hypothesis is that morphological and behavioral patterns of T. geversianus represent habitat-specific constrains; subsequently we expect an association between shell morphology, attachment behavior, and habitat. In order to test this hypothesis we compared individuals from intertidal and subtidal habitats, at three sites in Golfo Nuevo (Argentina). We analyzed shell morphology using classic morphometric variables, 3D geometric morphometrics and computing tomography scan. The results were complemented with field observations of attachment to substrate and turning time behavior, as well as of the number of shell scars produced by crab predation. Our results showed differences in shell size and shape between intertidal and subtidal-collected individuals. Centroid size, total weight and shell weight, as well as shell density and thickness were significantly lower in intertidal individuals than in subtidal ones. Gastropods from intertidal habitats presented a low-spired shell and an expanded aperture which might allow better attachment to the bottom substrate, while subtidal individuals presented a slender and narrower shell shape. The number of crab scars was significantly higher in shells from subtidal individuals. Observations of the behavior of gastropods placed at the intertidal splash zone showed 100% of attachment to the bottom in the intertidal individuals, while subtidal specimens only attached in average in 32% of the cases. These latter took 12 times longer to re-attach to the bottom when faced up. Phylogenetic analysis of COI gene fragments showed no consistent differences among individuals sampled in both habitats. All these results suggest that T. geversianus has developed two ecomorphs with distinct morphological and behavioral responses to physically stressful conditions registered in north Patagonian intertidals, as opposed to

  10. Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.

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    Nicole Soranzo

    2009-04-01

    Full Text Available Recent genome-wide (GW scans have identified several independent loci affecting human stature, but their contribution through the different skeletal components of height is still poorly understood. We carried out a genome-wide scan in 12,611 participants, followed by replication in an additional 7,187 individuals, and identified 17 genomic regions with GW-significant association with height. Of these, two are entirely novel (rs11809207 in CATSPER4, combined P-value = 6.1x10(-8 and rs910316 in TMED10, P-value = 1.4x10(-7 and two had previously been described with weak statistical support (rs10472828 in NPR3, P-value = 3x10(-7 and rs849141 in JAZF1, P-value = 3.2x10(-11. One locus (rs1182188 at GNA12 identifies the first height eQTL. We also assessed the contribution of height loci to the upper- (trunk and lower-body (hip axis and femur skeletal components of height. We find evidence for several loci associated with trunk length (including rs6570507 in GPR126, P-value = 4x10(-5 and rs6817306 in LCORL, P-value = 4x10(-4, hip axis length (including rs6830062 at LCORL, P-value = 4.8x10(-4 and rs4911494 at UQCC, P-value = 1.9x10(-4, and femur length (including rs710841 at PRKG2, P-value = 2.4x10(-5 and rs10946808 at HIST1H1D, P-value = 6.4x10(-6. Finally, we used conditional analyses to explore a possible differential contribution of the height loci to these different skeletal size measurements. In addition to validating four novel loci controlling adult stature, our study represents the first effort to assess the contribution of genetic loci to three skeletal components of height. Further statistical tests in larger numbers of individuals will be required to verify if the height loci affect height preferentially through these subcomponents of height.

  11. Gene Network Analysis and Functional Studies of Senescence-associated Genes Reveal Novel Regulators of Arabidopsis Leaf Senescence

    Institute of Scientific and Technical Information of China (English)

    Zhonghai Li; Jinying Peng; Xing Wen; Hongwei Guo

    2012-01-01

    Plant leaf senescence has been recognized as the last phase of plant development,a highly ordered process regulated by genes known as senescence associated genes (SAGs).However,the function of most of SAGs in regulating leaf senescence as well as regulators of those functionally known SAGs are still unclear.We have previously developed a curated database of genes potentially associated with leaf senescence,the Leaf Senescence Database (LSD).In this study,we built gene networks to identify common regulators of leaf senescence in Arabidopsis thaliana using promoting or delaying senescence genes in LSD.Our results demonstrated that plant hormones cytokinin,auxin,nitric oxide as well as small molecules,such as Ca2+,delay leaf senescence.By contrast,ethylene,ABA,SA and JA as well as small molecules,such as oxygen,promote leaf senescence,altogether supporting the idea that phytohormones play a critical role in regulating leaf senescence.Functional analysis of candidate SAGs in LSD revealed that a WRKY transcription factor WRKY75 and a Cys2/His2-type transcription factor AZF2 are positive regulators of leaf senescence and loss-of-function of WRKY75 or AZF2 delayed leaf senescence.We also found that silencing of a protein phosphatase,AtMKP2,promoted early senescence.Collectively,LSD can serve as a comprehensive resource for systematic study of the molecular mechanism of leaf senescence as well as offer candidate genes for functional analyses.

  12. The tell-tale heart: population-based surveillance reveals an association of rofecoxib and celecoxib with myocardial infarction.

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    John S Brownstein

    Full Text Available BACKGROUND: COX-2 selective inhibitors are associated with myocardial infarction (MI. We sought to determine whether population health monitoring would have revealed the effect of COX-2 inhibitors on population-level patterns of MI. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective study of inpatients at two Boston hospitals, from January 1997 to March 2006. There was a population-level rise in the rate of MI that reached 52.0 MI-related hospitalizations per 100,000 (a two standard deviation exceedence in January of 2000, eight months after the introduction of rofecoxib and one year after celecoxib. The exceedence vanished within one month of the withdrawal of rofecoxib. Trends in inpatient stay due to MI were tightly coupled to the rise and fall of prescriptions of COX-2 inhibitors, with an 18.5% increase in inpatient stays for MI when both rofecoxib and celecoxib were on the market (P<0.001. For every million prescriptions of rofecoxib and celecoxib, there was a 0.5% increase in MI (95%CI 0.1 to 0.9 explaining 50.3% of the deviance in yearly variation of MI-related hospitalizations. There was a negative association between mean age at MI and volume of prescriptions for celecoxib and rofecoxib (Spearman correlation, -0.67, P<0.05. CONCLUSIONS/SIGNIFICANCE: The strong relationship between prescribing and outcome time series supports a population-level impact of COX-2 inhibitors on MI incidence. Further, mean age at MI appears to have been lowered by use of these medications. Use of a population monitoring approach as an adjunct to pharmacovigilence methods might have helped confirm the suspected association, providing earlier support for the market withdrawal of rofecoxib.

  13. Blood microvascular organization of the nasal-associated lymphoid tissue of the guinea pig: a scanning electron microscopic study of corrosion casts.

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    Okada,Satoko

    1995-08-01

    Full Text Available It has previously been confirmed that the guinea pig has aggregations of 10-20 lymphoid follicles at the junction of the nasal cavity and the nasopharyngeal duct. The vascular architecture of this nasal-associated lymphoid tissue (NALT was studied by the corrosion cast/scanning electron microscope method. The NALT was supplied by branches of the inferior nasal artery. These afferent arterial branches gave off arterioles to the follicles and the interfollicular regions, where the arterioles ramified into capillaries. Some of these arterioles reached the subepithelial region to form a single-layer dense capillary network. The subepithelial capillaries gathered into short collecting venules, which in turn drained into high endothelial venules (HEV in the interfollicular region. The HEV, which also receives tributaries from the follicular and interfollicular capillary plexuses, descended in the interfollicular regions and finally flowed into the efferent veins at the bottom of the NALT. Indentations impressed by high endothelial cells (HEC were prominent on the surface of the HEV casts, and their frequency was larger in the upper course or segments than in the lower. This suggests that the incidence of HEC in the upper segments is higher than in the lower segments, and these findings are consistent with the hypothesis that some substances which are taken up into the subepithelial capillaries and transported to the venules induce differentiation and maintain of HEVs.

  14. Helix Scan: A Scan Design for Diagnosis

    Institute of Scientific and Technical Information of China (English)

    WANG Fei; HU Yu; LI Xiaowei

    2007-01-01

    Scan design is a widely used design-for-testability technique to improve test quality and efficiency. For the scan-designed circuit, test and diagnosis of the scan chain and the circuit is an important process for silicon debug and yield learning. However, conventional scan designs and diagnosis methods abort the subsequent diagnosis process after diagnosing the scan chain if the scan chain is faulty. In this work, we propose a design-for-diagnosis scan strategy called helix scan and a diagnosis algorithm to address this issue. Unlike previous proposed methods, helix scan has the capability to carry on the diagnosis process without losing information when the scan chain is faulty. What is more, it simplifies scan chain diagnosis and achieves high diagnostic resolution as well as accuracy. Experimental results demonstrate the effectiveness of our design.

  15. As Old as the hills: montane scorpions in Southwestern North America reveal ancient associations between biotic diversification and landscape history.

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    Robert W Bryson

    Full Text Available BACKGROUND: The age of lineages has become a fundamental datum in studies exploring the interaction between geological transformation and biotic diversification. However, phylogeographical studies are often biased towards lineages that are younger than the geological features of the landscapes they inhabit. A temporally deeper historical biogeography framework may be required to address episodes of biotic diversification associated with geologically older landscape changes. Signatures of such associations may be retained in the genomes of ecologically specialized (stenotopic taxa with limited vagility. In the study presented here, genetic data from montane scorpions in the Vaejovis vorhiesi group, restricted to humid rocky habitats in mountains across southwestern North America, were used to explore the relationship between scorpion diversification and regional geological history. RESULTS: Strong phylogeographical signal was evident within the vorhiesi group, with 27 geographically cohesive lineages inferred from a mitochondrial phylogeny. A time-calibrated multilocus species tree revealed a pattern of Miocene and Pliocene (the Neogene period lineage diversification. An estimated 21 out of 26 cladogenetic events probably occurred prior to the onset of the Pleistocene, 2.6 million years ago. The best-fit density-dependent model suggested diversification rate in the vorhiesi group gradually decreased through time. CONCLUSIONS: Scorpions of the vorhiesi group have had a long history in the highlands of southwestern North America. Diversification among these stenotopic scorpions appears to have occurred almost entirely within the Neogene period, and is temporally consistent with the dynamic geological history of the Basin and Range, and Colorado Plateau physiographical provinces. The persistence of separate lineages at small spatial scales suggests that a combination of ecological stenotopy and limited vagility may make these scorpions particularly

  16. A further look at porcine chromosome 7 reveals VRTN variants associated with vertebral number in Chinese and Western pigs.

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    Yin Fan

    Full Text Available The number of vertebrae is an economically important trait that affects carcass length and meat production in pigs. A major quantitative trait locus (QTL for thoracic vertebral number has been repeatedly identified on pig chromosome (SSC 7. To dissect the genetic basis of the major locus, we herein genotyped a large sample of animals from 3 experimental populations of Chinese and Western origins using 60K DNA chips. Genome-wide association studies consistently identified the locus across the 3 populations and mapped the locus to a 947-Kb region on SSC7. An identical-by-descent sharing assay refined the locus to a 100-Kb segment that harbors only two genes including VRTN and SYNDIG1L. Of them, VRNT has been proposed as a strong candidate of the major locus in Western modern breeds. Further, we resequenced the VRTN gene using DNA samples of 35 parental animals with known QTL genotypes by progeny testing. Concordance tests revealed 4 candidate causal variants as their genotypes showed the perfect segregation with QTL genotypes of the tested animals. An integrative analysis of evolutional constraints and functional elements supported two VRTN variants in a complete linkage disequilibrium phase as the most likely causal mutations. The promising variants significantly affect the number of thoracic vertebrae (one vertebra in large scale outbred animals, and are segregating at rather high frequencies in Western pigs and at relatively low frequencies in a number of Chinese breeds. Altogether, we show that VRTN variants are significantly associated with the number of thoracic vertebrae in both Chinese and Western pigs. The finding advances our understanding of the genetic architecture of the vertebral number in pigs. Furthermore, our finding is of economical importance as it provides a robust breeding tool for the improvement of vertebral number and meat production in both Chinese indigenous pigs and Western present-day commercial pigs.

  17. A further look at porcine chromosome 7 reveals VRTN variants associated with vertebral number in Chinese and Western pigs.

    Science.gov (United States)

    Fan, Yin; Xing, Yuyun; Zhang, Zhiyan; Ai, Huashui; Ouyang, Zixuan; Ouyang, Jing; Yang, Ming; Li, Pinghua; Chen, Yijie; Gao, Jun; Li, Lin; Huang, Lusheng; Ren, Jun

    2013-01-01

    The number of vertebrae is an economically important trait that affects carcass length and meat production in pigs. A major quantitative trait locus (QTL) for thoracic vertebral number has been repeatedly identified on pig chromosome (SSC) 7. To dissect the genetic basis of the major locus, we herein genotyped a large sample of animals from 3 experimental populations of Chinese and Western origins using 60K DNA chips. Genome-wide association studies consistently identified the locus across the 3 populations and mapped the locus to a 947-Kb region on SSC7. An identical-by-descent sharing assay refined the locus to a 100-Kb segment that harbors only two genes including VRTN and SYNDIG1L. Of them, VRNT has been proposed as a strong candidate of the major locus in Western modern breeds. Further, we resequenced the VRTN gene using DNA samples of 35 parental animals with known QTL genotypes by progeny testing. Concordance tests revealed 4 candidate causal variants as their genotypes showed the perfect segregation with QTL genotypes of the tested animals. An integrative analysis of evolutional constraints and functional elements supported two VRTN variants in a complete linkage disequilibrium phase as the most likely causal mutations. The promising variants significantly affect the number of thoracic vertebrae (one vertebra) in large scale outbred animals, and are segregating at rather high frequencies in Western pigs and at relatively low frequencies in a number of Chinese breeds. Altogether, we show that VRTN variants are significantly associated with the number of thoracic vertebrae in both Chinese and Western pigs. The finding advances our understanding of the genetic architecture of the vertebral number in pigs. Furthermore, our finding is of economical importance as it provides a robust breeding tool for the improvement of vertebral number and meat production in both Chinese indigenous pigs and Western present-day commercial pigs.

  18. Characterization of the chromosomal inversion associated with the Koa mutation in the mouse revealed the cause of skeletal abnormalities

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    Suzuki Hiroetsu

    2009-09-01

    Full Text Available Abstract Background Koala (Koa is a dominant mutation in mice causing bushy muzzle and pinna, and is associated with a chromosomal inversion on the distal half of chromosome 15. To identify the gene responsible for the Koa phenotypes, we investigated phenotypes of Koa homozygous mice and determined the breakpoints of the inversion with a genetic method using recombination between two different chromosomal inversions. Results Skeletal preparation of Koa homozygotes showed marked deformity of the ribs and a wider skull with extended zygomatic arches, in addition to a general reduction in the lengths of long bones. They also had open eyelids at birth caused by a defect in the extension of eyelid anlagen during the embryonic stages. The proximal and distal breakpoints of the Koa inversion were determined to be 0.8-Mb distal to the Trsps1 gene and to 0.1-Mb distal to the Hoxc4 gene, respectively, as previously reported. The phenotypes of mice with the recombinant inverted chromosomes revealed the localization of the gene responsible the Koa phenotype in the vicinity of the proximal recombinant breakpoint. Expression of the Trsps1 gene in this region was significantly reduced in the Koa homozygous and heterozygous embryos. Conclusion While no gene was disrupted by the chromosomal inversion, an association between the Koa phenotype and the proximal recombinant breakpoint, phenotypic similarities with Trps1-deficient mice or human patients with TRSP1 mutations, and the reduced expression of the Trsps1 gene in Koa mice, indicated that the phenotypes of the Koa mice are caused by the altered expression of the Trps1 gene.

  19. AM fungal diversity and modularity reveal different trends in the mycorrhizal association with generalist and specialist plant species.

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    Torrecillas, Emma; del Mar Alguacil, Mª; Roldán, Antonio; Díaz, Gisela; Montesinos-Navarro, Alicia; Torres, Mª Pilar

    2013-04-01

    The plant communities present on gypsum soils include one of the most remarkable groups of edaphic "specialists", which coexist with edaphic "generalists". This study hypothesized that plant-arbuscular mycorrhizal fungi(AMF) associations can be related with specific functional plant strategies in gypsum soils.We analyzed, using network analysis, a plant-AMF mutualistic system in a gypsum environment, to characterize the plant-AMF interaction patterns according to their modularity or the tendency of species to be grouped into modules.Taking into account the total area studied (gypsum soil and marly-limestone soil), our results show that the factors determining the AM fungal community's distribution were soil type and plant species, with gypsovags harboring a different AM fungal community in gypsum and non-gypsum soils. But, there were no differences in the community diversity between specialist and generalist plants. Modularity analysis revealed that, when only gypsum soils are considered, there were some AM fungal groups with a tendency to interact differently with gypsophytes(specialists) and gypsovags (generalists).

  20. Diagnostic investigation of new disease syndromes in farmed Australian saltwater crocodiles (Crocodylus porosus) reveals associations with herpesviral infection.

    Science.gov (United States)

    Shilton, Catherine M; Jerrett, Ian V; Davis, Steven; Walsh, Susan; Benedict, Suresh; Isberg, Sally R; Webb, Grahame J W; Manolis, Charlie; Hyndman, Timothy H; Phalen, David; Brown, Gregory P; Melville, Lorna

    2016-05-01

    Since 2006, 3 new disease syndromes have emerged in farmed saltwater crocodiles (Crocodylus porosus) in the Northern Territory of Australia. We describe the syndromes through a retrospective study of laboratory findings from 187 diagnostic cases submitted to Berrimah Veterinary Laboratories between 2005 and 2014. The first syndrome was characterized by conjunctivitis and/or pharyngitis (CP), primarily in hatchlings. Herpesviruses were isolated in primary crocodile cell culture, or were detected by PCR directly from conjunctiva or pharyngeal tissue, in 21 of 39 cases of CP (54%), compared with 9 of 64 crocodiles without the syndrome (14%, p pharyngeal tissue of 55% of 29 CP cases tested, and of these, 81% also contained herpesvirus. The second syndrome occurred in juveniles and growers exhibiting poor growth, and was characterized histologically by systemic lymphoid proliferation and nonsuppurative encephalitis (SLPE). Herpesviruses were isolated or detected by PCR from at least 1 internal organ in 31 of 33 SLPE cases (94%) compared with 5 of 95 crocodiles without the syndrome (5%, p < 0.0001). The third syndrome, characterized by multifocal lymphohistiocytic infiltration of the dermis (LNS), occurred in 6 harvest-sized crocodiles. Herpesviruses were isolated from at least 1 skin lesion in 4 of these 6 cases. Although our study revealed strong associations between herpesvirus and the CP and SLPE syndromes, the precise nature of the role of herpesvirus, along with the pathogenesis and epidemiology of the syndromes, requires further investigation. PMID:27075848

  1. Genome-wide linkage scan to identify loci associated with type 2 diabetes and blood lipid phenotypes in the Sikh Diabetes Study.

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    Dharambir K Sanghera

    Full Text Available In this investigation, we have carried out an autosomal genome-wide linkage analysis to map genes associated with type 2 diabetes (T2D and five quantitative traits of blood lipids including total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, very low-density lipoprotein (VLDL cholesterol, and triglycerides in a unique family-based cohort from the Sikh Diabetes Study (SDS. A total of 870 individuals (526 male/344 female from 321 families were successfully genotyped using 398 polymorphic microsatellite markers with an average spacing of 9.26 cM on the autosomes. Results of non-parametric multipoint linkage analysis using S(all statistics (implemented in Merlin did not reveal any chromosomal region to be significantly associated with T2D in this Sikh cohort. However, linkage analysis for lipid traits using QTL-ALL analysis revealed promising linkage signals with p≤0.005 for total cholesterol, LDL cholesterol, and HDL cholesterol at chromosomes 5p15, 9q21, 10p11, 10q21, and 22q13. The most significant signal (p = 0.0011 occurred at 10q21.2 for HDL cholesterol. We also observed linkage signals for total cholesterol at 22q13.32 (p = 0.0016 and 5p15.33 (p = 0.0031 and for LDL cholesterol at 10p11.23 (p = 0.0045. Interestingly, some of linkage regions identified in this Sikh population coincide with plausible candidate genes reported in recent genome-wide association and meta-analysis studies for lipid traits. Our study provides the first evidence of linkage for loci associated with quantitative lipid traits at four chromosomal regions in this Asian Indian population from Punjab. More detailed examination of these regions with more informative genotyping, sequencing, and functional studies should lead to rapid detection of novel targets of therapeutic importance.

  2. An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12.

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    Bridget H Maher

    Full Text Available Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci.An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1 × 10(-5 ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92 × 10(-4, whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65 × 10(-4. Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women's Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05.Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63 × 10(-5 is located within the 5'UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.

  3. Cleaning ability of chlorhexidine gel and sodium hypochlorite associated or not with EDTA as root canal irrigants: a scanning electron microscopy study

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    Bruno Carvalho de Vasconcelos

    2007-10-01

    Full Text Available The aim of this study was to evaluate the cleaning efficacy of 2% chlorhexidine gluconate gel (CHX compared to 2.5% sodium hypochlorite solution (NaOCl associated or not with 17% EDTA used as irrigants during the biomechanical preparation. Fifty freshly extracted single-rooted human teeth with complete apex formation were randomly divided into five groups: G1 - sterile saline, G2 - 2.5% NaOCl, G3 - 2% CHX, G4 - 2.5% NaOCl + EDTA and G5 - 2% CHX + EDTA. The specimens of G1 were subdivided into two control groups. The teeth were decoronated and the coronal and middle root thirds were prepared with Gates-Glidden burs, and the apical third was reserved to manual instrumentation. All procedures were performed by a single operator. In all groups, 2 mL of irrigant was delivered between each file change. The teeth were sectioned and prepared for analyses under scanning electron microscopy (SEM. SEM micrographs were graded according to a score scale by two examiners. Data were analyzed statistically by Kruskal-Wallis and Dunn tests at 1% significance level. The best results were obtained in the groups in which the irrigant was used followed by the chelating agent. No statistically significant difference was observed among G4, G5 and the positive control group (p<0.01. The groups G2 and G3 were significantly different from the others, presenting the worst cleaning capacity. In conclusion, the use of the chelating agent is necessary to obtain clean canal walls, with open tubules and no heavy debris. The use of 2% chlorhexidine gluconate gel alone is not able to remove the smear layer.

  4. Transcript profiling of crown rootless1 mutant stem base reveals new elements associated with crown root development in rice

    Directory of Open Access Journals (Sweden)

    Van Anh Le Thi

    2011-08-01

    Full Text Available Abstract Background In rice, the major part of the post-embryonic root system is made of stem-derived roots named crown roots (CR. Among the few characterized rice mutants affected in root development, crown rootless1 mutant is unable to initiate crown root primordia. CROWN ROOTLESS1 (CRL1 is induced by auxin and encodes an AS2/LOB-domain transcription factor that acts upstream of the gene regulatory network controlling CR development. Results To identify genes involved in CR development, we compared global gene expression profile in stem bases of crl1 mutant and wild-type (WT plants. Our analysis revealed that 250 and 236 genes are down- and up-regulated respectively in the crl1 mutant. Auxin induces CRL1 expression and consequently it is expected that auxin also alters the expression of genes that are early regulated by CRL1. To identify genes under the early control of CRL1, we monitored the expression kinetics of a selected subset of genes, mainly chosen among those exhibiting differential expression, in crl1 and WT following exogenous auxin treatment. This analysis revealed that most of these genes, mainly related to hormone, water and nutrient, development and homeostasis, were likely not regulated directly by CRL1. We hypothesized that the differential expression for these genes observed in the crl1 mutant is likely a consequence of the absence of CR formation. Otherwise, three CRL1-dependent auxin-responsive genes: FSM (FLATENNED SHOOT MERISTEM/FAS1 (FASCIATA1, GTE4 (GENERAL TRANSCRIPTION FACTOR GROUP E4 and MAP (MICROTUBULE-ASSOCIATED PROTEIN were identified. FSM/FAS1 and GTE4 are known in rice and Arabidopsis to be involved in the maintenance of root meristem through chromatin remodelling and cell cycle regulation respectively. Conclusion Our data showed that the differential regulation of most genes in crl1 versus WT may be an indirect consequence of CRL1 inactivation resulting from the absence of CR in the crl1 mutant. Nevertheless

  5. Use of expiratory CT pulmonary angiography to reduce inspiration and breath-hold associated artefact: Contrast dynamics and implications for scan protocol

    Energy Technology Data Exchange (ETDEWEB)

    Mortimer, A.M., E-mail: alex_mortimer@hotmail.com [Department of Radiology, Bristol Royal Infirmary, Bristol (United Kingdom); Singh, R.K.; Hughes, J.; Greenwood, R.; Hamilton, M.C.K. [Department of Radiology, Bristol Royal Infirmary, Bristol (United Kingdom)

    2011-12-15

    Aim: To investigate the effects of scanning in expiration during computed tomography pulmonary angiography (CTPA). Materials and methods: One hundred and eighty-one consecutive expiratory CTPA examinations were compared with 145 inspiratory CTPA examinations performed using a standardized protocol through assessment of attenuation seen in the cardiac chambers, pulmonary artery (PA), and ascending aorta. Results: Expiratory scans showed greater attenuation at the pulmonary trunk, right PA, left PA, lobar and segmental PAs (p < 0.05). Expiratory scans showed a lower incidence of transient contrast medium interruption (p < 0.001) and generalized unsatisfactory PA opacification (p < 0.05). Scans with generalized low PA attenuation had lower attenuation in the right ventricle, left heart, and ascending aorta (p < 0.001) suggesting that contrast medium delivery or dilution prior to contrast medium entry into the PA is responsible. Expiratory scans showed lower quality scores (p < 0.001) for depiction of lung parenchyma. Conclusion: Expiratory scanning could be used as an optimal protocol for dedicated PA imaging. However, it suffers from inferior parenchymal imaging and should probably be reserved for failed inspiratory breath-hold CTPA.

  6. Use of expiratory CT pulmonary angiography to reduce inspiration and breath-hold associated artefact: Contrast dynamics and implications for scan protocol

    International Nuclear Information System (INIS)

    Aim: To investigate the effects of scanning in expiration during computed tomography pulmonary angiography (CTPA). Materials and methods: One hundred and eighty-one consecutive expiratory CTPA examinations were compared with 145 inspiratory CTPA examinations performed using a standardized protocol through assessment of attenuation seen in the cardiac chambers, pulmonary artery (PA), and ascending aorta. Results: Expiratory scans showed greater attenuation at the pulmonary trunk, right PA, left PA, lobar and segmental PAs (p < 0.05). Expiratory scans showed a lower incidence of transient contrast medium interruption (p < 0.001) and generalized unsatisfactory PA opacification (p < 0.05). Scans with generalized low PA attenuation had lower attenuation in the right ventricle, left heart, and ascending aorta (p < 0.001) suggesting that contrast medium delivery or dilution prior to contrast medium entry into the PA is responsible. Expiratory scans showed lower quality scores (p < 0.001) for depiction of lung parenchyma. Conclusion: Expiratory scanning could be used as an optimal protocol for dedicated PA imaging. However, it suffers from inferior parenchymal imaging and should probably be reserved for failed inspiratory breath-hold CTPA.

  7. Transcriptome Profiling of Tomato Fruit Development Reveals Transcription Factors Associated with Ascorbic Acid, Carotenoid and Flavonoid Biosynthesis.

    Science.gov (United States)

    Ye, Jie; Hu, Tixu; Yang, Congmei; Li, Hanxia; Yang, Mingze; Ijaz, Raina; Ye, Zhibiao; Zhang, Yuyang

    2015-01-01

    Tomato (Solanum lycopersicum) serves as a research model for fruit development; however, while it is an important dietary source of antioxidant nutrients, the transcriptional regulation of genes that determine nutrient levels remains poorly understood. Here, the transcriptomes of fruit at seven developmental stages (7, 14, 21, 28, 35, 42 and 49 days after flowering) from two tomato cultivars (Ailsa Craig and HG6-61) were evaluated using the Illumina sequencing platform. A total of 26,397 genes, which were expressed in at least one developmental stage, were detected in the two cultivars, and the expression patterns of those genes could be divided into 20 groups using a K-mean cluster analysis. Gene Ontology term enrichment analysis indicated that genes involved in RNA regulation, secondary metabolism, hormone metabolism and cell wall metabolism were the most highly differentially expressed genes during fruit development and ripening. A co-expression analysis revealed several transcription factors whose expression patterns correlated with those of genes associated with ascorbic acid, carotenoid and flavonoid biosynthesis. This transcriptional correlation was confirmed by agroinfiltration mediated transient expression, which showed that most of the enzymatic genes in the ascorbic acid biosynthesis were regulated by the overexpression of each of the three transcription factors that were tested. The metabolic dynamics of ascorbic acid, carotenoid and flavonoid were investigated during fruit development and ripening, and some selected transcription factors showed transcriptional correlation with the accumulation of ascorbic acid, carotenoid and flavonoid. This transcriptome study provides insight into the regulatory mechanism of fruit development and presents candidate transcription factors involved in secondary metabolism.

  8. Transcriptome Profiling of Tomato Fruit Development Reveals Transcription Factors Associated with Ascorbic Acid, Carotenoid and Flavonoid Biosynthesis.

    Directory of Open Access Journals (Sweden)

    Jie Ye

    Full Text Available Tomato (Solanum lycopersicum serves as a research model for fruit development; however, while it is an important dietary source of antioxidant nutrients, the transcriptional regulation of genes that determine nutrient levels remains poorly understood. Here, the transcriptomes of fruit at seven developmental stages (7, 14, 21, 28, 35, 42 and 49 days after flowering from two tomato cultivars (Ailsa Craig and HG6-61 were evaluated using the Illumina sequencing platform. A total of 26,397 genes, which were expressed in at least one developmental stage, were detected in the two cultivars, and the expression patterns of those genes could be divided into 20 groups using a K-mean cluster analysis. Gene Ontology term enrichment analysis indicated that genes involved in RNA regulation, secondary metabolism, hormone metabolism and cell wall metabolism were the most highly differentially expressed genes during fruit development and ripening. A co-expression analysis revealed several transcription factors whose expression patterns correlated with those of genes associated with ascorbic acid, carotenoid and flavonoid biosynthesis. This transcriptional correlation was confirmed by agroinfiltration mediated transient expression, which showed that most of the enzymatic genes in the ascorbic acid biosynthesis were regulated by the overexpression of each of the three transcription factors that were tested. The metabolic dynamics of ascorbic acid, carotenoid and flavonoid were investigated during fruit development and ripening, and some selected transcription factors showed transcriptional correlation with the accumulation of ascorbic acid, carotenoid and flavonoid. This transcriptome study provides insight into the regulatory mechanism of fruit development and presents candidate transcription factors involved in secondary metabolism.

  9. Quantification of human-associated fecal indicators reveal sewage from urban watersheds as a source of pollution to Lake Michigan

    Science.gov (United States)

    Templar, Hayley A.; Dila, Deborah K.; Bootsma, Melinda J.; Corsi, Steven; McLellan, Sandra L.

    2016-01-01

    Sewage contamination of urban waterways from sewer overflows and failing infrastructure is a major environmental and public health concern. Fecal coliforms (FC) are commonly employed as fecal indicator bacteria, but do not distinguish between human and non-human sources of fecal contamination. Human Bacteroides and humanLachnospiraceae, two genetic markers for human-associated indicator bacteria, were used to identify sewage signals in two urban rivers and the estuary that drains to Lake Michigan. Grab samples were collected from the rivers throughout 2012 and 2013 and hourly samples were collected in the estuary across the hydrograph during summer 2013. Human Bacteroides and human Lachnospiraceae were highly correlated with each other in river samples (Pearson’s r = 0.86), with average concentrations at most sites elevated during wet weather. These human indicators were found during baseflow, indicating that sewage contamination is chronic in these waterways. FC are used for determining total maximum daily loads (TMDLs) in management plans; however, FC concentrations alone failed to prioritize river reaches with potential health risks. While 84% of samples with >1000 CFU/100 ml FC had sewage contamination, 52% of samples with moderate (200–1000 CFU/100 ml) and 46% of samples with low (<200 CFU/100 ml) FC levels also had evidence of human sewage. Load calculations in the in the Milwaukee estuary revealed storm-driven sewage contamination varied greatly among events and was highest during an event with a short duration of intense rain. This work demonstrates urban areas have unrecognized sewage inputs that may not be adequately prioritized for remediation by the TMDL process. Further analysis using these approaches could determine relationships between land use, storm characteristics, and other factors that drive sewage contamination in urban waterways.

  10. Noninvasive Imaging Reveals Stable Transgene Expression in Mouse Airways After Delivery of a Nonintegrating Recombinant Adeno-Associated Viral Vector.

    Science.gov (United States)

    Vidović, Dragana; Gijsbers, Rik; Jimenez, Ana Quiles; Dooley, James; Van den Haute, Chris; Van der Perren, Anke; Liston, Adrian; Baekelandt, Veerle; Debyser, Zeger; Carlon, Marianne Sylvia

    2016-01-01

    Gene therapy holds promise to cure a wide range of genetic and acquired diseases. Recent successes in recombinant adeno-associated viral vector (rAAV)-based gene therapy in the clinic for hereditary disorders such as Leber's congenital amaurosis and hemophilia B encouraged us to reexplore an rAAV approach for pulmonary gene transfer. Only limited clinical successes have been achieved for airway gene transfer so far, underscoring the need for further preclinical development of rAAV-based gene therapy for pulmonary disorders. We sought to determine the preclinical potential of an airway-tropic serotype, rAAV2/5, encoding reporter genes when delivered to mouse airways. Although several groups have assessed the stability of gene transfer using a nonintegrating rAAV in mouse airways, long-term stability for more than a year has not been reported. Additionally, an extensive quantitative analysis of the specific cell types targeted by rAAV2/5 using cell-specific markers is lacking. We obtained sustained gene expression in upper and lower airways up to 15 months after vector administration, a substantial proportion of the lifespan of a laboratory mouse. In addition, we demonstrated that readministration of rAAV2/5 to the airways is feasible and increases gene expression 14 months after primary vector administration, despite the presence of circulating neutralizing antibodies. Finally, identification of transduced cell types revealed different subpopulations being targeted by rAAV2/5, with 64% of β-galactosidase-positive cells being ciliated cells, 34% club cells in the conducting airways, and 75% alveolar type II cells in the alveoli at 1 month postinjection. This underscores the therapeutic potential of a nonintegrating rAAV vector to develop a gene therapeutic drug for a variety of pulmonary disorders, such as cystic fibrosis, primary ciliary dyskinesia, and surfactant deficiencies. PMID:26567984

  11. The early asthmatic response is associated with glycolysis, calcium binding and mitochondria activity as revealed by proteomic analysis in rats

    Directory of Open Access Journals (Sweden)

    Xu Yu-Dong

    2010-08-01

    Full Text Available Abstract Background The inhalation of allergens by allergic asthmatics results in the early asthmatic response (EAR, which is characterized by acute airway obstruction beginning within a few minutes. The EAR is the earliest indicator of the pathological progression of allergic asthma. Because the molecular mechanism underlying the EAR is not fully defined, this study will contribute to a better understanding of asthma. Methods In order to gain insight into the molecular basis of the EAR, we examined changes in protein expression patterns in the lung tissue of asthmatic rats during the EAR using 2-DE/MS-based proteomic techniques. Bioinformatic analysis of the proteomic data was then performed using PPI Spider and KEGG Spider to investigate the underlying molecular mechanism. Results In total, 44 differentially expressed protein spots were detected in the 2-DE gels. Of these 44 protein spots, 42 corresponded to 36 unique proteins successfully identified using mass spectrometry. During subsequent bioinformatic analysis, the gene ontology classification, the protein-protein interaction networking and the biological pathway exploration demonstrated that the identified proteins were mainly involved in glycolysis, calcium binding and mitochondrial activity. Using western blot and semi-quantitative RT-PCR, we confirmed the changes in expression of five selected proteins, which further supports our proteomic and bioinformatic analyses. Conclusions Our results reveal that the allergen-induced EAR in asthmatic rats is associated with glycolysis, calcium binding and mitochondrial activity, which could establish a functional network in which calcium binding may play a central role in promoting the progression of asthma.

  12. Succession patterns of fungi associated to wound-induced agarwood in wild Aquilaria malaccensis revealed from quantitative PCR assay.

    Science.gov (United States)

    Mohamed, Rozi; Jong, Phai Lee; Nurul Irdayu, Ismail

    2014-09-01

    Aquilaria malaccensis produces agarwood in response to wounding and fungal attack. However, information is limited regarding Aquilaria's interaction with its diverse fungal community. In this study, time-related changes of three natural fungal colonizers in two wounded wild A. malaccensis were tracked, beginning a few hours after wounding up to 12 months. Using species-specific primers derived from their nrITS sequences in quantitative real-time PCR (qPCR), we quantified the amount of Cunninghamella bainieri, Fusarium solani and Lasiodiplodia theobromae. Because time is a major factor affecting agarwood quantity and quality, 14 wood samples were collected at different time points, i.e., 0-18 h, 2-13 days, 2-18 weeks, and 6-12 months after wounding. qPCR data revealed that the abundance of the three species decreased over time. The fungi were detected in high numbers during the first few hours and days after wounding (40- to 25,000-fold higher levels compared with initial counts) and in low numbers (<1- to 3,200-fold higher than initially) many months later. Consistent with its role in defense response, the accumulation of secondary metabolites at the wounding site could have caused the decline in fungal abundance. Succession patterns of the two trees were not identical, indicating that fungal populations may have been affected by tree environment and wound microclimate. Our results are important for understanding the diversity of microbial community in wild Aquilaria species and their association to wound-induced agarwood formation. Fungi could be secondary triggers to agarwood production in situations where trees are wounded in attempt to induce agarwood. PMID:24840100

  13. Comparative Genomics of Campylobacter fetus from Reptiles and Mammals Reveals Divergent Evolution in Host-Associated Lineages.

    Science.gov (United States)

    Gilbert, Maarten J; Miller, William G; Yee, Emma; Zomer, Aldert L; van der Graaf-van Bloois, Linda; Fitzgerald, Collette; Forbes, Ken J; Méric, Guillaume; Sheppard, Samuel K; Wagenaar, Jaap A; Duim, Birgitta

    2016-01-01

    Campylobacter fetus currently comprises three recognized subspecies, which display distinct host association. Campylobacter fetus subsp. fetus and C fetus subsp. venerealis are both associated with endothermic mammals, primarily ruminants, whereas C fetus subsp. testudinum is primarily associated with ectothermic reptiles. Both C. fetus subsp. testudinum and C. fetus subsp. fetus have been associated with severe infections, often with a systemic component, in immunocompromised humans. To study the genetic factors associated with the distinct host dichotomy in C. fetus, whole-genome sequencing and comparison of mammal- and reptile-associated C fetus was performed. The genomes of C fetus subsp. testudinum isolated from either reptiles or humans were compared with elucidate the genetic factors associated with pathogenicity in humans. Genomic comparisons showed conservation of gene content and organization among C fetus subspecies, but a clear distinction between mammal- and reptile-associated C fetus was observed. Several genomic regions appeared to be subspecies specific, including a putative tricarballylate catabolism pathway, exclusively present in C fetus subsp. testudinum strains. Within C fetus subsp. testudinum, sapA, sapB, and sapAB type strains were observed. The recombinant locus iamABC (mlaFED) was exclusively associated with invasive C fetus subsp. testudinum strains isolated from humans. A phylogenetic reconstruction was consistent with divergent evolution in host-associated strains and the existence of a barrier to lateral gene transfer between mammal- and reptile-associated C fetus Overall, this study shows that reptile-associated C fetus subsp. testudinum is genetically divergent from mammal-associated C fetus subspecies. PMID:27333878

  14. Comparative Genomics of Campylobacter fetus from Reptiles and Mammals Reveals Divergent Evolution in Host-Associated Lineages

    Science.gov (United States)

    Gilbert, Maarten J.; Miller, William G.; Yee, Emma; Zomer, Aldert L.; van der Graaf-van Bloois, Linda; Fitzgerald, Collette; Forbes, Ken J.; Méric, Guillaume; Sheppard, Samuel K.; Wagenaar, Jaap A.; Duim, Birgitta

    2016-01-01

    Campylobacter fetus currently comprises three recognized subspecies, which display distinct host association. Campylobacter fetus subsp. fetus and C. fetus subsp. venerealis are both associated with endothermic mammals, primarily ruminants, whereas C. fetus subsp. testudinum is primarily associated with ectothermic reptiles. Both C. fetus subsp. testudinum and C. fetus subsp. fetus have been associated with severe infections, often with a systemic component, in immunocompromised humans. To study the genetic factors associated with the distinct host dichotomy in C. fetus, whole-genome sequencing and comparison of mammal- and reptile-associated C. fetus was performed. The genomes of C. fetus subsp. testudinum isolated from either reptiles or humans were compared with elucidate the genetic factors associated with pathogenicity in humans. Genomic comparisons showed conservation of gene content and organization among C. fetus subspecies, but a clear distinction between mammal- and reptile-associated C. fetus was observed. Several genomic regions appeared to be subspecies specific, including a putative tricarballylate catabolism pathway, exclusively present in C. fetus subsp. testudinum strains. Within C. fetus subsp. testudinum, sapA, sapB, and sapAB type strains were observed. The recombinant locus iamABC (mlaFED) was exclusively associated with invasive C. fetus subsp. testudinum strains isolated from humans. A phylogenetic reconstruction was consistent with divergent evolution in host-associated strains and the existence of a barrier to lateral gene transfer between mammal- and reptile-associated C. fetus. Overall, this study shows that reptile-associated C. fetus subsp. testudinum is genetically divergent from mammal-associated C. fetus subspecies. PMID:27333878

  15. Metagenome Survey of a Multispecies and Alga-Associated Biofilm Revealed Key Elements of Bacterial-Algal Interactions in Photobioreactors

    OpenAIRE

    Krohn-Molt, Ines; Wemheuer, Bernd; Alawi, Malik; Poehlein, Anja; Güllert, Simon; Schmeisser, Christel; Pommerening-Röser, Andreas; Grundhoff, Adam; Daniel, Rolf; Hanelt, Dieter; Wolfgang R Streit

    2013-01-01

    Photobioreactors (PBRs) are very attractive for sunlight-driven production of biofuels and capturing of anthropogenic CO2. One major problem associated with PBRs however, is that the bacteria usually associated with microalgae in nonaxenic cultures can lead to biofouling and thereby affect algal productivity. Here, we report on a phylogenetic, metagenome, and functional analysis of a mixed-species bacterial biofilm associated with the microalgae Chlorella vulgaris and Scenedesmus obliquus in ...

  16. Heart PET scan

    Science.gov (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  17. Coronary Calcium Scan

    Science.gov (United States)

    ... the NHLBI on Twitter. What Is a Coronary Calcium Scan? A coronary calcium scan is a test ... you have calcifications in your coronary arteries. Coronary Calcium Scan Figure A shows the position of the ...

  18. Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

    NARCIS (Netherlands)

    Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindstrom, Sara; Brennan, Paul; Bickeboller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Al Olama, Ali Amin; Berndt, Sonja I.; Giovannucci, Edward L.; Gronberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J.; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter C.; Goode, Ellen L.; Permuth, Jennifer B.; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomaki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine D.; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Muller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Buchanan, Daniel D.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Gallinger, Steven; Haile, Robert W.; Jenkins, Mark; Le Marchand, Loic; Li, Li; Lindor, Noralene M.; Schmit, Stephanie L.; Thibodeau, Stephen N.; Woods, Michael O.; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bosse, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

    2016-01-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 c

  19. Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

    NARCIS (Netherlands)

    Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D P; Eeles, Rosalind A; Chatterjee, Nilanjan; Schumacher, Fredrick R; Schildkraut, Joellen M; Lindstrom, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S; Landi, Maria Teresa; Caporaso, Neil E; Risch, Angela; Amin Al Olama, Ali; Berndt, Sonja I; Giovannucci, Edward; Gronberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J; Stevens, Victoria L; Wiklund, Fredrik; Willett, Walter C; Goode, Ellen L; Permuth, Jennifer B; Risch, Harvey A; Reid, Brett M; Bezieau, Stéphane; Brenner, Hermann; Chan, Andrew T; Chang-Claude, Jenny; Hudson, Thomas J; Kocarnik, Jonathan; Newcomb, Polly A; Schoen, Robert E; Slattery, Martha L; White, Emily; Adank, Muriel A; Ahsan, Habibul; Aittomaki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos Santos Silva, Isabel; Eliassen, A Heather; Figueroa, Jonine D; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G; Lichtner, Peter; Liu, Jian Jun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A; Nevanlinna, Heli; Peeters, Petra H; Peto, Julian; Prentice, Ross L; Rahman, Nazneen; Sanchez, Maria-Jose; Schmidt, Daniel F; Schmutzler, Rita K; Southey, Melissa C; Tamimi, Rulla M; Travis, Ruth C; Turnbull, Clare; Uitterlinden, Andre G; Wang, Zhaoming; Whittemore, Alice S; Yang, Xiaohong R; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N; Stefansson, Kari; Sulem, Patrick; Chen, Y Ann; Tyrer, Jonathan P; Christiani, David C; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J; Gong, Jian; Peters, Ulrike; Gruber, Stephen B; Amos, Christopher I; Sellers, Thomas A; Easton, Douglas F; Hunter, David J; Haiman, Christopher A; Henderson, Brian E; Hung, Rayjean J

    2016-01-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 c

  20. Scan BIST with biased scan test signals

    Institute of Scientific and Technical Information of China (English)

    XIANG Dong; CHEN MingJing; SUN JiaGuang

    2008-01-01

    The conventional test-per-scan built-in self-test (BIST) scheme needs a number of shift cycles followed by one capture cycle.Fault effects received by the scan flip-flops are shifted out while shifting in the next test vector like scan testing.Unlike deterministic testing,it is unnecessary to apply a complete test vector to the scan chains.A new scan-based BIST scheme is proposed by properly controlling the test signals of the scan chains,Different biased random values are assigned to the test signals of scan flip-flops in separate scan chains.Capture cycles can be inserted at any clock cycle if necessary.A new testability estimation procedure according to the proposed testing scheme is presented.A greedy procedure is proposed to select a weight for each scan chain.Experimental results show that the proposed method can improve test effectiveness of scan-based BIST greatly,and most circuits can obtain complete fault coverage or very close to complete fault coverage.

  1. A genome-wide association study for primary open angle glaucoma and macular degeneration reveals novel Loci.

    Directory of Open Access Journals (Sweden)

    Todd E Scheetz

    Full Text Available Glaucoma and age-related macular degeneration (AMD are the two leading causes of visual loss in the United States. We utilized a novel study design to perform a genome-wide association for both primary open angle glaucoma (POAG and AMD. This study design utilized a two-stage process for hypothesis generation and validation, in which each disease cohort was utilized as a control for the other. A total of 400 POAG patients and 400 AMD patients were ascertained and genotyped at 500,000 loci. This study identified a novel association of complement component 7 (C7 to POAG. Additionally, an association of central corneal thickness, a known risk factor for POAG, was found to be associated with ribophorin II (RPN2. Linked monogenic loci for POAG and AMD were also evaluated for evidence of association, none of which were found to be significantly associated. However, several yielded putative associations requiring validation. Our data suggest that POAG is more genetically complex than AMD, with no common risk alleles of large effect.

  2. Genome-wide association study reveals a set of genes associated with resistance to the Mediterranean corn borer (Sesamia nonagrioides L.) in a maize diversity panel

    Science.gov (United States)

    Corn borers are the primary maize pest in many environments; their feeding on the pith of the stem results in yield losses because stem damage interferes with assimilate movement to developing kernels. In this study, we performed genome-wide association study (GWAS) to identify SNPs associated with ...

  3. Combination of hydrogel nanoparticles and proteomics to reveal secreted proteins associated with decidualization of human uterine stromal cells

    Directory of Open Access Journals (Sweden)

    Stephens Andrew N

    2011-09-01

    Full Text Available Abstract Background Identification of secreted proteins of low abundance is often limited by abundant and high molecular weight (MW proteins. We have optimised a procedure to overcome this limitation. Results Low MW proteins in the conditioned media of cultured cells were first captured using dual-size exclusion/affinity hydrogel nanoparticles and their identities were then revealed by proteomics. Conclusions This technique enables the analysis of secreted proteins of cultured cells low MW and low abundance.

  4. Genome-Wide Association Study Reveals Novel Quantitative Trait Loci Associated with Resistance to Multiple Leaf Spot Diseases of Spring Wheat

    OpenAIRE

    Gurung, Suraj; Mamidi, Sujan; Bonman, J Michael; Xiong, Mai; Brown-Guedira, Gina; Adhikari, Tika B.

    2014-01-01

    Accelerated wheat development and deployment of high-yielding, climate resilient, and disease resistant cultivars can contribute to enhanced food security and sustainable intensification. To facilitate gene discovery, we assembled an association mapping panel of 528 spring wheat landraces of diverse geographic origin for a genome-wide association study (GWAS). All accessions were genotyped using an Illumina Infinium 9K wheat single nucleotide polymorphism (SNP) chip and 4781 polymorphic SNPs ...

  5. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

    DEFF Research Database (Denmark)

    Fox, Caroline S; Liu, Yongmei; White, Charles C;

    2012-01-01

    tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio......Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants...... of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose...

  6. Association analysis revealed one susceptibility locus for vitiligo with immune-related diseases in the Chinese Han population.

    Science.gov (United States)

    Li, Shu; Yao, Weiyi; Pan, Qian; Tang, Xianfa; Zhao, Suli; Wang, Wenjun; Zhu, Zhengwei; Gao, Jinping; Sheng, Yujun; Zhou, Fusheng; Zheng, Xiaodong; Zuo, Xianbo; Sun, Liangdan; Zhang, Anping

    2015-07-01

    Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) (P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls (P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset.

  7. Conventional cerebrospinal fluid scanning

    Energy Technology Data Exchange (ETDEWEB)

    Schicha, H.

    1985-06-01

    Conventional cerebrospinal fluid scanning (CSF scanning) today is mainly carried out in addition to computerized tomography to obtain information about liquor flow kinetics. Especially in patients with communicating obstructive hydrocephalus, CSF scanning is clinically useful for the decision for shunt surgery. In patients with intracranial cysts, CSF scanning can provide information about liquor circulation. Further indications for CSF scanning include the assessment of shunt patency especially in children, as well as the detection and localization of cerebrospinal fluid leaks.

  8. Phylogenetic analyses of Podaxis specimens from Southern Africa reveal hidden diversity and new insights into associations with termites

    NARCIS (Netherlands)

    Conlon, Benjamin H.; Beer, de Z.W.; Fine Licht, De Henrik H.; Aanen, Duur K.; Poulsen, Michael

    2016-01-01

    Although frequently found on mounds of the grass-cutting termite genus . Trinervitermes, virtually nothing is known about the natural history of the fungal genus . Podaxis (Agaricaceae) nor why it associates with termite mounds. More than 40 species of this secotioid genus have been described sin

  9. Focal Uncaging of GABA Reveals a Temporally Defined Role for GABAergic Inhibition during Appetitive Associative Olfactory Conditioning in Honeybees

    Science.gov (United States)

    Raccuglia, Davide; Mueller, Uli

    2013-01-01

    Throughout the animal kingdom, the inhibitory neurotransmitter ?-aminobutyric acid (GABA) is a key modulator of physiological processes including learning. With respect to associative learning, the exact time in which GABA interferes with the molecular events of learning has not yet been clearly defined. To address this issue, we used two…

  10. Genome-wide mapping of cytosine methylation revealed dynamic DNA methylation patterns associated with genes and centromeres in rice.

    Science.gov (United States)

    Yan, Huihuang; Kikuchi, Shinji; Neumann, Pavel; Zhang, Wenli; Wu, Yufeng; Chen, Feng; Jiang, Jiming

    2010-08-01

    We conducted genome-wide mapping of cytosine methylation using methylcytosine immunoprecipitation combined with Illumina sequencing. The chromosomal distribution pattern of methylated DNA is similar to the heterochromatin distribution pattern on rice chromosomes. The DNA methylation patterns of rice genes are similar to those in Arabidopsis thaliana, including distinct methylation patterns asssociated with gene bodies and promoters. The DNA sequences in the core domains of rice Cen4, Cen5 and Cen8 showed elevated methylation levels compared with sequences in the pericentromeric regions. In addition, elevated methylation levels were associated with the DNA sequences in the CENH3-binding subdomains, compared with the sequences in the flanking H3 subdomains. In contrast, the centromeric domain of Cen11, which is composed exclusively of centromeric satellite DNA, is hypomethylated compared with the pericentromeric domains. Thus, the DNA sequences associated with functional centromeres can be either hypomethylated or hypermethylated. The methylation patterns of centromeric DNA appear to be correlated with the composition of the associated DNA sequences. We propose that both hypomethylation and hypermethylation of CENH3-associated DNA sequences can serve as epigenetic marks to distinguish where CENH3 deposition will occur within the surrounding H3 chromatin.

  11. Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants.

    Science.gov (United States)

    Panoutsopoulou, Kalliope; Hatzikotoulas, Konstantinos; Xifara, Dionysia Kiara; Colonna, Vincenza; Farmaki, Aliki-Eleni; Ritchie, Graham R S; Southam, Lorraine; Gilly, Arthur; Tachmazidou, Ioanna; Fatumo, Segun; Matchan, Angela; Rayner, Nigel W; Ntalla, Ioanna; Mezzavilla, Massimo; Chen, Yuan; Kiagiadaki, Chrysoula; Zengini, Eleni; Mamakou, Vasiliki; Athanasiadis, Antonis; Giannakopoulou, Margarita; Kariakli, Vassiliki-Eirini; Nsubuga, Rebecca N; Karabarinde, Alex; Sandhu, Manjinder; McVean, Gil; Tyler-Smith, Chris; Tsafantakis, Emmanouil; Karaleftheri, Maria; Xue, Yali; Dedoussis, George; Zeggini, Eleftheria

    2014-01-01

    Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10(-26)). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10(-36)). We demonstrate significant power gains in detecting medical trait associations.

  12. Characterization of the active microbiotas associated with honey bees reveals healthier and broader communities when colonies are genetically diverse

    NARCIS (Netherlands)

    Mattila, H.R.; Rios, D.; Walker-Sperling, V.E.; Roeselers, G.; Newton, I.L.G.

    2012-01-01

    Recent losses of honey bee colonies have led to increased interest in the microbial communities that are associated with these important pollinators. A critical function that bacteria perform for their honey bee hosts, but one that is poorly understood, is the transformation of worker-collected poll

  13. RNA Expression and Post-Transcriptional Editing Analyses of Cucumber Plastids Reveals Genetic Differences Associated with Chilling Tolerance

    Science.gov (United States)

    Tolerance to chilling injury in cucumber (Cucumis sativus L.) is associated with three plastomic single nucleotide polymorphisms (ptSNPs) at bp positions 4,813, 56,561, and 126,349 that are co-inherited. An understanding of the genetic expression of these ptSNPs as a response to chilling is critical...

  14. DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts

    NARCIS (Netherlands)

    Zhernakova, Daria V.; de Klerk, Eleonora; Westra, Harm-Jan; Mastrokolias, Anastasios; Amini, Shoaib; Ariyurek, Yavuz; Jansen, Rick; Penninx, Brenda W.; Hottenga, Jouke J.; Willemsen, Gonneke; de Geus, Eco J.; Boomsma, Dorret I.; Veldink, Jan H.; van den Berg, Leonard H.; Wijmenga, Cisca; den Dunnen, Johan T.; van Ommen, Gert-Jan B.; 't Hoen, Peter A. C.; Franke, Lude

    2013-01-01

    Many disease-associated variants affect gene expression levels (expression quantitative trait loci, eQTLs) and expression profiling using next generation sequencing (NGS) technology is a powerful way to detect these eQTLs. We analyzed 94 total blood samples from healthy volunteers with DeepSAGE to g

  15. Interesting bone scans - unusual findings

    Energy Technology Data Exchange (ETDEWEB)

    Dobson, M.; Wadhwa, S.S.; Mansberg, R.; Fernandes, V.B. [Wollongong Hospital, Wollongong, NSW (Australia)

    1997-12-01

    A 59-year-old female with carcinoma of the colon and known liver metastatic disease was referred for bone scan to evaluate for bone metastases. Although no bone metastases were found, there was abnormal uptake noted in the liver corresponding to a metastatic calcified lesion. The only other findings were of degenerative disease in the cervical spine, right shoulder and small joints of the hands. A 69-year-old male with carcinoma of the prostate and right side low back pain was referred for bone scan. No focal abnormalities to suggest metastatic disease were identified; findings within the cervical spine, lumber spine and knees were presumed secondary to degenerative disease. Intermittent pain persisted and the patient was referred for a repeat bone scan six months later. Previous scan findings of degenerative disease and no metastatic disease were confirmed; however, closer inspection revealed an enlarged right kidney with significant retention of tracer in the pelvicalyceal system suggesting possible obstruction. A Retrograde pyelogram was performed, and no obvious obstruction demonstrated. As bone scan findings were very suggestive of obstruction, a DTPA scan with lasix was performed showing a dilated right collecting system with no functional obstruction. Given the degree of dilation, it is possible that the patient experiences intermittent PUJ obstruction causing his symptoms. A 33-year-old male with insulin dependent diabetes mellitus and viral arthritis was referred for a bone scan. A three phase revealed increased uptake in the region of the knee and leR proximal tibia. Delayed whole body images revealed multiple focal areas of osteoblastic activity in the leR tibia. Abnormal uptake was also seen in the upper third of the leR femur. The remainder of the skeletal survey was normal. X-ray correlation of the leR tibia and femoral findings was undertaken. Combinating unilateral changes on bone scan and X-ray although very suggestive of sclerotic polyostotic

  16. Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis.

    Directory of Open Access Journals (Sweden)

    Katarina Tengvall

    2013-05-01

    Full Text Available Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD, caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD is a high-risk breed for canine AD (CAD. In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1 × 10(-5 in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3, which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n cases = 91, n controls = 88. IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0 × 10(-9, thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (praw = 3.1 × 10(-7, pgenome = 0.03. The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ~209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.

  17. Transcriptome Analysis of an Anthracnose-Resistant Tea Plant Cultivar Reveals Genes Associated with Resistance to Colletotrichum camelliae.

    Directory of Open Access Journals (Sweden)

    Lu Wang

    Full Text Available Tea plant breeding is a topic of great economic importance. However, disease remains a major cause of yield and quality losses. In this study, an anthracnose-resistant cultivar, ZC108, was developed. An infection assay revealed different responses to Colletotrichum sp. infection between ZC108 and its parent cultivar LJ43. ZC108 had greater resistance than LJ43 to Colletotrichum camelliae. Additionally, ZC108 exhibited earlier sprouting in the spring, as well as different leaf shape and plant architecture. Microarray data revealed that the genes that are differentially expressed between LJ43 and ZC108 mapped to secondary metabolism-related pathways, including phenylpropanoid biosynthesis, phenylalanine metabolism, and flavonoid biosynthesis pathways. In addition, genes involved in plant hormone biosynthesis and signaling as well as plant-pathogen interaction pathways were also changed. Quantitative real-time PCR was used to examine the expression of 27 selected genes in infected and uninfected tea plant leaves. Genes encoding a MADS-box transcription factor, NBS-LRR disease-resistance protein, and phenylpropanoid metabolism pathway components (CAD, CCR, POD, beta-glucosidase, ALDH and PAL were among those differentially expressed in ZC108.

  18. Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.

    Science.gov (United States)

    Stuart, Philip E; Nair, Rajan P; Tsoi, Lam C; Tejasvi, Trilokraj; Das, Sayantan; Kang, Hyun Min; Ellinghaus, Eva; Chandran, Vinod; Callis-Duffin, Kristina; Ike, Robert; Li, Yanming; Wen, Xiaoquan; Enerbäck, Charlotta; Gudjonsson, Johann E; Kõks, Sulev; Kingo, Külli; Esko, Tõnu; Mrowietz, Ulrich; Reis, Andre; Wichmann, H Erich; Gieger, Christian; Hoffmann, Per; Nöthen, Markus M; Winkelmann, Juliane; Kunz, Manfred; Moreta, Elvia G; Mease, Philip J; Ritchlin, Christopher T; Bowcock, Anne M; Krueger, Gerald G; Lim, Henry W; Weidinger, Stephan; Weichenthal, Michael; Voorhees, John J; Rahman, Proton; Gregersen, Peter K; Franke, Andre; Gladman, Dafna D; Abecasis, Gonçalo R; Elder, James T

    2015-12-01

    Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA. PMID:26626624

  19. Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.

    Science.gov (United States)

    Stuart, Philip E; Nair, Rajan P; Tsoi, Lam C; Tejasvi, Trilokraj; Das, Sayantan; Kang, Hyun Min; Ellinghaus, Eva; Chandran, Vinod; Callis-Duffin, Kristina; Ike, Robert; Li, Yanming; Wen, Xiaoquan; Enerbäck, Charlotta; Gudjonsson, Johann E; Kõks, Sulev; Kingo, Külli; Esko, Tõnu; Mrowietz, Ulrich; Reis, Andre; Wichmann, H Erich; Gieger, Christian; Hoffmann, Per; Nöthen, Markus M; Winkelmann, Juliane; Kunz, Manfred; Moreta, Elvia G; Mease, Philip J; Ritchlin, Christopher T; Bowcock, Anne M; Krueger, Gerald G; Lim, Henry W; Weidinger, Stephan; Weichenthal, Michael; Voorhees, John J; Rahman, Proton; Gregersen, Peter K; Franke, Andre; Gladman, Dafna D; Abecasis, Gonçalo R; Elder, James T

    2015-12-01

    Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Meta-analysis of this study with three other GWASs and two targeted genotyping studies, encompassing a total of 9,293 PsV case subjects, 3,061 PsA case subjects, 3,110 PsC case subjects, and 13,670 unaffected control subjects of European descent, detected 10 regions associated with PsA and 11 with PsC at genome-wide (GW) significance. Several of these association signals (IFNLR1, IFIH1, NFKBIA for PsA; TNFRSF9, LCE3C/B, TRAF3IP2, IL23A, NFKBIA for PsC) have not previously achieved GW significance. After replication, we also identified a PsV-associated SNP near CDKAL1 (rs4712528, odds ratio [OR] = 1.16, p = 8.4 × 10(-11)). Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022). The PsA-specific variants were independent of previously identified psoriasis variants near IL23R and TNFAIP3. We also found multiple independent susceptibility variants in the IL12B, NOS2, and IFIH1 regions. These results provide insights into the pathogenetic similarities and differences between PsC and PsA.

  20. Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene

    DEFF Research Database (Denmark)

    Jakkula, Eveliina; Leppä, Virpi; Sulonen, Anna-Maija;

    2010-01-01

    in 711 cases and 1029 controls from Finland, and the top two findings were validated in 3859 cases and 9110 controls from more heterogeneous populations. SNP (rs744166) within the STAT3 gene was associated to MS (p = 2.75 x 10(-10), OR 0.87, confidence interval 0.83-0.91). The protective haplotype for MS...

  1. Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci

    NARCIS (Netherlands)

    G. Paré (Guillaume); P.M. Ridker (Paul); L.M. Rose (Lynda); M. Barbalic (maja); J. Dupuis (Josée); A. Dehghan (Abbas); J.C. Bis (Joshua); E.J. Benjamin (Emelia); D. Shiffman (Dov); A.N. Parker (Alexander); D.I. Chasman (Daniel)

    2011-01-01

    textabstractSoluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far

  2. Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

    DEFF Research Database (Denmark)

    Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik;

    2010-01-01

    overall structure of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPA-uPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This...... study identifies a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

  3. Genomic analyses of cherry rusty mottle group and cherry twisted leaf-associated viruses reveal a possible new genus within the family betaflexiviridae.

    Science.gov (United States)

    Villamor, D E V; Susaimuthu, J; Eastwell, K C

    2015-03-01

    It is demonstrated that closely related viruses within the family Betaflexiviridae are associated with a number of diseases that affect sweet cherry (Prunus avium) and other Prunus spp. Cherry rusty mottle-associated virus (CRMaV) is correlated with the appearance of cherry rusty mottle disease (CRMD), and Cherry twisted leaf-associated virus (CTLaV) is linked to cherry twisted leaf disease (CTLD) and apricot ringpox disease (ARPD). Comprehensive analysis of previously reported full genomic sequences plus those determined in this study representing isolates of CTLaV, CRMaV, Cherry green ring mottle virus, and Cherry necrotic rusty mottle virus revealed segregation of sequences into four clades corresponding to distinct virus species. High-throughput sequencing of RNA from representative source trees for CRMD, CTLD, and ARPD did not reveal additional unique virus sequences that might be associated with these diseases, thereby further substantiating the association of CRMaV and CTLaV with CRMD and CTLD or ARPD, respectively. Based on comparison of the nucleotide and amino acid sequence identity values, phylogenetic relationships with other triple-gene block-coding viruses within the family Betaflexiviridae, genome organization, and natural host range, a new genus (Robigovirus) is suggested. PMID:25496302

  4. Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ERα in Tamoxifen-Associated Endometrial Carcinomas.

    Science.gov (United States)

    Droog, Marjolein; Nevedomskaya, Ekaterina; Kim, Yongsoo; Severson, Tesa; Flach, Koen D; Opdam, Mark; Schuurman, Karianne; Gradowska, Patrycja; Hauptmann, Michael; Dackus, Gwen; Hollema, Harry; Mourits, Marian; Nederlof, Petra; van Boven, Hester; Linn, Sabine C; Wessels, Lodewyk; van Leeuwen, Flora E; Zwart, Wilbert

    2016-07-01

    Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERα was found at active enhancers in endometrial cancer cells as marked by the presence of RNA polymerase II and the histone marker H3K27Ac. These ERα binding sites were highly conserved between breast and endometrial cancer and enriched in binding motifs for the transcription factor FOXA1, which displayed substantial overlap with ERα binding sites proximal to genes involved in classical ERα target genes. Multifactorial ChIP-seq data integration from the endometrial cancer cell line Ishikawa illustrated a functional genomic network involving ERα and FOXA1 together with the enhancer-enriched transcriptional regulators p300, FOXM1, TEAD4, FNFIC, CEBP8, and TCF12. Immunohistochemical analysis of 230 primary endometrial tumor specimens showed that lack of FOXA1 and ERα expression was associated with a longer interval between breast cancer and the emergence of endometrial cancer, exclusively in tamoxifen-treated patients. Our results define conserved sites for a genomic interplay between FOXA1 and ERα in breast cancer and tamoxifen-associated endometrial cancer. In addition, FOXA1 and ERα are associated with the interval time between breast cancer and endometrial cancer only in tamoxifen-treated breast cancer patients. Cancer Res; 76(13); 3773-84. ©2016 AACR. PMID:27197147

  5. Genome-wide association mapping revealed a diverse genetic basis of seed dormancy across subpopulations in rice (Oryza sativa L.)

    OpenAIRE

    Magwa, Risper Auma; Zhao, Hu; Xing, Yongzhong

    2016-01-01

    Background Seed dormancy is an adaptive trait employed by flowering plants to avoid harsh environmental conditions for the continuity of their next generations. In cereal crops, moderate seed dormancy could help prevent pre-harvest sprouting and improve grain yield and quality. We performed a genome wide association study (GWAS) for dormancy, based on seed germination percentage (GP) in freshly harvested seeds (FHS) and after-ripened seeds (ARS) in 350 worldwide accessions that were character...

  6. Characterization of the active microbiotas associated with honey bees reveals healthier and broader communities when colonies are genetically diverse

    OpenAIRE

    Mattila, Heather R.; Daniela Rios; Walker-Sperling, Victoria E.; Guus Roeselers; Newton, Irene L.G.

    2012-01-01

    Recent losses of honey bee colonies have led to increased interest in the microbial communities that are associated with these important pollinators. A critical function that bacteria perform for their honey bee hosts, but one that is poorly understood, is the transformation of worker-collected pollen into bee bread, a nutritious food product that can be stored for long periods in colonies. We used 16S rRNA pyrosequencing to comprehensively characterize in genetically diverse and genetically ...

  7. Indicators of Early and Late Processing Reveal the Importance of Within-Trial-Time for Theories of Associative Learning

    OpenAIRE

    Lachnit, Harald; Thorwart, Anna; Schultheis, Holger; Lotz, Anja; Koenig, Stephan; Uengoer, Metin

    2013-01-01

    In four human learning experiments (Pavlovian skin conductance, causal learning, speeded classification task), we evaluated several associative learning theories that assume either an elemental (modified unique cue model and Harris’ model) or a configural (Pearce’s configural theory and an extension of it) form of stimulus processing. The experiments used two modified patterning problems (A/B/C+, AB/BC/AC+ vs. ABC-; A+, BC+ vs. ABC-). Pearce’s configural theory successfully predicted all of o...

  8. Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami

    OpenAIRE

    Huyghe, Jeroen R; Fransen, Erik; Hannula, Samuli; Van Laer, Lut; Van Eyken, Els; Mäki-Torkko, Elina; Lysholm-Bernacchi, Alana; Aikio, Pekka; Stephan, Dietrich A.; Sorri, Martti; Huentelman, Matthew J; Van Camp, Guy

    2009-01-01

    The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet as...

  9. Multi-locus sequence typing of Bartonella henselae isolates from three continents reveals hypervirulent and feline-associated clones.

    Directory of Open Access Journals (Sweden)

    Mardjan Arvand

    Full Text Available Bartonella henselae is a zoonotic pathogen and the causative agent of cat scratch disease and a variety of other disease manifestations in humans. Previous investigations have suggested that a limited subset of B. henselae isolates may be associated with human disease. In the present study, 182 human and feline B. henselae isolates from Europe, North America and Australia were analysed by multi-locus sequence typing (MLST to detect any associations between sequence type (ST, host species and geographical distribution of the isolates. A total of 14 sequence types were detected, but over 66% (16/24 of the isolates recovered from human disease corresponded to a single genotype, ST1, and this type was detected in all three continents. In contrast, 27.2% (43/158 of the feline isolates corresponded to ST7, but this ST was not recovered from humans and was restricted to Europe. The difference in host association of STs 1 (human and 7 (feline was statistically significant (P< or =0.001. eBURST analysis assigned the 14 STs to three clonal lineages, which contained two or more STs, and a singleton comprising ST7. These groups were broadly consistent with a neighbour-joining tree, although splits decomposition analysis was indicative of a history of recombination. These data indicate that B. henselae lineages differ in their virulence properties for humans and contribute to a better understanding of the population structure of B. henselae.

  10. Geomorphological changes associated with underground coal mining in the Fushun area, northeast China revealed by multitemporal satellite remote sensing data

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Y.F.; Fu, B.H.; Ninomiya, Y. [China Earthquake Administration, Beijing (China). Inst. of Earthquake Science

    2009-07-01

    Fushun is a famous coal-mining city in northeastern China with more than 100 years of history. Long-term underground coal mining has caused serious surface subsidence in the eastern part of the city. In this study, multitemporal and multi-source satellite remote sensing data were used to detect subsidence and geomorphological changes associated with underground coal mining over a 10-year period (1996-2006). A digital elevation model (DEM) was generated through Synthetic Aperture Radar (SAR) interferometry processing using data from a pair of European Remote Sensing Satellite (ERS) SAR images acquired in 1996. In addition, a Shuttle Radar Topography Mission (SRTM) DEM obtained from data in 2000 and an Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) DEM from 2006 were used for this study. The multitemporal DEMs indicated that the maximum vertical displacement due to subsidence was around 13 m from 1996 to 2006. Multitemporal ASTER images showed that the flooded water area associated with subsidence had increased by 1.73 km{sup 2} over the same time period. Field investigations and ground level measurements confirmed that the results obtained from the multitemporal remote sensing data agreed well with ground truth data. This study demonstrates that DEMs derived from multisource satellite remote sensing data can provide a powerful tool to map geomorphological changes associated with underground mining activities.

  11. Culture-free survey reveals diverse and distinctive fungal communities associated with developing figs (Ficus spp.) in Panama.

    Science.gov (United States)

    Martinson, Ellen O; Herre, Edward Allen; Machado, Carlos A; Arnold, A Elizabeth

    2012-11-01

    The ancient association of figs (Ficus spp.) and their pollinating wasps (fig wasps; Chalcidoidea, Hymenoptera) is one of the most interdependent plant-insect mutualisms known. In addition to pollinating wasps, a diverse community of organisms develops within the microcosm of the fig inflorescence and fruit. To better understand the multipartite context of the fig-fig wasp association, we used a culture-free approach to examine fungal communities associated with syconia of six species of Ficus and their pollinating wasps in lowland Panama. Diverse fungi were recovered from surface-sterilized flowers of all Ficus species, including gall- and seed flowers at four developmental stages. Fungal communities in syconia and on pollinating wasps were similar, dominated by diverse and previously unknown Saccharomycotina, and distinct from leaf- and stem endophyte communities in the same region. Before pollination, fungal communities were similar between gall- and seed flowers and among Ficus species. However, fungal communities differed significantly in flowers after pollination vs. before pollination, and between anciently diverged lineages of Ficus with active vs. passive pollination syndromes. Within groups of relatively closely related figs, there was little evidence for strict-sense host specificity between figs and particular fungal species. Instead, mixing of fungal communities among related figs, coupled with evidence for possible transfer by pollinating wasps, is consistent with recent suggestions of pollinator mixing within syconia. In turn, changes in fungal communities during fig development and ripening suggest an unexplored role of yeasts in the context of the fig-pollinator wasp mutualism. PMID:22729017

  12. Association of calcineurin with the COPI protein Sec28 and the COPII protein Sec13 revealed by quantitative proteomics.

    Directory of Open Access Journals (Sweden)

    Lukasz Kozubowski

    Full Text Available Calcineurin is a calcium-calmodulin-dependent serine/threonine specific protein phosphatase operating in key cellular processes governing responses to extracellular cues. Calcineurin is essential for growth at high temperature and virulence of the human fungal pathogen Cryptococcus neoformans but the underlying mechanism is unknown. We performed a mass spectrometry analysis to identify proteins that associate with the calcineurin A catalytic subunit (Cna1 in C. neoformans cells grown under non-stress and high temperature stress conditions. A novel prioritization strategy for mass spectrometry data from immunoprecipitation experiments identified putative substrates and proteins potentially operating with calcineurin in common pathways. Cna1 co-purified with proteins involved in membrane trafficking including the COPI component Sec28 and the COPII component Sec13. The association of Cna1 with Sec28 and Sec13 was confirmed by co-immunoprecipitation. Cna1 exhibited a dramatic change in subcellular localization during high temperature stress from diffuse cytoplasmic to ER-associated puncta and the mother-bud neck and co-localized with Sec28 and Sec13.

  13. Anomalous enrichment of molybdenum and associated metals in Lower Jurassic (Lias Group) black shales of central England, as revealed by systematic geochemical surveys

    OpenAIRE

    Breward, N.; Kemp, S.J.; Ambrose, K.; Powell, J. H.; Morigi, A.; Wagner, D.

    2015-01-01

    Systematic multi-media geochemical surveying by the British Geological Survey's Geochemical Baseline Survey of the Environment (G-BASE) project has revealed significant anomalous patterns of enrichment for a suite of elements – copper (Cu) and uranium (U) – with exceptionally high levels of molybdenum (Mo), in soils and stream sediments in central England. Enrichment of these elements is most often associated with organic-rich, sulphidic ‘black shale’ lithofacies, typical of oxygen-deficient,...

  14. Deep Sequencing of Myxilla (Ectyomyxilla) methanophila, an Epibiotic Sponge on Cold-Seep Tubeworms, Reveals Methylotrophic, Thiotrophic, and Putative Hydrocarbon-Degrading Microbial Associations

    KAUST Repository

    Arellano, Shawn M.

    2012-10-11

    The encrusting sponge Myxilla (Ectyomyxilla) methanophila (Poecilosclerida: Myxillidae) is an epibiont on vestimentiferan tubeworms at hydrocarbon seeps on the upper Louisiana slope of the Gulf of Mexico. It has long been suggested that this sponge harbors methylotrophic bacteria due to its low δ13C value and high methanol dehydrogenase activity, yet the full community of microbial associations in M. methanophila remained uncharacterized. In this study, we sequenced 16S rRNA genes representing the microbial community in M. methanophila collected from two hydrocarbon-seep sites (GC234 and Bush Hill) using both Sanger sequencing and next-generation 454 pyrosequencing technologies. Additionally, we compared the microbial community in M. methanophila to that of the biofilm collected from the associated tubeworm. Our results revealed that the microbial diversity in the sponges from both sites was low but the community structure was largely similar, showing a high proportion of methylotrophic bacteria of the genus Methylohalomonas and polycyclic aromatic hydrocarbon (PAH)-degrading bacteria of the genera Cycloclasticus and Neptunomonas. Furthermore, the sponge microbial clone library revealed the dominance of thioautotrophic gammaproteobacterial symbionts in M. methanophila. In contrast, the biofilm communities on the tubeworms were more diverse and dominated by the chemoorganotrophic Moritella at GC234 and methylotrophic Methylomonas and Methylohalomonas at Bush Hill. Overall, our study provides evidence to support previous suggestion that M. methanophila harbors methylotrophic symbionts and also reveals the association of PAH-degrading and thioautotrophic microbes in the sponge. © 2012 Springer Science+Business Media New York.

  15. Genome wide association studies using a new nonparametric model reveal the genetic architecture of 17 agronomic traits in an enlarged maize association panel.

    Science.gov (United States)

    Yang, Ning; Lu, Yanli; Yang, Xiaohong; Huang, Juan; Zhou, Yang; Ali, Farhan; Wen, Weiwei; Liu, Jie; Li, Jiansheng; Yan, Jianbing

    2014-09-01

    Association mapping is a powerful approach for dissecting the genetic architecture of complex quantitative traits using high-density SNP markers in maize. Here, we expanded our association panel size from 368 to 513 inbred lines with 0.5 million high quality SNPs using a two-step data-imputation method which combines identity by descent (IBD) based projection and k-nearest neighbor (KNN) algorithm. Genome-wide association studies (GWAS) were carried out for 17 agronomic traits with a panel of 513 inbred lines applying both mixed linear model (MLM) and a new method, the Anderson-Darling (A-D) test. Ten loci for five traits were identified using the MLM method at the Bonferroni-corrected threshold -log10 (P) >5.74 (α=1). Many loci ranging from one to 34 loci (107 loci for plant height) were identified for 17 traits using the A-D test at the Bonferroni-corrected threshold -log10 (P) >7.05 (α=0.05) using 556809 SNPs. Many known loci and new candidate loci were only observed by the A-D test, a few of which were also detected in independent linkage analysis. This study indicates that combining IBD based projection and KNN algorithm is an efficient imputation method for inferring large missing genotype segments. In addition, we showed that the A-D test is a useful complement for GWAS analysis of complex quantitative traits. Especially for traits with abnormal phenotype distribution, controlled by moderate effect loci or rare variations, the A-D test balances false positives and statistical power. The candidate SNPs and associated genes also provide a rich resource for maize genetics and breeding.

  16. Genome wide association studies using a new nonparametric model reveal the genetic architecture of 17 agronomic traits in an enlarged maize association panel.

    Directory of Open Access Journals (Sweden)

    Ning Yang

    2014-09-01

    Full Text Available Association mapping is a powerful approach for dissecting the genetic architecture of complex quantitative traits using high-density SNP markers in maize. Here, we expanded our association panel size from 368 to 513 inbred lines with 0.5 million high quality SNPs using a two-step data-imputation method which combines identity by descent (IBD based projection and k-nearest neighbor (KNN algorithm. Genome-wide association studies (GWAS were carried out for 17 agronomic traits with a panel of 513 inbred lines applying both mixed linear model (MLM and a new method, the Anderson-Darling (A-D test. Ten loci for five traits were identified using the MLM method at the Bonferroni-corrected threshold -log10 (P >5.74 (α=1. Many loci ranging from one to 34 loci (107 loci for plant height were identified for 17 traits using the A-D test at the Bonferroni-corrected threshold -log10 (P >7.05 (α=0.05 using 556809 SNPs. Many known loci and new candidate loci were only observed by the A-D test, a few of which were also detected in independent linkage analysis. This study indicates that combining IBD based projection and KNN algorithm is an efficient imputation method for inferring large missing genotype segments. In addition, we showed that the A-D test is a useful complement for GWAS analysis of complex quantitative traits. Especially for traits with abnormal phenotype distribution, controlled by moderate effect loci or rare variations, the A-D test balances false positives and statistical power. The candidate SNPs and associated genes also provide a rich resource for maize genetics and breeding.

  17. Bacterial communities of two ubiquitous Great Barrier Reef corals reveals both site- and species-specificity of common bacterial associates.

    Directory of Open Access Journals (Sweden)

    E Charlotte E Kvennefors

    Full Text Available BACKGROUND: Coral-associated bacteria are increasingly considered to be important in coral health, and altered bacterial community structures have been linked to both coral disease and bleaching. Despite this, assessments of bacterial communities on corals rarely apply sufficient replication to adequately describe the natural variability. Replicated data such as these are crucial in determining potential roles of bacteria on coral. METHODOLOGY/PRINCIPAL FINDINGS: Denaturing Gradient Gel Electrophoresis (DGGE of the V3 region of the 16S ribosomal DNA was used in a highly replicated approach to analyse bacterial communities on both healthy and diseased corals. Although site-specific variations in the bacterial communities of healthy corals were present, host species-specific bacterial associates within a distinct cluster of gamma-proteobacteria could be identified, which are potentially linked to coral health. Corals affected by "White Syndrome" (WS underwent pronounced changes in their bacterial communities in comparison to healthy colonies. However, the community structure and bacterial ribotypes identified in diseased corals did not support the previously suggested theory of a bacterial pathogen as the causative agent of the syndrome. CONCLUSIONS/SIGNIFICANCE: This is the first study to employ large numbers of replicated samples to assess the bacterial communities of healthy and diseased corals, and the first culture-independent assessment of bacterial communities on WS affected Acroporid corals on the GBR. Results indicate that a minimum of 6 replicate samples are required in order to draw inferences on species, spatial or health-related changes in community composition, as a set of clearly distinct bacterial community profiles exist in healthy corals. Coral bacterial communities may be both site and species specific. Furthermore, a cluster of gamma-proteobacterial ribotypes may represent a group of specific common coral and marine

  18. Sexually Dimorphic Gene Expression Associated with Growth and Reproduction of Tongue Sole (Cynoglossus semilaevis) Revealed by Brain Transcriptome Analysis.

    Science.gov (United States)

    Wang, Pingping; Zheng, Min; Liu, Jian; Liu, Yongzhuang; Lu, Jianguo; Sun, Xiaowen

    2016-01-01

    In this study, we performed a comprehensive analysis of the transcriptome of one- and two-year-old male and female brains of Cynoglossus semilaevis by high-throughput Illumina sequencing. A total of 77,066 transcripts, corresponding to 21,475 unigenes, were obtained with a N50 value of 4349 bp. Of these unigenes, 33 genes were found to have significant differential expression and potentially associated with growth, from which 18 genes were down-regulated and 12 genes were up-regulated in two-year-old males, most of these genes had no significant differences in expression among one-year-old males and females and two-year-old females. A similar analysis was conducted to look for genes associated with reproduction; 25 genes were identified, among them, five genes were found to be down regulated and 20 genes up regulated in two-year-old males, again, most of the genes had no significant expression differences among the other three. The performance of up regulated genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was significantly different between two-year-old males and females. Males had a high gene expression in genetic information processing, while female's highly expressed genes were mainly enriched on organismal systems. Our work identified a set of sex-biased genes potentially associated with growth and reproduction that might be the candidate factors affecting sexual dimorphism of tongue sole, laying the foundation to understand the complex process of sex determination of this economic valuable species. PMID:27571066

  19. Phylogeographic Analysis of Blastomyces dermatitidis and Blastomyces gilchristii Reveals an Association with North American Freshwater Drainage Basins

    Science.gov (United States)

    McTaggart, Lisa R.; Brown, Elizabeth M.; Richardson, Susan E.

    2016-01-01

    Blastomyces dermatitidis and Blastomyces gilchristii are dimorphic fungal pathogens that cause serious pulmonary and systemic infections in humans. Although their natural habitat is in the environment, little is known about their specific ecologic niche(s). Here, we analyzed 25 microsatellite loci from 169 strains collected from various regions throughout their known endemic range in North America, representing the largest and most geographically diverse collection of isolates studied to date. Genetic analysis of multilocus microsatellite data divided the strains into four populations of B. dermatitidis and four populations of B. gilchristii. B. dermatitidis isolates were recovered from areas throughout North America, while the B. gilchristii strains were restricted to Canada and some northern US states. Furthermore, the populations of both species were associated with major freshwater drainage basins. The four B. dermatitidis populations were partitioned among (1) the Nelson River drainage basin, (2) the St. Lawrence River and northeast Atlantic Ocean Seaboard drainage basins, (3) the Mississippi River System drainage basin, and (4) the Gulf of Mexico Seaboard and southeast Atlantic Ocean Seaboard drainage basins. A similar partitioning of the B. gilchristii populations was observed among the more northerly drainage basins only. These associations suggest that the ecologic niche where the sexual reproduction, growth, and dispersal of B. dermatitidis and B. gilchristii occur is intimately linked to freshwater systems. For most populations, sexual reproduction was rare enough to produce significant linkage disequilibrium among loci but frequent enough that mating-type idiomorphic ratios were not skewed from 1:1. Furthermore, the evolutionary divergence of B. dermatitidis and B. gilchristii was estimated at 1.9 MYA during the Pleistocene epoch. We suggest that repeated glaciations during the Pleistocene period and resulting biotic refugia may have provided the

  20. Phylogeographic Analysis of Blastomyces dermatitidis and Blastomyces gilchristii Reveals an Association with North American Freshwater Drainage Basins.

    Science.gov (United States)

    McTaggart, Lisa R; Brown, Elizabeth M; Richardson, Susan E

    2016-01-01

    Blastomyces dermatitidis and Blastomyces gilchristii are dimorphic fungal pathogens that cause serious pulmonary and systemic infections in humans. Although their natural habitat is in the environment, little is known about their specific ecologic niche(s). Here, we analyzed 25 microsatellite loci from 169 strains collected from various regions throughout their known endemic range in North America, representing the largest and most geographically diverse collection of isolates studied to date. Genetic analysis of multilocus microsatellite data divided the strains into four populations of B. dermatitidis and four populations of B. gilchristii. B. dermatitidis isolates were recovered from areas throughout North America, while the B. gilchristii strains were restricted to Canada and some northern US states. Furthermore, the populations of both species were associated with major freshwater drainage basins. The four B. dermatitidis populations were partitioned among (1) the Nelson River drainage basin, (2) the St. Lawrence River and northeast Atlantic Ocean Seaboard drainage basins, (3) the Mississippi River System drainage basin, and (4) the Gulf of Mexico Seaboard and southeast Atlantic Ocean Seaboard drainage basins. A similar partitioning of the B. gilchristii populations was observed among the more northerly drainage basins only. These associations suggest that the ecologic niche where the sexual reproduction, growth, and dispersal of B. dermatitidis and B. gilchristii occur is intimately linked to freshwater systems. For most populations, sexual reproduction was rare enough to produce significant linkage disequilibrium among loci but frequent enough that mating-type idiomorphic ratios were not skewed from 1:1. Furthermore, the evolutionary divergence of B. dermatitidis and B. gilchristii was estimated at 1.9 MYA during the Pleistocene epoch. We suggest that repeated glaciations during the Pleistocene period and resulting biotic refugia may have provided the

  1. Phylogeographic Analysis of Blastomyces dermatitidis and Blastomyces gilchristii Reveals an Association with North American Freshwater Drainage Basins.

    Directory of Open Access Journals (Sweden)

    Lisa R McTaggart

    Full Text Available Blastomyces dermatitidis and Blastomyces gilchristii are dimorphic fungal pathogens that cause serious pulmonary and systemic infections in humans. Although their natural habitat is in the environment, little is known about their specific ecologic niche(s. Here, we analyzed 25 microsatellite loci from 169 strains collected from various regions throughout their known endemic range in North America, representing the largest and most geographically diverse collection of isolates studied to date. Genetic analysis of multilocus microsatellite data divided the strains into four populations of B. dermatitidis and four populations of B. gilchristii. B. dermatitidis isolates were recovered from areas throughout North America, while the B. gilchristii strains were restricted to Canada and some northern US states. Furthermore, the populations of both species were associated with major freshwater drainage basins. The four B. dermatitidis populations were partitioned among (1 the Nelson River drainage basin, (2 the St. Lawrence River and northeast Atlantic Ocean Seaboard drainage basins, (3 the Mississippi River System drainage basin, and (4 the Gulf of Mexico Seaboard and southeast Atlantic Ocean Seaboard drainage basins. A similar partitioning of the B. gilchristii populations was observed among the more northerly drainage basins only. These associations suggest that the ecologic niche where the sexual reproduction, growth, and dispersal of B. dermatitidis and B. gilchristii occur is intimately linked to freshwater systems. For most populations, sexual reproduction was rare enough to produce significant linkage disequilibrium among loci but frequent enough that mating-type idiomorphic ratios were not skewed from 1:1. Furthermore, the evolutionary divergence of B. dermatitidis and B. gilchristii was estimated at 1.9 MYA during the Pleistocene epoch. We suggest that repeated glaciations during the Pleistocene period and resulting biotic refugia may have

  2. Promising Loci and Genes for Yolk and Ovary Weight in Chickens Revealed by a Genome-Wide Association Study.

    Directory of Open Access Journals (Sweden)

    Congjiao Sun

    Full Text Available Because it serves as the cytoplasm of the oocyte and provides a large amount of reserves, the egg yolk has biological significance for developing embryos. The ovary and its hierarchy of follicles are the main reproductive organs responsible for yolk deposition in chickens. However, the genetic architecture underlying the yolk and ovarian follicle weights remains elusive. Here, we measured the yolk weight (YW at 11 age points from onset of egg laying to 72 weeks of age and measured the follicle weight (FW and ovary weight (OW at 73 weeks as part of a comprehensive genome-wide association study (GWAS in 1,534 F2 hens derived from reciprocal crosses between White Leghorn (WL and Dongxiang chickens (DX. For all ages, YWs exhibited moderate single nucleotide polymorphism (SNP-based heritability estimates (0.25-0.38, while the estimates for FW (0.16 and OW (0.20 were relatively low. Independent univariate genome-wide screens for each trait identified 12, 3, and 31 novel significant associations with YW, FW, and OW, respectively. A list of candidate genes such as ZAR1, STARD13, ACER1b, ACSBG2, and DHRS12 were identified for having a plausible function in yolk and follicle development. These genes are important to the initiation of embryogenesis, lipid transport, lipoprotein synthesis, lipid droplet promotion, and steroid hormone metabolism, respectively. Our study provides for the first time a genome-wide association (GWA analysis for follicle and ovary weight. Identification of the promising loci as well as potential candidate genes will greatly advance our understanding of the genetic basis underlying dynamic yolk weight and ovarian follicle development and has practical significance in breeding programs for the alteration of yolk weight at different age points.

  3. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

    DEFF Research Database (Denmark)

    Bigdeli, Tim B; Ripke, Stephan; Bacanu, Silviu-Alin;

    2015-01-01

    of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N...... of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia...

  4. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP.

    Directory of Open Access Journals (Sweden)

    Struan F A Grant

    Full Text Available Recently an association was demonstrated between the single nucleotide polymorphism (SNP, rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA. Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile, 2,270 Caucasian controls (BMI<95th percentile, 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2 = 1 in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR of 1.27 (95% CI 1.08-1.47; P = 0.0022. Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49 and of 1.31 (95% CI 1.050-1.643; P = 0.017 respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.

  5. Transcriptome analysis reveals unique metabolic features in the Cryptosporidium parvum Oocysts associated with environmental survival and stresses

    Directory of Open Access Journals (Sweden)

    Zhang Haili

    2012-11-01

    Full Text Available Abstract Background Cryptosporidium parvum is a globally distributed zoonotic parasite and an important opportunistic pathogen in immunocompromised patients. Little is known on the metabolic dynamics of the parasite, and study is hampered by the lack of molecular and genetic tools. Here we report the development of the first Agilent microarray for C. parvum (CpArray15K that covers all predicted ORFs in the parasite genome. Global transcriptome analysis using CpArray15K coupled with real-time qRT-PCR uncovered a number of unique metabolic features in oocysts, the infectious and environmental stage of the parasite. Results Oocyst stage parasites were found to be highly active in protein synthesis, based on the high transcript levels of genes associated with ribosome biogenesis, transcription and translation. The proteasome and ubiquitin associated components were also highly active, implying that oocysts might employ protein degradation pathways to recycle amino acids in order to overcome the inability to synthesize amino acids de novo. Energy metabolism in oocysts was featured by the highest level of expression of lactate dehydrogenase (LDH gene. We also studied parasite responses to UV-irradiation, and observed complex and dynamic regulations of gene expression. Notable changes included increased transcript levels of genes involved in DNA repair and intracellular trafficking. Among the stress-related genes, TCP-1 family members and some thioredoxin-associated genes appear to play more important roles in the recovery of UV-induced damages in the oocysts. Our observations also suggest that UV irradiation of oocysts results in increased activities in cytoskeletal rearrangement and intracellular membrane trafficking. Conclusions CpArray15K is the first microarray chip developed for C. parvum, which provides the Cryptosporidium research community a needed tool to study the parasite transcriptome and functional genomics. CpArray15K has been

  6. Genome-wide Association and Longitudinal Analyses Reveal Genetic Loci Linking Pubertal Height Growth, Pubertal Timing, and Childhood Adiposity

    DEFF Research Database (Denmark)

    Cousminer, Diana L; Berry, Diane J; Timpson, Nicholas J;

    2013-01-01

    adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty, and cancer progression, pointing to shared underlying mechanisms.To discover genetic loci influencing pubertal height and growth and place them in......The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. While little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and...

  7. Rapid Frequency Scan EPR

    OpenAIRE

    Tseitlin, Mark; Rinard, George A.; Quine, Richard W.; Eaton, Sandra S.; Eaton, Gareth R.

    2011-01-01

    In rapid frequency scan EPR with triangular scans, sufficient time must be allowed to insure that the magnetization in the x,y plane decays to baseline at the end of the scan, which typically is about 5 T2 after the spins are excited. To permit relaxation of signals excited toward the extremes of the scan the total scan time required may be much longer than 5 T2. However, with periodic, saw-tooth excitation, the slow-scan EPR spectrum can be recovered by Fourier deconvolution of data recorded...

  8. Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic.

    Directory of Open Access Journals (Sweden)

    Fang Han

    2013-10-01

    Full Text Available Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9 OR 0.77, ZNF365 (rs10995245 max P = 1.2 × 10(-11 OR 1.23, and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9 OR 0.75. Variants in the Human Leukocyte Antigen (HLA- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9 beta -1.9 years and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10 OR 0.57. These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

  9. Simulations of HIV capsid protein dimerization reveal the effect of chemistry and topography on the mechanism of hydrophobic protein association

    CERN Document Server

    Yu, Naiyin

    2015-01-01

    Recent work has shown that the hydrophobic protein surfaces in aqueous solution sit near a drying transition. The tendency for these surfaces to expel water from their vicinity leads to self assembly of macromolecular complexes. In this article we show with a realistic model for a biologically pertinent system how this phenomenon appears at the molecular level. We focus on the association of the C-terminal domain (CA-C) of the human immunodeficiency virus (HIV) capsid protein. By combining all-atom simulations with specialized sampling techniques we measure the water density distribution during the approach of two CA-C proteins as a function of separation and amino acid sequence in the interfacial region. The simulations demonstrate that CA-C protein-protein interactions sit at the edge of a dewetting transition and that this mesoscopic manifestation of the underlying liquid-vapor phase transition can be readily manipulated by biology or protein engineering to significantly affect association behavior. While ...

  10. Population and pedigree studies reveal a lack of association between the dopamine D sub 2 receptor gene and alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Bolos, A.M.; Goldman, D.; Brown, G.L. (National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (USA)); Lucas-Derse, S.; Ramsburg, M. (Program Resources Inc., Frederick, MD (USA))

    1990-12-26

    Using the dopamine D{sub 2} receptor clone {lambda}hD2G1, Blum et al recently found that the D{sub 2}/Taq 1 allele (A1) was present in 69{percent} of 35 deceased alcoholics but in only 20{percent} of an equal number of controls. To assess this association further, the authors evaluated the D{sub 2}/Taq 1 polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3{prime} noncoding region of the D{sub 2} receptor gene. They studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D{sub 2}/Taq 1 or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP polymorphism provided independent information against linkage at the D{sub 2} receptor locus. This study does not support a widespread or consistent association between the D{sub 2} receptor gene and alcoholism.

  11. Phylogenetic analyses of Podaxis specimens from Southern Africa reveal hidden diversity and new insights into associations with termites.

    Science.gov (United States)

    Conlon, Benjamin H; de Beer, Z Wilhelm; De Fine Licht, Henrik H; Aanen, Duur K; Poulsen, Michael

    2016-09-01

    Although frequently found on mounds of the grass-cutting termite genus Trinervitermes, virtually nothing is known about the natural history of the fungal genus Podaxis (Agaricaceae) nor why it associates with termite mounds. More than 40 species of this secotioid genus have been described since Linnaeus characterised the first species in 1771. However, taxonomic confusion arose when most of these species were reduced to synonymy with Podaxis pistillaris in 1933. Although a few more species have since been described, the vast majority of specimens worldwide are still treated as P. pistillaris. Using 45 fresh and herbarium specimens from Southern Africa, four from North America and one each from Ethiopia, and Kenya, we constructed the first comprehensive phylogeny of the genus. Four of the genotyped specimens were more than 100 y old. With the exception of the type specimen of Podaxis rugospora, all herbarium specimens were labelled as P. pistillaris or Podaxis sp. However, our data shows that the genus contains at least five well-supported clades with significant inter-clade differences in spore length, width and wall thickness, and fruiting body length, supporting that clades likely represent distinct Podaxis species. Certain clades consistently associate with termites while others appear entirely free-living. PMID:27567713

  12. Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Copp& #233; , Jean-Philippe; Patil, Christopher; Rodier, Francis; Sun, Yu; Munoz, Denise; Goldstein, Joshua; Nelson, Peter; Desprez, Pierre-Yves; Campisi, Judith

    2008-10-24

    Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.

  13. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor.

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Coppé

    2008-12-01

    Full Text Available Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA-damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial-mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment.

  14. Sequence analysis of three canine adipokine genes revealed an association between TNF polymorphisms and obesity in Labrador dogs.

    Science.gov (United States)

    Mankowska, M; Stachowiak, M; Graczyk, A; Ciazynska, P; Gogulski, M; Nizanski, W; Switonski, M

    2016-04-01

    Obesity is an emerging health problem in purebred dogs. Due to their crucial role in energy homeostasis control, genes encoding adipokines are considered candidate genes, and their variants may be associated with predisposition to obesity. Searching for polymorphism was carried out in three adipokine genes (TNF, RETN and IL6). The study was performed on 260 dogs, including lean (n = 109), overweight (n = 88) and obese (n = 63) dogs. The largest cohort was represented by Labrador Retrievers (n = 136). Altogether, 24 novel polymorphisms were identified: 12 in TNF (including one missense SNP), eight in RETN (including one missense SNP) and four in IL6. Distributions of five common SNPs (two in TNF, two in RETN and one in IL6) were further analyzed with regard to body condition score. Two SNPs in the non-coding parts of TNF (c.-40A>C and c.233+14G>A) were associated with obesity in Labrador dogs. The obtained results showed that the studied adipokine genes are highly polymorphic and two polymorphisms in the TNF gene may be considered as markers predisposing Labrador dogs to obesity.

  15. Association with AflR in Endosomes Reveals New Functions for AflJ in Aflatoxin Biosynthesis

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    John E. Linz

    2012-12-01

    Full Text Available Aflatoxins are the most potent naturally occurring carcinogens of fungal origin. Biosynthesis of aflatoxin involves the coordinated expression of more than 25 genes. The function of one gene in the aflatoxin gene cluster, aflJ, is not entirely understood but, because previous studies demonstrated a physical interaction between the Zn2Cys6 transcription factor AflR and AflJ, AflJ was proposed to act as a transcriptional co-activator. Image analysis revealed that, in the absence of aflJ in A. parasiticus, endosomes cluster within cells and near septa. AflJ fused to yellow fluorescent protein complemented the mutation in A. parasiticus ΔaflJ and localized mainly in endosomes. We found that AflJ co-localizes with AflR both in endosomes and in nuclei. Chromatin immunoprecipitation did not detect AflJ binding at known AflR DNA recognition sites suggesting that AflJ either does not bind to these sites or binds to them transiently. Based on these data, we hypothesize that AflJ assists in AflR transport to or from the nucleus, thus controlling the availability of AflR for transcriptional activation of aflatoxin biosynthesis cluster genes. AflJ may also assist in directing endosomes to the cytoplasmic membrane for aflatoxin export.

  16. Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis.

    Science.gov (United States)

    Matz-Soja, Madlen; Rennert, Christiane; Schönefeld, Kristin; Aleithe, Susanne; Boettger, Jan; Schmidt-Heck, Wolfgang; Weiss, Thomas S; Hovhannisyan, Amalya; Zellmer, Sebastian; Klöting, Nora; Schulz, Angela; Kratzsch, Jürgen; Guthke, Reinhardt; Gebhardt, Rolf

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and is increasing in prevalence. The pathomechanisms, however, are poorly understood. This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatotic human livers. Conversely, activation of the Hedgehog pathway reversed the "Gli-code" and mitigated hepatic steatosis. Collectively, our results reveal that dysfunctions in the Hedgehog pathway play an important role in hepatic steatosis and beyond. PMID:27185526

  17. Synergy analysis reveals association between insulin signaling and desmoplakin expression in palmitate treated HepG2 cells.

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    Xuewei Wang

    Full Text Available The regulation of complex cellular activities in palmitate treated HepG2 cells, and the ensuing cytotoxic phenotype, involves cooperative interactions between genes. While previous approaches have largely focused on identifying individual target genes, elucidating interacting genes has thus far remained elusive. We applied the concept of information synergy to reconstruct a "gene-cooperativity" network for palmititate-induced cytotoxicity in liver cells. Our approach integrated gene expression data with metabolic profiles to select a subset of genes for network reconstruction. Subsequent analysis of the network revealed insulin signaling as the most significantly enriched pathway, and desmoplakin (DSP as its top neighbor. We determined that palmitate significantly reduces DSP expression, and treatment with insulin restores the lost expression of DSP. Insulin resistance is a common pathological feature of fatty liver and related ailments, whereas loss of DSP has been noted in liver carcinoma. Reduced DSP expression can lead to loss of cell-cell adhesion via desmosomes, and disrupt the keratin intermediate filament network. Our findings suggest that DSP expression may be perturbed by palmitate and, along with insulin resistance, may play a role in palmitate induced cytotoxicity, and serve as potential targets for further studies on non-alcoholic fatty liver disease (NAFLD.

  18. Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia

    Science.gov (United States)

    Cui, Liang; Zheng, Dahai; Lee, Yie Hou; Chan, Tze Khee; Kumar, Yadunanda; Ho, Wanxing Eugene; Chen, Jian Zhu; Tannenbaum, Steven R.; Ong, Choon Nam

    2016-01-01

    Influenza virus infection (IVI) can cause primary viral pneumonia, which may progress to acute lung injury (ALI) and respiratory failure with a potentially fatal outcome. At present, the interactions between host and influenza virus at molecular levels and the underlying mechanisms that give rise to IVI-induced ALI are poorly understood. We conducted a comprehensive mass spectrometry-based metabolic profiling of serum, lung tissue and bronchoalveolar lavage fluid (BALF) from a non-lethal mouse model with influenza A virus at 0, 6, 10, 14, 21 and 28 days post infection (dpi), representing the major stages of IVI. Distinct metabolite signatures were observed in mice sera, lung tissues and BALF, indicating the molecular differences between systematic and localized host responses to IVI. More than 100 differential metabolites were captured in mice sera, lung tissues and BALF, including purines, pyrimidines, acylcarnitines, fatty acids, amino acids, glucocorticoids, sphingolipids, phospholipids, etc. Many of these metabolites belonged to pulmonary surfactants, indicating IVI-induced aberrations of the pulmonary surfactant system might play an important role in the etiology of respiratory failure and repair. Our findings revealed dynamic host responses to IVI and various metabolic pathways linked to disease progression, and provided mechanistic insights into IVI-induced ALI and repair process. PMID:27188343

  19. Viral Transmission Dynamics at Single-Cell Resolution Reveal Transiently Immune Subpopulations Caused by a Carrier State Association

    Science.gov (United States)

    Cenens, William; Makumi, Angela; Govers, Sander K.; Lavigne, Rob; Aertsen, Abram

    2015-01-01

    Monitoring the complex transmission dynamics of a bacterial virus (temperate phage P22) throughout a population of its host (Salmonella Typhimurium) at single cell resolution revealed the unexpected existence of a transiently immune subpopulation of host cells that emerged from peculiarities preceding the process of lysogenization. More specifically, an infection event ultimately leading to a lysogen first yielded a phage carrier cell harboring a polarly tethered P22 episome. Upon subsequent division, the daughter cell inheriting this episome became lysogenized by an integration event yielding a prophage, while the other daughter cell became P22-free. However, since the phage carrier cell was shown to overproduce immunity factors that are cytoplasmically inherited by the P22-free daughter cell and further passed down to its siblings, a transiently resistant subpopulation was generated that upon dilution of these immunity factors again became susceptible to P22 infection. The iterative emergence and infection of transiently resistant subpopulations suggests a new bet-hedging strategy by which viruses could manage to sustain both vertical and horizontal transmission routes throughout an infected population without compromising a stable co-existence with their host. PMID:26720743

  20. The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential Involvement of Brown and Beige/Brite Adipocyte Cell Lineages.

    Directory of Open Access Journals (Sweden)

    Rubén Cereijo

    Full Text Available Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area ("buffalo hump" has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from "buffalo hump" and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, non-fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-β-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e.g. UCP1 and, specifically, of "classical" brown adipocytes (e.g. ZIC1 but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-"classical brown adipocyte" phenotype

  1. Molecular dating of human-to-bovid host jumps by Staphylococcus aureus reveals an association with the spread of domestication.

    Science.gov (United States)

    Weinert, Lucy A; Welch, John J; Suchard, Marc A; Lemey, Philippe; Rambaut, Andrew; Fitzgerald, J Ross

    2012-10-23

    Host species switches by bacterial pathogens leading to new endemic infections are important evolutionary events that are difficult to reconstruct over the long term. We investigated the host switching of Staphylococcus aureus over a long evolutionary timeframe by developing Bayesian phylogenetic methods to account for uncertainty about past host associations and using estimates of evolutionary rates from serially sampled whole-genome data. Results suggest multiple jumps back and forth between human and bovids with the first switch from humans to bovids taking place around 5500 BP, coinciding with the expansion of cattle domestication throughout the Old World. The first switch to poultry is estimated at around 275 BP, long after domestication but still preceding large-scale commercial farming. These results are consistent with a central role for anthropogenic change in the emergence of new endemic diseases.

  2. Satellite-based measurements of surface deformation reveal fluid flow associated with the geological storage of carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Vasco, D.W.; Rucci, A.; Ferretti, A.; Novali, F.; Bissell, R.; Ringrose, P.; Mathieson, A.; Wright, I.

    2009-10-15

    Interferometric Synthetic Aperture Radar (InSAR), gathered over the In Salah CO{sub 2} storage project in Algeria, provides an early indication that satellite-based geodetic methods can be effective in monitoring the geological storage of carbon dioxide. An injected volume of 3 million tons of carbon dioxide, from one of the first large-scale carbon sequestration efforts, produces a measurable surface displacement of approximately 5 mm/year. Using geophysical inverse techniques we are able to infer flow within the reservoir layer and within a seismically detected fracture/ fault zone intersecting the reservoir. We find that, if we use the best available elastic Earth model, the fluid flow need only occur in the vicinity of the reservoir layer. However, flow associated with the injection of the carbon dioxide does appear to extend several kilometers laterally within the reservoir, following the fracture/fault zone.

  3. Indicators of early and late processing reveal the importance of within-trial-time for theories of associative learning.

    Directory of Open Access Journals (Sweden)

    Harald Lachnit

    Full Text Available In four human learning experiments (Pavlovian skin conductance, causal learning, speeded classification task, we evaluated several associative learning theories that assume either an elemental (modified unique cue model and Harris' model or a configural (Pearce's configural theory and an extension of it form of stimulus processing. The experiments used two modified patterning problems (A/B/C+, AB/BC/AC+ vs. ABC-; A+, BC+ vs. ABC-. Pearce's configural theory successfully predicted all of our data reflecting early stimulus processing, while the predictions of the elemental theories were in accord with all of our data reflecting later stages of stimulus processing. Our results suggest that the form of stimulus representation depends on the amount of time available for stimulus processing. Our findings highlight the necessity to investigate stimulus processing during conditioning on a finer time scale than usually done in contemporary research.

  4. Metagenomic profiling reveals lignocellulose degrading system in a microbial community associated with a wood-feeding beetle.

    Directory of Open Access Journals (Sweden)

    Erin D Scully

    Full Text Available The Asian longhorned beetle (Anoplophoraglabripennis is an invasive, wood-boring pest that thrives in the heartwood of deciduous tree species. A large impediment faced by A. glabripennis as it feeds on woody tissue is lignin, a highly recalcitrant biopolymer that reduces access to sugars and other nutrients locked in cellulose and hemicellulose. We previously demonstrated that lignin, cellulose, and hemicellulose are actively deconstructed in the beetle gut and that the gut harbors an assemblage of microbes hypothesized to make significant contributions to these processes. While lignin degrading mechanisms have been well characterized in pure cultures of white rot basidiomycetes, little is known about such processes in microbial communities associated with wood-feeding insects. The goals of this study were to develop a taxonomic and functional profile of a gut community derived from an invasive population of larval A. glabripennis collected from infested host trees and to identify genes that could be relevant for the digestion of woody tissue and nutrient acquisition. To accomplish this goal, we taxonomically and functionally characterized the A. glabripennis midgut microbiota through amplicon and shotgun metagenome sequencing and conducted a large-scale comparison with the metagenomes from a variety of other herbivore-associated communities. This analysis distinguished the A. glabripennis larval gut metagenome from the gut communities of other herbivores, including previously sequenced termite hindgut metagenomes. Genes encoding enzymes were identified in the A. glabripennis gut metagenome that could have key roles in woody tissue digestion including candidate lignin degrading genes (laccases, dye-decolorizing peroxidases, novel peroxidases and β-etherases, 36 families of glycoside hydrolases (such as cellulases and xylanases, and genes that could facilitate nutrient recovery, essential nutrient synthesis, and detoxification. This community

  5. Phage-Induced Expression of CRISPR-Associated Proteins is Revealed by Shotgun Proteomics in Streptococcus thermophilus

    Energy Technology Data Exchange (ETDEWEB)

    Young, Jacque C [ORNL; Dill, Brian [ORNL; Pan, Chongle [ORNL; Hettich, Robert {Bob} L [ORNL; Banfield, Jillian F. [University of California, Berkeley; Shah, Manesh B [ORNL; Fremaux, Christophe [Danisco France SAS; Horvath, Philippe [Danisco France SAS; Barrangou, Rodolphe [Danisco USA; Verberkmoes, Nathan C [ORNL

    2012-01-01

    The CRISPR/Cas system, comprised of clustered regularly interspaced short palindromic repeats along with their associated (Cas) proteins, protects bacteria and archaea from viral predation and invading nucleic acids. While the mechanism of action for this acquired immunity is currently under investigation, the response of Cas protein expression to phage infection has yet to be elucidated. In this study, we employed shotgun proteomics to measure the global proteome expression in a model system for studying the CRISPR/Cas response: infection of S. thermophilus DGCC7710 with phage 2972. Host and viral proteins were simultaneously measured following inoculation at two different multiplicities of infection and across various time points using two-dimensional liquid chromatography tandem mass spectroscopy. Thirty-seven out of forty predicted viral proteins were detected, including all proteins of the structural virome and viral effector proteins. In total, 1,013 of 2,079 predicted S. thermophilus proteins were detected, facilitating the monitoring of host protein synthesis changes in response to virus infection. Importantly, Cas proteins from all four CRISPR loci in the S. thermophilus DGCC7710 genome were detected, including loci previously thought to be inactive. Many Cas proteins were found to be constitutively expressed, but several demonstrated increased abundance during peak infection, including the Cas9 proteins from the CRISPR1 and CRISPR3 loci, which are key players in the interference phase of the CRISPR/Cas response. Altogether, these results provide novel insights into the proteomic response of S. thermophilus, specifically CRISPR-associated proteins, upon phage 2972 infection.

  6. The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.

    Directory of Open Access Journals (Sweden)

    Nicholas M Kanaan

    Full Text Available We hypothesized that the study of gene expression at 1, 2, 4, 6 and 16 weeks in the substantia nigra (SN after intrastriatal 6-OHDA in the Sprague-Dawley rat (rattus norvegicus would identify cellular responses during the degenerative process that could be axoprotective. Specifically, we hypothesized that genes expressed within the SN that followed a profile of being highly upregulated early after the lesion (during active axonal degeneration and then progressively declined to baseline over 16 weeks as DA neurons died are indicative of potential protective responses to the striatal 6-OHDA insult. Utilizing a κ-means cluster analysis strategy, we demonstrated that one such cluster followed this hypothesized expression pattern over time, and that this cluster contained several interrelated transcripts that are classified as regeneration-associated genes (RAGs including Atf3, Sprr1a, Ecel1, Gadd45a, Gpnmb, Sox11, Mmp19, Srgap1, Rab15,Lifr, Trib3, Tgfb1, and Sema3c. All exemplar transcripts tested from this cluster (Sprr1a, Ecel1, Gadd45a, Atf3 and Sox11 were validated by qPCR and a smaller subset (Sprr1a, Gadd45a and Sox11 were shown to be exclusively localized to SN DA neurons using a dual label approach with RNAScope in situ hybridization and immunohistochemistry. Upregulation of RAGs is typically associated with the response to axonal injury in the peripheral nerves and was not previously reported as part of the axodegenerative process for DA neurons of the SN. Interestingly, as part of this cluster, other transcripts were identified based on their expression pattern but without a RAG provenance in the literature. These "RAG-like" transcripts need further characterization to determine if they possess similar functions to or interact with known RAG transcripts. Ultimately, it is hoped that some of the newly identified axodegeneration-reactive transcripts could be exploited as axoprotective therapies in PD and other neurodegenerative diseases.

  7. Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

    Science.gov (United States)

    Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L; Nalls, Michael A; Sung, Yun Ju; Tayo, Bamidele O; Sun, Yan V; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D; Young, J Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L; Andrews, Jeanette S; Smith, Jennifer A; Faul, Jessica D; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S; Musani, Solomon K; Srinivasan, Sathanur; Velez Edwards, Digna R; Wang, Heming; Becker, Lewis C; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W; Evans, Michele K; Guo, Xiuqing; Garcia, Melissa E; Jensen, Rich; Keller, Margaux F; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W; Moore, Jason H; Morrison, Alanna C; Mosley, Thomas H; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F; Ridker, Paul M; Salako, Babatunde; Singleton, Andrew B; Shriner, Daniel; Taylor, Kent D; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M; Yanek, Lisa R; Zhao, Wei; Zonderman, Alan B; Becker, Diane M; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N; Howard, Virginia J; Karczewsk, Konrad J; Lanktree, Matthew B; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Psaty, Bruce M; Schork, Nicholas J; Weir, David R; Rotimi, Charles N; Sale, Michele M; Harris, Tamara; Kardia, Sharon L R; Hunt, Steven C; Arnett, Donna; Redline, Susan; Cooper, Richard S; Risch, Neil J; Rao, D C; Rotter, Jerome I; Chakravarti, Aravinda; Reiner, Alex P; Levy, Daniel; Keating, Brendan J; Zhu, Xiaofeng

    2013-09-01

    High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

  8. Host-Associated Genomic Features of the Novel Uncultured Intracellular Pathogen Ca. Ichthyocystis Revealed by Direct Sequencing of Epitheliocysts.

    Science.gov (United States)

    Qi, Weihong; Vaughan, Lloyd; Katharios, Pantelis; Schlapbach, Ralph; Seth-Smith, Helena M B

    2016-01-01

    Advances in single-cell and mini-metagenome sequencing have enabled important investigations into uncultured bacteria. In this study, we applied the mini-metagenome sequencing method to assemble genome drafts of the uncultured causative agents of epitheliocystis, an emerging infectious disease in the Mediterranean aquaculture species gilthead seabream. We sequenced multiple cyst samples and constructed 11 genome drafts from a novel beta-proteobacterial lineage, Candidatus Ichthyocystis. The draft genomes demonstrate features typical of pathogenic bacteria with an obligate intracellular lifestyle: a reduced genome of up to 2.6 Mb, reduced G + C content, and reduced metabolic capacity. Reconstruction of metabolic pathways reveals that Ca Ichthyocystis genomes lack all amino acid synthesis pathways, compelling them to scavenge from the fish host. All genomes encode type II, III, and IV secretion systems, a large repertoire of predicted effectors, and a type IV pilus. These are all considered to be virulence factors, required for adherence, invasion, and host manipulation. However, no evidence of lipopolysaccharide synthesis could be found. Beyond the core functions shared within the genus, alignments showed distinction into different species, characterized by alternative large gene families. These comprise up to a third of each genome, appear to have arisen through duplication and diversification, encode many effector proteins, and are seemingly critical for virulence. Thus, Ca Ichthyocystis represents a novel obligatory intracellular pathogenic beta-proteobacterial lineage. The methods used: mini-metagenome analysis and manual annotation, have generated important insights into the lifestyle and evolution of the novel, uncultured pathogens, elucidating many putative virulence factors including an unprecedented array of novel gene families. PMID:27190004

  9. RBC nuclear scan

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003835.htm RBC nuclear scan To use the sharing features on this page, please enable JavaScript. An RBC nuclear scan uses small amounts of radioactive material to ...

  10. Genetic association analysis of ATP binding cassette protein family reveals a novel association of ABCB1 genetic variants with epilepsy risk, but not with drug-resistance.

    Directory of Open Access Journals (Sweden)

    Shabeesh Balan

    Full Text Available Epilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS (prototype for AED-resistant epilepsy; juvenile myoclonic epilepsy (JME (prototype for AED-responsive epilepsy; and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004. This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004 and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05 cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency

  11. Genetic association analysis of ATP binding cassette protein family reveals a novel association of ABCB1 genetic variants with epilepsy risk, but not with drug-resistance.

    Science.gov (United States)

    Balan, Shabeesh; Bharathan, Sumitha Prameela; Vellichiramal, Neetha Nanoth; Sathyan, Sanish; Joseph, Vijai; Radhakrishnan, Kurupath; Banerjee, Moinak

    2014-01-01

    Epilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED)-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype for AED-resistant epilepsy); juvenile myoclonic epilepsy (JME) (prototype for AED-responsive epilepsy); and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T) rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004). This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004) and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05) cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency for MTLE

  12. Validation of the Reveal(®) 2.0 Group D1 Salmonella Test for Detection of Salmonella Enteritidis in Raw Shell Eggs and Poultry-Associated Matrixes.

    Science.gov (United States)

    Mozola, Mark; Biswas, Preetha; Viator, Ryan; Feldpausch, Emily; Foti, Debra; Li, Lin; Le, Quynh-Nhi; Alles, Susan; Rice, Jennifer

    2016-07-01

    A study was conducted to assess the performance of the Reveal(®) 2.0 Group D1 Salmonella lateral flow immunoassay for use in detection of Salmonella Enteritidis (SE) in raw shell eggs and poultry-associated matrixes, including chicken carcass rinse and poultry feed. In inclusivity testing, the Reveal 2.0 test detected all 37 strains of SE tested. The test also detected all but one of 18 non-Enteritidis somatic group D1 Salmonella serovars examined. In exclusivity testing, none of 42 strains tested was detected. The exclusivity panel included Salmonella strains of somatic groups other than D1, as well as strains of other genera of Gram-negative bacteria. In matrix testing, performance of the Reveal 2.0 test was compared to that of the U.S. Department of Agriculture, Food Safety and Inspection Service Microbiology Laboratory Guidebook reference culture procedure for chicken carcass rinse and to that of the U.S. Food and Drug Administration Bacteriological Analytical Manual for raw shell eggs and poultry feed. For all matrixes evaluated, there were no significant differences in the ability to detect SE when comparing the Reveal 2.0 method and the appropriate reference culture procedure as determined by probability of detection statistical analysis. The ability of the Reveal 2.0 test to withstand modest perturbations to normal operating parameters was examined in robustness experiments. Results showed that the test can withstand deviations in up to three operating parameters simultaneously without significantly affecting performance. Real-time stability testing of multiple lots of Reveal 2.0 devices established the shelf life of the test device at 16 months postmanufacture. PMID:27214854

  13. Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel.

    Directory of Open Access Journals (Sweden)

    Mathilde Bayet-Robert

    Full Text Available BACKGROUND: Curcumin (CUR has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated. METHODOLOGY/PRINCIPAL FINDINGS: (1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX. In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx increased at low dose CUR (≤ 10 mg.l(-1-28 µM- (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01, but decreased at high dose (≥ 25 mg.l(-1 -70 µM- (-49%, in MCF7 cells, P<0.02, and -56% in MDA-MB-231 cells, P<0.025. At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (-60 to -80%, all, P<0.05. Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025, and decrease of glycerophospho-ethanolamine and -choline (about -60%, P<0.025. Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l(-1 in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR. CONCLUSIONS/SIGNIFICANCE: Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted

  14. Quantitative DNA methylation analyses reveal stage dependent DNA methylation and association to clinico-pathological factors in breast tumors

    International Nuclear Information System (INIS)

    Aberrant DNA methylation of regulatory genes has frequently been found in human breast cancers and correlated to clinical outcome. In the present study we investigate stage specific changes in the DNA methylation patterns in order to identify valuable markers to understand how these changes affect breast cancer progression. Quantitative DNA methylation analyses of 12 candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B, PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast cancer tissue samples from DCIS to invasive tumors stage I to IV. Significant differences in methylation levels between the DCIS and invasive stage II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in late stage compared to the early stage breast carcinoma. Z-score analysis revealed significantly lower methylation levels in DCIS and stage I tumors compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B, FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had significantly lower overall methylation levels compared to tumors with wild type TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed that HER2 positive tumors had significantly higher z-scores of methylation compared to the HER2 negative tumors. Univariate survival analysis identifies methylation status of PPP2R2B as significant predictor of overall survival and breast cancer specific survival. In the present study we report that the level of aberrant DNA methylation is higher in late stage compared with early stage of invasive breast cancers and DCIS for genes mentioned above

  15. Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis.

    Science.gov (United States)

    Neems, Daniel S; Garza-Gongora, Arturo G; Smith, Erica D; Kosak, Steven T

    2016-03-22

    The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineage-enriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation. PMID:26957603

  16. Quantification of human-associated fecal indicators reveal sewage from urban watersheds as a source of pollution to Lake Michigan.

    Science.gov (United States)

    Templar, Hayley A; Dila, Deborah K; Bootsma, Melinda J; Corsi, Steven R; McLellan, Sandra L

    2016-09-01

    Sewage contamination of urban waterways from sewer overflows and failing infrastructure is a major environmental and public health concern. Fecal coliforms (FC) are commonly employed as fecal indicator bacteria, but do not distinguish between human and non-human sources of fecal contamination. Human Bacteroides and human Lachnospiraceae, two genetic markers for human-associated indicator bacteria, were used to identify sewage signals in two urban rivers and the estuary that drains to Lake Michigan. Grab samples were collected from the rivers throughout 2012 and 2013 and hourly samples were collected in the estuary across the hydrograph during summer 2013. Human Bacteroides and human Lachnospiraceae were highly correlated with each other in river samples (Pearson's r = 0.86), with average concentrations at most sites elevated during wet weather. These human indicators were found during baseflow, indicating that sewage contamination is chronic in these waterways. FC are used for determining total maximum daily loads (TMDLs) in management plans; however, FC concentrations alone failed to prioritize river reaches with potential health risks. While 84% of samples with >1000 CFU/100 ml FC had sewage contamination, 52% of samples with moderate (200-1000 CFU/100 ml) and 46% of samples with low (land use, storm characteristics, and other factors that drive sewage contamination in urban waterways. PMID:27236594

  17. Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models.

    Science.gov (United States)

    Wang, Zhen; Zhang, Jifeng; Li, Hong; Li, Junyi; Niimi, Manabu; Ding, Guohui; Chen, Haifeng; Xu, Jie; Zhang, Hongjiu; Xu, Ze; Dai, Yulin; Gui, Tuantuan; Li, Shengdi; Liu, Zhi; Wu, Sujuan; Cao, Mushui; Zhou, Lu; Lu, Xingyu; Wang, Junxia; Yang, Jing; Fu, Yunhe; Yang, Dongshan; Song, Jun; Zhu, Tianqing; Li, Shen; Ning, Bo; Wang, Ziyun; Koike, Tomonari; Shiomi, Masashi; Liu, Enqi; Chen, Luonan; Fan, Jianglin; Chen, Y Eugene; Li, Yixue

    2016-01-01

    The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models. PMID:27245873

  18. Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Amelia M Gallaher

    Full Text Available Kaposi's sarcoma (KS is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV. The virus expresses unique microRNAs (miRNAs, but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1 following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1α, and up-regulation of a protein involved in stimulating angiogenesis (HMOX1. This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis.

  19. Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics.

    Directory of Open Access Journals (Sweden)

    Deborah L Diamond

    2010-01-01

    Full Text Available Proteomic and lipidomic profiling was performed over a time course of acute hepatitis C virus (HCV infection in cultured Huh-7.5 cells to gain new insights into the intracellular processes influenced by this virus. Our proteomic data suggest that HCV induces early perturbations in glycolysis, the pentose phosphate pathway, and the citric acid cycle, which favor host biosynthetic activities supporting viral replication and propagation. This is followed by a compensatory shift in metabolism aimed at maintaining energy homeostasis and cell viability during elevated viral replication and increasing cellular stress. Complementary lipidomic analyses identified numerous temporal perturbations in select lipid species (e.g. phospholipids and sphingomyelins predicted to play important roles in viral replication and downstream assembly and secretion events. The elevation of lipotoxic ceramide species suggests a potential link between HCV-associated biochemical alterations and the direct cytopathic effect observed in this in vitro system. Using innovative computational modeling approaches, we further identified mitochondrial fatty acid oxidation enzymes, which are comparably regulated during in vitro infection and in patients with histological evidence of fibrosis, as possible targets through which HCV regulates temporal alterations in cellular metabolic homeostasis.

  20. Multigenic Control of Pod Shattering Resistance in Chinese Rapeseed Germplasm Revealed by Genome-Wide Association and Linkage Analyses.

    Science.gov (United States)

    Liu, Jia; Wang, Jun; Wang, Hui; Wang, Wenxiang; Zhou, Rijin; Mei, Desheng; Cheng, Hongtao; Yang, Juan; Raman, Harsh; Hu, Qiong

    2016-01-01

    The majority of rapeseed cultivars shatter seeds upon maturity especially under hot-dry and windy conditions, reducing yield and gross margin return to growers. Here, we identified quantitative trait loci (QTL) for resistance to pod shatter in an unstructured diverse panel of 143 rapeseed accessions, and two structured populations derived from bi-parental doubled haploid (DH) and inter-mated (IF2) crosses derived from R1 (resistant to pod shattering) and R2 (prone to pod shattering) accessions. Genome-wide association analysis identified six significant QTL for resistance to pod shatter located on chromosomes A01, A06, A07, A09, C02, and C05. Two of the QTL, qSRI.A09 delimited with the SNP marker Bn-A09-p30171993 (A09) and qSRI.A06 delimited with the SNP marker Bn-A06-p115948 (A06) could be repeatedly detected across environments in a diversity panel, DH and IF2 populations, suggesting that at least two loci on chromosomes A06 and A09 were the main contributors to pod shatter resistance in Chinese germplasm. Significant SNP markers identified in this study especially those that appeared repeatedly across environments provide a cost-effective and an efficient method for introgression and pyramiding of favorable alleles for pod shatter resistance via marker-assisted selection in rapeseed improvement programs. PMID:27493651

  1. Hyperlipidemia-associated gene variations and expression patterns revealed by whole-genome and transcriptome sequencing of rabbit models

    Science.gov (United States)

    Wang, Zhen; Zhang, Jifeng; Li, Hong; Li, Junyi; Niimi, Manabu; Ding, Guohui; Chen, Haifeng; Xu, Jie; Zhang, Hongjiu; Xu, Ze; Dai, Yulin; Gui, Tuantuan; Li, Shengdi; Liu, Zhi; Wu, Sujuan; Cao, Mushui; Zhou, Lu; Lu, Xingyu; Wang, Junxia; Yang, Jing; Fu, Yunhe; Yang, Dongshan; Song, Jun; Zhu, Tianqing; Li, Shen; Ning, Bo; Wang, Ziyun; Koike, Tomonari; Shiomi, Masashi; Liu, Enqi; Chen, Luonan; Fan, Jianglin; Chen, Y. Eugene; Li, Yixue

    2016-01-01

    The rabbit (Oryctolagus cuniculus) is an important experimental animal for studying human diseases, such as hypercholesterolemia and atherosclerosis. Despite this, genetic information and RNA expression profiling of laboratory rabbits are lacking. Here, we characterized the whole-genome variants of three breeds of the most popular experimental rabbits, New Zealand White (NZW), Japanese White (JW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Although the genetic diversity of WHHL rabbits was relatively low, they accumulated a large proportion of high-frequency deleterious mutations due to the small population size. Some of the deleterious mutations were associated with the pathophysiology of WHHL rabbits in addition to the LDLR deficiency. Furthermore, we conducted transcriptome sequencing of different organs of both WHHL and cholesterol-rich diet (Chol)-fed NZW rabbits. We found that gene expression profiles of the two rabbit models were essentially similar in the aorta, even though they exhibited different types of hypercholesterolemia. In contrast, Chol-fed rabbits, but not WHHL rabbits, exhibited pronounced inflammatory responses and abnormal lipid metabolism in the liver. These results provide valuable insights into identifying therapeutic targets of hypercholesterolemia and atherosclerosis with rabbit models. PMID:27245873

  2. Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies.

    Science.gov (United States)

    Furuita, Kyoko; Jee, JunGoo; Fukada, Harumi; Mishima, Masaki; Kojima, Chojiro

    2010-04-23

    Oxysterol-binding protein (OSBP), a cytosolic receptor of cholesterol and oxysterols, is recruited to the endoplasmic reticulum by binding to the cytoplasmic major sperm protein (MSP) domain of integral endoplasmic reticulum protein VAMP-associated protein-A (VAP-A), a process essential for the stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. To delineate the interaction mechanism between VAP-A and OSBP, we determined the complex structure between the VAP-A MSP domain (VAP-A(MSP)) and the OSBP fragment containing a VAP-A binding motif FFAT (OSBP(F)) by NMR. This solution structure explained that five of six conserved residues in the FFAT motif are required for the stable complex formation, and three of five, including three critical intermolecular electrostatic interactions, were not explained before. By combining NMR relaxation and titration, isothermal titration calorimetry, and mutagenesis experiments with structural information, we further elucidated the detailed roles of the FFAT motif and underlying motions of VAP-A(MSP), OSBP(F), and the complex. Our results show that OSBP(F) is disordered in the free state, and VAP-A(MSP) and OSBP(F) form a final complex by means of intermediates, where electrostatic interactions through acidic residues, including an acid patch preceding the FFAT motif, probably play a collective role. Additionally, we report that the mutation that causes the familial motor neuron disease decreases the stability of the MSP domain.

  3. Electrostatic Interaction between Oxysterol-binding Protein and VAMP-associated Protein A Revealed by NMR and Mutagenesis Studies*

    Science.gov (United States)

    Furuita, Kyoko; Jee, JunGoo; Fukada, Harumi; Mishima, Masaki; Kojima, Chojiro

    2010-01-01

    Oxysterol-binding protein (OSBP), a cytosolic receptor of cholesterol and oxysterols, is recruited to the endoplasmic reticulum by binding to the cytoplasmic major sperm protein (MSP) domain of integral endoplasmic reticulum protein VAMP-associated protein-A (VAP-A), a process essential for the stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. To delineate the interaction mechanism between VAP-A and OSBP, we determined the complex structure between the VAP-A MSP domain (VAP-AMSP) and the OSBP fragment containing a VAP-A binding motif FFAT (OSBPF) by NMR. This solution structure explained that five of six conserved residues in the FFAT motif are required for the stable complex formation, and three of five, including three critical intermolecular electrostatic interactions, were not explained before. By combining NMR relaxation and titration, isothermal titration calorimetry, and mutagenesis experiments with structural information, we further elucidated the detailed roles of the FFAT motif and underlying motions of VAP-AMSP, OSBPF, and the complex. Our results show that OSBPF is disordered in the free state, and VAP-AMSP and OSBPF form a final complex by means of intermediates, where electrostatic interactions through acidic residues, including an acid patch preceding the FFAT motif, probably play a collective role. Additionally, we report that the mutation that causes the familial motor neuron disease decreases the stability of the MSP domain. PMID:20178991

  4. Pulmonary ventilation/perfusion scan

    Science.gov (United States)

    V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health care ...

  5. Pulmonary ventilation/perfusion scan

    Science.gov (United States)

    V/Q scan; Ventilation/perfusion scan; Lung ventilation/perfusion scan ... A pulmonary ventilation/perfusion scan is actually two tests. They may be done separately or together. During the perfusion scan, a health ...

  6. Cross-hemispheric collaboration and segregation associated with task difficulty as revealed by structural and functional connectivity.

    Science.gov (United States)

    Davis, Simon W; Cabeza, Roberto

    2015-05-27

    Although it is known that brain regions in one hemisphere may interact very closely with their corresponding contralateral regions (collaboration) or operate relatively independent of them (segregation), the specific brain regions (where) and conditions (how) associated with collaboration or segregation are largely unknown. We investigated these issues using a split field-matching task in which participants matched the meaning of words or the visual features of faces presented to the same (unilateral) or to different (bilateral) visual fields. Matching difficulty was manipulated by varying the semantic similarity of words or the visual similarity of faces. We assessed the white matter using the fractional anisotropy (FA) measure provided by diffusion tensor imaging (DTI) and cross-hemispheric communication in terms of fMRI-based connectivity between homotopic pairs of cortical regions. For both perceptual and semantic matching, bilateral trials became faster than unilateral trials as difficulty increased (bilateral processing advantage, BPA). The study yielded three novel findings. First, whereas FA in anterior corpus callosum (genu) correlated with word-matching BPA, FA in posterior corpus callosum (splenium-occipital) correlated with face-matching BPA. Second, as matching difficulty intensified, cross-hemispheric functional connectivity (CFC) increased in domain-general frontopolar cortex (for both word and face matching) but decreased in domain-specific ventral temporal lobe regions (temporal pole for word matching and fusiform gyrus for face matching). Last, a mediation analysis linking DTI and fMRI data showed that CFC mediated the effect of callosal FA on BPA. These findings clarify the mechanisms by which the hemispheres interact to perform complex cognitive tasks.

  7. A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis.

    Directory of Open Access Journals (Sweden)

    Varun ePandey

    2013-09-01

    Full Text Available Pantothenate Kinase-Associated Neurodegeneration (PKAN is a neurodegenerative disorder with a poorly understood molecular mechanism. It is caused by mutations in Pantothenate Kinase, the first enzyme in the Coenzyme A (CoA biosynthetic pathway. Here, we developed a Drosophila model of PKAN (tim-fbl flies that allows us to continuously monitor the modeled disease in the brain. In tim-fbl flies, downregulation of fumble, the Drosophila PanK homologue in the cells containing a circadian clock results in characteristic features of PKAN such as developmental lethality, hypersensitivity to oxidative stress, and diminished life span. Despite quasi-normal circadian transcriptional rhythms, tim-fbl flies display brain-specific aberrant circadian locomotor rhythms, and a unique transcriptional signature. Comparison with expression data from flies exposed to paraquat demonstrates that, as previously suggested, pathways others than oxidative stress are affected by PANK downregulation. Surprisingly we found a significant decrease in the expression of key components of the photoreceptor recycling pathways, which could lead to retinal degeneration, a hallmark of PKAN. Importantly, these defects are not accompanied by changes in structural components in eye genes suggesting that changes in gene expression in the eye precede and may cause the retinal degeneration. Indeed tim-fbl flies have diminished response to light transitions, and their altered day/night patterns of activity demonstrates defects in light perception. This suggest that retinal lesions are not solely due to oxidative stress and demonstrates a role for the transcriptional response to CoA deficiency underlying the defects observed in dPanK deficient flies. Moreover, in the present study we developed a new fly model that can be applied to other diseases and that allows the assessment of neurodegeneration in the brains of living flies.

  8. Transcriptome and quantitative proteome analysis reveals molecular processes associated with larval metamorphosis in the polychaete pseudopolydora vexillosa

    KAUST Repository

    Chandramouli, Kondethimmanahalli

    2013-03-01

    Larval growth of the polychaete worm Pseudopolydora vexillosa involves the formation of segment-specific structures. When larvae attain competency to settle, they discard swimming chaetae and secrete mucus. The larvae build tubes around themselves and metamorphose into benthic juveniles. Understanding the molecular processes, which regulate this complex and unique transition, remains a major challenge because of the limited molecular information available. To improve this situation, we conducted high-throughput RNA sequencing and quantitative proteome analysis of the larval stages of P. vexillosa. Based on gene ontology (GO) analysis, transcripts related to cellular and metabolic processes, binding, and catalytic activities were highly represented during larval-adult transition. Mitogen-activated protein kinase (MAPK), calcium-signaling, Wnt/β-catenin, and notch signaling metabolic pathways were enriched in transcriptome data. Quantitative proteomics identified 107 differentially expressed proteins in three distinct larval stages. Fourteen and 53 proteins exhibited specific differential expression during competency and metamorphosis, respectively. Dramatic up-regulation of proteins involved in signaling, metabolism, and cytoskeleton functions were found during the larval-juvenile transition. Several proteins involved in cell signaling, cytoskeleton and metabolism were up-regulated, whereas proteins related to transcription and oxidative phosphorylation were down-regulated during competency. The integration of high-throughput RNA sequencing and quantitative proteomics allowed a global scale analysis of larval transcripts/proteins associated molecular processes in the metamorphosis of polychaete worms. Further, transcriptomic and proteomic insights provide a new direction to understand the fundamental mechanisms that regulate larval metamorphosis in polychaetes. © 2013 American Chemical Society.

  9. Solution NMR and X-ray Crystal Structures of Membrane-associated Lipoprotein-17 Domain Reveal a Novel Fold

    Energy Technology Data Exchange (ETDEWEB)

    R Mani; S Vorobiev; G Swapna; H Neely; H Janjua; C Ciccosanti; D Xiao; J Hunt; G Montelione; et al.

    2011-12-31

    The conserved Lipoprotein-17 domain of membrane-associated protein Q9PRA0{_}UREPA from Ureaplasma parvum was selected for structure determination by the Northeast Structural Genomics Consortium, as part of the Protein Structure Initiative's program on structure-function analysis of protein domains from large domain sequence families lacking structural representatives. The 100-residue Lipoprotein-17 domain is a 'domain of unknown function' (DUF) that is a member of Pfam protein family PF04200, a large domain family for which no members have characterized biochemical functions. The three-dimensional structure of the Lipoprotein-17 domain of protein Q9PRA0{_}UREPA was determined by both solution NMR and by X-ray crystallography at 2.5 {angstrom}. The two structures are in good agreement with each other. The domain structure features three {alpha}-helices, {alpha}1 through {alpha}3, and five {beta}-strands. Strands {beta}1/{beta}2, {beta}3/{beta}4, {beta}4/{beta}5 are anti-parallel to each other. Strands {beta}1 and {beta}2 are orthogonal to strands {beta}3, {beta}4, {beta}5, while helix {alpha}3 is formed between the strands {beta}3 and {beta}4. One-turn helix {alpha}2 is formed between the strands {beta}1 and {beta}2, while helix {alpha}1 occurs in the N-terminal polypeptide segment. Searches of the Protein Data Bank do not identify any other protein with significant structural similarity to Lipoprotein-17 domain of Q9PRA0{_}UREPA, indicating that it is a novel protein fold.

  10. Imaging of zebrafish in vivo with second-harmonic generation reveals shortened sarcomeres associated with myopathy induced by statin.

    Directory of Open Access Journals (Sweden)

    Shih-Hao Huang

    Full Text Available We employed second-harmonic generation (SHG imaging and the zebrafish model to investigate the myopathy caused by statin in vivo with emphasis on the altered microstructures of the muscle sarcomere, the fundamental contractile element of muscles. This approach derives an advantage of SHG imaging to observe the striated skeletal muscle of living zebrafish based on signals produced mainly from the thick myosin filament of sarcomeres without employing exogenous labels, and eliminates concern about the distortion of muscle structures caused by sample preparation in conventional histological examination. The treatment with statin caused a significantly shortened sarcomere relative to an untreated control (1.73±0.09 µm vs 1.91±0.08 µm, P<0.05 while the morphological integrity of the muscle fibers remained largely intact. Mechanistic tests indicated that this microstructural disorder was associated with the biosynthetic pathway of cholesterol, or, specifically, with the impaired production of mevalonate by statins. This microstructural disorder exhibited a strong dependence on both the dosage and the duration of treatment, indicating a possibility to assess the severity of muscle injury according to the altered length of the sarcomeres. In contrast to a conventional assessment of muscle injury using clinical biomarkers in blood, such as creatine kinase that is released from only disrupted myocytes, the ability to determine microstructural modification of sarcomeres allows diagnosis of muscle injury before an onset of conventional clinical symptoms. In light of the increasing prevalence of the incidence of muscle injuries caused by new therapies, our work consolidates the combined use of the zebrafish and SHG imaging as an effective and sensitive means to evaluate the safety profile of new therapeutic targets in vivo.

  11. Genome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene

    OpenAIRE

    Johnson, Matthew P.; Shaun P Brennecke; East, Christine E.; Göring, Harald H. H.; Kent, Jack W.; Thomas D Dyer; Said, Joanne M.; Roten, Linda T; Iversen, Ann-Charlotte; Abraham, Lawrence J.; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli

    2012-01-01

    Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10−7, OR = 1.57; rs12711941, p = 4.26×10−7, OR = 1.56) satisfied our genome-wide signific...

  12. Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene

    OpenAIRE

    Johnson, Matthew P.; Shaun P Brennecke; East, Christine; Göring, Harald H. H.; Kent, Jack W.; Thomas D Dyer; Said, Joanne M.; Roten, Linda Tømmerdal; Iversen, Ann-Charlotte; Abraham, Lawrence J.; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli

    2012-01-01

    Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10−7, OR = 1.57; rs12711941, p = 4.26×10−7, OR = 1.56) satisfied our genome-wide signific...

  13. The importance of context to the genetic architecture of diabetes-related traits is revealed in a genome-wide scan of a LG/J × SM/J murine model.

    Science.gov (United States)

    Lawson, Heather A; Lee, Arthur; Fawcett, Gloria L; Wang, Bing; Pletscher, L Susan; Maxwell, Taylor J; Ehrich, Thomas H; Kenney-Hunt, Jane P; Wolf, Jason B; Semenkovich, Clay F; Cheverud, James M

    2011-04-01

    Variations in diabetic phenotypes are caused by complex interactions of genetic effects, environmental factors, and the interplay between the two. We tease apart these complex interactions by examining genome-wide genetic and epigenetic effects on diabetes-related traits among different sex, diet, and sex-by-diet cohorts in a Mus musculus model. We conducted a genome-wide scan for quantitative trait loci that affect serum glucose and insulin levels and response to glucose stress in an F(16) Advanced Intercross Line of the LG/J and SM/J intercross (Wustl:LG,SM-G16). Half of each sibship was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (parent-of-origin imprinting) effects were characterized by partitioning animals into sex, diet, and sex-by-diet cohorts. We found that different cohorts often have unique genetic effects at the same loci, and that genetic signals can be masked or erroneously assigned to specific cohorts if they are not considered individually. Our data demonstrate that the effects of genes on complex trait variation are highly context-dependent and that the same genomic sequence can affect traits differently depending on an individual's sex and/or dietary environment. Our results have important implications for studies of complex traits in humans.

  14. Two conformational states of the membrane-associated Bacillus thuringiensis Cry4Ba δ-endotoxin complex revealed by electron crystallography: Implications for toxin-pore formation

    International Nuclear Information System (INIS)

    The insecticidal nature of Cry δ-endotoxins produced by Bacillus thuringiensis is generally believed to be caused by their ability to form lytic pores in the midgut cell membrane of susceptible insect larvae. Here we have analyzed membrane-associated structures of the 65-kDa dipteran-active Cry4Ba toxin by electron crystallography. The membrane-associated toxin complex was crystallized in the presence of DMPC via detergent dialysis. Depending upon the charge of the adsorbed surface, 2D crystals of the oligomeric toxin complex have been captured in two distinct conformations. The projection maps of those crystals have been generated at 17 A resolution. Both complexes appeared to be trimeric; as in one crystal form, its projection structure revealed a symmetrical pinwheel-like shape with virtually no depression in the middle of the complex. The other form revealed a propeller-like conformation displaying an obvious hole in the center region, presumably representing the toxin-induced pore. These crystallographic data thus demonstrate for the first time that the 65-kDa activated Cry4Ba toxin in association with lipid membranes could exist in at least two different trimeric conformations, conceivably implying the closed and open states of the pore

  15. HR-MAS MRS of the pancreas reveals reduced lipid and elevated lactate and taurine associated with early pancreatic cancer.

    Science.gov (United States)

    Wang, Alan S; Lodi, Alessia; Rivera, Lee B; Izquierdo-Garcia, Jose L; Firpo, Matthew A; Mulvihill, Sean J; Tempero, Margaret A; Bergers, Gabriele; Ronen, Sabrina M

    2014-11-01

    The prognosis for patients with pancreatic cancer is extremely poor, as evidenced by the disease's five-year survival rate of ~5%. New approaches are therefore urgently needed to improve detection, treatment, and monitoring of pancreatic cancer. MRS-detectable metabolic changes provide useful biomarkers for tumor detection and response-monitoring in other cancers. The goal of this study was to identify MRS-detectable biomarkers of pancreatic cancer that could enhance currently available imaging approaches. We used (1) H high-resolution magic angle spinning MRS to probe metabolite levels in pancreatic tissue samples from mouse models and patients. In mice, the levels of lipids dropped significantly in pancreata with lipopolysaccharide-induced inflammation, in pancreata with pre-cancerous metaplasia (4 week old p48-Cre;LSL-Kras(G12D) mice), and in pancreata with pancreatic intraepithelial neoplasia, which precedes invasive pancreatic cancer (8 week old p48-Cre LSL-Kras(G12D) mice), to 26 ± 19% (p = 0.03), 19 ± 16% (p = 0.04), and 26 ± 10% (p = 0.05) of controls, respectively. Lactate and taurine remained unchanged in inflammation and in pre-cancerous metaplasia but increased significantly in pancreatic intraepithelial neoplasia to 266 ± 61% (p = 0.0001) and 999 ± 174% (p pancreatitis and in invasive cancer biopsies to 29 ± 15% (p = 0.01) and 26 ± 38% (p = 0.02) of normal tissue. In addition, lactate and taurine levels remained unchanged in inflammation but rose in tumor samples to 244 ± 155% (p = 0.02) and 188 ± 67% (p = 0.02), respectively, compared with normal tissue. Based on these findings, we propose that a drop in lipid levels could serve to inform on pancreatitis and cancer-associated inflammation, whereas elevated lactate and taurine could serve to identify the presence of pancreatic intraepithelial neoplasia and invasive tumor. Our findings may help enhance current imaging methods to improve early pancreatic cancer detection and monitoring.

  16. Triplex DNA-binding proteins are associated with clinical outcomes revealed by proteomic measurements in patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Nelson Laura D

    2012-06-01

    with ErbB1, mTOR, PTEN, and Stat5. Western blots confirmed that full-length and truncated beta-catenin expression correlated with U2AF65 expression in tumor extracts. Conclusions Increased triplex DNA-binding activity in vitro correlates with lymph node disease, metastasis, and reduced overall survival in colorectal cancer, and increased U2AF65 expression is associated with total and truncated beta-catenin expression in high-stage colorectal tumors.

  17. An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients

    Directory of Open Access Journals (Sweden)

    Orsia D. Konsta

    2015-08-01

    Full Text Available Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS, a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%, intronic sequences (55.6%, upstream/downstream genic regions (30.5%, and intergenic regions (8.3%. Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak and eQTL characterizes SS risk variants (94.4%. Next, screening SNPs in high linkage disequilibrium (r2 ≥ 0.8 in Caucasians revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells >> A549. Finally, we looked at SS risk variants for histone markers in B cells (GM12878, monocytes (CD14+ and epithelial cells (A548. Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results, that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells such as those observed at the FAM167A-BLK locus.

  18. Rapid frequency scan EPR.

    Science.gov (United States)

    Tseitlin, Mark; Rinard, George A; Quine, Richard W; Eaton, Sandra S; Eaton, Gareth R

    2011-08-01

    In rapid frequency scan EPR with triangular scans, sufficient time must be allowed to insure that the magnetization in the x, y plane decays to baseline at the end of the scan, which typically is about 5T(2) after the spins are excited. To permit relaxation of signals excited toward the extremes of the scan the total scan time required may be much longer than 5T(2). However, with periodic, saw-tooth excitation, the slow-scan EPR spectrum can be recovered by Fourier deconvolution of data recorded with a total scan period of 5T(2), even if some spins are excited later in the scan. This scan time is similar to polyphase excitation methods. The peak power required for either polyphase excitation or rapid frequency scans is substantially smaller than for pulsed EPR. The use of an arbitrary waveform generator (AWG) and cross loop resonator facilitated implementation of the rapid frequency scan experiments reported here. The use of constant continuous low B(1), periodic excitation waveform, and constant external magnetic field is similar to polyphase excitation, but could be implemented without the AWG that is required for polyphase excitation. PMID:21664848

  19. Genome-Wide Association Analysis for Blood Lipid Traits Measured in Three Pig Populations Reveals a Substantial Level of Genetic Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Hui Yang

    Full Text Available Serum lipids are associated with myocardial infarction and cardiovascular disease in humans. Here we dissected the genetic architecture of blood lipid traits by applying genome-wide association studies (GWAS in 1,256 pigs from Laiwu, Erhualian and Duroc × (Landrace × Yorkshire populations, and a meta-analysis of GWAS in more than 2,400 pigs from five diverse populations. A total of 22 genomic loci surpassing the suggestive significance level were detected on 11 pig chromosomes (SSC for six blood lipid traits. Meta-analysis of GWAS identified 5 novel loci associated with blood lipid traits. Comparison of GWAS loci across the tested populations revealed a substantial level of genetic heterogeneity for porcine blood lipid levels. We further evaluated the causality of nine polymorphisms nearby or within the APOB gene on SSC3 for serum LDL-C and TC levels. Of the 9 polymorphisms, an indel showed the most significant association with LDL-C and TC in Laiwu pigs. But the significant association was not identified in the White Duroc × Erhualian F2 resource population, in which the QTL for LDL-C and TC was also detected on SSC3. This indicates that population-specific signals may exist for the SSC3 QTL. Further investigations are warranted to validate this assumption.

  20. Genome-Wide Association Analysis for Blood Lipid Traits Measured in Three Pig Populations Reveals a Substantial Level of Genetic Heterogeneity.

    Science.gov (United States)

    Yang, Hui; Huang, Xiaochang; Zeng, Zhijun; Zhang, Wanchang; Liu, Chenlong; Fang, Shaoming; Huang, Lusheng; Chen, Congying

    2015-01-01

    Serum lipids are associated with myocardial infarction and cardiovascular disease in humans. Here we dissected the genetic architecture of blood lipid traits by applying genome-wide association studies (GWAS) in 1,256 pigs from Laiwu, Erhualian and Duroc × (Landrace × Yorkshire) populations, and a meta-analysis of GWAS in more than 2,400 pigs from five diverse populations. A total of 22 genomic loci surpassing the suggestive significance level were detected on 11 pig chromosomes (SSC) for six blood lipid traits. Meta-analysis of GWAS identified 5 novel loci associated with blood lipid traits. Comparison of GWAS loci across the tested populations revealed a substantial level of genetic heterogeneity for porcine blood lipid levels. We further evaluated the causality of nine polymorphisms nearby or within the APOB gene on SSC3 for serum LDL-C and TC levels. Of the 9 polymorphisms, an indel showed the most significant association with LDL-C and TC in Laiwu pigs. But the significant association was not identified in the White Duroc × Erhualian F2 resource population, in which the QTL for LDL-C and TC was also detected on SSC3. This indicates that population-specific signals may exist for the SSC3 QTL. Further investigations are warranted to validate this assumption.

  1. Line-scanning, stage scanning confocal microscope

    Science.gov (United States)

    Carucci, John A.; Stevenson, Mary; Gareau, Daniel

    2016-03-01

    We created a line-scanning, stage scanning confocal microscope as part of a new procedure: video assisted micrographic surgery (VAMS). The need for rapid pathological assessment of the tissue on the surface of skin excisions very large since there are 3.5 million new skin cancers diagnosed annually in the United States. The new design presented here is a confocal microscope without any scanning optics. Instead, a line is focused in space and the sample, which is flattened, is physically translated such that the line scans across its face in a direction perpendicular to the line its self. The line is 6mm long and the stage is capable of scanning 50 mm, hence the field of view is quite large. The theoretical diffraction-limited resolution is 0.7um lateral and 3.7um axial. However, in this preliminary report, we present initial results that are a factor of 5-7 poorer in resolution. The results are encouraging because they demonstrate that the linear array detector measures sufficient signal from fluorescently labeled tissue and also demonstrate the large field of view achievable with VAMS.

  2. Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation.

    LENUS (Irish Health Repository)

    Murphy, Derek M

    2009-01-01

    BACKGROUND: Neuroblastoma, a cancer derived from precursor cells of the sympathetic nervous system, is a major cause of childhood cancer related deaths. The single most important prognostic indicator of poor clinical outcome in this disease is genomic amplification of MYCN, a member of a family of oncogenic transcription factors. METHODOLOGY: We applied MYCN chromatin immunoprecipitation to microarrays (ChIP-chip) using MYCN amplified\\/non-amplified cell lines as well as a conditional knockdown cell line to determine the distribution of MYCN binding sites within all annotated promoter regions. CONCLUSION: Assessment of E-box usage within consistently positive MYCN binding sites revealed a predominance for the CATGTG motif (p<0.0016), with significant enrichment of additional motifs CATTTG, CATCTG, CAACTG in the MYCN amplified state. For cell lines over-expressing MYCN, gene ontology analysis revealed enrichment for the binding of MYCN at promoter regions of numerous molecular functional groups including DNA helicases and mRNA transcriptional regulation. In order to evaluate MYCN binding with respect to other genomic features, we determined the methylation status of all annotated CpG islands and promoter sequences using methylated DNA immunoprecipitation (MeDIP). The integration of MYCN ChIP-chip and MeDIP data revealed a highly significant positive correlation between MYCN binding and DNA hypermethylation. This association was also detected in regions of hemizygous loss, indicating that the observed association occurs on the same homologue. In summary, these findings suggest that MYCN binding occurs more commonly at CATGTG as opposed to the classic CACGTG E-box motif, and that disease associated over expression of MYCN leads to aberrant binding to additional weaker affinity E-box motifs in neuroblastoma. The co-localization of MYCN binding and DNA hypermethylation further supports the dual role of MYCN, namely that of a classical transcription factor affecting the

  3. Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation.

    Directory of Open Access Journals (Sweden)

    Derek M Murphy

    Full Text Available BACKGROUND: Neuroblastoma, a cancer derived from precursor cells of the sympathetic nervous system, is a major cause of childhood cancer related deaths. The single most important prognostic indicator of poor clinical outcome in this disease is genomic amplification of MYCN, a member of a family of oncogenic transcription factors. METHODOLOGY: We applied MYCN chromatin immunoprecipitation to microarrays (ChIP-chip using MYCN amplified/non-amplified cell lines as well as a conditional knockdown cell line to determine the distribution of MYCN binding sites within all annotated promoter regions. CONCLUSION: Assessment of E-box usage within consistently positive MYCN binding sites revealed a predominance for the CATGTG motif (p<0.0016, with significant enrichment of additional motifs CATTTG, CATCTG, CAACTG in the MYCN amplified state. For cell lines over-expressing MYCN, gene ontology analysis revealed enrichment for the binding of MYCN at promoter regions of numerous molecular functional groups including DNA helicases and mRNA transcriptional regulation. In order to evaluate MYCN binding with respect to other genomic features, we determined the methylation status of all annotated CpG islands and promoter sequences using methylated DNA immunoprecipitation (MeDIP. The integration of MYCN ChIP-chip and MeDIP data revealed a highly significant positive correlation between MYCN binding and DNA hypermethylation. This association was also detected in regions of hemizygous loss, indicating that the observed association occurs on the same homologue. In summary, these findings suggest that MYCN binding occurs more commonly at CATGTG as opposed to the classic CACGTG E-box motif, and that disease associated over expression of MYCN leads to aberrant binding to additional weaker affinity E-box motifs in neuroblastoma. The co-localization of MYCN binding and DNA hypermethylation further supports the dual role of MYCN, namely that of a classical transcription

  4. Analysis of Founder Mutations in Rare Tumors Associated With Hereditary Breast/Ovarian Cancer Reveals a Novel Association of BRCA2 Mutations with Ampulla of Vater Carcinomas.

    Science.gov (United States)

    Pinto, Pedro; Peixoto, Ana; Santos, Catarina; Rocha, Patrícia; Pinto, Carla; Pinheiro, Manuela; Leça, Luís; Martins, Ana Teresa; Ferreira, Verónica; Bartosch, Carla; Teixeira, Manuel R

    2016-01-01

    BRCA1 and BRCA2 mutations are responsible for hereditary breast and ovarian cancer, but they also confer an increased risk for the development of rarer cancers associated with this syndrome, namely, cancer of the pancreas, male breast, peritoneum, and fallopian tube. The objective of this work was to quantify the contribution of the founder mutations BRCA2 c.156_157insAlu and BRCA1 c.3331_3334del for cancer etiology in unselected hospital-based cohorts of Portuguese patients diagnosed with these rarer cancers, by using a strategy that included testing of archival tumor tissue. A total of 102 male breast, 68 pancreatic and 33 peritoneal/fallopian tube carcinoma cases were included in the study. The BRCA2 c.156_157insAlu mutation was observed with a frequency of 7.8% in male breast cancers, 3.0% in peritoneal/fallopian tube cancers, and 1.6% in pancreatic cancers, with estimated total contributions of germline BRCA2 mutations of 14.3%, 5.5%, and 2.8%, respectively. No carriers of the BRCA1 c.3331_3334del mutation were identified. During our study, a patient with an ampulla of Vater carcinoma was incidentally found to carry the BRCA2 c.156_157insAlu mutation, so we decided to test a consecutive series of additional 15 ampullary carcinomas for BRCA1/BRCA2 mutations using a combination of direct founder mutation testing and full gene analysis with next generation sequencing. BRCA2 mutations were observed with a frequency of 14.3% in ampulla of Vater carcinomas. In conclusion, taking into account the implications for both the individuals and their family members, we recommend that patients with these neoplasias should be offered BRCA1/BRCA2 genetic testing and we here show that it is feasible to test for founder mutations in archival tumor tissue. Furthermore, we identified for the first time a high frequency of germline BRCA2 mutations in ampullary cancers. PMID:27532258

  5. Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake

    Directory of Open Access Journals (Sweden)

    Duy Ngoc Do

    2014-09-01

    Full Text Available Residual feed intake (RFI is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs, candidate genes and biological pathways involved in regulating RFI using Genome-wide association (GWA and pathway analyses. A total of 596 Yorkshire boars with phenotypes for two different measures of RFI (RFI1 and 2 and 60k genotypic data was used. Genome-wide association analysis was performed using a univariate mixed model and 12 and 7 SNPs were found to be significantly associated with RFI1 and RFI2, respectively. Several genes such as XIRP2, TTC29, SOGA1, MAS1, GRK5, PROX1, GPR155 and ZFYVE26 were identified as putative candidates for RFI based on their genomic location in the vicinity of these SNPs. Genes located within 50 kilo base pairs of SNPs significantly associated with RFI and RFI2 (q-value ≤ 0.2 were subsequently used for pathway analyses. These analyses were performed by assigning genes to biological pathways and then testing the association of individual pathways with RFI using a Fisher’s exact test. Metabolic pathway was significantly associated with both RFIs. Other biological pathways regulating phagosome, tight junctions, olfactory transduction, and insulin secretion were significantly associated with both RFI traits when relaxed threshold for cut-off p-value was used (p ≤ 0.05. These results implied porcine RFI is regulated by multiple biological mechanisms, although the metabolic processes might be the most important. Olfactory transduction pathway controlling the perception of feed via smell, insulin pathway controlling food intake might be important pathways for RFI. Furthermore, our study revealed key genes and genetic variants that control feed efficiency that could potentially be useful for genetic selection of more feed efficient pigs.

  6. Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene.

    Directory of Open Access Journals (Sweden)

    Matthew P Johnson

    Full Text Available Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10(-7, OR = 1.57; rs12711941, p = 4.26×10(-7, OR = 1.56 satisfied our genome-wide significance threshold (modified Bonferroni p0.92. We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03. We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s.

  7. Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene.

    Science.gov (United States)

    Johnson, Matthew P; Brennecke, Shaun P; East, Christine E; Göring, Harald H H; Kent, Jack W; Dyer, Thomas D; Said, Joanne M; Roten, Linda T; Iversen, Ann-Charlotte; Abraham, Lawrence J; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K

    2012-01-01

    Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10(-7), OR = 1.57; rs12711941, p = 4.26×10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p0.92). We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03). We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s). PMID:22432041

  8. Identification of Nucleolus-Associated Chromatin Domains Reveals a Role for the Nucleolus in 3D Organization of the A. thaliana Genome.

    Science.gov (United States)

    Pontvianne, Frédéric; Carpentier, Marie-Christine; Durut, Nathalie; Pavlištová, Veronika; Jaške, Karin; Schořová, Šárka; Parrinello, Hugues; Rohmer, Marine; Pikaard, Craig S; Fojtová, Miloslava; Fajkus, Jiří; Sáez-Vásquez, Julio

    2016-08-01

    The nucleolus is the site of rRNA gene transcription, rRNA processing, and ribosome biogenesis. However, the nucleolus also plays additional roles in the cell. We isolated nucleoli using fluorescence-activated cell sorting (FACS) and identified nucleolus-associated chromatin domains (NADs) by deep sequencing, comparing wild-type plants and null mutants for the nucleolar protein NUCLEOLIN 1 (NUC1). NADs are primarily genomic regions with heterochromatic signatures and include transposable elements (TEs), sub-telomeric regions, and mostly inactive protein-coding genes. However, NADs also include active rRNA genes and the entire short arm of chromosome 4 adjacent to them. In nuc1 null mutants, which alter rRNA gene expression and overall nucleolar structure, NADs are altered, telomere association with the nucleolus is decreased, and telomeres become shorter. Collectively, our studies reveal roles for NUC1 and the nucleolus in the spatial organization of chromosomes as well as telomere maintenance.

  9. CLEANING ABILITY OF CHLORHEXIDINE GEL AND SODIUM HYPOCHLORITE ASSOCIATED OR NOT WITH EDTA AS ROOT CANAL IRRIGANTS: A SCANNING ELECTRON MICROSCOPY STUDY

    OpenAIRE

    Bruno Carvalho de Vasconcelos; Suyane Maria Luna-Cruz; Gustavo De-Deus; Ivaldo Gomes de Moraes; Claudio Maniglia-Ferreira; Eduardo Diogo Gurgel-Filho

    2007-01-01

    The aim of this study was to evaluate the cleaning efficacy of 2% chlorhexidine gluconate gel (CHX) compared to 2.5% sodium hypochlorite solution (NaOCl) associated or not with 17% EDTA used as irrigants during the biomechanical preparation. Fifty freshly extracted single-rooted human teeth with complete apex formation were randomly divided into five groups: G1 - sterile saline, G2 - 2.5% NaOCl, G3 - 2% CHX, G4 - 2.5% NaOCl + EDTA and G5 - 2% CHX + EDTA. The specimens of G1 were subdivided in...

  10. A trial-by-trial analysis reveals more intense physical activity is associated with better cognitive control performance in attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Hartanto, T A; Krafft, C E; Iosif, A M; Schweitzer, J B

    2016-01-01

    Hyperactivity is a key symptom and the most observable manifestation of attention-deficit/hyperactivity disorder (ADHD). The over-activity associated with ADHD can cause specific challenges in academic settings, extracurricular activities and social relationships. Cognitive control challenges are also well established in ADHD. The current study included 44 children between the ages of 10 and 17 diagnosed with ADHD or who were typically developing (TD), all of whom had no psychiatric co-morbidity or significant learning disorders. Participants wore an actometer on their ankle while performing a flanker paradigm in order to objectively measure their rates of activity in association with cognitive control. Analyses assessed the relationship between frequency and intensity of activity to task accuracy on a trial-by-trial basis. A significant interaction effect between group and performance revealed that more intense movement was associated with better performance in the ADHD group but not in the TD group. The ADHD group demonstrated more intense activity than the TD group during correct (but not error) trials. Within-group, children with ADHD generated higher intensity movements in their correct trials compared to their error trials, whereas the TD group did not demonstrate any within-group differences. These findings suggest that excessive motoric activity associated with clinically significant ADHD symptoms may reflect compensatory efforts to modulate attention and alertness. Future research should systematically explore the relationship between motion in ADHD and how it might be used to improve cognitive performance.

  11. Radionucleotide scanning in osteomyelitis

    International Nuclear Information System (INIS)

    Radionucleotide bone scanning can be an excellent adjunct to the standard radiograph and clinical findings in the diagnosis of osteomyelitis. Bone scans have the ability to detect osteomyelitis far in advance of the standard radiograph. The sequential use of technetium and gallium has been useful in differentiating cellulitis and osteomyelitis. Serial scanning with technetium and gallium may be used to monitor the response of osteomyelitis to antibiotic therapy

  12. Combined Isothermal Titration and Differential Scanning Calorimetry Define Three-State Thermodynamics of fALS-Associated Mutant Apo SOD1 Dimers and an Increased Population of Folded Monomer.

    Science.gov (United States)

    Broom, Helen R; Vassall, Kenrick A; Rumfeldt, Jessica A O; Doyle, Colleen M; Tong, Ming Sze; Bonner, Julia M; Meiering, Elizabeth M

    2016-01-26

    Many proteins are naturally homooligomers, homodimers most frequently. The overall stability of oligomeric proteins may be described in terms of the stability of the constituent monomers and the stability of their association; together, these stabilities determine the populations of different monomer and associated species, which generally have different roles in the function or dysfunction of the protein. Here we show how a new combined calorimetry approach, using isothermal titration calorimetry to define monomer association energetics together with differential scanning calorimetry to measure total energetics of oligomer unfolding, can be used to analyze homodimeric unmetalated (apo) superoxide dismutase (SOD1) and determine the effects on the stability of structurally diverse mutations associated with amyotrophic lateral sclerosis (ALS). Despite being located throughout the protein, all mutations studied weaken the dimer interface, while concomitantly either decreasing or increasing the marginal stability of the monomer. Analysis of the populations of dimer, monomer, and unfolded monomer under physiological conditions of temperature, pH, and protein concentration shows that all mutations promote the formation of folded monomers. These findings may help rationalize the key roles proposed for monomer forms of SOD1 in neurotoxic aggregation in ALS, as well as roles for other forms of SOD1. Thus, the results obtained here provide a valuable approach for the quantitative analysis of homooligomeric protein stabilities, which can be used to elucidate the natural and aberrant roles of different forms of these proteins and to improve methods for predicting protein stabilities.

  13. Differential scanning calorimetry of coal

    Science.gov (United States)

    Gold, P. I.

    1978-01-01

    Differential scanning calorimetry studies performed during the first year of this project demonstrated the occurrence of exothermic reactions associated with the production of volatile matter in or near the plastic region. The temperature and magnitude of the exothermic peak were observed to be strongly affected by the heating rate, sample mass and, to a lesser extent, by sample particle size. Thermal properties also were found to be influenced by oxidation of the coal sample due to weathering effects.

  14. Human 45,X Fibroblast Transcriptome Reveals Distinct Differentially Expressed Genes Including Long Noncoding RNAs Potentially Associated with the Pathophysiology of Turner Syndrome

    Science.gov (United States)

    Patowary, Ashok; Scaria, Vinod; Sivasubbu, Sridhar; Deobagkar, Deepti D.

    2014-01-01

    Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s) in the establishment of Turner syndrome phenotypes. PMID:24932682

  15. Crystal Structure of the Golgi-Associated Human Nα-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation.

    Science.gov (United States)

    Støve, Svein Isungset; Magin, Robert S; Foyn, Håvard; Haug, Bengt Erik; Marmorstein, Ronen; Arnesen, Thomas

    2016-07-01

    N-Terminal acetylation is a common and important protein modification catalyzed by N-terminal acetyltransferases (NATs). Six human NATs (NatA-NatF) contain one catalytic subunit each, Naa10 to Naa60, respectively. In contrast to the ribosome-associated NatA to NatE, NatF/Naa60 specifically associates with Golgi membranes and acetylates transmembrane proteins. To gain insight into the molecular basis for the function of Naa60, we developed an Naa60 bisubstrate CoA-peptide conjugate inhibitor, determined its X-ray structure when bound to CoA and inhibitor, and carried out biochemical experiments. We show that Naa60 adapts an overall fold similar to that of the catalytic subunits of ribosome-associated NATs, but with the addition of two novel elongated loops that play important roles in substrate-specific binding. One of these loops mediates a dimer to monomer transition upon substrate-specific binding. Naa60 employs a catalytic mechanism most similar to Naa50. Collectively, these data reveal the molecular basis for Naa60-specific acetyltransferase activity with implications for its Golgi-specific functions.

  16. Human 45,X fibroblast transcriptome reveals distinct differentially expressed genes including long noncoding RNAs potentially associated with the pathophysiology of Turner syndrome.

    Directory of Open Access Journals (Sweden)

    Shriram N Rajpathak

    Full Text Available Turner syndrome is a chromosomal abnormality characterized by the absence of whole or part of the X chromosome in females. This X aneuploidy condition is associated with a diverse set of clinical phenotypes such as gonadal dysfunction, short stature, osteoporosis and Type II diabetes mellitus, among others. These phenotypes differ in their severity and penetrance among the affected individuals. Haploinsufficiency for a few X linked genes has been associated with some of these disease phenotypes. RNA sequencing can provide valuable insights to understand molecular mechanism of disease process. In the current study, we have analysed the transcriptome profiles of human untransformed 45,X and 46,XX fibroblast cells and identified differential expression of genes in these two karyotypes. Functional analysis revealed that these differentially expressing genes are associated with bone differentiation, glucose metabolism and gonadal development pathways. We also report differential expression of lincRNAs in X monosomic cells. Our observations provide a basis for evaluation of cellular and molecular mechanism(s in the establishment of Turner syndrome phenotypes.

  17. Genome-wide association study reveals novel variants for growth and egg traits in Dongxiang blue-shelled and White Leghorn chickens.

    Science.gov (United States)

    Liao, R; Zhang, X; Chen, Q; Wang, Z; Wang, Q; Yang, C; Pan, Y

    2016-10-01

    This study was designed to investigate the genetic basis of growth and egg traits in Dongxiang blue-shelled chickens and White Leghorn chickens. In this study, we employed a reduced representation sequencing approach called genotyping by genome reducing and sequencing to detect genome-wide SNPs in 252 Dongxiang blue-shelled chickens and 252 White Leghorn chickens. The Dongxiang blue-shelled chicken breed has many specific traits and is characterized by blue-shelled eggs, black plumage, black skin, black bone and black organs. The White Leghorn chicken is an egg-type breed with high productivity. As multibreed genome-wide association studies (GWASs) can improve precision due to less linkage disequilibrium across breeds, a multibreed GWAS was performed with 156 575 SNPs to identify the associated variants underlying growth and egg traits within the two chicken breeds. The analysis revealed 32 SNPs exhibiting a significant genome-wide association with growth and egg traits. Some of the significant SNPs are located in genes that are known to impact growth and egg traits, but nearly half of the significant SNPs are located in genes with unclear functions in chickens. To our knowledge, this is the first multibreed genome-wide report for the genetics of growth and egg traits in the Dongxiang blue-shelled and White Leghorn chickens. PMID:27166871

  18. Pyrosequencing of the bacteria associated with Platygyra carnosus corals with skeletal growth anomalies reveals differences in bacterial community composition in apparently healthy and diseased tissues

    Directory of Open Access Journals (Sweden)

    Jenny Chun-Yee Ng

    2015-10-01

    Full Text Available Corals are rapidly declining globally due to coral diseases. Skeletal growth anomalies (SGA or coral tumors are a group of coral diseases that affect coral reefs worldwide, including Hong Kong waters in the Indo-Pacific region. To better understand how bacterial communities may vary in corals with SGA, for the first time, we examined the bacterial composition associated with the apparently healthy and the diseased tissues of SGA-affected Platgyra carnosus using 16S ribosomal rRNA gene pyrosequencing. Taxonomic analysis revealed Proteobacteria, Bacteroidetes, Cyanobacteria, and Actinobacteria as the main phyla in both the apparently healthy and the diseased tissues. A significant difference in the bacterial community composition was observed between the two conditions at the OTU level. Diseased tissues were associated with higher abundances of Acidobacteria and Gemmatimonadetes, and a lower abundance of Spirochaetes. Several OTUs belonging to Rhodobacteraceae, Rhizobiales, Gammaproteobacteria, and Cytophaga-Flavobacterium-Bacteroidetes (CFB were strongly associated with the diseased tissues. These groups of bacteria may contain potential pathogens involved with the development of SGA or opportunistic secondary or tertiary colonizers that proliferated upon the health-compromised coral host. We suggest that these bacterial groups to be further studied based on inoculation experiments and testing of Koch’s postulates in efforts to understand the etiology and progression of SGA.

  19. 18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scan Findings for Ductal Carcinomas of Breast: Association of Standardized Uptake Value and Histological Findings

    Energy Technology Data Exchange (ETDEWEB)

    Bae, So Young; Lee, Eun Hye [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Park, Jung Mi [Dept. of Nuclear Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of); Kwak, Jeong Ja [Dept. of Pathology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2012-02-15

    To evaluate the factors associated with variations in 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) uptake in ductal carcinomas of the breast. We enrolled 216 ductal carcinoma cases that underwent 18F-FDG PET/CT. We evaluated the positivity and measured peak standardized uptake value (pSUV) of lesions that underwent 18F-FDG PET/CT. We analyzed the correlation between pSUV and invasiveness, lesion size, and the histologic factors of invasive ductal carcinoma (IDC). In the 18F-FDG PET/CT of ductal carcinomas, sensitivity was 90.2%, positive and negative predictive values were 99.5% and 25.0%, respectively. In ductal carcinoma in situ (DCIS) and IDC, the sensitivities were 68.8% and 92.0%, respectively. The mean pSUV of true positive (TP) DCIS and IDC were 2.6 and 5.1 (p < 0.05), respectively, whereas the false negative (FN) were 1.3 and 1.2 (p > 0.05), respectively, and that of false positive (FP) and true negative (TN) lesions were 2.2 and 0.9, respectively. The mean size of TP DCIS and IDC were 4.5 cm and 2.7 cm (p < 0.05), respectively, whereas the mean size of FN DCIS and IDC were 1.5 cm and 1.4 cm (p > 0.05), respectively, and that of FP and TN lesions were 1.8 cm and 1.2 cm respectively. Among the histological factors affecting IDC, mitosis showed the best correlation with pSUV (rho = 0.5). For 18F-FDG PET/CT of ductal carcinomas, the positive predictive value was 99.5% and the FN rate was 9.7%. False negative factors included DCIS and an IDC < 1.5 cm, whereas mitosis was the TP factor.

  20. Getting a CAT Scan

    Medline Plus

    Full Text Available ... Crushes What's a Booger? Getting a CAT Scan (Video) KidsHealth > For Kids > Getting a CAT Scan (Video) Print A A A Text Size en español Obtención de una tomografía computada (video) CAT stands for "computerized axial tomography." Translated, that ...

  1. Getting a CAT Scan

    Medline Plus

    Full Text Available ... Here's Help White House Lunch Recipes Getting a CAT Scan (Video) KidsHealth > For Kids > Getting a CAT Scan (Video) Print A A A Text Size en español Obtención de una tomografía computada (video) CAT stands for "computerized axial tomography." Translated, that means ...

  2. Frequency scanning microstrip antennas

    DEFF Research Database (Denmark)

    Danielsen, Magnus; Jørgensen, Rolf

    1979-01-01

    The principles of using radiating microstrip resonators as elements in a frequency scanning antenna array are described. The resonators are cascade-coupled. This gives a scan of the main lobe due to the phase-shift in the resonator in addition to that created by the transmission line phase...

  3. Abdominal CT scan

    Science.gov (United States)

    ... than regular x-rays. Many x-rays or CT scans over time may increase your risk for cancer. However, the risk from any one scan is small. Talk to your doctor about this risk and the benefit of the test for getting a correct diagnosis ...

  4. Environmental Scanning Report.

    Science.gov (United States)

    Truckee Meadows Community Coll., Sparks, NV.

    This report describes Truckee Meadows Community College's (Nevada) environmental scanning process and results. The college decided that environmental scanning and forecasting techniques should be used to plan for both short-term and long-term external factors that impact programs, enrollment, and budgets. Strategic goals include: (1) keeping pace…

  5. Optical Scanning Applications.

    Science.gov (United States)

    Wagner, Hans

    The successful use of optical scanning at the University of the Pacific (UOP) indicates that such techniques can simplify a number of administrative data processing tasks. Optical scanning is regularly used at UOP to assist with data processing in the areas of admissions, registration and grade reporting and also has applications for other tasks…

  6. Knee CT scan

    Science.gov (United States)

    Risks of CT scans include: Exposure to radiation Allergy to contrast dye CT scans give off more radiation than ... injected contrast dye. The most common type of contrast contains ... you have this an iodine allergy. If you need to have this kind of ...

  7. Getting a CAT Scan

    Medline Plus

    Full Text Available ... Dictionary of Medical Words En Español What Other Kids Are Reading Movie: Digestive System Winter Sports: Sledding, ... Booger? Getting a CAT Scan (Video) KidsHealth > For Kids > Getting a CAT Scan (Video) Print A A ...

  8. Getting a CAT Scan

    Medline Plus

    Full Text Available ... Skiing, Snowboarding, Skating Crushes What's a Booger? Getting a CAT Scan (Video) KidsHealth > For Kids > Getting a CAT Scan (Video) Print A A A Text Size en español Obtención de ...

  9. Getting a CAT Scan

    Medline Plus

    Full Text Available ... Snowboarding, Skating Crushes What's a Booger? Getting a CAT Scan (Video) KidsHealth > For Kids > Getting a CAT Scan (Video) Print A A A Text Size en español Obtención de una tomografía computada (video) CAT stands for "computerized axial tomography." Translated, that means ...

  10. Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Yen Ling Low

    2010-07-01

    Full Text Available Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway, polymorphisms within the pathway have not been consistently associated with these cancers. We posit that this is due to the complexity of multiple weak genetic effects within the metabolic pathway that can only be effectively detected through multi-variant analysis. We conducted a comprehensive association analysis of the estrogen metabolic pathway by interrogating 239 tagSNPs within 35 genes of the pathway in three tumor samples. The discovery sample consisted of 1,596 breast cancer cases, 719 endometrial cancer cases, and 1,730 controls from Sweden; and the validation sample included 2,245 breast cancer cases and 1,287 controls from Finland. We performed admixture maximum likelihood (AML-based global tests to evaluate the cumulative effect from multiple SNPs within the whole metabolic pathway and three sub-pathways for androgen synthesis, androgen-to-estrogen conversion, and estrogen removal. In the discovery sample, although no single polymorphism was significant after correction for multiple testing, the pathway-based AML global test suggested association with both breast (p(global = 0.034 and endometrial (p(global = 0.052 cancers. Further testing revealed the association to be focused on polymorphisms within the androgen-to-estrogen conversion sub-pathway, for both breast (p(global = 0.008 and endometrial cancer (p(global = 0.014. The sub-pathway association was validated in the Finnish sample of breast cancer (p(global = 0.015. Further tumor subtype analysis demonstrated that the association of the androgen-to-estrogen conversion sub-pathway was confined to postmenopausal women with sporadic estrogen receptor positive tumors (p(global = 0.0003. Gene-based AML analysis suggested CYP19A1 and UGT2B4 to be the major players within the sub-pathway. Our study indicates that the composite

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  13. Analyses of expressed sequence tags in Neurospora reveal rapid evolution of genes associated with the early stages of sexual reproduction in fungi

    Directory of Open Access Journals (Sweden)

    Nygren Kristiina

    2012-11-01

    Full Text Available Abstract Background The broadly accepted pattern of rapid evolution of reproductive genes is primarily based on studies of animal systems, although several examples of rapidly evolving genes involved in reproduction are found in diverse additional taxa. In fungi, genes involved in mate recognition have been found to evolve rapidly. However, the examples are too few to draw conclusions on a genome scale. Results In this study, we performed microarray hybridizations between RNA from sexual and vegetative tissues of two strains of the heterothallic (self-sterile filamentous ascomycete Neurospora intermedia, to identify a set of sex-associated genes in this species. We aligned Expressed Sequence Tags (ESTs from sexual and vegetative tissue of N. intermedia to orthologs from three closely related species: N. crassa, N. discreta and N. tetrasperma. The resulting four-species alignments provided a dataset for molecular evolutionary analyses. Our results confirm a general pattern of rapid evolution of fungal sex-associated genes, compared to control genes with constitutive expression or a high relative expression during vegetative growth. Among the rapidly evolving sex-associated genes, we identified candidates that could be of importance for mating or fruiting-body development. Analyses of five of these candidate genes from additional species of heterothallic Neurospora revealed that three of them evolve under positive selection. Conclusions Taken together, our study represents a novel finding of a genome-wide pattern of rapid evolution of sex-associated genes in the fungal kingdom, and provides a list of candidate genes important for reproductive isolation in Neurospora.

  14. Transcriptome meta-analysis reveals a dysregulation in extra cellular matrix and cell junction associated gene signatures during Dengue virus infection

    Science.gov (United States)

    Afroz, Sumbul; Giddaluru, Jeevan; Abbas, Mohd. Manzar; Khan, Nooruddin

    2016-01-01

    Dengue Viruses (DENVs) cause one of the most prevalent arthropod-borne viral diseases affecting millions of people worldwide. Identification of genes involved in DENV pathogenesis would help in deciphering molecular mechanisms responsible for the disease progression. Here, we carried out a meta-analysis of publicly available gene expression data of dengue patients and further validated the meta-profile using in-vitro infection in THP-1 cells. Our findings reveal that DENV infection modulates expression of several genes and signalling pathways including interferons, detoxification of ROS and viral assembly. Interestingly, we have identified novel gene signatures comprising of INADL/PATJ and CRTAP (Cartilage Associated Protein), which were significantly down-regulated across all patient data sets as well as in DENV infected THP-1 cells. PATJ and CRTAP genes are involved in maintaining cell junction integrity and collagen assembly (extracellular matrix component) respectively, which together play a crucial role in cell-cell adhesion. Our results categorically reveal that overexpression of CRTAP and PATJ genes restrict DENV infection, thereby suggesting a critical role of these genes in DENV pathogenesis. Conclusively, these findings emphasize the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease pathogenesis and possibly lead towards the development of better therapeutic interventions. PMID:27651116

  15. Transcriptome meta-analysis reveals a dysregulation in extra cellular matrix and cell junction associated gene signatures during Dengue virus infection.

    Science.gov (United States)

    Afroz, Sumbul; Giddaluru, Jeevan; Abbas, Mohd Manzar; Khan, Nooruddin

    2016-01-01

    Dengue Viruses (DENVs) cause one of the most prevalent arthropod-borne viral diseases affecting millions of people worldwide. Identification of genes involved in DENV pathogenesis would help in deciphering molecular mechanisms responsible for the disease progression. Here, we carried out a meta-analysis of publicly available gene expression data of dengue patients and further validated the meta-profile using in-vitro infection in THP-1 cells. Our findings reveal that DENV infection modulates expression of several genes and signalling pathways including interferons, detoxification of ROS and viral assembly. Interestingly, we have identified novel gene signatures comprising of INADL/PATJ and CRTAP (Cartilage Associated Protein), which were significantly down-regulated across all patient data sets as well as in DENV infected THP-1 cells. PATJ and CRTAP genes are involved in maintaining cell junction integrity and collagen assembly (extracellular matrix component) respectively, which together play a crucial role in cell-cell adhesion. Our results categorically reveal that overexpression of CRTAP and PATJ genes restrict DENV infection, thereby suggesting a critical role of these genes in DENV pathogenesis. Conclusively, these findings emphasize the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease pathogenesis and possibly lead towards the development of better therapeutic interventions. PMID:27651116

  16. Scanning with Iodine-125

    International Nuclear Information System (INIS)

    The use of I125 as I125-iodide for scanning of the thyroid and of thyroid carcinoma métastasés and as I125-labelled Rose Bengal for scanning of the liver has been investigated in our laboratories. In some patients, the thyroid scans and the scans of thyroid carcinoma metastases were repeated with I131. The liver scans were repeated with colloidal Au198. Cold nodules in the thyroid which could not be detected with I131 were clearly seen with I125. Anterior métastasés in the lungs could be differentiated from posterior métastasés with I125, while with I131 this was not possible. Using the same doses of radioactivity the background with I131 was much higher and could not be eliminated, as this would have reduced the counting rate over the lesions to levels which could not be detected. Some of the photoscans and mechanical scans of livers carried out with colloidal Au198 could not be interpreted. However, ''cold'' lesions were clearly seen on the scans of the same livers with I125-labelled Rose Bengal. (author)

  17. Structural context of disease-associated mutations and putative mechanism of autoinhibition revealed by X-ray crystallographic analysis of the EZH2-SET domain.

    Directory of Open Access Journals (Sweden)

    Stephen Antonysamy

    Full Text Available The enhancer-of-zeste homolog 2 (EZH2 gene product is an 87 kDa polycomb group (PcG protein containing a C-terminal methyltransferase SET domain. EZH2, along with binding partners, i.e., EED and SUZ12, upon which it is dependent for activity forms the core of the polycomb repressive complex 2 (PRC2. PRC2 regulates gene silencing by catalyzing the methylation of histone H3 at lysine 27. Both overexpression and mutation of EZH2 are associated with the incidence and aggressiveness of various cancers. The novel crystal structure of the SET domain was determined in order to understand disease-associated EZH2 mutations and derive an explanation for its inactivity independent of complex formation. The 2.00 Å crystal structure reveals that, in its uncomplexed form, the EZH2 C-terminus folds back into the active site blocking engagement with substrate. Furthermore, the S-adenosyl-L-methionine (SAM binding pocket observed in the crystal structure of homologous SET domains is notably absent. This suggests that a conformational change in the EZH2 SET domain, dependent upon complex formation, must take place for cofactor and substrate binding activities to be recapitulated. In addition, the data provide a structural context for clinically significant mutations found in the EZH2 SET domain.

  18. Analysis of the metatranscriptome of microbial communities of an alkaline hot sulfur spring revealed different gene encoding pathway enzymes associated with energy metabolism.

    Science.gov (United States)

    Tripathy, Swetaleena; Padhi, Soumesh Kumar; Mohanty, Sriprakash; Samanta, Mrinal; Maiti, Nikhil Kumar

    2016-07-01

    Alkaline sulfur hot springs notable for their specialized and complex ecosystem powered by geothermal energy are abundantly rich in different chemotrophic and phototrophic thermophilic microorganisms. Survival and adaptation of these organisms in the extreme environment is specifically related to energy metabolism. To gain a better understanding of survival mechanism of the organisms in these ecosystems, we determined the different gene encoding enzymes associated with anaerobic pathways of energy metabolism by applying the metatranscriptomics approach. The analysis of the microbial population of hot sulfur spring revealed the presence of both aerobic and anaerobic organisms indicating dual mode of lifestyle of the community members. Proteobacteria (28.1 %) was the most dominant community. A total of 988 reads were associated with energy metabolism, out of which 33.7 % of the reads were assigned to nitrogen, sulfur, and methane metabolism based on KEGG classification. The major lineages of hot spring communities were linked with the anaerobic pathways. Different gene encoding enzymes (hao, nir, nar, cysH, cysI, acs) showed the involvement of microbial members in nitrification, denitrification, dissimilatory sulfate reduction, and methane generation. This study enhances our understanding of important gene encoding enzymes involved in energy metabolism, required for the survival and adaptation of microbial communities in the hot spring.

  19. Biophysical Studies on BEX3, the p75NTR-Associated Cell Death Executor, Reveal a High-Order Oligomer with Partially Folded Regions.

    Directory of Open Access Journals (Sweden)

    Katia M S Cabral

    Full Text Available BEX3 (Brain Expressed X-linked protein 3 is a member of a mammal-specific placental protein family. Several studies have found the BEX proteins to be associated with neurodegeneration, the cell cycle and cancer. BEX3 has been predicted to be intrinsically disordered and also to represent an intracellular hub for cell signaling. The pro-apoptotic activity of BEX3 in association with a number of additional proteins has been widely supported; however, to the best of our knowledge, very limited data are available on the conformation of any of the members of the BEX family. In this study, we structurally characterized BEX3 using biophysical experimental data. Small angle X-ray scattering and atomic force microscopy revealed that BEX3 forms a specific higher-order oligomer that is consistent with a globular molecule. Solution nuclear magnetic resonance, partial proteinase K digestion, circular dichroism spectroscopy, and fluorescence techniques that were performed on the recombinant protein indicated that the structure of BEX3 is composed of approximately 31% α-helix and 20% β-strand, contains partially folded regions near the N- and C-termini, and a core which is proteolysis-resistant around residues 55-120. The self-oligomerization of BEX3 has been previously reported in cell culture and is consistent with our in vitro data.

  20. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins

    International Nuclear Information System (INIS)

    The norepinephrine transporter (NET) terminates noradrenergic signals by clearing released NE at synapses. NET regulation by receptors and intracellular signaling pathways is supported by a growing list of associated proteins including syntaxin1A, protein phosphatase 2A (PP2A) catalytic subunit (PP2A-C), PICK1, and Hic-5. In the present study, we sought evidence for additional partnerships by mass spectrometry-based analysis of proteins co-immunoprecipitated with human NET (hNET) stably expressed in a mouse noradrenergic neuroblastoma cell line. Our initial proteomic analyses reveal multiple peptides derived from hNET, peptides arising from the mouse PP2A anchoring subunit (PP2A-Ar) and peptides derived from 14-3-3 proteins. We verified physical association of NET with PP2A-Ar via co-immunoprecipitation studies using mouse vas deferens extracts and with 14-3-3 via a fusion pull-down approach, implicating specifically the hNET NH2-terminus for interactions. The transporter complexes described likely support mechanisms regulating transporter activity, localization, and trafficking

  1. Structure of Rhodococcus equi virulence-associated protein B (VapB) reveals an eight-stranded antiparallel β-barrel consisting of two Greek-key motifs

    Energy Technology Data Exchange (ETDEWEB)

    Geerds, Christina [Bielefeld University, Universitaetsstrasse 25, 33615 Bielefeld (Germany); Wohlmann, Jens; Haas, Albert [University of Bonn, Ulrich-Haberland Strasse 61a, 53121 Bonn (Germany); Niemann, Hartmut H., E-mail: hartmut.niemann@uni-bielefeld.de [Bielefeld University, Universitaetsstrasse 25, 33615 Bielefeld (Germany)

    2014-06-18

    The structure of VapB, a member of the Vap protein family that is involved in virulence of the bacterial pathogen R. equi, was determined by SAD phasing and reveals an eight-stranded antiparallel β-barrel similar to avidin, suggestive of a binding function. Made up of two Greek-key motifs, the topology of VapB is unusual or even unique. Members of the virulence-associated protein (Vap) family from the pathogen Rhodococcus equi regulate virulence in an unknown manner. They do not share recognizable sequence homology with any protein of known structure. VapB and VapA are normally associated with isolates from pigs and horses, respectively. To contribute to a molecular understanding of Vap function, the crystal structure of a protease-resistant VapB fragment was determined at 1.4 Å resolution. The structure was solved by SAD phasing employing the anomalous signal of one endogenous S atom and two bound Co ions with low occupancy. VapB is an eight-stranded antiparallel β-barrel with a single helix. Structural similarity to avidins suggests a potential binding function. Unlike other eight- or ten-stranded β-barrels found in avidins, bacterial outer membrane proteins, fatty-acid-binding proteins and lysozyme inhibitors, Vaps do not have a next-neighbour arrangement but consist of two Greek-key motifs with strand order 41238567, suggesting an unusual or even unique topology.

  2. Scan path entropy and Arrow plots: Capturing scanning behavior of multiple observers

    Directory of Open Access Journals (Sweden)

    Ignace T C Hooge

    2013-12-01

    Full Text Available Designers of visual communication material want their material to attract and retain attention. In marketing research, heat maps, dwell time, and time to AOI first hit are often used as evaluation parameters. Here we present two additional measures 1 scan path entropy to quantify gaze guidance and 2 the arrow plot to visualize the average scan path. Both are based on string representations of scan paths. The latter also incorporates transition matrices and time required for 50% of the observers to first hit AOIs (T50. The new measures were tested in an eye tracking study (48 observers, 39 advertisements. Scan path entropy is a sensible measure for gaze guidance and the new visualization method reveals aspects of the average scan path and gives a better indication in what order global scanning takes place.

  3. Scan path entropy and arrow plots: capturing scanning behavior of multiple observers.

    Science.gov (United States)

    Hooge, Ignace; Camps, Guido

    2013-01-01

    Designers of visual communication material want their material to attract and retain attention. In marketing research, heat maps, dwell time, and time to AOI first hit are often used as evaluation parameters. Here we present two additional measures (1) "scan path entropy" to quantify gaze guidance and (2) the "arrow plot" to visualize the average scan path. Both are based on string representations of scan paths. The latter also incorporates transition matrices and time required for 50% of the observers to first hit AOIs (T50). The new measures were tested in an eye tracking study (48 observers, 39 advertisements). Scan path entropy is a sensible measure for gaze guidance and the new visualization method reveals aspects of the average scan path and gives a better indication in what order global scanning takes place. PMID:24399993

  4. Revealing mechanisms of selective, concentration-dependent potentials of 4-hydroxy-2-nonenal to induce apoptosis in cancer cells through inactivation of membrane-associated catalase.

    Science.gov (United States)

    Bauer, Georg; Zarkovic, Neven

    2015-04-01

    Tumor cells generate extracellular superoxide anions and are protected against superoxide anion-mediated intercellular apoptosis-inducing signaling by the expression of membrane-associated catalase. 4-Hydroxy-2-nonenal (4-HNE), a versatile second messenger generated during lipid peroxidation, has been shown to induce apoptosis selectively in malignant cells. The findings described in this paper reveal the strong, concentration-dependent potential of 4-HNE to specifically inactivate extracellular catalase of tumor cells both indirectly and directly and to consequently trigger apoptosis in malignant cells through superoxide anion-mediated intercellular apoptosis-inducing signaling. Namely, 4-HNE caused apoptosis selectively in NOX1-expressing tumor cells through inactivation of their membrane-associated catalase, thus reactivating subsequent intercellular signaling through the NO/peroxynitrite and HOCl pathways, followed by the mitochondrial pathway of apoptosis. Concentrations of 4-HNE of 1.2 µM and higher directly inactivated membrane-associated catalase of tumor cells, whereas at lower concentrations, 4-HNE triggered a complex amplificatory pathway based on initial singlet oxygen formation through H2O2 and peroxynitrite interaction. Singlet-oxygen-dependent activation of the FAS receptor and caspase-8 increased superoxide anion generation by NOX1 and amplification of singlet oxygen generation, which allowed singlet-oxygen-dependent inactivation of catalase. 4-HNE and singlet oxygen cooperate in complex autoamplificatory loops during this process. The finding of these novel anticancer pathways may be useful for understanding the role of 4-HNE in the control of malignant cells and for the optimization of ROS-dependent therapeutic approaches including antioxidant treatments.

  5. Association analyses of large-scale glycan microarray data reveal novel host-specific substructures in influenza A virus binding glycans

    Science.gov (United States)

    Zhao, Nan; Martin, Brigitte E.; Yang, Chun-Kai; Luo, Feng; Wan, Xiu-Feng

    2015-10-01

    Influenza A viruses can infect a wide variety of animal species and, occasionally, humans. Infection occurs through the binding formed by viral surface glycoprotein hemagglutinin and certain types of glycan receptors on host cell membranes. Studies have shown that the α2,3-linked sialic acid motif (SA2,3Gal) in avian, equine, and canine species; the α2,6-linked sialic acid motif (SA2,6Gal) in humans; and SA2,3Gal and SA2,6Gal in swine are responsible for the corresponding host tropisms. However, more detailed and refined substructures that determine host tropisms are still not clear. Thus, in this study, we applied association mining on a set of glycan microarray data for 211 influenza viruses from five host groups: humans, swine, canine, migratory waterfowl, and terrestrial birds. The results suggest that besides Neu5Acα2-6Galβ, human-origin viruses could bind glycans with Neu5Acα2-8Neu5Acα2-8Neu5Ac and Neu5Gcα2-6Galβ1-4GlcNAc substructures; Galβ and GlcNAcβ terminal substructures, without sialic acid branches, were associated with the binding of human-, swine-, and avian-origin viruses; sulfated Neu5Acα2-3 substructures were associated with the binding of human- and swine-origin viruses. Finally, through three-dimensional structure characterization, we revealed that the role of glycan chain shapes is more important than that of torsion angles or of overall structural similarities in virus host tropisms.

  6. A large cohort study reveals the association of elevated peripheral blood lymphocyte-to-monocyte ratio with favorable prognosis in nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available BACKGROUND: Nasopharyngeal carcinoma (NPC is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20-30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients. METHODS: A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS, disease-free survival (DFS, distant metastasis-free survival (DMFS and loco-regional recurrence-free survival (LRRFS, respectively. RESULTS: Univariate analysis revealed that higher LMR level (≥ 5.220 was significantly associated with superior OS, DFS and DMFS (P values <0.001. The higher lymphocyte count (≥ 2.145 × 10(9/L was significantly associated with better OS (P = 0.002 and DMFS (P = 0.031, respectively, while the lower monocyte count (<0.475 × 10(9/L was associated with better OS (P = 0.012, DFS (P = 0.011 and DMFS (P = 0.003, respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.558, 95% confidence interval or 95% CI = 0.417-0.748; P<0.001, DFS (HR = 0.669, 95% CI = 0.535-0.838; P<0.001 and DMFS (HR = 0.543, 95% CI = 0.403-0.732; P<0.001, respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053 and DMFS (P = 0.080. CONCLUSIONS: The

  7. The conical scan radiometer

    Science.gov (United States)

    Prosch, T.; Hennings, D.

    1982-07-01

    A satellite-borne conical scan radiometer (CSR) is proposed, offering multiangular and multispectral measurements of Earth radiation fields, including the total radiances, which are not available from conventional radiometers. Advantages of the CSR for meteorological studies are discussed. In comparison to conventional cross track scanning instruments, the CSR is unique with respect to the selected picture element size which is kept constant by means of a specially shaped detector matrix at all scan angles. The conical scan mode offers the chance to improve angular sampling. Angular sampling gaps of previous satellite-borne radiometers can be interpolated and complemented by CSR data. Radiances are measured through 10 radiometric channels which are selected to study cloudiness, water vapor, ozone, surface albedo, ground and mean stratospheric temperature, and aerosols.

  8. Pediatric CT Scans

    Science.gov (United States)

    The Radiation Epidemiology Branch and collaborators have initiated a retrospective cohort study to evaluate the relationship between radiation exposure from CT scans conducted during childhood and adolescence and the subsequent development of cancer.

  9. Pelvic CT scan

    Science.gov (United States)

    ... Abscess (collection of pus) Bladder stones Broken bone Cancer Diverticulitis ... scans over time may increase your risk of cancer. But the risk from any ... to contrast dye. Let your provider know if you have ever ...

  10. Sinus CT scan

    Science.gov (United States)

    ... may be due to: Birth defects Bone fractures Cancer Polyps in the sinuses Sinus infection (sinusitis) ... scans over time may increase your risk for cancer. However, the risk ... to contrast dye. Let your provider know if you have ever ...

  11. Improving diagnosis of appendicitis. Early autologous leukocyte scanning.

    Science.gov (United States)

    DeLaney, A R; Raviola, C A; Weber, P N; McDonald, P T; Navarro, D A; Jasko, I

    1989-10-01

    A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of apendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging111 In oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.

  12. Seismic scanning tunneling macroscope - Theory

    KAUST Repository

    Schuster, Gerard T.

    2012-09-01

    We propose a seismic scanning tunneling macroscope (SSTM) that can detect the presence of sub-wavelength scatterers in the near-field of either the source or the receivers. Analytic formulas for the time reverse mirror (TRM) profile associated with a single scatterer model show that the spatial resolution limit to be, unlike the Abbe limit of λ/2, independent of wavelength and linearly proportional to the source-scatterer separation as long as the point scatterer is in the near-field region; if the sub-wavelength scatterer is a spherical impedance discontinuity then the resolution will also be limited by the radius of the sphere. Therefore, superresolution imaging can be achieved as the scatterer approaches the source. This is analogous to an optical scanning tunneling microscope that has sub-wavelength resolution. Scaled to seismic frequencies, it is theoretically possible to extract 100 Hz information from 20 Hz data by imaging of near-field seismic energy.

  13. Scanning ultrafast electron microscopy

    OpenAIRE

    Yang, Ding-Shyue; Mohammed, Omar F.; Zewail, Ahmed H.

    2010-01-01

    Progress has been made in the development of four-dimensional ultrafast electron microscopy, which enables space-time imaging of structural dynamics in the condensed phase. In ultrafast electron microscopy, the electrons are accelerated, typically to 200 keV, and the microscope operates in the transmission mode. Here, we report the development of scanning ultrafast electron microscopy using a field-emission-source configuration. Scanning of pulses is made in the single-electron mode, for whic...

  14. Advanced Network Scanning

    Directory of Open Access Journals (Sweden)

    Ashiqur Rahman

    2016-07-01

    Full Text Available Network scanning is à procedure for identifying active hosts on a network, either for the purpose of attacking them or for network security assessment. Scanning procedures, such as ping sweeps and port scans, return information about which IP addresses map to live hosts that are active on the Internet and what services they offer. Another scanning method, inverse mapping, returns information about what IP addresses do not map to live hosts; this enables an attacker to make assumptions about viable addresses. Scanning is one of three components of intelligence gathering for an attacker. In the foot printing phase, the attacker creates a profile of the target organization, with information such as its domain name system (DNS and e-mail servers, and its IP address range. Most of this information is available online. In the scanning phase, the attacker finds information about the specific IP addresses that can be accessed over the Internet, their operating systems, the system architecture, and the services running on each computer. In the enumeration phase, the attacker gathers information such as network user and group names, routing tables, and Simple Network Management Protocol (SNMP data

  15. The deoxyhypusine synthase mutant dys1-1 reveals the association of eIF5A and Asc1 with cell wall integrity.

    Directory of Open Access Journals (Sweden)

    Fabio Carrilho Galvão

    Full Text Available The putative eukaryotic translation initiation factor 5A (eIF5A is a highly conserved protein among archaea and eukaryotes that has recently been implicated in the elongation step of translation. eIF5A undergoes an essential and conserved posttranslational modification at a specific lysine to generate the residue hypusine. The enzymes deoxyhypusine synthase (Dys1 and deoxyhypusine hydroxylase (Lia1 catalyze this two-step modification process. Although several Saccharomyces cerevisiae eIF5A mutants have importantly contributed to the study of eIF5A function, no conditional mutant of Dys1 has been described so far. In this study, we generated and characterized the dys1-1 mutant, which showed a strong depletion of mutated Dys1 protein, resulting in more than 2-fold decrease in hypusine levels relative to the wild type. The dys1-1 mutant demonstrated a defect in total protein synthesis, a defect in polysome profile indicative of a translation elongation defect and a reduced association of eIF5A with polysomes. The growth phenotype of dys1-1 mutant is severe, growing only in the presence of 1 M sorbitol, an osmotic stabilizer. Although this phenotype is characteristic of Pkc1 cell wall integrity mutants, the sorbitol requirement from dys1-1 is not associated with cell lysis. We observed that the dys1-1 genetically interacts with the sole yeast protein kinase C (Pkc1 and Asc1, a component of the 40S ribosomal subunit. The dys1-1 mutant was synthetically lethal in combination with asc1Δ and overexpression of TIF51A (eIF5A or DYS1 is toxic for an asc1Δ strain. Moreover, eIF5A is more associated with translating ribosomes in the absence of Asc1 in the cell. Finally, analysis of the sensitivity to cell wall-perturbing compounds revealed a more similar behavior of the dys1-1 and asc1Δ mutants in comparison with the pkc1Δ mutant. These data suggest a correlated role for eIF5A and Asc1 in coordinating the translational control of a subset of m

  16. Lung Ventilation/Perfusion Scan

    Science.gov (United States)

    ... two types of scans: ventilation and perfusion. The ventilation scan shows where air flows in your lungs. The perfusion scan shows where blood flows in your lungs. Both scans use radioisotopes (a low-risk radioactive substance). For the ventilation scan, you ...

  17. Scanning Probe Microscopy and Spectroscopy

    Science.gov (United States)

    Wiesendanger, Roland

    1994-09-01

    Preface; List of acronyms; Introduction; Part I. Experimental Methods and Theoretical Background of Scanning Probe Microscopy and Spectroscopy: 1. Scanning tunnelling microscopy; 2. Scanning force microscopy; 3. Related scanning probe techniques; Part II. Applications of Scanning Probe Microscopy and Spectroscopy: 4. Condensed matter physics; 5. Chemistry; 6. Organic materials; 7. Metrology and standards; 8. Nanotechnology; References; Index.

  18. In silico genomic analyses reveal three distinct lineages of Escherichia coli O157:H7, one of which is associated with hyper-virulence

    Directory of Open Access Journals (Sweden)

    Karmali Mohamed A

    2009-06-01

    Full Text Available Abstract Background Many approaches have been used to study the evolution, population structure and genetic diversity of Escherichia coli O157:H7; however, observations made with different genotyping systems are not easily relatable to each other. Three genetic lineages of E. coli O157:H7 designated I, II and I/II have been identified using octamer-based genome scanning and microarray comparative genomic hybridization (mCGH. Each lineage contains significant phenotypic differences, with lineage I strains being the most commonly associated with human infections. Similarly, a clade of hyper-virulent O157:H7 strains implicated in the 2006 spinach and lettuce outbreaks has been defined using single-nucleotide polymorphism (SNP typing. In this study an in silico comparison of six different genotyping approaches was performed on 19 E. coli genome sequences from 17 O157:H7 strains and single O145:NM and K12 MG1655 strains to provide an overall picture of diversity of the E. coli O157:H7 population, and to compare genotyping methods for O157:H7 strains. Results In silico determination of lineage, Shiga-toxin bacteriophage integration site, comparative genomic fingerprint, mCGH profile, novel region distribution profile, SNP type and multi-locus variable number tandem repeat analysis type was performed and a supernetwork based on the combination of these methods was produced. This supernetwork showed three distinct clusters of strains that were O157:H7 lineage-specific, with the SNP-based hyper-virulent clade 8 synonymous with O157:H7 lineage I/II. Lineage I/II/clade 8 strains clustered closest on the supernetwork to E. coli K12 and E. coli O55:H7, O145:NM and sorbitol-fermenting O157 strains. Conclusion The results of this study highlight the similarities in relationships derived from multi-locus genome sampling methods and suggest a "common genotyping language" may be devised for population genetics and epidemiological studies. Future genotyping

  19. Discovery and targeted LC-MS/MS of purified polerovirus reveals differences in the virus-host interactome associated with altered aphid transmission.

    Directory of Open Access Journals (Sweden)

    Michelle Cilia

    Full Text Available Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV, requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions.

  20. Discovery and targeted LC-MS/MS of purified polerovirus reveals differences in the virus-host interactome associated with altered aphid transmission.

    Science.gov (United States)

    Cilia, Michelle; Peter, Kari A; Bereman, Michael S; Howe, Kevin; Fish, Tara; Smith, Dawn; Gildow, Fredrick; MacCoss, Michael J; Thannhauser, Theodore W; Gray, Stewart M

    2012-01-01

    Circulative transmission of viruses in the Luteoviridae, such as cereal yellow dwarf virus (CYDV), requires a series of precisely orchestrated interactions between virus, plant, and aphid proteins. Natural selection has favored these viruses to be retained in the phloem to facilitate acquisition and transmission by aphids. We show that treatment of infected oat tissue homogenate with sodium sulfite reduces transmission of the purified virus by aphids. Transmission electron microscopy data indicated no gross change in virion morphology due to treatments. However, treated virions were not acquired by aphids through the hindgut epithelial cells and were not transmitted when injected directly into the hemocoel. Analysis of virus preparations using nanoflow liquid chromatography coupled to tandem mass spectrometry revealed a number of host plant proteins co-purifying with viruses, some of which were lost following sodium sulfite treatment. Using targeted mass spectrometry, we show data suggesting that several of the virus-associated host plant proteins accumulated to higher levels in aphids that were fed on CYDV-infected plants compared to healthy plants. We propose two hypotheses to explain these observations, and these are not mutually exclusive: (a) that sodium sulfite treatment disrupts critical virion-host protein interactions required for aphid transmission, or (b) that host infection with CYDV modulates phloem protein expression in a way that is favorable for virus uptake by aphids. Importantly, the genes coding for the plant proteins associated with virus may be examined as targets in breeding cereal crops for new modes of virus resistance that disrupt phloem-virus or aphid-virus interactions. PMID:23118947

  1. Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Arianna Aricò

    Full Text Available Canine Diffuse Large B-cell Lymphoma (cDLBCL is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs by high-resolution array comparative genomic hybridization (aCGH in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30% were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%. In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL.

  2. Molecular dynamics simulation of human serum paraoxonase 1 in DPPC bilayer reveals a critical role of transmembrane helix H1 for HDL association.

    Science.gov (United States)

    Patra, Mahesh Chandra; Rath, Surya Narayan; Pradhan, Sukanta Kumar; Maharana, Jitendra; De, Sachinandan

    2014-01-01

    Serum paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-bound mammalian enzyme exhibiting antiatherosclerotic activity. Despite years of research, an accurate model for the binding interaction between PON1 and HDL has not been established. However, it is reported that anchoring of PON1 to HDL is mainly governed by an N-terminal alpha helix H1 and another short helix H2. Here, we studied the molecular association of full-length human PON1 (huPON1) with a HDL-mimetic dipalmitoylphosphatidylcholine (DPPC) bilayer using homology modeling and molecular dynamics simulations. Our results indicate that H1 is the highly dynamic part of huPON1, showing clockwise rotation of up to 30° within the DPPC bilayer. However, without phospholipid molecules, H1 experiences helical distortions, illustrating an incompatible HDL-anchoring conformation. Snorkeling interactions of K3, R18, and R27 together with aromatic locks formed by Y187, Y190, W194, and W202 are highly essential for anchoring of huPON1 to HDL's surface. Molecular mechanics/Poisson-Boltzmann solvent-accessible surface area (MM/PBSA) binding free energy calculation revealed that H1 displays greater binding affinity towards lipid molecules compared with H2 and H3, suggesting that H1 is the most probable HDL-binding domain of PON1. Binding free energy decomposition showed that K3, R18, and R27 interact with polar headgroups of DPPC membrane through electrostatic interaction. Moreover, Y187, Y190, W194, and W202 interact with DPPC lipids mainly through van der Waals interaction. Taken together, these results show that the transmembrane helix H1 along with the interfacial positively charged and aromatic resides were crucial for PON1's association with HDL particle. The current study will be useful towards understanding the antiatherosclerotic and bioscavenging properties of this promiscuous enzyme. PMID:24297451

  3. Proteomic Dissection of Endosperm Starch Granule Associated Proteins Reveals a Network Coordinating Starch Biosynthesis and Amino Acid Metabolism and Glycolysis in Rice Endosperms

    Science.gov (United States)

    Yu, Huatao; Wang, Tai

    2016-01-01

    Starch biosynthesis and starch granule packaging in cereal endosperms involve a coordinated action of starch biosynthesis enzymes and coordination with other metabolisms. Because directly binding to starch granules, starch granule-associated proteins (SGAPs) are essential to understand the underlying mechanisms, however the information on SGAPs remains largely unknown. Here, we dissected developmentally changed SGAPs from developing rice endosperms from 10 to 20 days after flowering (DAF). Starch granule packaging was not completed at 10 DAF, and was finished in the central endosperm at 15 DAF and in the whole endosperm at 20 DAF. Proteomic analysis with two-dimensional differential in-gel electrophoresis and mass spectrometry revealed 115 developmentally changed SGAPs, representing 37 unique proteins. 65% of the unique proteins had isoforms. 39% of the identified SGAPs were involved in starch biosynthesis with main functions in polyglucan elongation and granule structure trimming. Almost all proteins involved in starch biosynthesis, amino acid biosynthesis, glycolysis, protein folding, and PPDK pathways increased abundance as the endosperm developed, and were predicted in an interaction network. The network represents an important mechanism to orchestrate carbon partitioning among starch biosynthesis, amino acid biosynthesis and glycolysis for efficient starch and protein storage. These results provide novel insights into mechanisms of starch biosynthesis and its coordination with amino acid metabolisms and glycolysis in cereal endosperms. PMID:27252723

  4. Transcriptome analysis of the couch potato (CPO) protein reveals an expression pattern associated with early development in the salmon louse Caligus rogercresseyi.

    Science.gov (United States)

    Gallardo-Escárate, Cristian; Valenzuela-Muñoz, Valentina; Nuñez-Acuña, Gustavo; Chávez-Mardones, Jacqueline; Maldonado-Aguayo, Waleska

    2014-02-15

    The couch potato (CPO) protein is a key biomolecule involved in regulating diapause through the RNA-binding process of the peripheral and central nervous systems in insects and also recently discovered in a few crustacean species. As such, ectoparasitic copepods are interesting model species that have no evidence of developmental arrest. The present study is the first to report on the cloning of a putative CPO gene from the salmon louse Caligus rogercresseyi (CrCPO), as identified by high-throughput transcriptome sequencing. In addition, the transcription expression in larvae and adults was evaluated using quantitative real-time PCR. The CrCPO cDNA sequence showed 3261 base pairs (bp), consisting of 713bp of 5' UTR, 1741bp of 3' UTR, and an open reading frame of 807bp encoding for 268 amino acids. The highly conserved RNA binding regions RNP2 (LFVSGL) and RNP1 (SPVGFVTF), as well the dimerization site (LEF), were also found. Furthermore, eight single nucleotide polymorphisms located in the untranslated regions and one located in the coding region were detected. Gene transcription analysis revealed that CrCPO has ubiquitous expression across larval stages and in adult individuals, with the highest expression from nauplius to copepodid stages. The present study suggests a putative biological function of CrCPO associated with the development of the nervous system in salmon lice and contributes molecular evidence for candidate genes related to host-parasite interactions. PMID:24342663

  5. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

    Science.gov (United States)

    Heid, Iris M; Jackson, Anne U; Randall, Joshua C; Winkler, Thomas W; Qi, Lu; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Zillikens, M Carola; Speliotes, Elizabeth K; Mägi, Reedik; Workalemahu, Tsegaselassie; White, Charles C; Bouatia-Naji, Nabila; Harris, Tamara B; Berndt, Sonja I; Ingelsson, Erik; Willer, Cristen J; Weedon, Michael N; Luan, Jian’An; Vedantam, Sailaja; Esko, Tõnu; Kilpeläinen, Tuomas O; Kutalik, Zoltán; Li, Shengxu; Monda, Keri L; Dixon, Anna L; Holmes, Christopher C; Kaplan, Lee M; Liang, Liming; Min, Josine L; Moffatt, Miriam F; Molony, Cliona; Nicholson, George; Schadt, Eric E; Zondervan, Krina T; Feitosa, Mary F; Ferreira, Teresa; Allen, Hana Lango; Weyant, Robert J; Wheeler, Eleanor; Wood, Andrew R; Estrada, Karol; Goddard, Michael E; Lettre, Guillaume; Mangino, Massimo; Nyholt, Dale R; Purcell, Shaun; Smith, Albert Vernon; Visscher, Peter M; Yang, Jian; McCarroll, Steven A; Nemesh, James; Voight, Benjamin F; Absher, Devin; Amin, Najaf; Aspelund, Thor; Coin, Lachlan; Glazer, Nicole L; Hayward, Caroline; Heard-costa, Nancy L; Hottenga, Jouke-Jan; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kapur, Karen; Ketkar, Shamika; Knowles, Joshua W; Kraft, Peter; Kraja, Aldi T; Lamina, Claudia; Leitzmann, Michael F; McKnight, Barbara; Morris, Andrew P; Ong, Ken K; Perry, John R B; Peters, Marjolein J; Polasek, Ozren; Prokopenko, Inga; Rayner, Nigel W; Ripatti, Samuli; Rivadeneira, Fernando; Robertson, Neil R; Sanna, Serena; Sovio, Ulla; Surakka, Ida; Teumer, Alexander; van Wingerden, Sophie; Vitart, Veronique; Zhao, Jing Hua; Cavalcanti-Proença, Christine; Chines, Peter S; Fisher, Eva; Kulzer, Jennifer R; Lecoeur, Cecile; Narisu, Narisu; Sandholt, Camilla; Scott, Laura J; Silander, Kaisa; Stark, Klaus; Tammesoo, Mari-Liis; Teslovich, Tanya M; Timpson, Nicholas John; Watanabe, Richard M; Welch, Ryan; Chasman, Daniel I; Cooper, Matthew N; Jansson, John-Olov; Kettunen, Johannes; Lawrence, Robert W; Pellikka, Niina; Perola, Markus; Vandenput, Liesbeth; Alavere, Helene; Almgren, Peter; Atwood, Larry D; Bennett, Amanda J; Biffar, Reiner; Bonnycastle, Lori L; Bornstein, Stefan R; Buchanan, Thomas A; Campbell, Harry; Day, Ian N M; Dei, Mariano; Dörr, Marcus; Elliott, Paul; Erdos, Michael R; Eriksson, Johan G; Freimer, Nelson B; Fu, Mao; Gaget, Stefan; Geus, Eco J C; Gjesing, Anette P; Grallert, Harald; Gräßler, Jürgen; Groves, Christopher J; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Havulinna, Aki S; Herzig, Karl-Heinz; Hicks, Andrew A; Hui, Jennie; Igl, Wilmar; Jousilahti, Pekka; Jula, Antti; Kajantie, Eero; Kinnunen, Leena; Kolcic, Ivana; Koskinen, Seppo; Kovacs, Peter; Kroemer, Heyo K; Krzelj, Vjekoslav; Kuusisto, Johanna; Kvaloy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lathrop, G Mark; Lokki, Marja-Liisa; Luben, Robert N; Ludwig, Barbara; McArdle, Wendy L; McCarthy, Anne; Morken, Mario A; Nelis, Mari; Neville, Matt J; Paré, Guillaume; Parker, Alex N; Peden, John F; Pichler, Irene; Pietiläinen, Kirsi H; Platou, Carl G P; Pouta, Anneli; Ridderstråle, Martin; Samani, Nilesh J; Saramies, Jouko; Sinisalo, Juha; Smit, Jan H; Strawbridge, Rona J; Stringham, Heather M; Swift, Amy J; Teder-Laving, Maris; Thomson, Brian; Usala, Gianluca; van Meurs, Joyce B J; van Ommen, Gert-Jan; Vatin, Vincent; Volpato, Claudia B; Wallaschofski, Henri; Walters, G Bragi; Widen, Elisabeth; Wild, Sarah H; Willemsen, Gonneke; Witte, Daniel R; Zgaga, Lina; Zitting, Paavo; Beilby, John P; James, Alan L; Kähönen, Mika; Lehtimäki, Terho; Nieminen, Markku S; Ohlsson, Claes; Palmer, Lyle J; Raitakari, Olli; Ridker, Paul M; Stumvoll, Michael; Tönjes, Anke; Viikari, Jorma; Balkau, Beverley; Ben-Shlomo, Yoav; Bergman, Richard N; Boeing, Heiner; Smith, George Davey; Ebrahim, Shah; Froguel, Philippe; Hansen, Torben; Hengstenberg, Christian; Hveem, Kristian; Isomaa, Bo; Jørgensen, Torben; Karpe, Fredrik; Khaw, Kay-Tee; Laakso, Markku; Lawlor, Debbie A; Marre, Michel; Meitinger, Thomas; Metspalu, Andres; Midthjell, Kristian; Pedersen, Oluf; Salomaa, Veikko; Schwarz, Peter E H; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Valle, Timo T; Wareham, Nicholas J; Arnold, Alice M; Beckmann, Jacques S; Bergmann, Sven; Boerwinkle, Eric; Boomsma, Dorret I; Caulfield, Mark J; Collins, Francis S; Eiriksdottir, Gudny; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Hattersley, Andrew T; Hofman, Albert; Hu, Frank B; Illig, Thomas; Iribarren, Carlos; Jarvelin, Marjo-Riitta; Kao, W H Linda; Kaprio, Jaakko; Launer, Lenore J

    2011-01-01

    Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. PMID:20935629

  6. Crystal Structure of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated Csn2 Protein Revealed Ca[superscript 2+]-dependent Double-stranded DNA Binding Activity

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong (Cornell); (NWU)

    2012-05-22

    Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 {angstrom} tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is {approx}26 {angstrom} wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an {alpha}/{beta} domain and an {alpha}-helical domain; significant hinge motion was observed between these two domains. Ca{sup 2+} was located at strategic positions in the oligomerization interface. We further showed that removal of Ca{sup 2+} ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca{sup 2+} ions.

  7. Crystal structure of clustered regularly interspaced short palindromic repeats (CRISPR)-associated Csn2 protein revealed Ca2+-dependent double-stranded DNA binding activity.

    Science.gov (United States)

    Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong

    2011-09-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 Å tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is ∼26 Å wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an α/β domain and an α-helical domain; significant hinge motion was observed between these two domains. Ca(2+) was located at strategic positions in the oligomerization interface. We further showed that removal of Ca(2+) ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptati