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Sample records for variable igk-v gene

  1. Genetic variability of the equine casein genes.

    Science.gov (United States)

    Brinkmann, J; Jagannathan, V; Drögemüller, C; Rieder, S; Leeb, T; Thaller, G; Tetens, J

    2016-07-01

    The casein genes are known to be highly variable in typical dairy species, such as cattle and goat, but the knowledge about equine casein genes is limited. Nevertheless, mare milk production and consumption is gaining importance because of its high nutritive value, use in naturopathy, and hypoallergenic properties with respect to cow milk protein allergies. In the current study, the open reading frames of the 4 casein genes CSN1S1 (αS1-casein), CSN2 (β-casein), CSN1S2 (αS2-casein), and CSN3 (κ-casein) were resequenced in 253 horses of 14 breeds. The analysis revealed 21 nonsynonymous nucleotide exchanges, as well as 11 synonymous nucleotide exchanges, leading to a total of 31 putative protein isoforms predicted at the DNA level, 26 of which considered novel. Although the majority of the alleles need to be confirmed at the transcript and protein level, a preliminary nomenclature was established for the equine casein alleles. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Capturing heterogeneity in gene expression studies by surrogate variable analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey T Leek

    2007-09-01

    Full Text Available It has unambiguously been shown that genetic, environmental, demographic, and technical factors may have substantial effects on gene expression levels. In addition to the measured variable(s of interest, there will tend to be sources of signal due to factors that are unknown, unmeasured, or too complicated to capture through simple models. We show that failing to incorporate these sources of heterogeneity into an analysis can have widespread and detrimental effects on the study. Not only can this reduce power or induce unwanted dependence across genes, but it can also introduce sources of spurious signal to many genes. This phenomenon is true even for well-designed, randomized studies. We introduce "surrogate variable analysis" (SVA to overcome the problems caused by heterogeneity in expression studies. SVA can be applied in conjunction with standard analysis techniques to accurately capture the relationship between expression and any modeled variables of interest. We apply SVA to disease class, time course, and genetics of gene expression studies. We show that SVA increases the biological accuracy and reproducibility of analyses in genome-wide expression studies.

  3. Genetics of wide compatible gene and variability studies in rice ...

    Indian Academy of Sciences (India)

    ... Discussion Meetings · Public Lectures · Lecture Workshops · Refresher Courses · Symposia. Home; Journals; Journal of Genetics; Volume 95; Issue 2. Genetics of wide compatible gene and variability studies in rice (Oryza sativa L.) S. REVATHI K. SAKTHIVEL S. MANONMANI M. UMADEVI R. USHAKUMARI S. ROBIN.

  4. Phenotypic effects of genetic variability in human clock genes on ...

    Indian Academy of Sciences (India)

    Several mouse models of clock gene null alleles have been demonstrated to have affected sleep homeostasis. Recent findings have shown that the variable number tandem polymorphism in PER3, previously linked to diurnal preference, has profound effects on sleep homeostasis and cognitive performance following sleep ...

  5. What is a Gene? A Question With Variable Answers

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 4. What is a Gene? A Question With Variable Answers. S C Lakhotia. General Article Volume 2 Issue 4 April 1997 pp 38-47. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/04/0038-0047 ...

  6. Gene variants associated with antisocial behaviour: a latent variable approach.

    Science.gov (United States)

    Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V; Lee, Maria; Yrigollen, Carolyn M; Pakstis, Andrew J; Katsovich, Liliya; Olds, David L; Grigorenko, Elena L; Leckman, James F

    2013-10-01

    The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a 15-year follow-up of a randomized trial of a prenatal and infancy nurse-home visitation programme in Elmira, New York. We then investigated, via a novel latent variable approach, 450 informative genetic polymorphisms in 71 genes previously associated with antisocial behaviour, drug use, affiliative behaviours and stress response in 241 consenting individuals for whom DNA was available. Haplotype and Pathway analyses were also performed. Eight single-nucleotide polymorphisms (SNPs) from eight genes contributed to the latent genetic variable that in turn accounted for 16.0% of the variance within the latent antisocial phenotype. The number of risk alleles was linearly related to the latent antisocial variable scores. Haplotypes that included the putative risk alleles for all eight genes were also associated with higher latent antisocial variable scores. In addition, 33 SNPs from 63 of the remaining genes were also significant when added to the final model. Many of these genes interact on a molecular level, forming molecular networks. The results support a role for genes related to dopamine, norepinephrine, serotonin, glutamate, opioid and cholinergic signalling as well as stress response pathways in mediating susceptibility to antisocial behaviour. This preliminary study supports use of relevant behavioural indicators and latent variable approaches to study the potential 'co-action' of gene variants associated with antisocial behaviour. It also underscores the cumulative relevance of common genetic variants for understanding the aetiology of complex behaviour. If replicated in future studies, this approach may allow the identification of a

  7. A variable gene delivery carrier-biotinylated chitosan/polyethyleneimine

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yi-Chen; Young, Tai-Horng [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, Taipei 106, Taiwan (China); Chang, Fu-Hsiung [Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Wei, Ming-Feng, E-mail: thyoung@ntu.edu.t [Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan (China)

    2010-12-15

    A variable gene delivery system has been developed based on conjugating chitosan to biotin through a functionalized poly(ethylene glycol) (PEG) spacer, which can be used to further bind different molecules on the outer layer of a polymer/DNA complex by streptavidin (SA)-biotin linkage. In this study, TAT-conjugated SA was used as the model molecule to prove the conjugation function of the prepared complex. In addition, low-molecular-weight poly(ethyleneimine) (PEI) was added into the polymer/DNA complex to increase the transfection efficiency. The results of the luciferase assay show that the transfection efficiency of the prepared complex was significantly correlated with the amount of PEI and was further enhanced when TAT was conjugated to the complex by SA-biotin linkage. Considered to have negligible cytotoxic effects, the variable gene delivery complex prepared in this study would be of considerable potential as carriers for in vitro applications.

  8. Syllidae mitochondrial gene order is unusually variable for Annelida.

    Science.gov (United States)

    Aguado, M Teresa; Richter, Sandy; Sontowski, Rebekka; Golombek, Anja; Struck, Torsten H; Bleidorn, Christoph

    2016-12-05

    Complete mitochondrial genomes of five syllids (Streptosyllis sp., Eusyllis blomstrandi, Myrianida brachycephala, Typosyllis antoni and Typosyllis sp.) have been obtained using Illumina sequencing. Together with two previous studied taxa (Ramisyllis multicaudata and Trypanobia cryptica), the analysed sequences represent most of the main lineages within the family Syllidae (Anoplosyllinae, Eusyllinae, Autolytinae and Syllinae). The genomic features, gene order and phylogenetic relationships are examined. Unusual for annelids, syllid mitochondrial genomes are highly variable in their gene order. Considering genomic features, such as length, skewness, gene content, and codon bias, most similar to the rest of annelids are the genomes of E. blomstrandi and M. brachycephala, while Streptosyllis sp. and the analysed sylline taxa (R. multicaudata, T. cryptica, T. antoni and Typosyllis sp.) are the most dissimilar. Two methionine tRNA's (trnM) have been found in T. antoni and Typosyllis sp. The mt genomes of these latter taxa are the longest with numerous non-coding regions. The 13 protein coding genes, as well as the rRNA's are used to perform phylogenetic analyses that recovered the relationships within the family explored before by previous authors. The gene order in Syllidae shows very different patterns. E. blomstrandi and M. prolifera show a similar pattern to the one found in Pleistoannelida; however this might have changed at least twice within Syllidae: in Streptosyllis sp. and within Syllinae. All analysed Syllinae show different gene orders, thereby illustrating more variability as all other pleistoannelids analysed so far. The information provided herein allows a more accurate reconstruction of the possible evolutionary scenarios in Syllidae. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Variability of the Transferrin Receptor 2 Gene in AMD

    Directory of Open Access Journals (Sweden)

    Daniel Wysokinski

    2014-01-01

    Full Text Available Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD. Iron may catalyze the Fenton reaction resulting in overproduction of reactive oxygen species. Transferrin receptor 2 plays a critical role in iron homeostasis and variability in its gene may influence oxidative stress and AMD occurrence. To verify this hypothesis we assessed the association between polymorphisms of the TFR2 gene and AMD. A total of 493 AMD patients and 171 matched controls were genotyped for the two polymorphisms of the TFR2 gene: c.1892C>T (rs2075674 and c.−258+123T>C (rs4434553. We also assessed the modulation of some AMD risk factors by these polymorphisms. The CC and TT genotypes of the c.1892C>T were associated with AMD occurrence but the latter only in obese patients. The other polymorphism was not associated with AMD occurrence, but the CC genotype was correlated with an increasing AMD frequency in subjects with BMIT and c.−258+123T>C polymorphisms of the TRF2 gene may be associated with AMD occurrence, either directly or by modulation of risk factors.

  10. Sequence Variability in Staphylococcal Enterotoxin Genes seb, sec, and sed

    Directory of Open Access Journals (Sweden)

    Sophia Johler

    2016-06-01

    Full Text Available Ingestion of staphylococcal enterotoxins preformed by Staphylococcus aureus in food leads to staphylococcal food poisoning, the most prevalent foodborne intoxication worldwide. There are five major staphylococcal enterotoxins: SEA, SEB, SEC, SED, and SEE. While variants of these toxins have been described and were linked to specific hosts or levels or enterotoxin production, data on sequence variation is still limited. In this study, we aim to extend the knowledge on promoter and gene variants of the major enterotoxins SEB, SEC, and SED. To this end, we determined seb, sec, and sed promoter and gene sequences of a well-characterized set of enterotoxigenic Staphylococcus aureus strains originating from foodborne outbreaks, human infections, human nasal colonization, rabbits, and cattle. New nucleotide sequence variants were detected for all three enterotoxins and a novel amino acid sequence variant of SED was detected in a strain associated with human nasal colonization. While the seb promoter and gene sequences exhibited a high degree of variability, the sec and sed promoter and gene were more conserved. Interestingly, a truncated variant of sed was detected in all tested sed harboring rabbit strains. The generated data represents a further step towards improved understanding of strain-specific differences in enterotoxin expression and host-specific variation in enterotoxin sequences.

  11. Sequence Variability in Staphylococcal Enterotoxin Genes seb, sec, and sed.

    Science.gov (United States)

    Johler, Sophia; Sihto, Henna-Maria; Macori, Guerrino; Stephan, Roger

    2016-06-01

    Ingestion of staphylococcal enterotoxins preformed by Staphylococcus aureus in food leads to staphylococcal food poisoning, the most prevalent foodborne intoxication worldwide. There are five major staphylococcal enterotoxins: SEA, SEB, SEC, SED, and SEE. While variants of these toxins have been described and were linked to specific hosts or levels or enterotoxin production, data on sequence variation is still limited. In this study, we aim to extend the knowledge on promoter and gene variants of the major enterotoxins SEB, SEC, and SED. To this end, we determined seb, sec, and sed promoter and gene sequences of a well-characterized set of enterotoxigenic Staphylococcus aureus strains originating from foodborne outbreaks, human infections, human nasal colonization, rabbits, and cattle. New nucleotide sequence variants were detected for all three enterotoxins and a novel amino acid sequence variant of SED was detected in a strain associated with human nasal colonization. While the seb promoter and gene sequences exhibited a high degree of variability, the sec and sed promoter and gene were more conserved. Interestingly, a truncated variant of sed was detected in all tested sed harboring rabbit strains. The generated data represents a further step towards improved understanding of strain-specific differences in enterotoxin expression and host-specific variation in enterotoxin sequences.

  12. Polymorphism of Genetic variability of gene in sheep

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    R. Rasero

    2010-01-01

    Full Text Available MUC1 gene encodes the polypeptide of a mucin present on the apical surface of the secreting mammary cells during lactation and on the surface of the milk fat globules (Mather, 2000. MUC1 contains a minisatellite region: the sequence, coding for the extracellular protein domain, consists mostly of a motif of 60 bp that in human, cattle and goat is tandemly repeated a variable number of times (VNTR polymorphism, giving rise to molecular variants of different size (Patton et al., 1995.

  13. Gene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters

    Science.gov (United States)

    Yang, Lun; Price, Elvin T.; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

    2013-01-01

    Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications. PMID:23637747

  14. Ultrahigh-dimensional variable selection method for whole-genome gene-gene interaction analysis

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    Ueki Masao

    2012-05-01

    Full Text Available Abstract Background Genome-wide gene-gene interaction analysis using single nucleotide polymorphisms (SNPs is an attractive way for identification of genetic components that confers susceptibility of human complex diseases. Individual hypothesis testing for SNP-SNP pairs as in common genome-wide association study (GWAS however involves difficulty in setting overall p-value due to complicated correlation structure, namely, the multiple testing problem that causes unacceptable false negative results. A large number of SNP-SNP pairs than sample size, so-called the large p small n problem, precludes simultaneous analysis using multiple regression. The method that overcomes above issues is thus needed. Results We adopt an up-to-date method for ultrahigh-dimensional variable selection termed the sure independence screening (SIS for appropriate handling of numerous number of SNP-SNP interactions by including them as predictor variables in logistic regression. We propose ranking strategy using promising dummy coding methods and following variable selection procedure in the SIS method suitably modified for gene-gene interaction analysis. We also implemented the procedures in a software program, EPISIS, using the cost-effective GPGPU (General-purpose computing on graphics processing units technology. EPISIS can complete exhaustive search for SNP-SNP interactions in standard GWAS dataset within several hours. The proposed method works successfully in simulation experiments and in application to real WTCCC (Wellcome Trust Case–control Consortium data. Conclusions Based on the machine-learning principle, the proposed method gives powerful and flexible genome-wide search for various patterns of gene-gene interaction.

  15. A study of variability of capsid protein genes of Radish mosaic virus

    OpenAIRE

    HOLÁ, Marcela

    2008-01-01

    The part of RNA2 genome segment of several isolates of Radish mosaic virus (RaMV) including capsid protein genes was sequenced. Variability of capsid protein genes among the isolates of Radish mosaic virus was studied.

  16. Gene Expression Variability as a Unifying Element of the Pluripotency Network

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    Elizabeth A. Mason

    2014-08-01

    Full Text Available Heterogeneity is a hallmark of stem cell populations, in part due to the molecular differences between cells undergoing self-renewal and those poised to differentiate. We examined phenotypic and molecular heterogeneity in pluripotent stem cell populations, using public gene expression data sets. A high degree of concordance was observed between global gene expression variability and the reported heterogeneity of different human pluripotent lines. Network analysis demonstrated that low-variability genes were the most highly connected, suggesting that these are the most stable elements of the gene regulatory network and are under the highest regulatory constraints. Known drivers of pluripotency were among these, with lowest expression variability of POU5F1 in cells with the highest capacity for self-renewal. Variability of gene expression provides a reliable measure of phenotypic and molecular heterogeneity and predicts those genes with the highest degree of regulatory constraint within the pluripotency network.

  17. Gene Variants Associated with Antisocial Behaviour: A Latent Variable Approach

    Science.gov (United States)

    Bentley, Mary Jane; Lin, Haiqun; Fernandez, Thomas V.; Lee, Maria; Yrigollen, Carolyn M.; Pakstis, Andrew J.; Katsovich, Liliya; Olds, David L.; Grigorenko, Elena L.; Leckman, James F.

    2013-01-01

    Objective: The aim of this study was to determine if a latent variable approach might be useful in identifying shared variance across genetic risk alleles that is associated with antisocial behaviour at age 15 years. Methods: Using a conventional latent variable approach, we derived an antisocial phenotype in 328 adolescents utilizing data from a…

  18. Regulation of cell-to-cell variability in divergent gene expression.

    Science.gov (United States)

    Yan, Chao; Wu, Shuyang; Pocetti, Christopher; Bai, Lu

    2016-03-24

    Cell-to-cell variability (noise) is an important feature of gene expression that impacts cell fitness and development. The regulatory mechanism of this variability is not fully understood. Here we investigate the effect on gene expression noise in divergent gene pairs (DGPs). We generated reporters driven by divergent promoters, rearranged their gene order, and probed their expressions using time-lapse fluorescence microscopy and single-molecule fluorescence in situ hybridization (smFISH). We show that two genes in a co-regulated DGP have higher expression covariance compared with the separate, tandem and convergent configurations, and this higher covariance is caused by more synchronized firing of the divergent transcriptions. For differentially regulated DGPs, the regulatory signal of one gene can stochastically 'leak' to the other, causing increased gene expression noise. We propose that the DGPs' function in limiting or promoting gene expression noise may enhance or compromise cell fitness, providing an explanation for the conservation pattern of DGPs.

  19. Transmission of the P250R mutation of the FGFR3 gene in four generations with highly variable phenotype

    DEFF Research Database (Denmark)

    Hove, Hanne Buciek; Dunø, Morten; Daugaard-Jensen, Jette

    Transmission of the P250R mutation of the FGFR3 gene in four generations with highly variable phenotype.......Transmission of the P250R mutation of the FGFR3 gene in four generations with highly variable phenotype....

  20. Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes.

    Science.gov (United States)

    Roth, C; Bringaud, F; Layden, R E; Baltz, T; Eisen, H

    1989-12-01

    The expression of genes coding for variable surface glycoproteins (VSGs) in Trypanosoma equiperdum is linked to duplicative transpositions of silent, basic copy sequences into telomere-linked expression sites. Examination of three independently derived late-appearing trypanosome clones expressing VSG-78 revealed that the expressed gene in all cases is composed of sequences derived from three or four individual silent genes. The 182 base pairs at the 3' end of the coding sequence are derived from one silent gene, the 3' donor. The remaining 5' segment is a mosaic structure containing variable-length segments derived from two, or perhaps three, related silent genes. All of the silent genes that participate in the construction of the VSG-78 expression-linked copy (ELC) genes contain multiple stop codons and are unable to code for VSGs. Individual silent pseudogenes complement one another in the mosaic structure of the 5' portions of the ELC genes and create functional VSG genes. The joining of the 3' and 5' portions of the composite genes occurs in short regions of homology and suggests a mechanism by which the ordered expression of the VSG genes is generated.

  1. Surface epitope localization and gene structure of a Babesia bovis 44-kilodalton variable merozoite surface antigen.

    Science.gov (United States)

    Jasmer, D P; Reduker, D W; Hines, S A; Perryman, L E; McGuire, T C

    1992-10-01

    Variation of Babesia bovis merozoite surface antigens occurs among geographic strains of the parasite. In this and a concurrent report, we investigate this variation at the gene and protein level. Using a monoclonal antibody (mAb 23/70.174), B. bovis gene sequences were identified that encoded a surface epitope of a 44-kDa merozoite surface antigen (MSA-2). This epitope is variably expressed among geographic isolates of B. bovis. Here, we describe the MSA-2 protein gene sequence, localize this surface epitope to a repeated amino acid sequence, and investigate the genomic organization of the gene in B. bovis strains from Mexico and Australia. The predicted protein sequence had hydrophobic regions at its amino and carboxy termini consistent with a signal peptide and a membrane anchor via glycosylphosphatidyl inositol, respectively. The surface epitope recognized by mAb 23/70.174 was localized within a 24-amino acid sequence which is repeated twice in tandem. Six different EcoRI bands hybridized to the MSA-2 gene sequence with varying intensities in genomic Southern blots of the homologous strain. Two of these appear to be alleles of the MSA-2 gene. Whereas 5' and 3' sequences of the MSA-2 gene sequence were detected in an Australia strain of B. bovis, internal gene sequences encoding the surface epitope were not. The 3' sequences of the MSA-2 gene also had significant sequence similarity with the MSA-1 gene of the Mexico strain B. bovis and a gene from the previously described BabR locus. These data indicate that the MSA-2 protein gene belongs to the BabR locus which encodes variable merozoite surface antigens.

  2. Variability in Metagenomic Count Data and Its Influence on the Identification of Differentially Abundant Genes.

    Science.gov (United States)

    Jonsson, Viktor; Österlund, Tobias; Nerman, Olle; Kristiansson, Erik

    2017-04-01

    Metagenomics is the study of microorganisms in environmental and clinical samples using high-throughput sequencing of random fragments of their DNA. Since metagenomics does not require any prior culturing of isolates, entire microbial communities can be studied directly in their natural state. In metagenomics, the abundance of genes is quantified by sorting and counting the DNA fragments. The resulting count data are high-dimensional and affected by high levels of technical and biological noise that make the statistical analysis challenging. In this article, we introduce an hierarchical overdispersed Poisson model to explore the variability in metagenomic data. By analyzing three comprehensive data sets, we show that the gene-specific variability varies substantially between genes and is dependent on biological function. We also assess the power of identifying differentially abundant genes and show that incorrect assumptions about the gene-specific variability can lead to unacceptable high rates of false positives. Finally, we evaluate shrinkage approaches to improve the variance estimation and show that the prior choice significantly affects the statistical power. The results presented in this study further elucidate the complex variance structure of metagenomic data and provide suggestions for accurate and reliable identification of differentially abundant genes.

  3. Anthropological features of the CFTR gene: Its variability in an African population.

    Science.gov (United States)

    Maria Ciminelli, Bianca; Bombieri, Cristina; Ciccacci, Cinzia; Belpinati, Francesca; Pompei, Fiorenza; Maselli, Roberta; Simporé, Jacques; Pignatti, Pier Franco; Modiano, Guido

    2011-03-01

    The CFTR gene (Cystic Fibrosis conductance Transmembrane Regulator) is the gene responsible for Cystic Fibrosis, the most common severe autosomal recessive disease in Europeans. It has been extensively explored in several European and European-derived populations, but poorly studied in the other major human groups. To characterize the variability of the CFTR gene in an African population. Using DGGE, all 27 exons (4443 bp) and 2184 bp of the flanking intronic regions of the CFTR gene were studied in a random sample of 45 Mossì from Burkina Faso (Western sub-Saharan Africa). Sixteen variable sites were found: 13 SNPs (one in the promoter region, four non-synonymous and five synonymous in the exons and three in the introns) and three intronic STRs. Only the promoter site ( - 94 G/T), slightly polymorphic in the present survey, was not variable in different European populations. Comparison between Western Africans, Eastern Africans, Europeans and Eastern Asians showed that alleles at two intronic STRs (T(n) and (TG)(m) in intron 8), four exonic (M470V, 2694 T/G, 4002 A/G and 4521 G/A) and one intronic (875+40 A/G) SNPs have very different frequencies among at least two major human groups. Moreover, the overall degree of non-synonymous variability in Mossì is much lower than that in Europeans. A possible interpretation of this finding is proposed. The CFTR gene has been since long hypothesized to have undergone selection in Europeans. The present study by comparing Africans and Europeans for the overall variability of the gene supports this hypothesis.

  4. Surrogate variable analysis using partial least squares (SVA-PLS) in gene expression studies.

    Science.gov (United States)

    Chakraborty, Sutirtha; Datta, Somnath; Datta, Susmita

    2012-03-15

    In a typical gene expression profiling study, our prime objective is to identify the genes that are differentially expressed between the samples from two different tissue types. Commonly, standard analysis of variance (ANOVA)/regression is implemented to identify the relative effects of these genes over the two types of samples from their respective arrays of expression levels. But, this technique becomes fundamentally flawed when there are unaccounted sources of variability in these arrays (latent variables attributable to different biological, environmental or other factors relevant in the context). These factors distort the true picture of differential gene expression between the two tissue types and introduce spurious signals of expression heterogeneity. As a result, many genes which are actually differentially expressed are not detected, whereas many others are falsely identified as positives. Moreover, these distortions can be different for different genes. Thus, it is also not possible to get rid of these variations by simple array normalizations. This both-way error can lead to a serious loss in sensitivity and specificity, thereby causing a severe inefficiency in the underlying multiple testing problem. In this work, we attempt to identify the hidden effects of the underlying latent factors in a gene expression profiling study by partial least squares (PLS) and apply ANCOVA technique with the PLS-identified signatures of these hidden effects as covariates, in order to identify the genes that are truly differentially expressed between the two concerned tissue types. We compare the performance of our method SVA-PLS with standard ANOVA and a relatively recent technique of surrogate variable analysis (SVA), on a wide variety of simulation settings (incorporating different effects of the hidden variable, under situations with varying signal intensities and gene groupings). In all settings, our method yields the highest sensitivity while maintaining relatively

  5. Genetic variability of bovine GHR, IGF-1 and IGFBP-3 genes in ...

    African Journals Online (AJOL)

    The identification of genetic polymorphisms in the genes that play a crucial role in regulatiing growth and development of livestock enables us to evaluate the biological similarities and to acquire a better perspective of quantitative traits. The present study was undertaken to characterize genetic variability in the bovine ...

  6. How changes in extracellular matrix mechanics and gene expression variability might combine to drive cancer progression.

    Directory of Open Access Journals (Sweden)

    Justin Werfel

    Full Text Available Changes in extracellular matrix (ECM structure or mechanics can actively drive cancer progression; however, the underlying mechanism remains unknown. Here we explore whether this process could be mediated by changes in cell shape that lead to increases in genetic noise, given that both factors have been independently shown to alter gene expression and induce cell fate switching. We do this using a computer simulation model that explores the impact of physical changes in the tissue microenvironment under conditions in which physical deformation of cells increases gene expression variability among genetically identical cells. The model reveals that cancerous tissue growth can be driven by physical changes in the microenvironment: when increases in cell shape variability due to growth-dependent increases in cell packing density enhance gene expression variation, heterogeneous autonomous growth and further structural disorganization can result, thereby driving cancer progression via positive feedback. The model parameters that led to this prediction are consistent with experimental measurements of mammary tissues that spontaneously undergo cancer progression in transgenic C3(1-SV40Tag female mice, which exhibit enhanced stiffness of mammary ducts, as well as progressive increases in variability of cell-cell relations and associated cell shape changes. These results demonstrate the potential for physical changes in the tissue microenvironment (e.g., altered ECM mechanics to induce a cancerous phenotype or accelerate cancer progression in a clonal population through local changes in cell geometry and increased phenotypic variability, even in the absence of gene mutation.

  7. Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Jessie M. Cameron

    2017-07-01

    Full Text Available Creatine deficiency syndrome (CDS comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase (GATM gene, glycine amidinotransferase, guanidinoacetate methyltransferase (GAMT gene, and creatine transporter deficiency (SLC6A8 gene, solute carrier family 6 member 8. CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism. We sequenced GATM, GAMT and SLC6A8 genes in 166 patients with autism (coding sequence, introns and adjacent untranslated regions. A total of 29, 16 and 25 variants were identified in each gene, respectively. Four variants were novel in GATM, and 5 in SLC6A8 (not present in the 1000 Genomes, Exome Sequencing Project (ESP or Exome Aggregation Consortium (ExAC databases. A single variant in each gene was identified as non-synonymous, and computationally predicted to be potentially damaging. Nine variants in GATM were shown to have a lower minor allele frequency (MAF in the autism population than in the 1000 Genomes database, specifically in the East Asian population (Fisher’s exact test. Two variants also had lower MAFs in the European population. In summary, there were no apparent associations of variants in GAMT and SLC6A8 genes with autism. The data implying there could be a lower association of some specific GATM gene variants with autism is an observation that would need to be corroborated in a larger group of autism patients, and with sub-populations of Asian ethnicities. Overall, our findings suggest that the genetic variability of creatine synthesis/transport is unlikely to play a part in the pathogenesis of autism

  8. Flux variability scanning based on enforced objective flux for identifying gene amplification targets

    Science.gov (United States)

    2012-01-01

    Background In order to reduce time and efforts to develop microbial strains with better capability of producing desired bioproducts, genome-scale metabolic simulations have proven useful in identifying gene knockout and amplification targets. Constraints-based flux analysis has successfully been employed for such simulation, but is limited in its ability to properly describe the complex nature of biological systems. Gene knockout simulations are relatively straightforward to implement, simply by constraining the flux values of the target reaction to zero, but the identification of reliable gene amplification targets is rather difficult. Here, we report a new algorithm which incorporates physiological data into a model to improve the model’s prediction capabilities and to capitalize on the relationships between genes and metabolic fluxes. Results We developed an algorithm, flux variability scanning based on enforced objective flux (FVSEOF) with grouping reaction (GR) constraints, in an effort to identify gene amplification targets by considering reactions that co-carry flux values based on physiological omics data via “GR constraints”. This method scans changes in the variabilities of metabolic fluxes in response to an artificially enforced objective flux of product formation. The gene amplification targets predicted using this method were validated by comparing the predicted effects with the previous experimental results obtained for the production of shikimic acid and putrescine in Escherichia coli. Moreover, new gene amplification targets for further enhancing putrescine production were validated through experiments involving the overexpression of each identified targeted gene under condition-controlled batch cultivation. Conclusions FVSEOF with GR constraints allows identification of gene amplification targets for metabolic engineering of microbial strains in order to enhance the production of desired bioproducts. The algorithm was validated through the

  9. Characterisation of silent and active genes for a variable large protein of Borrelia recurrentis

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    Scragg Ian G

    2002-10-01

    Full Text Available Abstract Background We report the characterisation of the variable large protein (vlp gene expressed by clinical isolate A1 of Borrelia recurrentis; the agent of the life-threatening disease louse-borne relapsing fever. Methods The major vlp protein of this isolate was characterised and a DNA probe created. Use of this together with standard molecular methods was used to determine the location of the vlp1B. recurrentis A1 gene in both this and other isolates. Results This isolate was found to carry silent and expressed copies of the vlp1B. recurrentis A1 gene on plasmids of 54 kbp and 24 kbp respectively, whereas a different isolate, A17, had only the silent vlp1B. recurrentis A17 on a 54 kbp plasmid. Silent and expressed vlp1 have identical mature protein coding regions but have different 5' regions, both containing different potential lipoprotein leader sequences. Only one form of vlp1 is transcribed in the A1 isolate of B. recurrentis, yet both 5' upstream sequences of this vlp1 gene possess features of bacterial promoters. Conclusion Taken together these results suggest that antigenic variation in B. recurrentis may result from recombination of variable large and small protein genes at the junction between lipoprotein leader sequence and mature protein coding region. However, this hypothetical model needs to be validated by further identification of expressed and silent variant protein genes in other B. recurrentis isolates.

  10. Prognostic modeling of oral cancer by gene profiles and clinicopathological co-variables.

    Science.gov (United States)

    Mes, Steven W; Te Beest, Dennis; Poli, Tito; Rossi, Silvia; Scheckenbach, Kathrin; van Wieringen, Wessel N; Brink, Arjen; Bertani, Nicoletta; Lanfranco, Davide; Silini, Enrico M; van Diest, Paul J; Bloemena, Elisabeth; Leemans, C René; van de Wiel, Mark A; Brakenhoff, Ruud H

    2017-08-29

    Accurate staging and outcome prediction is a major problem in clinical management of oral cancer patients, hampering high precision treatment and adjuvant therapy planning. Here, we have built and validated multivariable models that integrate gene signatures with clinical and pathological variables to improve staging and survival prediction of patients with oral squamous cell carcinoma (OSCC). Gene expression profiles from 249 human papillomavirus (HPV)-negative OSCCs were explored to identify a 22-gene lymph node metastasis signature (LNMsig) and a 40-gene overall survival signature (OSsig). To facilitate future clinical implementation and increase performance, these signatures were transferred to quantitative polymerase chain reaction (qPCR) assays and validated in an independent cohort of 125 HPV-negative tumors. When applied in the clinically relevant subgroup of early-stage (cT1-2N0) OSCC, the LNMsig could prevent overtreatment in two-third of the patients. Additionally, the integration of RT-qPCR gene signatures with clinical and pathological variables provided accurate prognostic models for oral cancer, strongly outperforming TNM. Finally, the OSsig gene signature identified a subpopulation of patients, currently considered at low-risk for disease-related survival, who showed an unexpected poor prognosis. These well-validated models will assist in personalizing primary treatment with respect to neck dissection and adjuvant therapies.

  11. Variable coordination of cotranscribed genes in Escherichia coli following antisense repression

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    Kulyté Agne

    2006-11-01

    Full Text Available Abstract Background A majority of bacterial genes belong to tight clusters and operons, which complicates gene functional studies using conventional knock-out methods. Antisense agents can down-regulate the expression of genes without disrupting the genome because they bind mRNA and block its expression. However, it is unclear how antisense inhibition affects expression from genes that are cotranscribed with the target. Results To examine the effects of antisense inhibition on cotranscribed genes, we constructed a plasmid expressing the two reporter genes gfp and DsRed as one transcriptional unit. Incubation with antisense peptide nucleic acid (PNA targeted to the mRNA start codon region of either the upstream gfp or the downstream DsRed gene resulted in a complete expression discoordination from this artificial construct. The same approach was applied to the three cotranscribed genes in the endogenously expressed lac-operon (lacZ, Y and A and partial downstream expression coordination was seen when the lacZ start codon was targeted with antisense PNA. Targeting the lacY mRNA start codon region showed no effect on the upstream lacZ gene expression whereas expression from the downstream lacA gene was affected as strongly as the lacY gene. Determination of lacZ and lacY mRNA levels revealed a pattern of reduction that was similar to the Lac-proteins, indicating a relation between translation inhibition and mRNA degradation as a response to antisense PNA treatment. Conclusion The results show that antisense mediated repression of genes within operons affect cotranscribed genes to a variable degree. Target transcript stability appears to be closely related to inhibition of translation and presumably depends on translating ribosomes protecting the mRNA from intrinsic decay mechanisms. Therefore, for genes within operons and clusters it is likely that the nature of the target transcript will determine the inhibitory effects on cotranscribed genes

  12. Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer's Disease.

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    Celeste Sassi

    Full Text Available The cerebral deposition of Aβ42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP, is a central event in Alzheimer's disease (AD(Amyloid hypothesis. Given the key role of APP-Aβ metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aβ degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test and cumulative (gene-based association test effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4genes mainly involved in Aβ extracellular degradation (TTR, ACE, clearance (LRP1 and APP trafficking and recycling (SORL1. These results were partially replicated in the gene-based analysis (c-alpha and SKAT tests, that reports ECE1, LYZ and TTR as nominally associated to AD (1.7e-3 variability in APP-Aβ genes is not a critical factor for AD development and 2 Aβ degradation and clearance, rather than Aβ production, may play a key role in the etiology of sporadic AD.

  13. Physiological, Diurnal and Stress-Related Variability of Cadmium-Metallothionein Gene Expression in Land Snails.

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    Veronika Pedrini-Martha

    Full Text Available The terrestrial Roman snail Helix pomatia has successfully adapted to strongly fluctuating conditions in its natural soil habitat. Part of the snail's stress defense strategy is its ability to express Metallothioneins (MTs. These are multifunctional, cysteine-rich proteins that bind and inactivate transition metal ions (Cd(2+, Zn(2+, Cu(+ with high affinity. In Helix pomatia a Cadmium (Cd-selective, inducible Metallothionein Isoform (CdMT is mainly involved in detoxification of this harmful metal. In addition, the snail CdMT has been shown to also respond to certain physiological stressors. The aim of the present study was to investigate the physiological and diurnal variability of CdMT gene expression in snails exposed to Cd and non-metallic stressors such as desiccation and oxygen depletion. CdMT gene expression was upregulated by Cd exposure and desiccation, whereas no significant impact on the expression of CdMT was measured due to oxygen depletion. Overall, Cd was clearly more effective as an inducer of the CdMT gene expression compared to the applied non-metallic stressors. In unexposed snails, diurnal rhythmicity of CdMT gene expression was observed with higher mRNA concentrations at night compared to daytime. This rhythmicity was severely disrupted in Cd-exposed snails which exhibited highest CdMT gene transcription rates in the morning. Apart from diurnal rhythmicity, feeding activity also had a strong impact on CdMT gene expression. Although underlying mechanisms are not completely understood, it is clear that factors increasing MT expression variability have to be considered when using MT mRNA quantification as a biomarker for environmental stressors.

  14. Physiological, Diurnal and Stress-Related Variability of Cadmium-Metallothionein Gene Expression in Land Snails.

    Science.gov (United States)

    Pedrini-Martha, Veronika; Niederwanger, Michael; Kopp, Renate; Schnegg, Raimund; Dallinger, Reinhard

    2016-01-01

    The terrestrial Roman snail Helix pomatia has successfully adapted to strongly fluctuating conditions in its natural soil habitat. Part of the snail's stress defense strategy is its ability to express Metallothioneins (MTs). These are multifunctional, cysteine-rich proteins that bind and inactivate transition metal ions (Cd(2+), Zn(2+), Cu(+)) with high affinity. In Helix pomatia a Cadmium (Cd)-selective, inducible Metallothionein Isoform (CdMT) is mainly involved in detoxification of this harmful metal. In addition, the snail CdMT has been shown to also respond to certain physiological stressors. The aim of the present study was to investigate the physiological and diurnal variability of CdMT gene expression in snails exposed to Cd and non-metallic stressors such as desiccation and oxygen depletion. CdMT gene expression was upregulated by Cd exposure and desiccation, whereas no significant impact on the expression of CdMT was measured due to oxygen depletion. Overall, Cd was clearly more effective as an inducer of the CdMT gene expression compared to the applied non-metallic stressors. In unexposed snails, diurnal rhythmicity of CdMT gene expression was observed with higher mRNA concentrations at night compared to daytime. This rhythmicity was severely disrupted in Cd-exposed snails which exhibited highest CdMT gene transcription rates in the morning. Apart from diurnal rhythmicity, feeding activity also had a strong impact on CdMT gene expression. Although underlying mechanisms are not completely understood, it is clear that factors increasing MT expression variability have to be considered when using MT mRNA quantification as a biomarker for environmental stressors.

  15. Antibody Heavy Chain Variable Domains of Different Germline Gene Origins Diversify through Different Paths

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    Ufuk Kirik

    2017-11-01

    Full Text Available B cells produce antibodies, key effector molecules in health and disease. They mature their properties, including their affinity for antigen, through hypermutation events; processes that involve, e.g., base substitution, codon insertion and deletion, often in association with an isotype switch. Investigations of antibody evolution define modes whereby particular antibody responses are able to form, and such studies provide insight important for instance for development of efficient vaccines. Antibody evolution is also used in vitro for the design of antibodies with improved properties. To better understand the basic concepts of antibody evolution, we analyzed the mutational paths, both in terms of amino acid substitution and insertions and deletions, taken by antibodies of the IgG isotype. The analysis focused on the evolution of the heavy chain variable domain of sets of antibodies, each with an origin in 1 of 11 different germline genes representing six human heavy chain germline gene subgroups. Investigated genes were isolated from cells of human bone marrow, a major site of antibody production, and characterized by next-generation sequencing and an in-house bioinformatics pipeline. Apart from substitutions within the complementarity determining regions, multiple framework residues including those in protein cores were targets of extensive diversification. Diversity, both in terms of substitutions, and insertions and deletions, in antibodies is focused to different positions in the sequence in a germline gene-unique manner. Altogether, our findings create a framework for understanding patterns of evolution of antibodies from defined germline genes.

  16. Antibody Heavy Chain Variable Domains of Different Germline Gene Origins Diversify through Different Paths

    Science.gov (United States)

    Kirik, Ufuk; Persson, Helena; Levander, Fredrik; Greiff, Lennart; Ohlin, Mats

    2017-01-01

    B cells produce antibodies, key effector molecules in health and disease. They mature their properties, including their affinity for antigen, through hypermutation events; processes that involve, e.g., base substitution, codon insertion and deletion, often in association with an isotype switch. Investigations of antibody evolution define modes whereby particular antibody responses are able to form, and such studies provide insight important for instance for development of efficient vaccines. Antibody evolution is also used in vitro for the design of antibodies with improved properties. To better understand the basic concepts of antibody evolution, we analyzed the mutational paths, both in terms of amino acid substitution and insertions and deletions, taken by antibodies of the IgG isotype. The analysis focused on the evolution of the heavy chain variable domain of sets of antibodies, each with an origin in 1 of 11 different germline genes representing six human heavy chain germline gene subgroups. Investigated genes were isolated from cells of human bone marrow, a major site of antibody production, and characterized by next-generation sequencing and an in-house bioinformatics pipeline. Apart from substitutions within the complementarity determining regions, multiple framework residues including those in protein cores were targets of extensive diversification. Diversity, both in terms of substitutions, and insertions and deletions, in antibodies is focused to different positions in the sequence in a germline gene-unique manner. Altogether, our findings create a framework for understanding patterns of evolution of antibodies from defined germline genes. PMID:29180996

  17. svapls: an R package to correct for hidden factors of variability in gene expression studies.

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    Chakraborty, Sutirtha; Datta, Somnath; Datta, Susmita

    2013-07-24

    Hidden variability is a fundamentally important issue in the context of gene expression studies. Collected tissue samples may have a wide variety of hidden effects that may alter their transcriptional landscape significantly. As a result their actual differential expression pattern can be potentially distorted, leading to inaccurate results from a genome-wide testing for the important transcripts. We present an R package svapls that can be used to identify several types of unknown sample-specific sources of heterogeneity in a gene expression study and adjust for them in order to provide a more accurate inference on the original expression pattern of the genes over different varieties of samples. The proposed method implements Partial Least Squares regression to extract the hidden signals of sample-specific heterogeneity in the data and uses them to find the genes that are actually correlated with the phenotype of interest. We also compare our package with three other popular softwares for testing differential gene expression along with a detailed illustration on the widely popular Golub dataset. Results from the sensitivity analyes on simulated data with widely different hidden variation patterns reveal the improved detection power of our R package compared to the other softwares along with reasonably smaller error rates. Application on the real-life dataset exhibits the efficacy of the R package in detecting potential batch effects from the dataset. Overall, Our R package provides the user with a simplified framework for analyzing gene expression data with a wide range of hidden variation patterns and delivering a differential gene expression analysis with substantially improved power and accuracy.The R package svapls is freely available at http://cran.r-project.org/web/packages/svapls/index.html.

  18. Genetic variability in mitochondrial and nuclear genes of Larus dominicanus (Charadriiformes, Laridae) from the Brazilian coast

    Science.gov (United States)

    de Mendonça Dantas, Gisele Pires; Meyer, Diogo; Godinho, Raquel; Ferrand, Nuno; Morgante, João Stenghel

    2012-01-01

    Several phylogeographic studies of seabirds have documented low genetic diversity that has been attributed to bottleneck events or individual capacity for dispersal. Few studies have been done in seabirds on the Brazilian coast and all have shown low genetic differentiation on a wide geographic scale. The Kelp Gull is a common species with a wide distribution in the Southern Hemisphere. In this study, we used mitochondrial and nuclear markers to examine the genetic variability of Kelp Gull populations on the Brazilian coast and compared this variability with that of sub-Antarctic island populations of this species. Kelp Gulls showed extremely low genetic variability for mitochondrial markers (cytb and ATPase) and high diversity for a nuclear locus (intron 7 of the β-fibrinogen). The intraspecific evolutionary history of Kelp Gulls showed that the variability found in intron 7 of the β-fibrinogen gene was compatible with the variability expected under neutral evolution but suggested an increase in population size during the last 10,000 years. However, none of the markers revealed evidence of a bottleneck population. These findings indicate that the recent origin of Kelp Gulls is the main explanation for their nuclear diversity, although selective pressure on the mtDNA of this species cannot be discarded. PMID:23271950

  19. Genetic variability in mitochondrial and nuclear genes of Larus dominicanus (Charadriiformes, Laridae) from the Brazilian coast.

    Science.gov (United States)

    de Mendonça Dantas, Gisele Pires; Meyer, Diogo; Godinho, Raquel; Ferrand, Nuno; Morgante, João Stenghel

    2012-12-01

    Several phylogeographic studies of seabirds have documented low genetic diversity that has been attributed to bottleneck events or individual capacity for dispersal. Few studies have been done in seabirds on the Brazilian coast and all have shown low genetic differentiation on a wide geographic scale. The Kelp Gull is a common species with a wide distribution in the Southern Hemisphere. In this study, we used mitochondrial and nuclear markers to examine the genetic variability of Kelp Gull populations on the Brazilian coast and compared this variability with that of sub-Antarctic island populations of this species. Kelp Gulls showed extremely low genetic variability for mitochondrial markers (cytb and ATPase) and high diversity for a nuclear locus (intron 7 of the β-fibrinogen). The intraspecific evolutionary history of Kelp Gulls showed that the variability found in intron 7 of the β-fibrinogen gene was compatible with the variability expected under neutral evolution but suggested an increase in population size during the last 10,000 years. However, none of the markers revealed evidence of a bottleneck population. These findings indicate that the recent origin of Kelp Gulls is the main explanation for their nuclear diversity, although selective pressure on the mtDNA of this species cannot be discarded.

  20. Genetic variability in mitochondrial and nuclear genes of Larus dominicanus (Charadriiformes, Laridae from the Brazilian coast

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    Gisele Pires de Mendonça Dantas

    2012-01-01

    Full Text Available Several phylogeographic studies of seabirds have documented low genetic diversity that has been attributed to bottleneck events or individual capacity for dispersal. Few studies have been done in seabirds on the Brazilian coast and all have shown low genetic differentiation on a wide geographic scale. The Kelp Gull is a common species with a wide distribution in the Southern Hemisphere. In this study, we used mitochondrial and nuclear markers to examine the genetic variability of Kelp Gull populations on the Brazilian coast and compared this variability with that of sub-Antarctic island populations of this species. Kelp Gulls showed extremely low genetic variability for mitochondrial markers (cytb and ATPase and high diversity for a nuclear locus (intron 7 of the β-fibrinogen. The intraspecific evolutionary history of Kelp Gulls showed that the variability found in intron 7 of the β-fibrinogen gene was compatible with the variability expected under neutral evolution but suggested an increase in population size during the last 10,000 years. However, none of the markers revealed evidence of a bottleneck population. These findings indicate that the recent origin of Kelp Gulls is the main explanation for their nuclear diversity, although selective pressure on the mtDNA of this species cannot be discarded.

  1. Locating disease genes using Bayesian variable selection with the Haseman-Elston method

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    He Qimei

    2003-12-01

    Full Text Available Abstract Background We applied stochastic search variable selection (SSVS, a Bayesian model selection method, to the simulated data of Genetic Analysis Workshop 13. We used SSVS with the revisited Haseman-Elston method to find the markers linked to the loci determining change in cholesterol over time. To study gene-gene interaction (epistasis and gene-environment interaction, we adopted prior structures, which incorporate the relationship among the predictors. This allows SSVS to search in the model space more efficiently and avoid the less likely models. Results In applying SSVS, instead of looking at the posterior distribution of each of the candidate models, which is sensitive to the setting of the prior, we ranked the candidate variables (markers according to their marginal posterior probability, which was shown to be more robust to the prior. Compared with traditional methods that consider one marker at a time, our method considers all markers simultaneously and obtains more favorable results. Conclusions We showed that SSVS is a powerful method for identifying linked markers using the Haseman-Elston method, even for weak effects. SSVS is very effective because it does a smart search over the entire model space.

  2. Re-expression of an inactivated variable surface glycoprotein gene in Trypanosoma equiperdum.

    Science.gov (United States)

    Buck, G A; Jacquemot, C; Baltz, T; Eisen, H

    1984-12-01

    Variable surface glycoprotein (VSG) genes in African trypanosomes are often activated by the duplicative transposition of a silent basic copy (BC) gene into an unlinked telomerically located expression site, producing an active expression-linked copy (ELC) of that gene. However, some BC genes that are already linked to a telomere are activated without apparent duplication or transposition. We have recently shown that an active VSG ELC can be inactivated in situ, apparently without rearrangement. To explain these observations it has been suggested that VSG genes that are associated with chromosome telomeres are activated by chromosome end exchanges that occur at a considerable distance upstream from the genes themselves and place them cis to a unique VSG expression element. In an attempt to test this model we derived five VSG-1 expressing variants from BoTat-2, a VSG-2 expressing variant of Trypanosoma equiperdum which carries an inactive residual VSG-1 ELC (R-ELC) as well as the active VSG-2 ELC near unlinked chromosome telomeres. We examined the fates of the VSG-2 ELC and the VSG-1 R-ELC in these variants. All five had maintained the VSG-1 R-ELC; three in a reactivated form and two in an inactive state. The latter two variants carried new, active VSG-1 ELCs: one in the site that had previously contained the VSG-2 ELC and one in a previously unidentified site. The VSG-2 ELC was lost in all five of the variants. The results are not consistent with the simple chromosome end exchange model, which predicts that the VSG-2 ELC would be inactivated but not deleted when the VSG-1 R-ELC was reactivated.

  3. CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations.

    Science.gov (United States)

    Drury, Douglas W; Dapper, Amy L; Siniard, Dylan J; Zentner, Gabriel E; Wade, Michael J

    2017-05-01

    Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum, we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.

  4. Modeling suggests that gene circuit architecture controls phenotypic variability in a bacterial persistence network.

    Science.gov (United States)

    Koh, Rachel S; Dunlop, Mary J

    2012-05-20

    Bacterial persistence is a non-inherited bet-hedging mechanism where a subpopulation of cells enters a dormant state, allowing those cells to survive environmental stress such as treatment with antibiotics. Persister cells are not mutants; they are formed by natural stochastic variation in gene expression. Understanding how regulatory architecture influences the level of phenotypic variability can help us explain how the frequency of persistence events can be tuned. We present a model of the regulatory network controlling the HipBA toxin-antitoxin system from Escherichia coli. Using a biologically realistic model we first determine that the persistence phenotype is not the result of bistability within the network. Next, we develop a stochastic model and show that cells can enter persistence due to random fluctuations in transcription, translation, degradation, and complex formation. We then examine alternative gene circuit architectures for controlling hipBA expression and show that networks with more noise (more persisters) and less noise (fewer persisters) are straightforward to achieve. Thus, we propose that the gene circuit architecture can be used to tune the frequency of persistence, a trait that can be selected for by evolution. We develop deterministic and stochastic models describing how the regulation of toxin and antitoxin expression influences phenotypic variation within a population. Persistence events are the result of stochastic fluctuations in toxin levels that cross a threshold, and their frequency is controlled by the regulatory topology governing gene expression.

  5. Modeling suggests that gene circuit architecture controls phenotypic variability in a bacterial persistence network

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    Koh Rachel S

    2012-05-01

    Full Text Available Abstract Background Bacterial persistence is a non-inherited bet-hedging mechanism where a subpopulation of cells enters a dormant state, allowing those cells to survive environmental stress such as treatment with antibiotics. Persister cells are not mutants; they are formed by natural stochastic variation in gene expression. Understanding how regulatory architecture influences the level of phenotypic variability can help us explain how the frequency of persistence events can be tuned. Results We present a model of the regulatory network controlling the HipBA toxin-antitoxin system from Escherichia coli. Using a biologically realistic model we first determine that the persistence phenotype is not the result of bistability within the network. Next, we develop a stochastic model and show that cells can enter persistence due to random fluctuations in transcription, translation, degradation, and complex formation. We then examine alternative gene circuit architectures for controlling hipBA expression and show that networks with more noise (more persisters and less noise (fewer persisters are straightforward to achieve. Thus, we propose that the gene circuit architecture can be used to tune the frequency of persistence, a trait that can be selected for by evolution. Conclusions We develop deterministic and stochastic models describing how the regulation of toxin and antitoxin expression influences phenotypic variation within a population. Persistence events are the result of stochastic fluctuations in toxin levels that cross a threshold, and their frequency is controlled by the regulatory topology governing gene expression.

  6. The variability of bx1 DIMBOA biosynthesis gene in maize inbred lines

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    Mikić Sanja

    2016-01-01

    Full Text Available 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA is a secondary metabolite in plants that renders defense against phytopatogenic bacteria, fungi, insects and other pest organisms. The biosynthesis of DIMBOA is controlled by nine genes, the first bx1 gene governs the transcription of a key enzyme in DIMBOA biosynthesis. The aim of this study was to genotype maize inbred lines used in breeding programmes for the presence of resistant allele in order to identify the source of biotic stress resistance. The variability of bx1 gene was assessed in a set of 96 diverse inbred lines with a functional microsatellite marker umc1022 located in bx1 gene. Two marker alleles, the length of 91 and 97 bp, were found in the majority of inbred lines, the former being predominant among Lancaster inbred lines and the latter in the BSSS heterotic group. By comparing previous findings on the inbred lines with high level of DIMBOA and resistance with the pedigree information of the maize inbred lines analyzed in this study, we postulated that the allele 91 bp could be associate with DIMBOA accumulation and pest resistance. The DIMBOA quantification and evaluation of pest infestations in field trials are needed to verify our results.

  7. Common variable immune deficiency with mutated TNFSRF13B gene presenting with autoimmune hematologic manifestations

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    Elpis Mantadakis

    2016-10-01

    Full Text Available Patients with common variable immunodeficiency (CVID develop autoimmune hematologic manifestations. We report a 14-year-old boy with Evans syndrome, who presented at the age of 11.5 years with autoimmune hemolysis and was successfully managed with corticosteroids. Initially, the serum immunoglobulins were within the low-normal range for age, but two years after presentation he definitely fulfilled the diagnostic criteria for CVID, despite a negative history for serious infections. DNA sequencing by PCR of the TNFSRF13B gene that encodes the TACI receptor disclosed the heterozygous mutation C104R that is found in approximately 10–15% of patients with CVID. Common variable immunodeficiency should be considered in the differential diagnosis of autoimmune hematologic manifestations, since its timely diagnosis may considerably affect clinical management and patient outcome.

  8. FCERI and Histamine Metabolism Gene Variability in Selective Responders to NSAIDS.

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    Amo, Gemma; Cornejo-García, José A; García-Menaya, Jesus M; Cordobes, Concepcion; Torres, M J; Esguevillas, Gara; Mayorga, Cristobalina; Martinez, Carmen; Blanca-Lopez, Natalia; Canto, Gabriela; Ramos, Alfonso; Blanca, Miguel; Agúndez, José A G; García-Martín, Elena

    2016-01-01

    The high-affinity IgE receptor (Fcε RI) is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ, and Fcε RIγ (αβγ2) encoded by three genes designated as FCER1A, FCER1B (MS4A2), and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated) non-steroidal anti-inflammatory (NSAID) hypersensitivity. From a cohort of 314 patients suffering from selective hypersensitivity to metamizole, ibuprofen, diclofenac, paracetamol, acetylsalicylic acid (ASA), propifenazone, naproxen, ketoprofen, dexketoprofen, etofenamate, aceclofenac, etoricoxib, dexibuprofen, indomethacin, oxyphenylbutazone, or piroxicam, and 585 unrelated healthy controls that tolerated these NSAIDs, we analyzed the putative effects of the FCERI SNPs FCER1A rs2494262, rs2427837, and rs2251746; FCER1B rs1441586, rs569108, and rs512555; FCER1G rs11587213, rs2070901, and rs11421. Furthermore, in order to identify additional genetic markers which might be associated with the risk of developing selective NSAID hypersensitivity, or which may modify the putative association of FCERI gene variations with risk, we analyzed polymorphisms known to affect histamine synthesis or metabolism, such as rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742, and rs1049793 in the HDC, HNMT, and DAO genes. No major genetic associations with risk or with clinical presentation, and no gene-gene interactions, or gene-phenotype interactions (including age, gender, IgE concentration, antecedents of atopy, culprit drug, or clinical presentation) were identified in patients. However, logistic regression analyses indicated that the presence of antecedents of atopy and the DAO SNP rs2052129 (GG

  9. FCERI AND HISTAMINE METABOLISM GENE VARIABILITY IN SELECTIVE RESPONDERS TO NSAIDS

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    Gemma Amo

    2016-09-01

    Full Text Available The high-affinity IgE receptor (Fcε RI is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ and Fcε RIγ (αβγ2 encoded by three genes designated as FCER1A, FCER1B (MS4A2 and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated non-steroidal anti-inflammatory (NSAID hypersensitivity.From a cohort of 314 patients suffering from selective hypersensitivity to metamizole, ibuprofen, diclofenac, paracetamol, acetylsalicylic acid (ASA, propifenazone, naproxen, ketoprofen, dexketoprofen, etofenamate, aceclofenac, etoricoxib, dexibuprofen, indomethacin, oxyphenylbutazone or piroxicam, and 585 unrelated healthy controls that tolerated these NSAIDs, we analyzed the putative effects of the FCERI SNPs FCER1A rs2494262, rs2427837 and rs2251746; FCER1B rs1441586, rs569108 and rs512555; FCER1G rs11587213, rs2070901 and rs11421. Furthermore, in order to identify additional genetic markers which might be associated with the risk of developing selective NSAID hypersensitivity, or which may modify the putative association of FCERI gene variations with risk, we analyzed polymorphisms known to affect histamine synthesis or metabolism, such as rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes.No major genetic associations with risk or with clinical presentation, and no gene-gene interactions, or gene-phenotype interactions (including age, gender, IgE concentration, antecedents of atopy, culprit drug or clinical presentation were identified in patients. However, logistic regression analyses indicated that the presence of antecedents of atopy and the DAO SNP rs2052129 (GG

  10. Expression analysis of the Theileria parva subtelomere-encoded variable secreted protein gene family.

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    Jacqueline Schmuckli-Maurer

    Full Text Available The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm.We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals.Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic

  11. Effect of Interaction between Chromatin Loops on Cell-to-Cell Variability in Gene Expression.

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    Tuoqi Liu

    2016-05-01

    Full Text Available According to recent experimental evidence, the interaction between chromatin loops, which can be characterized by three factors-connection pattern, distance between regulatory elements, and communication form, play an important role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effect that addresses the question of how changes in these factors affect variability at the expression level in a systematic rather than case-by-case fashion. Here we make such an effort, based on a mechanic model that maps three fundamental patterns for two interacting DNA loops into a 4-state model of stochastic transcription. We first show that in contrast to side-by-side loops, nested loops enhance mRNA expression and reduce expression noise whereas alternating loops have just opposite effects. Then, we compare effects of facilitated tracking and direct looping on gene expression. We find that the former performs better than the latter in controlling mean expression and in tuning expression noise, but this control or tuning is distance-dependent, remarkable for moderate loop lengths, and there is a limit loop length such that the difference in effect between two communication forms almost disappears. Our analysis and results justify the facilitated chromatin-looping hypothesis.

  12. Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene

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    Yang Ming

    2012-07-01

    Full Text Available Abstract Background MUC4 is a type of membrane anchored glycoprotein and serves as the major constituent of mucus that covers epithelial surfaces of many tissues such as trachea, colon and cervix. MUC4 plays important roles in the lubrication and protection of the surface epithelium, cell proliferation and differentiation, immune response, cell adhesion and cancer development. To gain insights into the evolution of the porcine MUC4 gene, we surveyed the nucleotide variability and linkage disequilibrium (LD within this gene in Chinese indigenous breeds and Western commercial breeds. Results A total of 53 SNPs covering the MUC4 gene were genotyped on 5 wild boars and 307 domestic pigs representing 11 Chinese breeds and 3 Western breeds. The nucleotide variability, haplotype phylogeny and LD extent of MUC4 were analyzed in these breeds. Both Chinese and Western breeds had considerable nucleotide diversity at the MUC4 locus. Western pig breeds like Duroc and Large White have comparable nucleotide diversity as many of Chinese breeds, thus artificial selection for lean pork production have not reduced the genetic variability of MUC4 in Western commercial breeds. Haplotype phylogeny analyses indicated that MUC4 had evolved divergently in Chinese and Western pigs. The dendrogram of genetic differentiation between breeds generally reflected demographic history and geographical distribution of these breeds. LD patterns were unexpectedly similar between Chinese and Western breeds, in which LD usually extended less than 20 kb. This is different from the presumed high LD extent (more than 100 kb in Western commercial breeds. The significant positive Tajima’D, and Fu and Li’s D statistics in a few Chinese and Western breeds implied that MUC4 might undergo balancing selection in domestic breeds. Nevertheless, we cautioned that the significant statistics could be upward biased by SNP ascertainment process. Conclusions Chinese and Western breeds have

  13. A large-scale study of the random variability of a coding sequence: a study on the CFTR gene.

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    Modiano, Guido; Bombieri, Cristina; Ciminelli, Bianca Maria; Belpinati, Francesca; Giorgi, Silvia; Georges, Marie des; Scotet, Virginie; Pompei, Fiorenza; Ciccacci, Cinzia; Guittard, Caroline; Audrézet, Marie Pierre; Begnini, Angela; Toepfer, Michael; Macek, Milan; Ferec, Claude; Claustres, Mireille; Pignatti, Pier Franco

    2005-02-01

    Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (n(g) approximately 100-150 genes). In the present investigation, a large random European population sample (average n(g) approximately 1500) was studied for a single gene, the CFTR (Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q > 0.005), much lower than that of the synonymous (S) substitutions, but they showed a similar rate of subpolymorphic (q < 0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic.

  14. Tools to minimize interlaboratory variability in vitellogenin gene expression monitoring programs

    Science.gov (United States)

    Jastrow, Aaron; Gordon, Denise A.; Auger, Kasie M.; Punska, Elizabeth C.; Arcaro, Kathleen F.; Keteles, Kristen; Winkelman, Dana L.; Lattier, David; Biales, Adam; Lazorchak, James M.

    2017-01-01

    The egg yolk precursor protein vitellogenin is widely used as a biomarker of estrogen exposure in male fish. However, standardized methodology is lacking and little is known regarding the reproducibility of results among laboratories using different equipment, reagents, protocols, and data analysis programs. To address this data gap we tested the reproducibility across laboratories to evaluate vitellogenin gene (vtg) expression and assessed the value of using a freely available software data analysis program. Samples collected from studies of male fathead minnows (Pimephales promelas) exposed to 17α-ethinylestradiol (EE2) and minnows exposed to processed wastewater effluent were evaluated for vtg expression in 4 laboratories. Our results indicate reasonable consistency among laboratories if the free software for expression analysis LinRegPCR is used, with 3 of 4 laboratories detecting vtg in fish exposed to 5 ng/L EE2 (n = 5). All 4 laboratories detected significantly increased vtg levels in 15 male fish exposed to wastewater effluent compared with 15 male fish held in a control stream. Finally, we were able to determine that the source of high interlaboratory variability from complementary deoxyribonucleic acid (cDNA) to quantitative polymerase chain reaction (qPCR) analyses was the expression analysis software unique to each real-time qPCR machine. We successfully eliminated the interlaboratory variability by reanalyzing raw fluorescence data with independent freeware, which yielded cycle thresholds and polymerase chain reaction (PCR) efficiencies that calculated results independently of proprietary software. Our results suggest that laboratories engaged in monitoring programs should validate their PCR protocols and analyze their gene expression data following the guidelines established in the present study for all gene expression biomarkers. 

  15. Do motor control genes contribute to interindividual variability in decreased movement in patients with pain?

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    Mishra Bikash K

    2007-07-01

    Full Text Available Abstract Background Because excessive reduction in activities after back injury may impair recovery, it is important to understand and address the factors contributing to the variability in motor responses to pain. The current dominant theory is the "fear-avoidance model", in which the some patients' heightened fears of further injury cause them to avoid movement. We propose that in addition to psychological factors, neurochemical variants in the circuits controlling movement and their modification by pain may contribute to this variability. A systematic search of the motor research literature and genetic databases yielded a prioritized list of polymorphic motor control candidate genes. We demonstrate an analytic method that we applied to 14 of these genes in 290 patients with acute sciatica, whose reduction in movement was estimated by items from the Roland-Morris Disability Questionnaire. Results We genotyped a total of 121 single nucleotide polymorphisms (SNPs in 14 of these genes, which code for the dopamine D2 receptor, GTP cyclohydrolase I, glycine receptor α1 subunit, GABA-A receptor α2 subunit, GABA-A receptor β1 subunit, α-adrenergic 1C, 2A, and 2C receptors, serotonin 1A and 2A receptors, cannabinoid CB-1 receptor, M1 muscarinic receptor, and the tyrosine hydroxylase, and tachykinin precursor-1 molecules. No SNP showed a significant association with the movement score after a Bonferroni correction for the 14 genes tested. Haplotype analysis of one of the blocks in the GABA-A receptor β1 subunit showed that a haplotype of 11% frequency was associated with less limitation of movement at a nominal significance level value (p = 0.0025 almost strong enough to correct for testing 22 haplotype blocks. Conclusion If confirmed, the current results may suggest that a common haplotype in the GABA-A β1 subunit acts like an "endogenous muscle relaxant" in an individual with subacute sciatica. Similar methods might be applied a larger set of

  16. IGF-I gene variability is associated with an increased risk for AD.

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    Vargas, Teo; Martinez-Garcia, Ana; Antequera, Desiree; Vilella, Elisabet; Clarimon, Jordi; Mateo, Ignacio; Sanchez-Juan, Pascual; Rodriguez-Rodriguez, Eloy; Frank, Ana; Rosich-Estrago, Marcel; Lleo, Alberto; Molina-Porcel, Laura; Blesa, Rafael; Gomez-Isla, Teresa; Combarros, Onofre; Bermejo-Pareja, Felix; Valdivieso, Fernando; Bullido, Maria Jesus; Carro, Eva

    2011-03-01

    Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide spectrum of actions in the adult brain, is involved in the pathogenesis of Alzheimer's disease (AD). Circulating levels of IGF-I change in AD patients and are implicated in the clearance of brain amyloid beta (Aβ) complexes. To investigate this hypothesis, we screened the IGF-I gene for various well known single nucleotide polymorphisms (SNPs) covering % of the gene variability in a population of 2352 individuals. Genetic analysis indicated different distribution of genotypes of 1 single nucleotide polymorphism, and 1 extended haplotype in the AD population compared with healthy control subjects. In particular, the frequency of rs972936 GG genotype was significantly greater in AD patients than in control subjects (63% vs. 55%). The rs972936 GG genotype was associated with an increased risk for disease, independently of apolipoprotein E genotype, and with enhanced circulating levels of IGF-I. These findings suggest that polymorphisms within the IGF-I gene could infer greater risk for AD through their effect on IGF-I levels, and confirm the physiological role IGF-I in the pathogenesis of AD. Copyright © 2011 IBRO. Published by Elsevier Inc. All rights reserved.

  17. Variability of Pasteurella multocida isolated from Icelandic sheep and detection of the toxA gene.

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    Einarsdottir, Thorbjorg; Gunnarsson, Eggert; Sigurdardottir, Olof G; Jorundsson, Einar; Fridriksdottir, Vala; Thorarinsdottir, Gudridur E; Hjartardottir, Sigridur

    2016-09-01

    Pasteurella multocida can be part of the upper respiratory flora of animals, but under conditions of stress or immunocompromisation, the bacteria can cause severe respiratory symptoms. In this study, we compared 10 P. multocida isolates from Icelandic sheep with respiratory symptoms and 19 isolates from apparently healthy abattoir sheep. We examined capsule type, genetic variability and the presence of the toxA gene in the two groups. Surprisingly, we found that all ovine P. multocida isolates examined in this study carried the toxA gene, which markedly differs from what has been published from other studies. Interestingly, all isolates from abattoir animals were capsule type D, whilst bacteria isolated from animals with clinical respiratory symptoms had capsule type A, D or F. Examination of seven housekeeping genes indicated that the clinical respiratory isolates were significantly more heterogeneous than the abattoir isolates (Pmultocida in sheep - a genetically homogeneous group that resides in the respiratory tract and a genetically heterogeneous group that is the predominant cause of disease.

  18. Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma.

    Science.gov (United States)

    Kleinfield, R; Hardy, R R; Tarlinton, D; Dangl, J; Herzenberg, L A; Weigert, M

    The early stages of murine B-cell differentiation are characterized by a series of immunoglobulin gene rearrangements which are required for the assembly of heavy(H) and light(L)-chain variable regions from germline gene segments. Rearrangement at the heavy-chain locus is initiated first and consists of the joining of a diversity (DH) gene segment to a joining (JH) gene segment. This forms a DJH intermediate to which a variable (VH) gene segment is subsequently added. Light-chain gene rearrangement follows and consists of the joining of a VL gene segment to a JL gene segment: once a productive light-chain gene has been formed the cell initiates synthesis of surface immunoglobulin M (sIgM) receptors (reviewed in ref. 1). These receptors are clonally distributed and may undergo further diversification either by somatic mutation or possibly by continued recombinational events. Such recombinational events have been detected in the Ly 1+ B-cell lymphoma NFS-5, which has been shown to rearrange both lambda and H-chain genes subsequent to the formation of sIgM (mu kappa) molecules. Here we have analysed a rearrangement of the productive allele of NFS-5 and found that it is due to a novel recombination event between VH genes which results in the replacement of most or all of the coding sequence of the initial VHQ52 rearrangement by a germline VH7183 gene. Embedded in the VH coding sequence close to the site of the cross-over is the sequence 5' TACTGTG 3', which is identical to the signal heptamer found 5' of many DH gene segments. This embedded heptamer is conserved in over 70% of known VH genes. We suggest that this heptamer mediates VH gene replacement and may play an important part in the development of the antibody repertoire.

  19. Analysis of biological and technical variability in gene expression assays from formalin-fixed paraffin-embedded classical Hodgkin lymphomas.

    Science.gov (United States)

    Vera-Lozada, Gabriela; Scholl, Vanesa; Barros, Mário Henrique M; Sisti, Davide; Guescini, Michele; Stocchi, Vilberto; Stefanoff, Claudio Gustavo; Hassan, Rocio

    2014-12-01

    Formalin-fixed paraffin-embedded (FFPE) tissues are invaluable sources of biological material for research and diagnostic purposes. In this study, we aimed to identify biological and technical variability in RT-qPCR TaqMan® assays performed with FFPE-RNA from lymph nodes of classical Hodgkin lymphoma samples. An ANOVA-nested 6-level design was employed to evaluate BCL2, CASP3, IRF4, LYZ and STAT1 gene expression. The most variable genes were CASP3 (low expression) and LYZ (high expression). Total variability decreased after normalization for all genes, except by LYZ. Genes with moderate and low expression were identified and suffered more the effects of the technical manipulation than high-expression genes. Pre-amplification was shown to introduce significant technical variability, which was partially alleviated by lowering to a half the amount of input RNA. Ct and Cy0 quantification methods, based on cycle-threshold and the kinetic of amplification curves, respectively, were compared. Cy0 method resulted in higher quantification values, leading to the decrease of total variability in CASP3 and LYZ genes. The mean individual noise was 0.45 (0.31 to 0.61 SD), indicating a variation of gene expression over ~1.5 folds from one case to another. We showed that total variability in RT-qPCR from FFPE-RNA is not higher than that reported for fresh complex tissues, and identified gene-, and expression level-sources of biological and technical variability, which can allow better strategies for designing RT-qPCR assays from highly degraded and inhibited samples. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Genetic variability and mRNA editing frequencies of the phosphoprotein genes of wild-type measles viruses.

    Science.gov (United States)

    Bankamp, B; Lopareva, E N; Kremer, J R; Tian, Y; Clemens, M S; Patel, R; Fowlkes, A L; Kessler, J R; Muller, C P; Bellini, W J; Rota, P A

    2008-08-01

    The sequences of the nucleoprotein (N) and hemagglutinin (H) genes are routinely used for molecular epidemiologic studies of measles virus (MV). However, the amount of genetic diversity contained in other genes of MV has not been thoroughly evaluated. In this report, the nucleotide sequences of the phosphoprotein (P) genes from 34 wild-type strains representing 15 genotypes of MV were analyzed and found to be almost as variable as the H genes but less variable than the N genes. Deduced amino acid sequences of the three proteins encoded by the P gene, P, V and C, demonstrated considerably higher variability than the H proteins. Phylogenetic analysis showed the same tree topography for the P gene sequences as previously seen for the N and H genes. RNA editing of P gene transcripts affects the relative ratios of P and V proteins, which may have consequences for pathogenicity. Wild-type isolates produced more transcripts with more than one G insertion; however, there was no significant difference in the use of P and V open reading frames, suggesting that the relative amounts of P and V proteins in infected cells would be similar for both vaccine and wild-type strains.

  1. Genetic variability in the methylenetetrahydrofolate reductase gene (MTHFR) affects clinical expression of Wilson's disease.

    Science.gov (United States)

    Gromadzka, Grażyna; Rudnicka, Magdalena; Chabik, Grzegorz; Przybyłkowski, Adam; Członkowska, Anna

    2011-10-01

    Wilson's disease (WND) is an autosomal recessive disorder of copper (Cu) transport, resulting from pathogenic mutations in the ATP7B gene. The reason for the high variability in phenotypic expressions of WND is unknown. Hepatotoxic and neurotoxic effects of homocysteine (Hcy), as well as interrelationships between Hcy and Cu toxicity, were documented. We genotyped the two 5,10-methylenetetrahydrofolate reductase (one of the key folate/Hcy pathway enzymes) gene (MTHFR) polymorphisms: C677T and A1298C in 245 WND patients. Next, we tested the modulation of WND phenotypes by genotypes of MTHFR. MTHFR C677T genotype distribution deviated from that expected from a population in Hardy-Weinberg equilibrium (C677T, χ(2) = 12.14, p = 0.0005). Patients with the MTHFR 1298C allele were younger at symptoms' onset than those without this allele (median (IQR) age, 24.9 (14.0) years vs. 28.5 (12.0) years, p = 0.006). Carriers of MTHFR "high activity" diplotype (double wild-type homozygotes 677CC/1298AA) manifested WND at older age, than non-carriers (median (IQR) age, 33.5 (9.0) years vs. 25.0 (13.0) years, p = 0.0009). Patients with the MTHFR 677T allele less frequently exhibited the neurological WND phenotype (31 (29.5%) vs. 36 (48.0%)), and more frequently presented with hepatic WND (44 (41.9%) vs. 22 (29.3%)), compared with subjects MTHFR 677T(-). We postulate that MTHFR polymorphism contributes to the phenotypic variability of WND. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Fruit specific variability in capsaicinoid accumulation and transcription of structural and regulatory genes in Capsicum fruit

    Science.gov (United States)

    Keyhaninejad, Neda; Curry, Jeanne; Romero, Joslynn; O’Connell, Mary A.

    2013-01-01

    Accumulation of capsaicinoids in the placental tissue of ripening chile (Capsicum spp.) fruit follows the coordinated expression of multiple biosynthetic enzymes producing the substrates for capsaicin synthase. Transcription factors are likely agents to regulate expression of these biosynthetic genes. Placental RNAs from habanero fruit (C. chinense) were screened for expression of candidate transcription factors; with two candidate genes identified, both in the ERF family of transcription factors. Characterization of these transcription factors, Erf and Jerf, in nine chile cultivars with distinct capsaicinoid contents demonstrated a correlation of expression with pungency. Amino acid variants were observed in both ERF and JERF from different chile cultivars; none of these changes involved the DNA binding domains. Little to no transcription of Erf was detected in non-pungent C. annuum or C. chinense mutants. This correlation was characterized at an individual fruit level in a set of jalapeño (C. annuum) lines again with distinct and variable capsaicinoid contents. Both Erf and Jerf are expressed early in fruit development, 16–20 days post-anthesis, at times prior to the accumulation of capsaicinoids in the placental tissues. These data support the hypothesis that these two members of the complex ERF family participate in regulation of the pungency phenotype in chile. PMID:24388515

  3. Biofilm formation and genetic variability of BCR1 gene in the Candida parapsilosis complex.

    Science.gov (United States)

    Treviño-Rangel, Rogelio de J; Rodríguez-Sánchez, Irám P; Rosas-Taraco, Adrián G; Hernández-Bello, Romel; González, José G; González, Gloria M

    2015-01-01

    Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis are cryptic species that belong to the C. parapsilosis complex, which has been increasingly associated to fungemia in various geographic regions, principally due to the capability of these yeasts to form biofilms on indwelling medical devices. BCR1 is one of the most studied genes related to Candida spp. biofilms. To evaluate the biofilm forming capability of a subset of 65 clinical isolates of the C. parapsilosis complex using two conventional approaches, and to look for an association between the biofilm forming phenotype and genetic variants of a fragment of BCR1. The biofilm determination was carried out by crystal violet staining and tetrazolium reduction assay. On the other hand, a segment of BCR1 gene was sequenced by Sanger methodology. C. parapsilosis sensu stricto was statistically associated with a low biofilm production phenotype, while C. orthopsilosis was significantly associated with both phenotypes (high and low biofilm producers). According to the BCR1 sequence analysis, genetic variability was detected in C. orthopsilosis and C. metapsilosis without a particular biofilm formation phenotype association. Under the adopted experimental design, C. parapsilosis sensu stricto was associated with the low biofilm phenotype and C. orthopsilosis with both phenotypes (high and low biofilm producers). On the other hand, an association between a biofilm forming phenotype and a particular genetic variant of the analyzed BCR1 fragment was not found. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  4. Clinicopathological variables predicting HER-2 gene status in immunohistochemistry-equivocal (2+) invasive breast cancer.

    Science.gov (United States)

    Ji, Yongling; Sheng, Liming; Du, Xianghui; Qiu, Guoqin; Chen, Bo; Wang, Xiaojia

    2014-07-01

    Human epidermal growth factor receptor-2 (HER-2) gene status is crucial to guide treatment decisions regarding the use of HER-2-targeted therapies in breast cancer. An invasive breast cancer with HER-2 2+ score is regarded as HER-2 status equivocal and should further determine by fluorescent in situ hybridization (FISH), which is considered the standard test for HER-2 status. Here, we aimed to establish a risk score to allow for prediction of the presence of HER-2 gene status. A total of 182 HER-2 2+ by immunohistochemistry (IHC) invasive breast cancer cases were enrolled in this study. The association between clinicopathological variables like age, sex, tumor grade, hormone receptor (HR) status, P53 and proliferation index (Ki67), and FISH result using US Food and Drug Administration (FDA) criteria was evaluated. Also, we compared the HER-2 FISH results using FDA criteria and 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline. The study population had a median age of 48 years (range, 29-78 years). Estrogen receptor (ER) was expressed in 131 (72.0%) patients. 73.1% of patients (133/182) were progesterone receptor (PR) positive. The median Ki67 value was 20% (range, 3-90%). There was good agreement between the FDA and 2013 ASCO/CAP guideline. Sixty-three of all patients were HER-2 FISH amplified (positive) based on FDA criteria. Tumors with HER-2 amplified were more likely to harbor ER negative (58.8% vs. 25.2%, PHER-2 amplified groups (P=0.006). We created a risk score that comprised HR, P53 and Ki67. A significant association between risk score and HER-2 FISH amplification was observed (χ(2)=30.41, PHER-2 gene status in invasive breast cancer.

  5. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis.

    Science.gov (United States)

    Davisson, Muriel T; Cook, Susan A; Akeson, Ellen C; Liu, Don; Heffner, Caleb; Gudis, Polyxeni; Fairfield, Heather; Murray, Stephen A

    2015-06-15

    Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis. Copyright © 2015 the American Physiological Society.

  6. Multiple and variable NHEJ-like genes are involved in resistance to DNA damage in Streptomyces ambofaciens

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    Grégory Hoff

    2016-11-01

    Full Text Available Non homologous end-joining (NHEJ is a double strand break (DSB repair pathway which does not require any homologous template and can ligate two DNA ends together. The basic bacterial NHEJ machinery involves two partners: the Ku protein, a DNA end binding protein for DSB recognition and the multifunctional LigD protein composed a ligase, a nuclease and a polymerase domain, for end processing and ligation of the broken ends. In silico analyses performed in the 38 sequenced genomes of Streptomyces species revealed the existence of a large panel of NHEJ-like genes. Indeed, ku genes or ligD domain homologues are scattered throughout the genome in multiple copies and can be distinguished in two categories: the core NHEJ gene set constituted of conserved loci and the variable NHEJ gene set constituted of NHEJ-like genes present in only a part of the species. In Streptomyces ambofaciens ATCC 23877, not only the deletion of core genes but also that of variable genes led to an increased sensitivity to DNA damage induced by electron beam irradiation. Multiple mutants of ku, ligase or polymerase encoding genes showed an aggravated phenotype compared to single mutants. Biochemical assays revealed the ability of Ku-like proteins to protect and to stimulate ligation of DNA ends. RT-qPCR and GFP fusion experiments suggested that ku-like genes show a growth phase dependent expression profile consistent with their involvement in DNA repair during spores formation and/or germination.

  7. Role of Metastasis in Hypertabastic Survival Analysis of Breast Cancer: Interaction with Clinical and Gene Expression Variables

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    Mohammad A. Tabatabai Ph.D.

    2012-01-01

    Full Text Available This paper analyzes the survival of breast cancer patients, exploring the role of a metastasis variable in combination with clinical and gene expression variables. We use the hypertabastic model in a detailed analysis of 295 breast cancer patients from the Netherlands Cancer Institute given in. 1 In comparison to Cox regression the increase in accuracy is complemented by the ability to analyze the time course of the disease progression using the explicitly described hazard and survival curves. We also demonstrate the ability to compute deciles for survival and probability of survival to a given time. Our primary concern in this article is the introduction of a variable representing the existence of metastasis and the effects on the other clinical and gene expression variables. In addition to making a quantitative assessment of the impact of metastasis on the prospects for survival, we are able to look at its interactions with the other prognostic variables. The estrogen receptor status increase in importance, while the significance of the gene expression variables used in the combined model diminishes. When considering only the subgroup of patients who experienced metastasis, the covariates in the model are only the clinical variables for estrogen receptor status and tumor grade.

  8. Hidden variability of floral homeotic B genes in Solanaceae provides a molecular basis for the evolution of novel functions.

    Science.gov (United States)

    Geuten, Koen; Irish, Vivian

    2010-08-01

    B-class MADS box genes specify petal and stamen identities in several core eudicot species. Members of the Solanaceae possess duplicate copies of these genes, allowing for diversification of function. To examine the changing roles of such duplicate orthologs, we assessed the functions of B-class genes in Nicotiana benthamiana and tomato (Solanum lycopersicum) using virus-induced gene silencing and RNA interference approaches. Loss of function of individual duplicates can have distinct phenotypes, yet complete loss of B-class gene function results in extreme homeotic transformations of petal and stamen identities. We also show that these duplicate gene products have qualitatively different protein-protein interaction capabilities and different regulatory roles. Thus, compensatory changes in B-class MADS box gene duplicate function have occurred in the Solanaceae, in that individual gene roles are distinct, but their combined functions are equivalent. Furthermore, we show that species-specific differences in the stamen regulatory network are associated with differences in the expression of the microRNA miR169. Whereas there is considerable plasticity in individual B-class MADS box transcription factor function, there is overall conservation in the roles of the multimeric MADS box B-class protein complexes, providing robustness in the specification of petal and stamen identities. Such hidden variability in gene function as we observe for individual B-class genes can provide a molecular basis for the evolution of regulatory functions that result in novel morphologies.

  9. High variability of expression profiles of homeologous genes for Wnt, Hh, Notch, and Hippo signaling pathways in Xenopus laevis.

    Science.gov (United States)

    Michiue, Tatsuo; Yamamoto, Takayoshi; Yasuoka, Yuuri; Goto, Toshiyasu; Ikeda, Takafumi; Nagura, Kei; Nakayama, Takuya; Taira, Masanori; Kinoshita, Tsutomu

    2017-06-15

    Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeologous gene pairs and 29 singletons). This conservation rate of homeologs is much higher than that of all genes in the X. laevis genome (86.9% vs 60.2%). Among singletons, 24 genes are retained in the L subgenome, a rate similar to the average for all genes (82.8% vs 74.6%). In addition, as general components of signal transduction, we also analyzed 32 heparan sulfate proteoglycan (HSPG)-related genes and eight TLE/Groucho transcriptional corepressors-related genes. In these gene sets, all homeologous pairs have been retained. Transcriptome analysis using RNA-seq data from developmental stages and adult tissues demonstrated that most homeologous pairs of signaling components have variable expression patterns, in contrast to the conservative expression profiles of homeologs for transcription factors. Our results indicate that homeologous gene pairs for cell signaling regulation have tended to become subfunctionalized after allotetraploidization. Diversification of signaling pathways by subfunctionalization of homeologs may enhance environmental adaptability. These results provide insights into the evolution of signaling pathways after polyploidization. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The Variability of Growth Hormone Gene Associated with Ultrasound Imaging of Longissimus dorsi Muscle and Perirenal Fat in Rabbits

    Directory of Open Access Journals (Sweden)

    T. I. Amalianingsih

    2014-04-01

    Full Text Available Identification of genes in rabbits correlated to economic traits were intended to improve and develop their genetic quality. The objective of this research was to analyze the variability of growth hormone gene (GH in three rabbit breeds, i.e. Rex, Satin, and Reza (Rex and Satin crosses then was associated with ultrasound imaging of Longissimus dorsi muscle and perirenal fat thickness. Identification of the variability of growth hormone gene was analyzed using PCR RFLP technique from blood samples of 33 mature male rabbits in Indonesian Research Institute for Animal Production (IRIAP. Thickness of Longissimus dorsi muscle and perirenal fat were imaged and measured by using ultrasound unit at 2nd to 3rd lumbar vertebrae in the left body side. PCR product of GH gene fragment (231 base pair /bp was digested with restriction enzyme Bsh1236I. PCR-RFLP patterns were allele T resulted in an undigested fragment of 231 bp; allele C resulted in fragment of 169 bp and 62 bp. The result showed that Bsh1236I GH gene had three genotypes, i.e. CC, TT, and CT. There were signifficant association of Longissimus dorsi muscle thickness between rabbit breed (P<0.05. There was no significant association between GH Bsh1236I gene polymorphism and imaging ultrasound of Longissimus dorsi muscle and perirenal fat thickness. The association of characteristic genotype of GH|Bsh1236I gene with measurement phenotype was not significant, however it had potency as marker assisted selection (MAS.

  11. Genetic variability in ESAG6 genes among Trypanosoma evansi isolates and in comparison to other Trypanozoon members.

    Science.gov (United States)

    Witola, William H; Sarataphan, Nopporn; Inoue, Noboru; Ohashi, Kazuhiko; Onuma, Misao

    2005-01-01

    Bloodstream trypanosomes take up iron needed for their propagation through the transferrin receptor that, in Trypanosoma brucei, is encoded by expression-site-associated genes (ESAGs), ESAG6 and 7 genes located in variant surface glycoprotein expression sites. ESAG6 and 7 genes in different expression sites have been shown to encode transferrin receptors with varying affinities for polymorphic transferrins. T. brucei could cope with the different host transferrins by switching between expression sites. ESAG6- and 7-encoded transferrin receptor appear to be present in Trypanosoma evansi but the genes have not yet been characterized. In this study, we cloned and sequenced different members of ESAG6 genes in seven isolates of T. evansi from geographically distinct localities in Thailand. We assessed the intra- and inter-species genetic variability in the transferrin receptor gene regions involved in transferrin binding and established that T. evansi, like T. brucei, has widely diverse ESAG6 genes. In addition, T. evansi possess a clade of ESAG6 variants not observed in T. brucei and different T. evansi strains share at least two conserved variants. We further noted that T. evansi possesses all the reported T. equiperdum ESAG6 variants as a subset. Our findings depict a correlation between the genetic diversity in the transferrin-binding regions of ESAG6 genes with the broad host range of T. evansi and T. brucei compared to the narrow host range of Trypanosoma equiperdum.

  12. Associations between period 3 gene polymorphisms and sleep- /chronotype-related variables in patients with late-life insomnia.

    Science.gov (United States)

    Mansour, Hader A; Wood, Joel; Chowdari, Kodavali V; Tumuluru, Divya; Bamne, Mikhil; Monk, Timothy H; Hall, Martica H; Buysse, Daniel J; Nimgaonkar, Vishwajit L

    2017-01-01

    A variable number tandem repeat polymorphism (VNTR) in the period 3 (PER3) gene has been associated with heritable sleep and circadian variables, including self-rated chronotypes, polysomnographic (PSG) variables, insomnia and circadian sleep-wake disorders. This report describes novel molecular and clinical analyses of PER3 VNTR polymorphisms to better define their functional consequences. As the PER3 VNTR is located in the exonic (protein coding) region of PER3, we initially investigated whether both alleles (variants) are transcribed into messenger RNA in human fibroblasts. The VNTR showed bi-allelic gene expression. We next investigated genetic associations in relation to clinical variables in 274 older adult Caucasian individuals. Independent variables included genotypes for the PER3 VNTR as well as a representative set of single nucleotide polymorphisms (SNPs) that tag common variants at the PER3 locus (linkage disequilibrium (LD) between genetic variants variables analyzed individually in prior analyses, dependent measures included PSG total sleep time and sleep latency, self-rated chronotype, estimated with the Composite Scale (CS), and lifestyle regularity, estimated using the social rhythm metric (SRM). Initially, genetic polymorphisms were individually analyzed in relation to each outcome variable using analysis of variance (ANOVA). Nominally significant associations were further tested using regression analyses that incorporated individual ANOVA-associated DNA variants as potential predictors and each of the selected sleep/circadian variables as outcomes. The covariates included age, gender, body mass index and an index of medical co-morbidity. Significant genetic associations with the VNTR were not detected with the sleep or circadian variables. Nominally significant associations were detected between SNP rs1012477 and CS scores (p = 0.003) and between rs10462021 and SRM (p = 0.047); rs11579477 and average delta power (p = 0.043) (analyses uncorrected

  13. Non-classical HLA-E gene variability in Brazilians: a nearly invariable locus surrounded by the most variable genes in the human genome.

    Science.gov (United States)

    Veiga-Castelli, L C; Castelli, E C; Mendes, C T; da Silva, W A; Faucher, M-C; Beauchemin, K; Roger, M; Moreau, P; Donadi, E A

    2012-01-01

    The non-classical human leukocyte antigen (HLA) class I genes present a very low rate of variation. So far, only 10 HLA-E alleles encoding three proteins have been described, but only two are frequently found in worldwide populations. Because of its historical background, Brazilians are very suitable for population genetic studies. Therefore, 104 bone marrow donors from Brazil were evaluated for HLA-E exons 1-4. Seven variation sites were found, including two known single nucleotide polymorphisms (SNPs) at positions +424 and +756 and five new SNPs at positions +170 (intron 1), +1294 (intron 3), +1625, +1645 and +1857 (exon 4). Haplotyping analysis did show eight haplotypes, three of them known as E*01:01:01, E*01:03:01 and E*01:03:02:01 and five HLA-E new alleles that carry the new variation sites. The HLA-E*01:01:01 allele was the predominant haplotype (62.50%), followed by E*01:03:02:01 (24.52%). Selective neutrality tests have disclosed an interesting pattern of selective pressures in which balancing selection is probably shaping allele frequency distributions at an SNP at exon 3 (codon 107), sequence diversity at exon 4 and the non-coding regions is facing significant purifying pressure. Even in an admixed population such as the Brazilian one, the HLA-E locus is very conserved, presenting few polymorphic SNPs in the coding region. © 2011 John Wiley & Sons A/S.

  14. Microbiome characterization using SMRT sequencing on 16S rRNA genes across a range of amplicon sizes and variable region content

    Science.gov (United States)

    The sequence of variable regions along the 16S ribosomal RNA gene is often used to conduct metagenomic surveys of bacterial populations in specific habitats, because of the inter-species variability in these regions and because it is possible to design amplification primers in sections of the gene t...

  15. Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere's disease.

    Science.gov (United States)

    Martín-Sierra, Carmen; Gallego-Martinez, Alvaro; Requena, Teresa; Frejo, Lidia; Batuecas-Caletrío, Angel; Lopez-Escamez, Jose A

    2017-02-01

    Autosomal dominant (AD) familial Meniere's disease (FMD) is a rare disorder involving the inner ear defined by sensorineural hearing loss, tinnitus and episodic vertigo. Here, we have identified two novel and rare heterozygous variants in the SEMA3D and DPT genes segregating with the complete phenotype that have variable expressivity in two pedigrees with AD-FMD. A detailed characterization of the phenotype within each family illustrates the clinical heterogeneity in the onset and progression of the disease. We also showed the expression of both genes in the human cochlea and performed in silico analyses of these variants. Three-dimensional protein modelling showed changes in the structure of the protein indicating potential physical interactions. These results confirm a genetic heterogeneity in FMD with incomplete penetrance and variable expressivity.

  16. Variable penetrance of hypogonadism in a sibship with Kallmann syndrome due to a deletion of the KAL gene

    Energy Technology Data Exchange (ETDEWEB)

    Parenti, G.; Rizzolo, M.G.; Ghezzi, M. [Federico II University, Naples (Italy)] [and others

    1995-07-03

    We report on the clinical and molecular characterization of 3 sibs with X-linked ichthyosis and variable expression of Kallmann syndrome. One of the affected brothers had mild hyposmia and showed normal pubertal progression. However, we demonstrated the same partial deletion of the X-linked Kallmann gene, sparing the first exon in the mildly affected patient as well as in one of his severely affected brothers. 13 refs., 1 fig., 1 tab.

  17. The orthologs of HLA-DQ and -DP genes display abundant levels of variability in macaque species.

    Science.gov (United States)

    Otting, Nel; van der Wiel, Marit K H; de Groot, Nanine; de Vos-Rouweler, Annemiek J M; de Groot, Natasja G; Doxiadis, Gaby G M; Wiseman, Roger W; O'Connor, David H; Bontrop, Ronald E

    2017-02-01

    The human major histocompatibility complex (MHC) region encodes three types of class II molecules designated HLA-DR, -DQ, and -DP. Both the HLA-DQ and -DP gene region comprise a duplicated tandem of A and B genes, whereas in macaques, only one set of genes is present per region. A substantial sequencing project on the DQ and DP genes in various macaque populations resulted in the detection of previously 304 unreported full-length alleles. Phylogenetic studies showed that humans and macaques share trans-species lineages for the DQA1 and DQB1 genes, whereas the DPA1 and DPB1 lineages in macaques appear to be species-specific. Amino acid variability plot analyses revealed that each of the four genes displays more allelic variation in macaques than is encountered in humans. Moreover, the numbers of different amino acids at certain positions in the encoded proteins are higher than in humans. This phenomenon is remarkably prominent at the contact positions of the peptide-binding sites of the deduced macaque DPβ-chains. These differences in the MHC class II DP regions of macaques and humans suggest separate evolutionary mechanisms in the generation of diversity.

  18. Biological characterization and variability of the nucleocapsid protein gene of Groundnut bud necrosis virus isolates infecting pea from India

    Directory of Open Access Journals (Sweden)

    Mohammad AKRAM

    2012-09-01

    Full Text Available A disease of pea characterized by browning in veins, leaves and stems, mostly in growing tips, and brown circular spots on pods, was recorded in four districts of Uttar Pradesh, India. The causal agent of this disease was detected by reverse transcription-polymerase chain reaction (RT-PCR using primers pair HRP 26/HRP 28 and identified as Groundnut bud necrosis virus (GBNV on the basis of nucleocapsid protein (NP gene sequence. Virus isolates from Bareilly (BRY, Kanpur (KNP, Udham Singh Nagar (USN and Shahjahanpur (SJP were designated as GBNV-[Pea_BRY], GBNV-[Pea_KNP], GBNV-[Pea_USN] and GBNV-[Pea_SJP] and their NP genes sequenced. The sequence data of each isolate were deposited at NCBI database (JF281101-JF281104. The complete nucleotide sequence of the NP genes of all the GBNV isolates had a single open reading frame of 831 nucleotides and 276 amino acids. The isolates had among them 2% variability at amino acid level and 2‒3 variability at nucleotide level, but had variability with other GBNV isolates of fabaceous hosts in the range of 0‒6% at amino acid level and 1‒8% at nucleotide level. Though this variation in nucleotide sequences of GBNV isolates from fabaceous hosts is within the limits of species demarcation for tospoviruses, formation of a separate cluster within the GBNV isolates indicates the possibility of distinct variants in GBNV.

  19. Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942

    Directory of Open Access Journals (Sweden)

    Peretó Juli

    2011-01-01

    Full Text Available Abstract Background Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival. Results By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a unusual G+C content; b unusual phylogenetic similarity; and/or c a small number of the highly iterated palindrome 1 (HIP1 motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems. Conclusions Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell.

  20. Logic Learning Machine and standard supervised methods for Hodgkin's lymphoma prognosis using gene expression data and clinical variables.

    Science.gov (United States)

    Parodi, Stefano; Manneschi, Chiara; Verda, Damiano; Ferrari, Enrico; Muselli, Marco

    2018-03-01

    This study evaluates the performance of a set of machine learning techniques in predicting the prognosis of Hodgkin's lymphoma using clinical factors and gene expression data. Analysed samples from 130 Hodgkin's lymphoma patients included a small set of clinical variables and more than 54,000 gene features. Machine learning classifiers included three black-box algorithms ( k-nearest neighbour, Artificial Neural Network, and Support Vector Machine) and two methods based on intelligible rules (Decision Tree and the innovative Logic Learning Machine method). Support Vector Machine clearly outperformed any of the other methods. Among the two rule-based algorithms, Logic Learning Machine performed better and identified a set of simple intelligible rules based on a combination of clinical variables and gene expressions. Decision Tree identified a non-coding gene ( XIST) involved in the early phases of X chromosome inactivation that was overexpressed in females and in non-relapsed patients. XIST expression might be responsible for the better prognosis of female Hodgkin's lymphoma patients.

  1. Phage exposure causes dynamic shifts in the expression states of specific phase-variable genes of Campylobacter jejuni

    DEFF Research Database (Denmark)

    Aidley, Jack; Holst Sørensen, Martine C.; Bayliss, Christopher D.

    2017-01-01

    Phase variation (PV) creates phenotypic heterogeneity at high frequencies and in a reversible manner. This phenomenon allows bacteria to adapt to a variety of different environments and selective pressures. In Campylobacter jejuni this reversible adaptive process is mediated by mutations...... in homopolymeric G/C tracts. Many C. jejuni-specific phages are dependent on phase-variable surface structures for successful infection. We previously identified the capsular polysaccharide (CPS) moiety, MeOPN-GalfNAc, as a receptor for phage F336 and showed that phase-variable expression of the transferase...... for this CPS modification, cj1421, and two other phase-variable CPS genes generated phage resistance in C. jejuni. Here we investigate the population dynamics of C. jejuni NCTC11168 when exposed to phage F336 in vitro using a newly described method - the 28-locus-CJ11168 PV analysis. Dynamic switching...

  2. Monoamine Oxidase A (MAOA Gene and Personality Traits from Late Adolescence through Early Adulthood: A Latent Variable Investigation

    Directory of Open Access Journals (Sweden)

    Man K. Xu

    2017-10-01

    Full Text Available Very few molecular genetic studies of personality traits have used longitudinal phenotypic data, therefore molecular basis for developmental change and stability of personality remains to be explored. We examined the role of the monoamine oxidase A gene (MAOA on extraversion and neuroticism from adolescence to adulthood, using modern latent variable methods. A sample of 1,160 male and 1,180 female participants with complete genotyping data was drawn from a British national birth cohort, the MRC National Survey of Health and Development (NSHD. The predictor variable was based on a latent variable representing genetic variations of the MAOA gene measured by three SNPs (rs3788862, rs5906957, and rs979606. Latent phenotype variables were constructed using psychometric methods to represent cross-sectional and longitudinal phenotypes of extraversion and neuroticism measured at ages 16 and 26. In males, the MAOA genetic latent variable (AAG was associated with lower extraversion score at age 16 (β = −0.167; CI: −0.289, −0.045; p = 0.007, FDRp = 0.042, as well as greater increase in extraversion score from 16 to 26 years (β = 0.197; CI: 0.067, 0.328; p = 0.003, FDRp = 0.036. No genetic association was found for neuroticism after adjustment for multiple testing. Although, we did not find statistically significant associations after multiple testing correction in females, this result needs to be interpreted with caution due to issues related to x-inactivation in females. The latent variable method is an effective way of modeling phenotype- and genetic-based variances and may therefore improve the methodology of molecular genetic studies of complex psychological traits.

  3. Monoamine Oxidase A (MAOA) Gene and Personality Traits from Late Adolescence through Early Adulthood: A Latent Variable Investigation.

    Science.gov (United States)

    Xu, Man K; Gaysina, Darya; Tsonaka, Roula; Morin, Alexandre J S; Croudace, Tim J; Barnett, Jennifer H; Houwing-Duistermaat, Jeanine; Richards, Marcus; Jones, Peter B

    2017-01-01

    Very few molecular genetic studies of personality traits have used longitudinal phenotypic data, therefore molecular basis for developmental change and stability of personality remains to be explored. We examined the role of the monoamine oxidase A gene (MAOA) on extraversion and neuroticism from adolescence to adulthood, using modern latent variable methods. A sample of 1,160 male and 1,180 female participants with complete genotyping data was drawn from a British national birth cohort, the MRC National Survey of Health and Development (NSHD). The predictor variable was based on a latent variable representing genetic variations of the MAOA gene measured by three SNPs (rs3788862, rs5906957, and rs979606). Latent phenotype variables were constructed using psychometric methods to represent cross-sectional and longitudinal phenotypes of extraversion and neuroticism measured at ages 16 and 26. In males, the MAOA genetic latent variable (AAG) was associated with lower extraversion score at age 16 (β = -0.167; CI: -0.289, -0.045; p = 0.007, FDRp = 0.042), as well as greater increase in extraversion score from 16 to 26 years (β = 0.197; CI: 0.067, 0.328; p = 0.003, FDRp = 0.036). No genetic association was found for neuroticism after adjustment for multiple testing. Although, we did not find statistically significant associations after multiple testing correction in females, this result needs to be interpreted with caution due to issues related to x-inactivation in females. The latent variable method is an effective way of modeling phenotype- and genetic-based variances and may therefore improve the methodology of molecular genetic studies of complex psychological traits.

  4. Baseline Chromatin Modification Levels May Predict Interindividual Variability in Ozone-Induced Gene Expression

    Science.gov (United States)

    Traditional toxicological paradigms have relied on factors such as age, genotype, and disease status to explain variability in responsiveness to toxicant exposure; however, these are neither sufficient to faithfully identify differentially responsive individuals nor are they modi...

  5. Spatial, Temporal, and Matrix Variability of Clostridium botulinum Type E Toxin Gene Distribution at Great Lakes Beaches

    Science.gov (United States)

    Oster, Ryan J.; Haack, Sheridan K.; Fogarty, Lisa R.; Tucker, Taaja R.; Riley, Stephen C.

    2015-01-01

    Clostridium botulinum type E toxin is responsible for extensive mortality of birds and fish in the Great Lakes. The C. botulinum bontE gene that produces the type E toxin was amplified with quantitative PCR from 150 sloughed algal samples (primarily Cladophora species) collected during summer 2012 from 10 Great Lakes beaches in five states; concurrently, 74 sediment and 37 water samples from four sites were also analyzed. The bontE gene concentration in algae was significantly higher than in water and sediment (P Lake Front beaches (Lake Michigan) and Bay City State Recreation Area beach on Saginaw Bay (Lake Huron), where 77, 100, and 83% of these algal samples contained the bontE gene, respectively. The highest concentration of bontE was detected at Bay City (1.98 × 105 gene copies/ml of algae or 5.21 × 106 g [dry weight]). This study revealed that the bontE gene is abundant in the Great Lakes but that it has spatial, temporal, and matrix variability. Further, embayed beaches, low wave height, low wind velocity, and greater average water temperature enhance the bontE occurrence. PMID:25888178

  6. Quality assessment and data handling methods for Affymetrix Gene 1.0 ST arrays with variable RNA integrity.

    Science.gov (United States)

    Viljoen, Katie S; Blackburn, Jonathan M

    2013-01-16

    RNA and microarray quality assessment form an integral part of gene expression analysis and, although methods such as the RNA integrity number (RIN) algorithm reliably asses RNA integrity, the relevance of RNA integrity in gene expression analysis as well as analysis methods to accommodate the possible effects of degradation requires further investigation. We investigated the relationship between RNA integrity and array quality on the commonly used Affymetrix Gene 1.0 ST array platform using reliable within-array and between-array quality assessment measures. The possibility of a transcript specific bias in the apparent effect of RNA degradation on the measured gene expression signal was evaluated after either excluding quality-flagged arrays or compensation for RNA degradation at different steps in the analysis. Using probe-level and inter-array quality metrics to assess 34 Gene 1.0 ST array datasets derived from historical, paired tumour and normal primary colorectal cancer samples, 7 arrays (20.6%), with a mean sample RIN of 3.2 (SD = 0.42), were flagged during array quality assessment while 10 arrays from samples with RINs data from irreplaceable clinical samples to be retained in downstream analyses. Here, we demonstrate an effective array-quality assessment strategy, which will allow the user to recognize lower quality arrays that can be included in the analysis once appropriate measures are applied to account for known or unknown sources of variation, such as array quality- and batch- effects, by implementing ComBat or Surrogate Variable Analysis. This approach of quality control and analysis will be especially useful for clinical samples with variable and low RNA qualities, with RIN scores ≥ 2.

  7. Comparative genomics of four closely related Clostridium perfringens bacteriophages reveals variable evolution among core genes with therapeutic potential

    Directory of Open Access Journals (Sweden)

    Siragusa Gregory R

    2011-06-01

    Full Text Available Abstract Background Because biotechnological uses of bacteriophage gene products as alternatives to conventional antibiotics will require a thorough understanding of their genomic context, we sequenced and analyzed the genomes of four closely related phages isolated from Clostridium perfringens, an important agricultural and human pathogen. Results Phage whole-genome tetra-nucleotide signatures and proteomic tree topologies correlated closely with host phylogeny. Comparisons of our phage genomes to 26 others revealed three shared COGs; of particular interest within this core genome was an endolysin (PF01520, an N-acetylmuramoyl-L-alanine amidase and a holin (PF04531. Comparative analyses of the evolutionary history and genomic context of these common phage proteins revealed two important results: 1 strongly significant host-specific sequence variation within the endolysin, and 2 a protein domain architecture apparently unique to our phage genomes in which the endolysin is located upstream of its associated holin. Endolysin sequences from our phages were one of two very distinct genotypes distinguished by variability within the putative enzymatically-active domain. The shared or core genome was comprised of genes with multiple sequence types belonging to five pfam families, and genes belonging to 12 pfam families, including the holin genes, which were nearly identical. Conclusions Significant genomic diversity exists even among closely-related bacteriophages. Holins and endolysins represent conserved functions across divergent phage genomes and, as we demonstrate here, endolysins can have significant variability and host-specificity even among closely-related genomes. Endolysins in our phage genomes may be subject to different selective pressures than the rest of the genome. These findings may have important implications for potential biotechnological applications of phage gene products.

  8. cse, a Chimeric and variable gene, encodes an extracellular protein involved in cellular segregation in Streptococcus thermophilus.

    Science.gov (United States)

    Borges, Frédéric; Layec, Séverine; Thibessard, Annabelle; Fernandez, Annabelle; Gintz, Brigitte; Hols, Pascal; Decaris, Bernard; Leblond-Bourget, Nathalie

    2005-04-01

    The isolation of a Streptococcus thermophilus CNRZ368 mutant displaying a long-chain phenotype allowed us to identify the cse gene (for cellular segregation). The N terminus of Cse exhibits high similarity to Streptococcus agalactiae surface immunogenic protein (SIP), while its C terminus exhibits high similarity to S. thermophilus PcsB. In CNRZ368, deletion of the entire cse open reading frame leads to drastic lengthening of cell chains and altered colony morphology. Complementation of the Deltacse mutation with a wild-type allele restored both wild-type phenotypes. The central part of Cse is a repeat-rich region with low sequence complexity. Comparison of cse from CNRZ368 and LMG18311 strains reveals high variability of this repeat-rich region. To assess the impact of this central region variability, the central region of LMG18311 cse was exchanged with that of CNRZ368 cse. This replacement did not affect chain length, showing that divergence of the central part does not modify cell segregation activity of Cse. The structure of the cse locus suggests that the chimeric organization of cse results from insertion of a duplicated sequence deriving from the pcsB 3' end into an ancestral sip gene. Thus, the cse locus illustrates the module-shuffling mechanism of bacterial gene evolution.

  9. Genetic variability of a population of Aedes aegypti from Paraná, Brazil, using the mitochondrial ND4 gene

    Directory of Open Access Journals (Sweden)

    Adriana L. Twerdochlib

    2012-06-01

    Full Text Available Genetic variability of a population of Aedes aegypti from Paraná, Brazil, using the mitochondrial ND4 gene. To analyze the genetic variability of populations of Aedes aegypti, 156 samples were collected from 10 municipalities in the state of Paraná, Brazil. A 311 base pairs (bp region of the NADH dehydrogenase subunit 4 (ND4 mitochondrial gene was examined. An analysis of this fragment identified eight distinct haplotypes. The mean genetic diversity was high (h = 0.702; p = 0.01556. AMOVA analysis indicated that most of the variation (67% occurred within populations and the F ST value (0.32996 was highly significant. F ST values were significant in most comparisons among cities. The isolation by distance was not significant (r = -0.1216 and p = 0, 7550, indicating that genetic distance is not related to geographic distance. Neighbor-joining analysis showed two genetically distinct groups within Paraná. The DNA polymorphism and AMOVA data indicate a decreased gene flow in populations from Paraná, which can result in increased vectorial competence.

  10. MHC class I and MHC class II DRB gene variability in wild and captive Bengal tigers (Panthera tigris tigris).

    Science.gov (United States)

    Pokorny, Ina; Sharma, Reeta; Goyal, Surendra Prakash; Mishra, Sudanshu; Tiedemann, Ralph

    2010-10-01

    Bengal tigers are highly endangered and knowledge on adaptive genetic variation can be essential for efficient conservation and management. Here we present the first assessment of allelic variation in major histocompatibility complex (MHC) class I and MHC class II DRB genes for wild and captive tigers from India. We amplified, cloned, and sequenced alpha-1 and alpha-2 domain of MHC class I and beta-1 domain of MHC class II DRB genes in 16 tiger specimens of different geographic origin. We detected high variability in peptide-binding sites, presumably resulting from positive selection. Tigers exhibit a low number of MHC DRB alleles, similar to other endangered big cats. Our initial assessment-admittedly with limited geographic coverage and sample size-did not reveal significant differences between captive and wild tigers with regard to MHC variability. In addition, we successfully amplified MHC DRB alleles from scat samples. Our characterization of tiger MHC alleles forms a basis for further in-depth analyses of MHC variability in this illustrative threatened mammal.

  11. Characterization of MTNR1A gene in terms of genetic variability in a ...

    Indian Academy of Sciences (India)

    2015-12-07

    Dec 7, 2015 ... have been associated with seasonal reproductive pattern in sheep breeds like Merino d'arles (Pelletier et al. 2000), small tail Han sheep (Chu et al. 2006), Awasi (Faigl et al. 2008),. Sarda (Carcangiu et al. 2009) and Dorset (Mateescu et al. Keywords. MTNR1A gene; seasonality; genotype; polymorphism.

  12. CD1 gene polymorphisms and phenotypic variability in X-linked adrenoleukodystrophy.

    Directory of Open Access Journals (Sweden)

    Mathieu Barbier

    Full Text Available X-linked adrenoleukodystrophy (X-ALD is characterized by marked phenotypic variation ranging from adrenomyeloneuropathy (AMN to childhood cerebral ALD (CCALD. X-ALD is caused by mutations in the ABCD1 gene, but no genotype-phenotype correlation has been established so far and modifier gene variants are suspected to modulate phenotypes. Specific classes of lipids, enriched in very long-chain fatty acids that accumulate in plasma and tissues from X-ALD patients are suspected to be involved in the neuroinflammatory process of CCALD. CD1 proteins are lipid- antigen presenting molecules encoded by five CD1 genes in human (CD1A-E. Association studies with 23 tag SNPs covering the CD1 locus was performed in 52 patients with AMN and 87 patients with CCALD. The minor allele of rs973742 located 4-kb downstream from CD1D was significantly more frequent in AMN patients (χ² = 7.6; P = 0.006. However, this association was no longer significant after Bonferroni correction for multiple testing. The other polymorphisms of the CD1 locus did not reveal significant association. Further analysis of other CD1D polymorphisms did not detect stronger association with X-ALD phenotypes. Although the association with rs973742 warrants further investigations, these results indicate that the genetic variants of CD1 genes do not contribute markedly to the phenotypic variance of X-ALD.

  13. Intrahost and interhost variability of the HIV type 1 nef gene in Brazilian children.

    Science.gov (United States)

    Cavalieri, Elizabeth; Florido, Camila; Leal, Elcio; Machado, Daisy Maria; Camargo, Michelle; Diaz, Ricardo S; Janini, Luiz Mario

    2009-11-01

    Many aspects of HIV-1 pathogenesis are affected by Nef protein activity, and efforts have been made to study variation in the nef gene and how that variation relates to disease outcome. We studied the genetic diversity of the nef gene in distinct clones obtained from the same patient (intrahost) and in sequences obtained from different hosts (interhost). The set of sequences analyzed was obtained from HIV-1-infected Brazilian children and contained 112 clones from 25 children (intrahost samples), as well as 55 sequences from epidemiologically unlinked children (interhost samples). We found extensive site polymorphisms and amino acid length variations, mainly in the amino terminal region of the nef gene, between the myristoylation motif (MGxxxS) and the MHC-1 downregulation motif (Rxx). Analysis of the sequences deposited in the Los Alamos HIV sequences database ( www.hiv.lanl.gov ) indicated that the most frequent motif at the MHC-1 downregulation site in the subtype B strain is R(86%)A(64%)E(82%) (n = 1040) and R(78%)T(74%)E(56%) in the subtype C strain (n = 549). Conversely, the Brazilian subtype B isolates presented the motif R(81%)T(62%)E(67%) at this site (n = 64). A detailed analysis of selective pressures identified a concentration of codons under strong positive selection in the amino terminal region of the nef gene. We also determined that different sites are under positive selection in the subtype B and subtype C viruses. The amino acid composition in the MHC-1 downregulation motif of the nef gene in our sequences may indicate a distinct adaptive pattern of HIV-1 subtype B to the Brazilian host population.

  14. Genetic variability of Myzus persicae nicotianae densovirus based on partial NS and VP gene sequences.

    Science.gov (United States)

    Song, X R; Tang, S H; Tang, Z Q; Yang, X M; Wang, X W; Wang, X F; Xu, P J; Ren, G W

    2016-11-21

    We previously described a novel densovirus [Myzus persicae nicotianae densovirus (MpnDV)] infecting M. persicae nicotianae (Hemiptera: Aphididae) with 34% prevalence. This single-stranded DNA virus has a 5480-nucleotide ambisense genome and belongs to the Densovirinae subfamily within the family Parvoviridae. In the present study, we estimated the genetic diversity of MpnDV using partial nonstructural protein (NS) and capsid protein (VP) gene sequences from 10 locations in China. First, we identified MpnDV-positive samples by amplifying a 445-bp fragment with primers MpDVF/MpDVR. Subsequently, we amplified and sequenced COI genes with primers MpCOIF/ MpCOIR, and partial NS and VP sequences with primers MpnDVF1/MpnDVR1. The respective 655-, 1461-, and 423-bp COI, NS, and VP fragments were used to analyze the genetic diversity of MpnDV using MEGA 6.0 and DnaSP 5.0. The high level of identity shared by all COI sequences (>99%) suggested that the aphids sampled were of the same species, and indicated population homogeneity across the 10 locations investigated. The nucleotide diversity of MpnDV sequences (0.0020 ± 0.0025) was significantly higher than that of the COI genes (0.0002 ± 0.0005). The pairwise fixation index for MpnDV was 0.832, and the total gene flow was 0.05. Phylogenetic analysis revealed that the MpnDV haplotypes clustered according to geographical location, except for those from the Liaoning and Shanxi provinces. In conclusion, MpnDV demonstrated a low level of gene flow and high genetic diversity, suggesting that it is vertically transmitted, and implying that endosymbiotic viruses could be used as markers in studies of insect population genetics.

  15. Variable salinity responses of 12 alfalfa genotypes and comparative expression analyses of salt-response genes

    Science.gov (United States)

    Twelve alfalfa genotypes that were selected for biomass under salinity, differences in Na and Cl concentrations in shoots and K/Na ratio were evaluated in this long-term salinity experiment. The selected plants were cloned to reduce genetic variability within each genotype. Salt tolerance (ST) index...

  16. Age Dependent Variability in Gene Expression in Fischer 344 Rat Retina.

    Science.gov (United States)

    Recent evidence suggests older adults may be a sensitive population with regard to environmental exposure to toxic compounds. One source of this sensitivity could be an enhanced variability in response. Studies on phenotypic differences have suggested that variation in response d...

  17. The AGT Gene M235T Polymorphism and Response of Power-Related Variables to Aerobic Training

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    Zarębska Aleksandra, Jastrzębski Zbigniew, Moska Waldemar, Leońska-Duniec Agata, Kaczmarczyk Mariusz, Sawczuk Marek, Maciejewska-Skrendo Agnieszka, Żmijewski Piotr, Ficek Krzysztof, Trybek Grzegorz, Lulińska-Kuklik Ewelina, Ekaterina A. Semenova, Ildus I. Ahmetov, Cięszczyk Paweł

    2016-12-01

    Full Text Available The C allele of the M235T (rs699 polymorphism of the AGT gene correlates with higher levels of angiotensin II and has been associated with power and strength sport performance. The aim of the study was to investigate whether or not selected power-related variables and their response to a 12-week program of aerobic dance training are modulated by the AGT M235T genotype in healthy participants. Two hundred and one Polish Caucasian women aged 21 ± 1 years met the inclusion criteria and were included in the study. All women completed a 12-week program of low and high impact aerobics. Wingate peak power and total work capacity, 5 m, 10 m, and 30 m running times and jump height and jump power were determined before and after the training programme. All power-related variables improved significantly in response to aerobic dance training. We found a significant association between the M235T polymorphism and jump-based variables (squat jump (SJ height, p = 0.005; SJ power, p = 0.015; countermovement jump height, p = 0.025; average of 10 countermovement jumps with arm swing (ACMJ height, p = 0.001; ACMJ power, p = 0.035. Specifically, greater improvements were observed in the C allele carriers in comparison with TT homozygotes. In conclusion, aerobic dance, one of the most commonly practiced adult fitness activities in the world, provides sufficient training stimuli for augmenting the explosive strength necessary to increase vertical jump performance. The AGT gene M235T polymorphism seems to be not only a candidate gene variant for power/strength related phenotypes, but also a genetic marker for predicting response to training.

  18. Morphometric Analysis of Larval Rostellar Hooks in Taenia multiceps of Sheep in Iran and Its Association with Mitochondrial Gene Variability.

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    Sima Rostami

    2013-12-01

    Full Text Available The purposes of the present study were morphometric characterization of rostellar hooks of Taenia multiceps and to investigate the association of hook length variation and the variability within two mitochondrial genes of sheep isolates of the parasite.Up to 4500 sheep brains were examined for the presence of C. cerebralis. Biometric characters based on the larval rostellar hook size were measured for each individual isolate. Representative mitochondrial CO1 and 12S rRNA gene sequences for each of the isolates were obtained from NCBI GenBank. Morphometric and genetic data were analyzed using cluster analysis, Interclass Correlation Coefficient (ICC and random effects model.One hundred and fourteen sheep (2.5% were found infected with the coenuri. The minimum and maximum number of scoleces per cyst was 40 and 550 respectively. Each scolex contained 22-27 hooks arranged in two rows of large and small hooks. The average total length of the large and small hooks was 158.9 and 112.1 μm, respectively. Using ICC, statistically significant clusters of different hook sizes were identified within the isolates. The length of the large and small hooks was significantly associated with the variability in mitochondrial 12S rRNA gene.Taenia multiceps, is a relatively important zoonotic infection in Iranian sheep with the prevalence rate of 2.5%. Hook length analysis revealed statistically significant difference among individual isolates. Associations between the rostellar hook length and variability in the mitochondrial 12S rRNA was documented.

  19. Detecting variable (V, diversity (D and joining (J gene segment recombination using a two-colour fluorescence system

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    Scott Gina B

    2010-03-01

    Full Text Available Abstract Background Diversity of immunoglobulins and the T cell antigen receptors is achieved via the recombination activating gene (RAG-mediated rearrangement of variable (V, diversity (D and joining (J gene segments, and this underpins the efficient recognition of a seemingly limitless array of antigens. Analysis of V(DJ recombination activity is typically performed using extrachromosomal recombination substrates that are recovered from transfected cells and selected using bacterial transformation. We have developed a two-colour fluorescence-based system that simplifies detection of both deletion and inversion joining events mediated by RAG proteins. Results This system employs two fluorescent reporter genes that differentially mark unrearranged substrates and those that have undergone RAG-mediated deletion or inversion events. The recombination products bear the hallmarks of true V(DJ recombination and activity can be detected using fluorescence microscopy or flow cytometry. Recombination events can be detected without the need for cytotoxic selection of recombination products and the system allows analysis of recombination activity using substrates integrated into the genome. Conclusions This system will be useful in the analysis and exploitation of the V(DJ recombination machinery and suggests that similar approaches could be used to replace expression of one gene with another during lymphocyte development.

  20. Genetic variability of the serine-rich Entamoeba histolytica protein gene in clinical isolates from the United Arab Emirates.

    Science.gov (United States)

    ElBakri, Ali; Samie, Amidou; Ezzedine, Sinda; Odeh, Ra'ed Abu

    2014-06-01

    The genetic diversity of 20 Entamoeba histolytica isolates from asymptomatic individuals from the UAE was investigated by analyzing polymorphism in the serine-rich E. histolytica gene (SREHP) by nested polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP) on DNA extracted directly from stool samples. The SREHP gene was successfully amplified in 15 out of 20 E. histolytica-positive samples. Four out of the remaining five isolates did not amplify for the SREHP gene. Despite successful amplification of the SREHP gene in the fifth isolate, AluI digestion of the amplified PCR product revealed no bands. As a result, all five samples were excluded from the study. Twelve different profiles were obtained from the 15 successfully amplified isolates. Thus, demonstrating extensive genetic variability and reinforcing the argument that E. histolytica has an extremely polymorphic genetic structure. Despite the sample size limitation, a finding in the study was the occurrence of one profile common to one Indian isolate while another profile common to one Pakistani isolate; indicating the possibility of clonal infection. Furthermore, we found one isolate from a Bangladeshi expatriate identical to 2 asymptomatic Bangladeshi isolates reported in an earlier study. No clear association between the different genotypes and the study population demographics was noted. The results also indicated the possibility of strains clustering by region.

  1. DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

    DEFF Research Database (Denmark)

    Sander, Adam F.; Lavstsen, Thomas; Rask, Thomas Salhøj

    2014-01-01

    -wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum...... falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome...... of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens....

  2. Explaining natural variability in human memory with genes and brain-structure

    OpenAIRE

    Leann, K. L.

    2008-01-01

    The aim of this study was to investigate the influence of candidate genes and brain structure on memory performance. A foreign word-pair association paradigm was designed to provide several dissociable measures of different memory processes. Subjects deeply encoded foreign word pairs with a picture-word matching task. They were tested at five time points over one week which provided measures of learning and forgetting rates, dissociable between measures. Performance was evaluated with respect...

  3. Analysis of sequence variability in the CART gene in relation to obesity in a Caucasian population

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    Hercberg Serge

    2005-04-01

    Full Text Available Abstract Background Cocaine and amphetamine regulated transcript (CART is an anorectic neuropeptide located principally in hypothalamus. CART has been shown to be involved in control of feeding behavior, but a direct relationship with obesity has not been established. The aim of this study was to evaluate the effect of polymorphisms within the CART gene with regards to a possible association with obesity in a Caucasian population. Results Screening of the entire gene as well as a 3.7 kb region of 5' upstream sequence revealed 31 SNPs and 3 rare variants ; 14 of which were subsequently genotyped in 292 French morbidly obese subjects and 368 controls. Haplotype analysis suggested an association with obesity which was found to be mainly due to SNP-3608T>C (rs7379701 (p = 0.009. Genotyping additional cases and controls also of European Caucasian origin supported further this possible association between the CART SNP -3608T>C T allele and obesity (global p-value = 0.0005. Functional studies also suggested that the SNP -3608T>C could modulate nuclear protein binding. Conclusion CART SNP -3608T>C may possibly contribute to the genetic risk for obesity in the Caucasian population. However confirmation of the importance of the role of the CART gene in energy homeostasis and obesity will require investigation and replication in further populations.

  4. Variable Persister Gene Interactions with (pppGpp for Persister Formation in Escherichia coli

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    Shuang Liu

    2017-09-01

    Full Text Available Persisters comprise a group of phenotypically heterogeneous metabolically quiescent bacteria with multidrug tolerance and contribute to the recalcitrance of chronic infections. Although recent work has shown that toxin-antitoxin (TA system HipAB depends on stringent response effector (pppGppin persister formation, whether other persister pathways are also dependent on stringent response has not been explored. Here we examined the relationship of (pppGpp with 15 common persister genes (dnaK, clpB, rpoS, pspF, tnaA, sucB, ssrA, smpB, recA, umuD, uvrA, hipA, mqsR, relE, dinJ using Escherichia coli as a model. By comparing the persister levels of wild type with their single gene knockout and double knockout mutants with relA, we divided their interactions into five types, namely A “dependent” (dnaK, recA, B “positive reinforcement” (rpoS, pspF, ssrA, recA, C “antagonistic” (clpB, sucB, umuD, uvrA, hipA, mqsR, relE, dinJ, D “epistasis” (clpB, rpoS, tnaA, ssrA, smpB, hipA, and E “irrelevant” (dnaK, clpB, rpoS, tnaA, sucB, smpB, umuD, uvrA, hipA, mqsR, relE, dinJ. We found that the persister gene interactions are intimately dependent on bacterial culture age, cell concentrations (diluted versus undiluted culture, and drug classifications, where the same gene may belong to different groups with varying antibiotics, culture age or cell concentrations. Together, this study represents the first attempt to systematically characterize the intricate relationships among the different mechanisms of persistence and as such provide new insights into the complexity of the persistence phenomenon at the level of persister gene network interactions.

  5. Genetic variability in mitochondrial and nuclear genes of Larus dominicanus (Charadriiformes, Laridae) from the Brazilian coast

    OpenAIRE

    de Mendonça Dantas, Gisele Pires; Meyer, Diogo; Godinho, Raquel; Ferrand, Nuno; Morgante, João Stenghel

    2012-01-01

    Several phylogeographic studies of seabirds have documented low genetic diversity that has been attributed to bottleneck events or individual capacity for dispersal. Few studies have been done in seabirds on the Brazilian coast and all have shown low genetic differentiation on a wide geographic scale. The Kelp Gull is a common species with a wide distribution in the Southern Hemisphere. In this study, we used mitochondrial and nuclear markers to examine the genetic variability of Kelp Gull po...

  6. Genetic variability among Schistosoma japonicum isolates from the Philippines, Japan and China revealed by sequence analysis of three mitochondrial genes.

    Science.gov (United States)

    Chen, Fen; Li, Juan; Sugiyama, Hiromu; Zhou, Dong-Hui; Song, Hui-Qun; Zhao, Guang-Hui; Zhu, Xing-Quan

    2015-02-01

    The present study examined sequence variability in the mitochondrial (mt) protein-coding genes cytochrome b (cytb), NADH dehydrogenase subunits 2 and 6 (nad2 and nad6) among 24 isolates of Schistosoma japonicum from different endemic regions in the Philippines, Japan and China. The complete cytb, nad2 and nad6 genes were amplified and sequenced separately from individual schistosome. Sequence variations for isolates from the Philippines were 0-0.5% for cytb, 0-0.6% for nad2, and 0-0.9% for nad6. Variation was 0-0.5%, 0.1-0.8%, 0-0.7% for corresponding genes for schistosome samples from mainland China. For worms in Japan, genetic variations were 0-0.2%, 0.1-0.2% and 0 for the three genes, respectively. Sequence variations were 0-1.0%, 0-1.8% and 0-1.1% for cytb, nad2 and nad6, respectively, among schistosome isolates from different geographical strains in the Philippines, Japan and China. Of the three countries, lowest sequence variations were found between isolates from mainland China and the Philippines and highest were detected between Japan and the Philippines in three mtDNA genes. Phylogenetic analyses based on the combined sequences of cytb, nad2 and nad6 revealed that all isolates in the Philippines clustered together sistered to samples from Yunnan and Zhejiang provinces in China, while isolates from Yamanashi in Japan were in a solitary clade. These results demonstrated the usefulness of the combined three mtDNA sequences for studying genetic diversity and population structure among S. japonicum isolates from the Philippines, China and Japan.

  7. ADQUISICIÓN Y VISUALIZACIÓN DE ESCENAS CON FOCO VARIABLE UTILIZANDO PROCESAMIENTO DIGITAL DE IMÁGENES

    Directory of Open Access Journals (Sweden)

    Pedro Sandino Atencio Ortiz

    Full Text Available La profundidad de campo (DOF, por sus siglas en inglés o profundidad de foco es una característica de un sistema óptico con una configuración en particular, que hace referencia al rango espacial o de distancia que dicha configuración permite mantener de forma nítida o enfocada. Una DOF alta en un sistema óptico es deseada en aplicaciones de microscopía y fotografía macro entre otras aplicaciones. Una solución al problema de una DOF limitada en un sistema óptico consiste en tomar secuencias de imágenes con diferentes distancias focales y posteriormente fusionar dichas imágenes en una sola imagen completamente enfocada. Este proceso es conocido como fusión de imágenes multi-foco (FIMF. La literatura sobre técnicas de FIMF es extensa y de actual interés en la comunidad científica de fusión de imágenes y fotografía computacional. Por el contrario, la literatura que ilustra el proceso completo de FIMF es escasa. En este trabajo es propuesto un método general de FIMF, el cual comienza con la configuración y calibración del sistema óptico, seguido de la implementación de la técnica de fusión y termina con la visualización de dichas imágenes. En este trabajo se utilizó un sistema óptico de bajo costo con una profundidad de campo variable en el rango [0,18 m, ∞]. El método propuesto es aplicable de forma directa para sistemas de adquisición con configuraciones ópticas diferentes.

  8. The radish gene reveals a memory component with variable temporal properties.

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    Holly LaFerriere

    Full Text Available Memory phases, dependent on different neural and molecular mechanisms, strongly influence memory performance. Our understanding, however, of how memory phases interact is far from complete. In Drosophila, aversive olfactory learning is thought to progress from short-term through long-term memory phases. Another memory phase termed anesthesia resistant memory, dependent on the radish gene, influences memory hours after aversive olfactory learning. How does the radish-dependent phase influence memory performance in different tasks? It is found that the radish memory component does not scale with the stability of several memory traces, indicating a specific recruitment of this component to influence different memories, even within minutes of learning.

  9. Patterns of population subdivision, gene flow and genetic variability in the African wild dog (Lycaon pictus).

    Science.gov (United States)

    Girman, D J; Vilà, C; Geffen, E; Creel, S; Mills, M G; McNutt, J W; Ginsberg, J; Kat, P W; Mamiya, K H; Wayne, R K

    2001-07-01

    African wild dogs are large, highly mobile carnivores that are known to disperse over considerable distances and are rare throughout much of their geographical range. Consequently, genetic variation within and differentiation between geographically separated populations is predicted to be minimal. We determined the genetic diversity of mitochondrial DNA (mtDNA) control region sequences and microsatellite loci in seven populations of African wild dogs. Analysis of mtDNA nucleotide diversity suggests that, historically, wild dog populations have been small relative to other large carnivores. However, population declines due to recent habitat loss have not caused a dramatic reduction in genetic diversity. We found one historical and eight recent mtDNA genotypes in 280 individuals that defined two highly divergent clades. In contrast to a previous, more limited, mtDNA analysis, sequences from these clades are not geographically restricted to eastern or southern African populations. Rather, we found a large admixture zone spanning populations from Botswana, Zimbabwe and south-eastern Tanzania. Mitochondrial and microsatellite differentiation between populations was significant and unique mtDNA genotypes and alleles characterized the populations. However, gene flow estimates (Nm) based on microsatellite data were generally greater than one migrant per generation. In contrast, gene flow estimates based on the mtDNA control region were lower than expected given differences in the mode of inheritance of mitochondrial and nuclear markers which suggests a male bias in long-distance dispersal.

  10. Characterization of the Variability of Epstein-Barr Virus Genes in Nasopharyngeal Biopsies: Potential Predictors for Carcinoma Progression.

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    Ana V Banko

    Full Text Available Epstein-Barr virus (EBV infection is a significant factor in the pathogenesis of nasopharyngeal carcinoma, especially in the undifferentiated carcinoma of nasopharyngeal type (UCNT, World Health Organization type III, which is the dominant histopathological type in high-risk areas. The major EBV oncogene is latent membrane protein 1 (LMP1. LMP1 gene shows variability with different tumorigenic and immunogenic potentials. EBV nuclear antigen 1 (EBNA1 regulates progression of EBV-related tumors; however, the influence of EBNA1 sequence variability on tumor pathogenesis is controversial. The aims of this study were to characterize polymorphisms of EBV genes in non-endemic nasopharyngeal carcinoma biopsies and to investigate potential sequence patterns that correlate with the clinical presentation of nasopharyngeal carcinoma. In total, 116 tumor biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT, collected from 2008 to 2014, were evaluated in this study. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. The presence of EBV DNA was significantly distributed between TNM stages. LMP1 variability showed six variants, with the detection of the first China1 and North Carolina variants in European nasopharyngeal carcinoma biopsies. Newly discovered variants Srb1 and Srb2 were UCNT-specific LMP1 polymorphisms. The B95-8 and North Carolina variants are possible predictors for favorable TNM stages. In contrast, deletions in LMP1 are possible risk factors for the most disfavorable TNM stage, independent of EBNA2 or EBNA1 variability. A newly discovered EBNA1 subvariant, P-thr-sv-5, could be a potential diagnostic marker, as it represented a UCNT-specific EBNA1 subvariant. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, type 1/Med

  11. Segmental duplication as one of the driving forces underlying the diversity of the human immunoglobulin heavy chain variable gene region

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    Gao Richeng

    2011-01-01

    Full Text Available Abstract Background Segmental duplication and deletion were implicated for a region containing the human immunoglobulin heavy chain variable (IGHV gene segments, 1.9III/hv3005 (possible allelic variants of IGHV3-30 and hv3019b9 (a possible allelic variant of IGHV3-33. However, very little is known about the ranges of the duplication and the polymorphic region. This is mainly because of the difficulty associated with distinguishing between allelic and paralogous sequences in the IGHV region containing extensive repetitive sequences. Inability to separate the two parental haploid genomes in the subjects is another serious barrier. To address these issues, unique DNA sequence tags evenly distributed within and flanking the duplicated region implicated by the previous studies were selected. The selected tags in single sperm from six unrelated healthy donors were amplified by multiplex PCR followed by microarray detection. In this way, individual haplotypes of different parental origins in the sperm donors could be analyzed separately and precisely. The identified polymorphic region was further analyzed at the nucleotide sequence level using sequences from the three human genomic sequence assemblies in the database. Results A large polymorphic region was identified using the selected sequence tags. Four of the 12 haplotypes were shown to contain consecutively undetectable tags spanning in a variable range. Detailed analysis of sequences from the genomic sequence assemblies revealed two large duplicate sequence blocks of 24,696 bp and 24,387 bp, respectively, and an incomplete copy of 961 bp in this region. It contains up to 13 IGHV gene segments depending on haplotypes. A polymorphic region was found to be located within the duplicated blocks. The variants of this polymorphism unusually diverged at the nucleotide sequence level and in IGHV gene segment number, composition and organization, indicating a limited selection pressure in general. However

  12. Liver X receptor α gene polymorphisms and variable cardiovascular outcomes in patients treated with antihypertensive therapy: results from the INVEST-GENES study.

    Science.gov (United States)

    Price, Elvin Tyrone; Pacanowski, Michael A; Martin, Michael A; Cooper-DeHoff, Rhonda M; Pepine, Carl J; Zineh, Issam; Johnson, Julie A

    2011-06-01

    rarely coinherited and support the directionally opposite effects of the SNPs on the primary outcome. LXRA genotypes were associated with variable risk for cardiovascular outcomes and pharmacogenetic effect in INVEST-GENES. These novel findings suggest that LXRA is a genetic/pharmacogenetic target that should be further explored.

  13. Genetic variability of glutamate-gated chloride channel genes in ivermectin-susceptible and -resistant strains of Cooperia oncophora.

    Science.gov (United States)

    Njue, A I; Prichard, R K

    2004-12-01

    The glutamate-gated chloride channels (GluCls) are members of the ligand-gated ion channel superfamily that are thought to be involved in the mode of action of ivermectin and mechanism of resistance. Using reverse-transcriptase PCR techniques, 2 full-length GluCl cDNAs, encoding GluClalpha3 and GluClbeta subunits, were cloned from Cooperia oncophora, a nematode parasite of cattle. The two sequences show a high degree of identity to similar subunits from other nematodes. The C. oncophora GluClalpha3 subunit is most closely related to the Haemonchus contortus GluClalpha3B subunit, while C. oncophora GluClbeta subunit shares high sequence identity with the H. contortus GluClbeta subunit. Using single-strand conformation polymorphism, the genetic variability of these two genes was analysed in an ivermectin-susceptible isolate and an ivermectin-resistant field isolate of C. oncophora. Statistical analysis suggested an association between the C. oncophora GluClalpha3 gene and ivermectin resistance. No such association was seen with the GluClbeta gene.

  14. Prion protein gene M129V polymorphism and variability in age at migraine onset.

    Science.gov (United States)

    Palmirotta, Raffaele; Ludovici, Giorgia; Egeo, Gabriella; Ialongo, Cristiano; Aurilia, Cinzia; Fofi, Luisa; De Marchis, Maria Laura; Della-Morte, David; Barbanti, Piero; Guadagni, Fiorella

    2013-03-01

    Prion protein, a sialoglycoprotein with neuroprotective properties on oxidative stress damage, has been related with the mechanisms leading to migraine. In the present case-control study, we investigated the correlation between the common methionine/valine polymorphism at codon 129 within the prion protein gene (PRNP) and migraine. Genotyping of PRNP V129M variant was performed in 384 migraine patients and 185 age-, sex-, and race-ethnicity-matched healthy controls. The frequencies of the PRNP V129M genotype did not differ significantly between migraineurs and controls. The frequencies of 129VV genotype were significantly higher in patients with earlier age at migraine onset. No correlation was found between PRNP 129 genotype and demographics, and other clinical migraine features. Our data suggest that the PRNP 129VV polymorphism is not a direct migraine risk factor but is significantly associated with an earlier onset of the disease. © 2013 American Headache Society.

  15. Sequence variability in the coat protein gene of two groups of banana bunchy top isolates.

    Science.gov (United States)

    Wanitchakorn, R; Harding, R M; Dale, J L

    2000-01-01

    Complete nucleotide sequences of the coat protein gene (DNA-3) of banana bunchy top virus (BBTV) were obtained from five geographical isolates by PCR. Analysis of these sequences revealed two distinct groups of BBTV isolates with those from the Philippines, Taiwan and Vietnam forming the Asian group while the South Pacific/African group consisted of isolates from Australia, Burundi and Fiji. At the nucleotide level, the sequences of DNA-3 were more similar between isolates from the same group (maximum 5.86%) than between members of the two different groups (maximum 13.05%). At the amino acid level, the BBTV coat protein remained highly conserved, with a maximum of bananas. The high level of conservation in the BBTV coat protein suggests that any of the DNA-3 sequences presented in this study would probably be equally effective as transgene in attempts to generate transgenic banana plants with resistance to both groups of BBTV isolates.

  16. Variability of some genes of the somatotropic axis in the Piemontese cattle breed

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    S. Sartore

    2011-03-01

    Full Text Available Growth hormone (GH is a major participant in the control of several complex physiological processes, including growth and metabolism. The growth promoting aspects are generally mediated by the insulin-like growth factor 1 (IGF-1, produced primarily in the liver in response to GH, while the metabolic effects are mainly the result of the GH direct binding to its receptors (GHR on target cells. The production of GH is modulated by growth hormone releasing hormone (GHRH and somatostatin (SST; the former stimulates both the synthesis and the secretion of GH, the latter inhibits the GH release (Frohman and Jansson, 1986; Bonneau, 1991; Buyse and Decuypere, 1999; Duclos et al., 1999; Sodhi and Rajput, 2001. Due to the several effects of GH, the genes coding for GH and other hormones and factors involved in growth have been suggested.........

  17. Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

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    Yamini Kashimshetty

    Full Text Available Tropical lowland rain forest (TLRF biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG, which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively than spatial logging pattern (0.2% and 4.7% respectively, with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene

  18. Variable gene dispersal conditions and spatial deforestation patterns can interact to affect tropical tree conservation outcomes.

    Science.gov (United States)

    Kashimshetty, Yamini; Pelikan, Stephan; Rogstad, Steven H

    2015-01-01

    Tropical lowland rain forest (TLRF) biodiversity is under threat from anthropogenic factors including deforestation which creates forest fragments of different sizes that can further undergo various internal patterns of logging. Such interventions can modify previous equilibrium abundance and spatial distribution patterns of offspring recruitment and/or pollen dispersal. Little is known about how these aspects of deforestation and fragmentation might synergistically affect TLRF tree recovery demographics and population genetics in newly formed forest fragments. To investigate these TLRF anthropogenic disturbance processes we used the computer program NEWGARDEN (NG), which models spatially-explicit, individual-based plant populations, to simulate 10% deforestation in six different spatial logging patterns for the plant functional type of a long-lived TLRF canopy tree species. Further, each logging pattern was analyzed under nine varying patterns of offspring versus pollen dispersal distances that could have arisen post-fragmentation. Results indicated that gene dispersal condition (especially via offspring) had a greater effect on population growth and genetic diversity retention (explaining 98.5% and 88.8% of the variance respectively) than spatial logging pattern (0.2% and 4.7% respectively), with 'Near' distance dispersal maximizing population growth and genetic diversity relative to distant dispersal. Within logged regions of the fragment, deforestation patterns closer to fragment borders more often exhibited lower population recovery rates and founding genetic diversity retention relative to more centrally located logging. These results suggest newly isolated fragments have populations that are more sensitive to the way in which their offspring and pollen dispersers are affected than the spatial pattern in which subsequent logging occurs, and that large variation in the recovery rates of different TLRF tree species attributable to altered gene dispersal

  19. Lack of Association of Estrogen Receptor Alpha Gene Polymorphisms with Cardiorespiratory and Metabolic Variables in Young Women

    Directory of Open Access Journals (Sweden)

    Mario Hirata

    2012-10-01

    Full Text Available This study examined the association of estrogen receptor alpha gene (ESR1 polymorphisms with cardiorespiratory and metabolic parameters in young women. In total, 354 healthy women were selected for cardiopulmonary exercise testing and short-term heart rate (HR variability (HRV evaluation. The HRV analysis was determined by the temporal indices rMSSD (square root of the mean squared differences of successive R–R intervals (RRi divided by the number of RRi minus one, SDNN (root mean square of differences from mean RRi, divided by the number of RRi and power spectrum components by low frequency (LF, high frequency (HF and LF/HF ratio. Blood samples were obtained for serum lipids, estradiol and DNA extraction. ESR1 rs2234693 and rs9340799 polymorphisms were analyzed by PCR and fragment restriction analysis. HR and oxygen uptake (VO2 values did not differ between the ESR1 polymorphisms with respect to autonomic modulation. We not find a relationship between ESR1 T–A, T–G, C–A and C–G haplotypes and cardiorespiratory and metabolic variables. Multiple linear regression analysis demonstrated that VO2, total cholesterol and triglycerides influence HRV (p < 0.05. The results suggest that ESR1 variants have no effect on cardiorespiratory and metabolic variables, while HRV indices are influenced by aerobic capacity and lipids in healthy women.

  20. Variability in Dopamine Genes Dissociates Model-Based and Model-Free Reinforcement Learning.

    Science.gov (United States)

    Doll, Bradley B; Bath, Kevin G; Daw, Nathaniel D; Frank, Michael J

    2016-01-27

    Considerable evidence suggests that multiple learning systems can drive behavior. Choice can proceed reflexively from previous actions and their associated outcomes, as captured by "model-free" learning algorithms, or flexibly from prospective consideration of outcomes that might occur, as captured by "model-based" learning algorithms. However, differential contributions of dopamine to these systems are poorly understood. Dopamine is widely thought to support model-free learning by modulating plasticity in striatum. Model-based learning may also be affected by these striatal effects, or by other dopaminergic effects elsewhere, notably on prefrontal working memory function. Indeed, prominent demonstrations linking striatal dopamine to putatively model-free learning did not rule out model-based effects, whereas other studies have reported dopaminergic modulation of verifiably model-based learning, but without distinguishing a prefrontal versus striatal locus. To clarify the relationships between dopamine, neural systems, and learning strategies, we combine a genetic association approach in humans with two well-studied reinforcement learning tasks: one isolating model-based from model-free behavior and the other sensitive to key aspects of striatal plasticity. Prefrontal function was indexed by a polymorphism in the COMT gene, differences of which reflect dopamine levels in the prefrontal cortex. This polymorphism has been associated with differences in prefrontal activity and working memory. Striatal function was indexed by a gene coding for DARPP-32, which is densely expressed in the striatum where it is necessary for synaptic plasticity. We found evidence for our hypothesis that variations in prefrontal dopamine relate to model-based learning, whereas variations in striatal dopamine function relate to model-free learning. Decisions can stem reflexively from their previously associated outcomes or flexibly from deliberative consideration of potential choice outcomes

  1. A Latent Variable Approach for Meta-Analysis of Gene Expression Data from Multiple Microarray Experiments

    Directory of Open Access Journals (Sweden)

    Chinnaiyan Arul M

    2007-09-01

    Full Text Available Abstract Background With the explosion in data generated using microarray technology by different investigators working on similar experiments, it is of interest to combine results across multiple studies. Results In this article, we describe a general probabilistic framework for combining high-throughput genomic data from several related microarray experiments using mixture models. A key feature of the model is the use of latent variables that represent quantities that can be combined across diverse platforms. We consider two methods for estimation of an index termed the probability of expression (POE. The first, reported in previous work by the authors, involves Markov Chain Monte Carlo (MCMC techniques. The second method is a faster algorithm based on the expectation-maximization (EM algorithm. The methods are illustrated with application to a meta-analysis of datasets for metastatic cancer. Conclusion The statistical methods described in the paper are available as an R package, metaArray 1.8.1, which is at Bioconductor, whose URL is http://www.bioconductor.org/.

  2. Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age

    National Research Council Canada - National Science Library

    Coletta, Rocio R D; Jorge, Alexander A L; D'Alva, Catarina Brasil; Pinto, Emília M; Billerbeck, Ana Elisa C; Pachi, Paulo R; Longui, Carlos A; Garcia, Ricardo M; Boguszewski, Margaret; Arnhold, Ivo J P; Mendonca, Berenice B; Costa, Elaine M F

    2013-01-01

    To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age...

  3. Highly variable clinical phenotype of carbamylphosphate synthetase 1 deficiency in one family: an effect of allelic variation in gene expression?

    DEFF Research Database (Denmark)

    Klaus, V; Vermeulen, T; Minassian, B

    2009-01-01

    report two patients from one family with highly divergent clinical course, one presenting neonatally with a fatal form and the other at age 45 with benign diet-responsive disease. The patients are compound heterozygous for two mutations of the CPS1 gene, c.3558 + 1G > C and c.4101 + 2T > C...... of mRNA from the allele with the c.3558 + 1G > C mutation, whereas in the adult-onset case the two types of clones are equal, indicating skewed expression towards the c.4101 + 2T > C allele in the neonatal case. Although we are yet to understand the mechanism of this differential expression, our work...... suggests that allelic imbalance may explain clinical variability in CPS1 deficiency in some families....

  4. Relationship between mRNA secondary structure and sequence variability in Chloroplast genes: possible life history implications

    Directory of Open Access Journals (Sweden)

    Seligmann Hervé

    2008-01-01

    Full Text Available Abstract Background Synonymous sites are freer to vary because of redundancy in genetic code. Messenger RNA secondary structure restricts this freedom, as revealed by previous findings in mitochondrial genes that mutations at third codon position nucleotides in helices are more selected against than those in loops. This motivated us to explore the constraints imposed by mRNA secondary structure on evolutionary variability at all codon positions in general, in chloroplast systems. Results We found that the evolutionary variability and intrinsic secondary structure stability of these sequences share an inverse relationship. Simulations of most likely single nucleotide evolution in Psilotum nudum and Nephroselmis olivacea mRNAs, indicate that helix-forming propensities of mutated mRNAs are greater than those of the natural mRNAs for short sequences and vice-versa for long sequences. Moreover, helix-forming propensity estimated by the percentage of total mRNA in helices increases gradually with mRNA length, saturating beyond 1000 nucleotides. Protection levels of functionally important sites vary across plants and proteins: r-strategists minimize mutation costs in large genes; K-strategists do the opposite. Conclusion Mrna length presumably predisposes shorter mRNAs to evolve under different constraints than longer mRNAs. The positive correlation between secondary structure protection and functional importance of sites suggests that some sites might be conserved due to packing-protection constraints at the nucleic acid level in addition to protein level constraints. Consequently, nucleic acid secondary structure a priori biases mutations. The converse (exposure of conserved sites apparently occurs in a smaller number of cases, indicating a different evolutionary adaptive strategy in these plants. The differences between the protection levels of functionally important sites for r- and K-strategists reflect their respective molecular adaptive

  5. Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells.

    Science.gov (United States)

    Maul, Robert W; Cao, Zheng; Venkataraman, Lakshmi; Giorgetti, Carol A; Press, Joan L; Denizot, Yves; Du, Hansen; Sen, Ranjan; Gearhart, Patricia J

    2014-10-20

    Variable (V) genes of immunoglobulins undergo somatic hypermutation by activation-induced deaminase (AID) to generate amino acid substitutions that encode antibodies with increased affinity for antigen. Hypermutation is restricted to germinal center B cells and cannot be recapitulated in ex vivo-activated splenic cells, even though the latter express high levels of AID. This suggests that there is a specific feature of antigen activation in germinal centers that recruits AID to V genes which is absent in mitogen-activated cultured cells. Using two Igh knock-in mouse models, we found that RNA polymerase II accumulates in V regions in B cells after both types of stimulation for an extended distance of 1.2 kb from the TATA box. The paused polymerases generate abundant single-strand DNA targets for AID. However, there is a distinct accumulation of the initiating form of polymerase, along with the transcription cofactor Spt5 and AID, in the V region from germinal center cells, which is totally absent in cultured cells. These data support a model where mutations are prevalent in germinal center cells, but not in ex vivo cells, because the initiating form of polymerase is retained, which affects Spt5 and AID recruitment.

  6. Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo–activated cells

    Science.gov (United States)

    Maul, Robert W.; Cao, Zheng; Venkataraman, Lakshmi; Giorgetti, Carol A.; Press, Joan L.; Denizot, Yves; Du, Hansen; Sen, Ranjan

    2014-01-01

    Variable (V) genes of immunoglobulins undergo somatic hypermutation by activation-induced deaminase (AID) to generate amino acid substitutions that encode antibodies with increased affinity for antigen. Hypermutation is restricted to germinal center B cells and cannot be recapitulated in ex vivo–activated splenic cells, even though the latter express high levels of AID. This suggests that there is a specific feature of antigen activation in germinal centers that recruits AID to V genes which is absent in mitogen-activated cultured cells. Using two Igh knock-in mouse models, we found that RNA polymerase II accumulates in V regions in B cells after both types of stimulation for an extended distance of 1.2 kb from the TATA box. The paused polymerases generate abundant single-strand DNA targets for AID. However, there is a distinct accumulation of the initiating form of polymerase, along with the transcription cofactor Spt5 and AID, in the V region from germinal center cells, which is totally absent in cultured cells. These data support a model where mutations are prevalent in germinal center cells, but not in ex vivo cells, because the initiating form of polymerase is retained, which affects Spt5 and AID recruitment. PMID:25288395

  7. Identification and characterisation of a hyper-variable apoplastic effector gene family of the potato cyst nematodes.

    Directory of Open Access Journals (Sweden)

    Sebastian Eves-van den Akker

    2014-09-01

    Full Text Available Sedentary endoparasitic nematodes are obligate biotrophs that modify host root tissues, using a suite of effector proteins to create and maintain a feeding site that is their sole source of nutrition. Using assumptions about the characteristics of genes involved in plant-nematode biotrophic interactions to inform the identification strategy, we provide a description and characterisation of a novel group of hyper-variable extracellular effectors termed HYP, from the potato cyst nematode Globodera pallida. HYP effectors comprise a large gene family, with a modular structure, and have unparalleled diversity between individuals of the same population: no two nematodes tested had the same genetic complement of HYP effectors. Individuals vary in the number, size, and type of effector subfamilies. HYP effectors are expressed throughout the biotrophic stages in large secretory cells associated with the amphids of parasitic stage nematodes as confirmed by in situ hybridisation. The encoded proteins are secreted into the host roots where they are detectable by immunochemistry in the apoplasm, between the anterior end of the nematode and the feeding site. We have identified HYP effectors in three genera of plant parasitic nematodes capable of infecting a broad range of mono- and dicotyledon crop species. In planta RNAi targeted to all members of the effector family causes a reduction in successful parasitism.

  8. Genetic variability of the VP1 gene of BK and JC polyomaviruses in HIV-infected patients

    Directory of Open Access Journals (Sweden)

    Karalić Danijela

    2015-01-01

    Full Text Available Human polyomaviruses, BK virus (BKV and JC virus (JCV, are world widely distributed in human population. After primary infection, BKV and JCV establish latency in kidneys and upper part of urinary tract. In seropositive healthy individuals asymptomatic reactivation of both viruses occurs in in 0.5-20%. On the other hand, reactivation of these viruses in imunosuppressed patients, primarily in patients with T cell immunodeficiency, can lead to development of polyomavirus-associated diseases. Some of these diseases such as progressive multifocal leukoencephalopathy (PML, polyomavirus-induced nephropathy (PVN, hemorrhagic cystitis (HC are life-threatening diseases with high mortality and morbidity rate. However, they do not affect all immunosuppressed patients, suggesting that other factors, such as genetic variability of BKV and JCV, can contribute to their occurrence. Immunosuppression leads to increased levels of replication of both viruses. Increased levels of replication are associated with higher incidence of mutations in the VP1 gene. Mutations, especially those located in outer loops, may lead to changed tropism and generation of more aggressive variants of BKV and JCV. This review is focused on clinical significance of BK and JC virus infection in immunosuppressed patients, especially in HIV-infected, and sequence changes in the VP1 gene that can contribute to selection of more virulent variants of BKV and JCV via adaptive evolution.

  9. Highly variable individual donor cell fates characterize robust horizontal gene transfer of an integrative and conjugative element.

    Science.gov (United States)

    Delavat, François; Mitri, Sara; Pelet, Serge; van der Meer, Jan Roelof

    2016-06-14

    Horizontal gene transfer is an important evolutionary mechanism for bacterial adaptation. However, given the typical low transfer frequencies in a bacterial population, little is known about the fate and interplay of donor cells and the mobilized DNA during transfer. Here we study transfer of an integrative and conjugative element (ICE) among individual live bacterial cells. ICEs are widely distributed mobile DNA elements that are different than plasmids because they reside silent in the host chromosome and are maintained through vertical descent. Occasionally, ICEs become active, excise, and transmit their DNA to a new recipient, where it is reintegrated. We develop a fluorescent tool to differentiate excision, transfer, and reintegration of a model ICE named ICEclc (for carrying the clc genes for chlorocatechol metabolism) among single Pseudomonas cells by using time-lapse microscopy. We find that ICEclc activation is initiated in stationary phase cells, but excision and transfer predominantly occur only when such cells have been presented with new nutrients. Donors with activated ICE develop a number of different states, characterized by reduced cell division rates or growth arrest, persistence, or lysis, concomitant with ICE excision, and likely, ICE loss or replication. The donor cell state transitions can be described by using a stochastic model, which predicts that ICE fitness is optimal at low initiation rates in stationary phase. Despite highly variable donor cell fates, ICE transfer is remarkably robust overall, with 75% success after excision. Our results help to better understand ICE behavior and shed a new light on bacterial cellular differentiation during horizontal gene transfer.

  10. Genetic Variability and Phylogenetic Relationships within Trypanosoma cruzi I Isolated in Colombia Based on Miniexon Gene Sequences

    Directory of Open Access Journals (Sweden)

    Claudia Herrera

    2009-01-01

    Full Text Available Phylogenetic studies of Trypanosoma cruzi have identified the existence of two groups: T. cruzi I and T. cruzi II. There are aspects that still remain unknown about the genetic variability within the T. cruzi I group. Given its epidemiological importance, it is necessary to have a better understanding of T. cruzi transmission cycles. Our purpose was to corroborate the existence of haplotypes within the T. cruzi I group and to describe the genetic variability and phylogenetic relationships, based on single nucleotide polymorphisms (SNPs found in the miniexon gene intergenic region, for the isolates from different hosts and epidemiological transmission cycles in Colombian regions. 31 T. cruzi isolates were molecularly characterized. Phylogenetic relationships within T. cruzi I isolates showed four haplotype groups (Ia–Id, associated with their transmission cycle. In previous studies, we reported that haplotype Ia is mainly associated with the domestic cycle and domiciliated Rhodnius prolixus. Haplotype Ib is associated with the domestic cycle and peridomestic cycle, haplotype Ic is closely related with the peridomestic cycle, and haplotype Id is strongly associated with the sylvatic cycle. The phylogenetic methodologies applied in this study are tools that bolster the associations among isolates and thus shed light on Chagas disease epidemiology.

  11. Genetic Variability and Phylogenetic Relationships within Trypanosoma cruzi I Isolated in Colombia Based on Miniexon Gene Sequences

    Science.gov (United States)

    Herrera, Claudia; Guhl, Felipe; Falla, Alejandra; Fajardo, Anabella; Montilla, Marleny; Adolfo Vallejo, Gustavo; Bargues, M. Dolores

    2009-01-01

    Phylogenetic studies of Trypanosoma cruzi have identified the existence of two groups: T. cruzi I and T. cruzi II. There are aspects that still remain unknown about the genetic variability within the T. cruzi I group. Given its epidemiological importance, it is necessary to have a better understanding of T. cruzi transmission cycles. Our purpose was to corroborate the existence of haplotypes within the T. cruzi I group and to describe the genetic variability and phylogenetic relationships, based on single nucleotide polymorphisms (SNPs) found in the miniexon gene intergenic region, for the isolates from different hosts and epidemiological transmission cycles in Colombian regions. 31 T. cruzi isolates were molecularly characterized. Phylogenetic relationships within T. cruzi I isolates showed four haplotype groups (Ia–Id), associated with their transmission cycle. In previous studies, we reported that haplotype Ia is mainly associated with the domestic cycle and domiciliated Rhodnius prolixus. Haplotype Ib is associated with the domestic cycle and peridomestic cycle, haplotype Ic is closely related with the peridomestic cycle, and haplotype Id is strongly associated with the sylvatic cycle. The phylogenetic methodologies applied in this study are tools that bolster the associations among isolates and thus shed light on Chagas disease epidemiology. PMID:20798881

  12. Gene–Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

    Science.gov (United States)

    Gatz, Margaret; Christensen, Kaare; Christiansen, Lene; Dahl Aslan, Anna K.; Kaprio, Jaakko; Korhonen, Tellervo; Kremen, William S.; Krueger, Robert; McGue, Matt; Neiderhiser, Jenae M.; Pedersen, Nancy L.

    2016-01-01

    Despite emerging interest in gene–environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a ‘variability gene’ across these measures and whether it partly represents the ‘G’ in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable—with both increasing and decreasing age-cohort trends—for different cognitive measures. Results also suggested that APOE may represent a ‘variability gene’ for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE. PMID:26538244

  13. A latent variable approach to study gene-environment interactions in the presence of multiple correlated exposures.

    Science.gov (United States)

    Sánchez, Brisa N; Kang, Shan; Mukherjee, Bhramar

    2012-06-01

    Many existing cohort studies initially designed to investigate disease risk as a function of environmental exposures have collected genomic data in recent years with the objective of testing for gene-environment interaction (G × E) effects. In environmental epidemiology, interest in G × E arises primarily after a significant effect of the environmental exposure has been documented. Cohort studies often collect rich exposure data; as a result, assessing G × E effects in the presence of multiple exposure markers further increases the burden of multiple testing, an issue already present in both genetic and environment health studies. Latent variable (LV) models have been used in environmental epidemiology to reduce dimensionality of the exposure data, gain power by reducing multiplicity issues via condensing exposure data, and avoid collinearity problems due to presence of multiple correlated exposures. We extend the LV framework to characterize gene-environment interaction in presence of multiple correlated exposures and genotype categories. Further, similar to what has been done in case-control G × E studies, we use the assumption of gene-environment (G-E) independence to boost the power of tests for interaction. The consequences of making this assumption, or the issue of how to explicitly model G-E association has not been previously investigated in LV models. We postulate a hierarchy of assumptions about the LV model regarding the different forms of G-E dependence and show that making such assumptions may influence inferential results on the G, E, and G × E parameters. We implement a class of shrinkage estimators to data adaptively trade-off between the most restrictive to most flexible form of G-E dependence assumption and note that such class of compromise estimators can serve as a benchmark of model adequacy in LV models. We demonstrate the methods with an example from the Early Life Exposures in Mexico City to Neuro-Toxicants Study of lead exposure, iron

  14. Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

    DEFF Research Database (Denmark)

    Hansen, S K; Gjesing, A P; Rasmussen, S K

    2004-01-01

    The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced ins......The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose...

  15. Molecular and evolutionary analyses of a variable series of genes in Borrelia burgdorferi that are related to ospE and ospF, constitute a gene family, and share a common upstream homology box.

    Science.gov (United States)

    Marconi, R T; Sung, S Y; Hughes, C A; Carlyon, J A

    1996-10-01

    In this study we report on the molecular characterization of a series of genes that constitute a gene family related to ospE and ospF. Some members of this family appear to represent recombined or variant forms of ospE and ospF. Variant ospE and ospF genes were found in several Borrelia burgdorferi isolates, demonstrating that their occurrence is not a phenomenon relevant to only a single isolate. Hybridization analyses revealed that the upstream sequence originally identified 5' of the full-length ospEF operon exists in multiple copies ranging in number from two to six depending on the isolate. This repeated sequence, which we refer to as the upstream homology box (UHB), carries a putative promoter element. In some isolates, UHB elements were found to flank copies of ospE and ospF that exist independently of each other. We refer to this group of UHB-flanked genes collectively as the UHB gene family. The evolutionary relationships among UHB gene family members were assessed through DNA sequence analysis and gene tree construction. These analyses suggest that some UHB-flanked genes might actually represent divergent forms of other previously described genes. Analysis of the restriction fragment length polymorphism patterns of the UHB-flanked genes among B. burgdorferi isolates demonstrated that these patterns are highly variable among isolates, suggesting that these genes are not phylogenetically conserved. The variable restriction fragment length polymorphism patterns could indicate recombinational activity in these sequences. The presence of numerous copies of the UHB elements and the high degree of homology among UHB-flanked genes could provide the necessary elements to allow for homologous recombination, leading to the generation of recombination variants of UHB gene family members.

  16. Hidden Variability of Floral Homeotic B Genes in Solanaceae Provides a Molecular Basis for the Evolution of Novel Functions[C][W

    Science.gov (United States)

    Geuten, Koen; Irish, Vivian

    2010-01-01

    B-class MADS box genes specify petal and stamen identities in several core eudicot species. Members of the Solanaceae possess duplicate copies of these genes, allowing for diversification of function. To examine the changing roles of such duplicate orthologs, we assessed the functions of B-class genes in Nicotiana benthamiana and tomato (Solanum lycopersicum) using virus-induced gene silencing and RNA interference approaches. Loss of function of individual duplicates can have distinct phenotypes, yet complete loss of B-class gene function results in extreme homeotic transformations of petal and stamen identities. We also show that these duplicate gene products have qualitatively different protein–protein interaction capabilities and different regulatory roles. Thus, compensatory changes in B-class MADS box gene duplicate function have occurred in the Solanaceae, in that individual gene roles are distinct, but their combined functions are equivalent. Furthermore, we show that species-specific differences in the stamen regulatory network are associated with differences in the expression of the microRNA miR169. Whereas there is considerable plasticity in individual B-class MADS box transcription factor function, there is overall conservation in the roles of the multimeric MADS box B-class protein complexes, providing robustness in the specification of petal and stamen identities. Such hidden variability in gene function as we observe for individual B-class genes can provide a molecular basis for the evolution of regulatory functions that result in novel morphologies. PMID:20807882

  17. Identification and prioritization of candidate genes for symptom variability in breast cancer survivors based on disease characteristics at the cellular level.

    Science.gov (United States)

    Koleck, Theresa A; Conley, Yvette P

    2016-01-01

    Research is beginning to suggest that the presence and/or severity of symptoms reported by breast cancer survivors may be associated with disease-related factors of cancer. In this article, we present a novel approach to the identification and prioritization of biologically plausible candidate genes to investigate relationships between genomic variation and symptom variability in breast cancer survivors. Cognitive dysfunction is utilized as a representative breast cancer survivor symptom to elucidate the conceptualization of and justification for our cellular, disease-based approach to address symptom variability in cancer survivors. Initial candidate gene identification was based on genes evaluated as part of multigene expression profiles for breast cancer, which are commonly used in the clinical setting to characterize the biology of cancer cells for the purpose of describing overall tumor aggressiveness, prognostication, and individualization of therapy. A list of genes evaluated within five multigene expression profiles for breast cancer was compiled. In order to prioritize candidate genes for investigation, genes used in each profile were compared for duplication. Twenty-one genes (BAG1, BCL2, BIRC5, CCNB1, CENPA, CMC2, DIAPH3, ERBB2, ESR1, GRB7, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2) are utilized in two or more profiles, including five genes (CCNB1, CENPA, MELK, MYBL2, and ORC6) used in three profiles. To ensure that the parsimonious 21 gene set is representative of the more global biological hallmarks of cancer, an Ingenuity Pathway Analysis was conducted. Evaluation of genes known to impact pathways involved with cancer development and progression provide a means to evaluate the overlap between the biological underpinnings of cancer and symptom development within the context of cancer.

  18. [Cloning, ligation and expression of the variable region genes of the monoclonal antibody against human HnRNPA2/B1].

    Science.gov (United States)

    Wang, Xia; Peng, Xiao-dong; Li, Guang; Hu, Li-juan; Bi, Jian-hong

    2004-12-01

    To clone the variable region genes of the monoclonal antibody (McAb) against human heterogeneous nuclear ribonucleoprotein A2/B1 (HnRNPA2/B1), ligate them to assemble single chain Fv (ScFv) gene and express in Escherichia coli. The specificity of the anti-HnRNPA2/B1 McAb 3E8 to synthetic HnRNPA2/B1 peptide, HnRNPA2/B1 protein in lung cancer cells were examined by dot-immunobinding assay, Western blot and immunohistochemistry. The variable region genes of heavy chain (VH) and light chain (VL) were amplified from hybridoma cell by reverse transcription-polymerase chain reaction(RT-PCR), and then were linked by a linker peptide using SOE-PCR (splicing by overlap extension-PCR) to construct recombination ScFv gene. The latter was cloned into the expression vector pET28 (a+) and expressed in E coli BL21. The expressed product was identified by SDS-PAGE and competitive ELISA inhibition test. It was shown that the McAb combined specifically with synthetic HnRNPA2/B1 peptide and HnRNPA2/B1 protein in three lung cancer cells. The cloned VH gene and VL gene were 345 bp and 309 bp respectively and were linked successfully to obtain ScFv gene. The ScFv protein was expressed in the form of inclusion body, with molecular weight of 28,000 and immunoreactivity to HnRNPA2/B1. VH gene, VL gene and ScFv gene of anti-HnRNPA2/B1 antibody were cloned, constructed and functionally expressed in E coli. These results provide the experimental basis for elucidating the role of HnRNPA2/B1 in lung cancer.

  19. Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.

    Directory of Open Access Journals (Sweden)

    Marzia Dolcino

    Full Text Available BACKGROUND: Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice. METHODS: We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study. RESULTS: A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23⁻CD27⁻IgM⁻IgG⁻ B cells (centrocytes. CONCLUSIONS: Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency.

  20. A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO)

    OpenAIRE

    Berardo, Andres; Çoku, Jorida; Kurt,Bulent; DiMauro, Salvatore; Hirano, Michio

    2010-01-01

    We describe a 62-year-old woman with chronic progressive external ophthalmoplegia (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNAIle gene (MTTI). This is the first mutation at position 44 in the variable loop (V loop) of any mitochondrial tRNA.

  1. Functional glucocorticoid receptor gene variants do not underlie the high variability of 17-hydroxyprogesterone screening values in healthy newborns.

    Science.gov (United States)

    Schreiner, Felix; Tozakidou, Magdalini; Maslak, Rita; Holtkamp, Ute; Peter, Michael; Gohlke, Bettina; Woelfle, Joachim

    2009-04-01

    17-Hydroxyprogesterone (17-OHP) screening for classical congenital adrenal hyperplasia (CAH) is part of many newborn screening programs worldwide. Cut-off values are relatively high, and screening sensitivity does not reach 100%. Recently, the glucocorticoid receptor (GR) N363S-variant has been linked to relatively low degree of virilization and comparatively lower 17-OHP serum concentrations in clinically diagnosed female CAH patients. We sought to determine whether functional GR gene variants, either increasing (N363S, BclI) or decreasing GR sensitivity (R23K), underlie the variable 17-OHP screening levels in healthy newborns. GR genotypes were compared with 17-OHP screening values in 1000 random samples from routine screening. 17-OHP was measured by conventional immunoassay (TRFIA) and a liquid chromatography-tandem mass spectrometry method (LC-MS/MS), which has been shown to increase screening specificity by steroid profiling and avoiding cross-reactions of the 17-OHP-antibody. There was no significant association of 17-OHP with GR genotypes, even after inclusion of gestational and postnatal age as covariates. However, among LC-MS/MS steroid measurements, we observed some unexpected trends, including lower 11-deoxycortisol concentrations in both 363S- and 23K-carriers. For carriers of the frequent BclI variant, linear regression analysis revealed a significant increase of 4-androstenedione levels with every mutant allele inherited. Functional GR variants do not underlie the variation of 17-OHP values observed in healthy individuals. However, whether and to which extent genetically determined differences in individual GR sensitivity influence 17-OHP screening levels in conditions of a pathological hypothalamus-pituitary-adrenal gland-axis stimulation and thus may explain false-negative screening results in those affected by CAH remains to be investigated.

  2. A mouse variable gene fragment binds to DNA independently of the BCR context: a possible role for immature B-cell repertoire establishment.

    Directory of Open Access Journals (Sweden)

    Andrea Queiroz Maranhão

    Full Text Available B-cell maturation occurs in several steps and requires constant stimulus for its continuing development. From the emergence of the pre-B-cell receptor, signal transduction stimulates and supports B-cell development. Current viewpoints indicate that both positive selection pressure for autoantigens and tonic signaling constitutively stimulate B-cell maturation. In this work, we tested for the presence of a putative DNA binding site in a variable gene segment in a germline configuration, independently of VDJ recombination. After a survey of the public antibody databases, we chose a single mouse heavy variable gene segment that is highly represented in anti-nucleic acid antibodies and tested it for ssDNA binding. A phage display approach was used to search for intrinsic binding to oligo deoxythymidine. The results revealed that binding to an antigen can be influenced by the use of a specific DNA binding V[Formula: see text] gene segment. Our data support the idea that some variable genes have intrinsic reactivity towards specific types of endogenous autoantigens, and this property may contribute to the establishment of the immature B-cell repertoire.

  3. Identification of early target genes of aflatoxin B1 in human hepatocytes, inter-individual variability and comparison with other genotoxic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André, E-mail: andre.guillouzo@univ-rennes1.fr

    2012-01-15

    Gene expression profiling has recently emerged as a promising approach to identify early target genes and discriminate genotoxic carcinogens from non-genotoxic carcinogens and non-carcinogens. However, early gene changes induced by genotoxic compounds in human liver remain largely unknown. Primary human hepatocytes and differentiated HepaRG cells were exposed to aflatoxin B1 (AFB1) that induces DNA damage following enzyme-mediated bioactivation. Gene expression profile changes induced by a 24 h exposure of these hepatocyte models to 0.05 and 0.25 μM AFB1 were analyzed by using oligonucleotide pangenomic microarrays. The main altered signaling pathway was the p53 pathway and related functions such as cell cycle, apoptosis and DNA repair. Direct involvement of the p53 protein in response to AFB1 was verified by using siRNA directed against p53. Among the 83 well-annotated genes commonly modulated in two pools of three human hepatocyte populations and HepaRG cells, several genes were identified as altered by AFB1 for the first time. In addition, a subset of 10 AFB1-altered genes, selected upon basis of their function or tumor suppressor role, was tested in four human hepatocyte populations and in response to other chemicals. Although they exhibited large variable inter-donor fold-changes, several of these genes, particularly FHIT, BCAS3 and SMYD3, were found to be altered by various direct and other indirect genotoxic compounds and unaffected by non-genotoxic compounds. Overall, this comprehensive analysis of early gene expression changes induced by AFB1 in human hepatocytes identified a gene subset that included several genes representing potential biomarkers of genotoxic compounds. -- Highlights: ► Gene expression profile changes induced by aflatoxin B1 in human hepatocytes. ► AFB1 modulates various genes including tumor suppressor genes and proto-oncogenes. ► Important inter-individual variations in the response to AFB1. ► Some genes also altered by other

  4. [Identification of new conserved and variable regions in the 16S rRNA gene of acetic acid bacteria and acetobacteraceae family].

    Science.gov (United States)

    Chakravorty, S; Sarkar, S; Gachhui, R

    2015-01-01

    The Acetobacteraceae family of the class Alpha Proteobacteria is comprised of high sugar and acid tolerant bacteria. The Acetic Acid Bacteria are the economically most significant group of this family because of its association with food products like vinegar, wine etc. Acetobacteraceae are often hard to culture in laboratory conditions and they also maintain very low abundances in their natural habitats. Thus identification of the organisms in such environments is greatly dependent on modern tools of molecular biology which require a thorough knowledge of specific conserved gene sequences that may act as primers and or probes. Moreover unconserved domains in genes also become markers for differentiating closely related genera. In bacteria, the 16S rRNA gene is an ideal candidate for such conserved and variable domains. In order to study the conserved and variable domains of the 16S rRNA gene of Acetic Acid Bacteria and the Acetobacteraceae family, sequences from publicly available databases were aligned and compared. Near complete sequences of the gene were also obtained from Kombucha tea biofilm, a known Acetobacteraceae family habitat, in order to corroborate the domains obtained from the alignment studies. The study indicated that the degree of conservation in the gene is significantly higher among the Acetic Acid Bacteria than the whole Acetobacteraceae family. Moreover it was also observed that the previously described hypervariable regions V1, V3, V5, V6 and V7 were more or less conserved in the family and the spans of the variable regions are quite distinct as well.

  5. Genetic variability in the regulation of the expression cluster of MDR genes in patients with breast cancer.

    Science.gov (United States)

    Tsyganov, Matvey M; Freidin, Maxim B; Ibragimova, Marina K; Deryusheva, Irina V; Kazantseva, Polina V; Slonimskaya, Elena M; Cherdyntseva, Nadezhda V; Litviakov, Nikolai V

    2017-08-01

    We aimed to investigate the association between the polymorphism and expression patterns of multiple drug resistance genes (MDR) in breast cancer (BC). The MDR gene expression levels were measured in tumor tissues of 106 breast cancer patients using quantitative real-time PCR. Affymetrix CytoScan™ HD Array chips were used to assess genotypes. Pairwise correlation analysis for ABCB1, ABCC1, ABCC2 and ABCG2 gene expression levels was carried out to reveal co-expression clusters. Associations between SNPs of MDR genes and their preoperative expression levels were assessed using analysis of covariance adjusting for covariates. The SNPs associated with the expression of the ABCB1, ABCC1, ABCC2 and ABCG2 genes before NAC were detected. In addition, 21 SNPs associated with the expression of four ABC-transporter genes and involved in the expression regulation were identified. Validation in an independent sample confirmed the association between the MDR cluster genes and 11 SNPs. Four MDR genes: ABCB1, ABCC1, ABCC2 and ABCG2 were shown to form the functional expression cluster in breast tumor. Further studies are required to discover precise mechanisms of the cluster regulation, thereby providing new approaches and targets to combat the development of the MDR phenotype during chemotherapy.

  6. Variability of lysozyme and lactoferrin bioactive protein concentrations in equine milk in relation to LYZ and LTF gene polymorphisms and expression.

    Science.gov (United States)

    Cieslak, Jakub; Wodas, Lukasz; Borowska, Alicja; Sadoch, Jan; Pawlak, Piotr; Puppel, Kamila; Kuczynska, Beata; Mackowski, Mariusz

    2017-05-01

    Equine milk is considered to be an interesting product for human nutrition, mainly owing to its low allergenicity and significant amounts of bioactive proteins, including lysozyme (LYZ) and lactoferrin (LTF). The present study assessed the effect of genetic factors on LYZ and LTF concentration variability in mare's milk. Significant effects of horse breed and lactation stage on milk LYZ and LTF contents were observed. The highest level of LTF and the lowest concentration of LYZ were recorded for the Polish Warmblood Horse breed. The highest amounts of both proteins were found for the earliest investigated time point of lactation (5th week). Altogether 13 (nine novel) polymorphisms were found in the 5'-flanking regions of both genes, but they showed no significant relationship with milk LYZ and LTF contents. Several associations were found between selected SNPs and the LYZ gene relative transcript level. While the present study indicated the existence of intra- and interbreed variability of LYZ and LTF contents in mare's milk, this variation is rather unrelated to the 5'-flanking variants of genes encoding both proteins. This study is a good introduction for broader investigations focused on the genetic background for variability of bioactive protein contents in mare's milk. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  7. Antioxidants and Quality of Aging: Further Evidences for a Major Role of TXNRD1 Gene Variability on Physical Performance at Old Age

    Directory of Open Access Journals (Sweden)

    Serena Dato

    2015-01-01

    Full Text Available Oxidative stress is a major determinant of human aging and common hallmark of age-related diseases. A protective role against free radicals accumulation was shown for thioredoxin reductase TrxR1, a key antioxidant selenoprotein. The variability of encoding gene (TXNRD1 was previously found associated with physical status at old age and extreme survival in a Danish cohort. To further investigate the influence of the gene variability on age-related physiological decline, we analyzed 9 tagging SNPs in relation to markers of physical (Activity of Daily Living, Hand Grip, Chair stand, and Walking and cognitive (Mini Mental State Examination status, in a Southern-Italian cohort of 64–107 aged individuals. We replicated the association of TXNRD1 variability with physical performance, with three variants (rs4445711, rs1128446, and rs11111979 associated with physical functioning after 85 years of age (p<0.022. In addition, we found two SNPs borderline influencing longevity (rs4964728 and rs7310505 in our cohort, the last associated with health status and survival in Northern Europeans too. Overall, the evidences of association in a different population here reported extend the proposed role of TXNRD1 gene in modulating physical decline at extreme ages, further supporting the investigation of thioredoxin pathway in relation to the quality of human aging.

  8. The TP53 tumour suppressor gene in colorectal carcinomas. II. Relation to DNA ploidy pattern and clinicopathological variables.

    Science.gov (United States)

    Meling, G. I.; Lothe, R. A.; Børresen, A. L.; Graue, C.; Hauge, S.; Clausen, O. P.; Rognum, T. O.

    1993-01-01

    Heterozygous loss of the TP53 gene on chromosome arm 17p in colorectal carcinomas was strongly associated with DNA aneuploidy (P or = 1.1 and or = 1.3 had a significantly higher frequency of TP53 gene loss (85%) (P < 0.0001 and P < 0.0001, respectively). There was a significant association between loss of the TP53 gene and histological grade (P < 0.01), and there tended to be an association between loss of the TP53 gene and degree of cellular atypia (P < 0.05), with TP53 gene loss being most frequent in moderately differentiated carcinomas, and in carcinomas with severe cellular atypia, respectively. The proportion of tumours with loss of the TP53 gene increased significantly towards the distal part of the large bowel (P < 0.0001). These results indicate that different genetic mechanisms may be involved in the carcinogenesis in colon and rectum carcinomas, and in the two subsets of DNA aneuploid carcinomas. Furthermore, the data may suggest a role for the TP53 gene in the aneuploidisation process, possibly as a 'target' for a whole chromosome loss. PMID:8427784

  9. Conserved variation: identifying patterns of stability and variability in BCR and TCR V genes with different diversity and richness metrics

    Science.gov (United States)

    Schwartz, Gregory W.; Hershberg, Uri

    2013-06-01

    The immune system can detect most invading pathogens. The potential for detection of pathogens is dependent on the somatic diversity of the immune repertoires. While it is known that this somatic diversity is carefully generated, it is unclear how the diversity is distributed in the different genes encoding receptors of immune cells. Utilizing different metrics for richness and diversity at the level of small sequence fragments, we present here an analysis of the entire known human germline repertoire as represented by the sequences from the ImMunoGeneTics database of immune receptors. We have developed a fragment sequence quantification analysis to track variation of repertoires with different degrees of precision. Somatic diversity has previously been functionally characterized mostly by division of the V gene sequences into the more conserved and invariant framework (FR) of the receptor and more varied complementarity determining regions (CDR), that interact with the antigen. We find that CDR and FR can be explicitly identified with our sequence fragment diversity quantification technique. In terms of diversity, CDR and FR are especially distinct in B cell V genes. T cell V genes show less of the CDR/FR periodicity but are more diverse overall. Our analysis further shows that there are other areas of diversity outside the CDR and FR that are found widely dispersed in T cell receptor V genes and more tightly focused in FR1 and FR3 in the B cell receptor V genes. The diversity we observe is not dependent on allelic differences nor is this diversity segregated by individual V gene families. We would thus expect that each individual exhibit a diversity equivalent to that of the entire potential repertoire.

  10. Benign breast tissue composition in breast cancer patients: association with risk factors, clinical variables, and gene expression.

    Science.gov (United States)

    Sun, Xuezheng; Sandhu, Rupninder; Figueroa, Jonine D; Gierach, Gretchen L; Sherman, Mark E; Troester, Melissa A

    2014-12-01

    Breast tissue composition (epithelium, non-fatty stroma, and adipose) changes qualitatively and quantitatively throughout the lifespan, and may mediate relationships between risk factors and breast cancer initiation. We sought to identify relationships between tissue composition, risk factors, tumor characteristics, and gene expression. Participants were 146 patients from the Polish Breast Cancer Study, with data on risk factor and clinicopathological characteristics. Benign breast tissue composition was evaluated using digital image analysis of histologic sections. Whole-genome microarrays were performed on the same tissue blocks. Mean epithelial, non-fatty stromal, and adipose proportions were 8.4% (SD = 4.9%), 27.7% (SD = 24.0%), and 64.0% (SD = 24.0%), respectively. Among women associated with obesity (7.6% in nonobese vs. 10.1% in obese; P = 0.02) and with poorly differentiated tumors (7.8% in well/moderate vs. 9.9% in poor; P = 0.05). Gene expression signatures associated with epithelial and stromal proportion were identified and validated. Stroma-associated genes were in metabolism and stem cell maintenance pathways, whereas epithelial genes were enriched for cytokine and immune response pathways. Breast tissue composition was associated with age, body mass index, and tumor grade, with consequences for breast gene expression. Breast tissue morphologic factors may influence breast cancer etiology. Composition and gene expression may act as biomarkers of breast cancer risk and progression. ©2014 American Association for Cancer Research.

  11. Variable Autosomal and X Divergence Near and Far from Genes Affects Estimates of Male Mutation Bias in Great Apes.

    Science.gov (United States)

    Narang, Pooja; Wilson Sayres, Melissa A

    2016-12-31

    Male mutation bias, when more mutations are passed on via the male germline than via the female germline, is observed across mammals. One common way to infer the magnitude of male mutation bias, α, is to compare levels of neutral sequence divergence between genomic regions that spend different amounts of time in the male and female germline. For great apes, including human, we show that estimates of divergence are reduced in putatively unconstrained regions near genes relative to unconstrained regions far from genes. Divergence increases with increasing distance from genes on both the X chromosome and autosomes, but increases faster on the X chromosome than autosomes. As a result, ratios of X/A divergence increase with increasing distance from genes and corresponding estimates of male mutation bias are significantly higher in intergenic regions near genes versus far from genes. Future studies in other species will need to carefully consider the effect that genomic location will have on estimates of male mutation bias. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Science.gov (United States)

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen

    2017-01-01

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens) to 63 (Glycine max). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution. PMID:28991190

  13. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals.

    Science.gov (United States)

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen; Ma, Haoli

    2017-10-08

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens) to 63 (Glycine max). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  14. The medaka novel immune-type receptor (NITR gene clusters reveal an extraordinary degree of divergence in variable domains

    Directory of Open Access Journals (Sweden)

    Litman Gary W

    2008-06-01

    Full Text Available Abstract Background Novel immune-type receptor (NITR genes are members of diversified multigene families that are found in bony fish and encode type I transmembrane proteins containing one or two extracellular immunoglobulin (Ig domains. The majority of NITRs can be classified as inhibitory receptors that possess cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs. A much smaller number of NITRs can be classified as activating receptors by the lack of cytoplasmic ITIMs and presence of a positively charged residue within their transmembrane domain, which permits partnering with an activating adaptor protein. Results Forty-four NITR genes in medaka (Oryzias latipes are located in three gene clusters on chromosomes 10, 18 and 21 and can be organized into 24 families including inhibitory and activating forms. The particularly large dataset acquired in medaka makes direct comparison possible to another complete dataset acquired in zebrafish in which NITRs are localized in two clusters on different chromosomes. The two largest medaka NITR gene clusters share conserved synteny with the two zebrafish NITR gene clusters. Shared synteny between NITRs and CD8A/CD8B is limited but consistent with a potential common ancestry. Conclusion Comprehensive phylogenetic analyses between the complete datasets of NITRs from medaka and zebrafish indicate multiple species-specific expansions of different families of NITRs. The patterns of sequence variation among gene family members are consistent with recent birth-and-death events. Similar effects have been observed with mammalian immunoglobulin (Ig, T cell antigen receptor (TCR and killer cell immunoglobulin-like receptor (KIR genes. NITRs likely diverged along an independent pathway from that of the somatically rearranging antigen binding receptors but have undergone parallel evolution of V family diversity.

  15. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Directory of Open Access Journals (Sweden)

    Wentao Wu

    2017-10-01

    Full Text Available The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens to 63 (Glycine max. The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  16. Somatic diversification in the heavy chain variable region genes expressed by human autoantibodies bearing a lupus-associated nephritogenic anti-DNA idiotype

    Energy Technology Data Exchange (ETDEWEB)

    Demaison, C.; Chastagner, P.; Theze, J.; Zouali, M. (Institut Pasteur, Paris (France))

    1994-01-18

    Monoclonal anti-DNA antibodies bearing a lupus nephritis-associated idiotype were derived from five patients with systemic lupus erythematosus (SLE). Genes encoding their heavy (H)-chain variable (V[sub H]) regions were cloned and sequenced. When compared with their closest V[sub h] germ-line gene relatives, these sequences exhibit a number of silent (S) and replacement (R) substitutions. The ratios of R/S mutations were much higher in the complementarity-determining regions (CDRs) of the antibodies than in the framework regions. Molecular amplification of genomic V[sub H] genes and Southern hybridization with somatic CDR2-specific oligonucleotide probes showed that the configuration of the V[sub H] genes corresponding to V[sub H] sequences in the nephritogenic antibodies is not present in the patient's own germ-line DNA, implying that the B-cell clones underwent somatic mutation in vivo. These findings, together with the characteristics of the diversity and junctional gene elements utilized to form the antibody, indicate that these autoantibodies have been driven through somatic selection processes reminiscent of those that govern antibody responses triggered by exogenous stimuli.

  17. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus.

    Science.gov (United States)

    Blanchet, Patricia; Bebin, Martina; Bruet, Shaam; Cooper, Gregory M; Thompson, Michelle L; Duban-Bedu, Benedicte; Gerard, Benedicte; Piton, Amelie; Suckno, Sylvie; Deshpande, Charu; Clowes, Virginia; Vogt, Julie; Turnpenny, Peter; Williamson, Michael P; Alembik, Yves; Glasgow, Eric; McNeill, Alisdair

    2017-08-01

    Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs) in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense). The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms "mental retardation". To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus.

  18. Sequence variability in HC-Pro genes of Korean Soybean mosaic virus isolates is associated with differences in gene silencing suppression

    Science.gov (United States)

    Soybean mosaic virus (SMV), a member of the family Potyviridae, is an important viral pathogen affecting soybean production in Korea. The variability in helper component proteinase (HC-Pro) sequence and pathogenicity of SMV isolates from seven provinces of Korea was investigated and compared with th...

  19. Fluorescent protein-mediated colour polymorphism in reef corals: multicopy genes extend the adaptation/acclimatization potential to variable light environments.

    Science.gov (United States)

    Gittins, John R; D'Angelo, Cecilia; Oswald, Franz; Edwards, Richard J; Wiedenmann, Jörg

    2015-01-01

    The genomic framework that enables corals to adjust to unfavourable conditions is crucial for coral reef survival in a rapidly changing climate. We have explored the striking intraspecific variability in the expression of coral pigments from the green fluorescent protein (GFP) family to elucidate the genomic basis for the plasticity of stress responses among reef corals. We show that multicopy genes can greatly increase the dynamic range over which corals can modulate transcript levels in response to the light environment. Using the red fluorescent protein amilFP597 in the coral Acropora millepora as a model, we demonstrate that its expression increases with light intensity, but both the minimal and maximal gene transcript levels vary markedly among colour morphs. The pigment concentration in the tissue of different morphs is strongly correlated with the number of gene copies with a particular promoter type. These findings indicate that colour polymorphism in reef corals can be caused by the environmentally regulated expression of multicopy genes. High-level expression of amilFP597 is correlated with reduced photodamage of zooxanthellae under acute light stress, supporting a photoprotective function of this pigment. The cluster of light-regulated pigment genes can enable corals to invest either in expensive high-level pigmentation, offering benefits under light stress, or to rely on low tissue pigment concentrations and use the conserved resources for other purposes, which is preferable in less light-exposed environments. The genomic framework described here allows corals to pursue different strategies to succeed in habitats with highly variable light stress levels. In summary, our results suggest that the intraspecific plasticity of reef corals' stress responses is larger than previously thought. © 2014 The Authors Molecular Ecology Published by John Wiley & Sons Ltd.

  20. Detecting disease-associated genes with confounding variable adjustment and the impact on genomic meta-analysis: With application to major depressive disorder

    Directory of Open Access Journals (Sweden)

    Wang Xingbin

    2012-03-01

    Full Text Available Abstract Background Detecting candidate markers in transcriptomic studies often encounters difficulties in complex diseases, particularly when overall signals are weak and sample size is small. Covariates including demographic, clinical and technical variables are often confounded with the underlying disease effects, which further hampers accurate biomarker detection. Our motivating example came from an analysis of five microarray studies in major depressive disorder (MDD, a heterogeneous psychiatric illness with mostly uncharacterized genetic mechanisms. Results We applied a random intercept model to account for confounding variables and case-control paired design. A variable selection scheme was developed to determine the effective confounders in each gene. Meta-analysis methods were used to integrate information from five studies and post hoc analyses enhanced biological interpretations. Simulations and application results showed that the adjustment for confounding variables and meta-analysis improved detection of biomarkers and associated pathways. Conclusions The proposed framework simultaneously considers correction for confounding variables, selection of effective confounders, random effects from paired design and integration by meta-analysis. The approach improved disease-related biomarker and pathway detection, which greatly enhanced understanding of MDD neurobiology. The statistical framework can be applied to similar experimental design encountered in other complex and heterogeneous diseases.

  1. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  2. The Complete Mitochondrial Genomes of Six Heterodont Bivalves (Tellinoidea and Solenoidea): Variable Gene Arrangements and Phylogenetic Implications

    Science.gov (United States)

    Yuan, Yang; Li, Qi; Yu, Hong; Kong, Lingfeng

    2012-01-01

    Background Taxonomy and phylogeny of subclass Heterodonta including Tellinoidea are long-debated issues and a complete agreement has not been reached yet. Mitochondrial (mt) genomes have been proved to be a powerful tool in resolving phylogenetic relationship. However, to date, only ten complete mitochondrial genomes of Heterodonta, which is by far the most diverse major group of Bivalvia, have been determined. In this paper, we newly sequenced the complete mt genomes of six species belonging to Heterodonta in order to resolve some problematical relationships among this subclass. Principal Findings The complete mt genomes of six species vary in size from 16,352 bp to 18,182. Hairpin-like secondary structures are found in the largest non-coding regions of six freshly sequenced mt genomes, five of which contain tandem repeats. It is noteworthy that two species belonging to the same genus show different gene arrangements with three translocations. The phylogenetic analysis of Heterodonta indicates that Sinonovacula constricta, distant from the Solecurtidae belonging to Tellinoidea, is as a sister group with Solen grandis of family Solenidae. Besides, all five species of Tellinoidea cluster together, while Sanguinolaria diphos has closer relationship with Solecurtus divaricatus, Moerella iridescens and Semele scaba rather than with Sanguinolaria olivacea. Conclusions/Significance By comparative study of gene order rearrangements and phylogenetic relationships of the five species belonging to Tellinoidea, our results support that comparisons of mt gene order rearrangements, to some extent, are a useful tool for phylogenetic studies. Based on phylogenetic analyses of multiple protein-coding genes, we prefer classifying the genus Sinonovacula within the superfamily Solenoidea and not the superfamily Tellinoidea. Besides, both gene order and sequence data agree that Sanguinolaria (Psammobiidae) is not monophyletic. Nevertheless, more studies based on more mt genomes via

  3. The complete mitochondrial genomes of six heterodont bivalves (Tellinoidea and Solenoidea: variable gene arrangements and phylogenetic implications.

    Directory of Open Access Journals (Sweden)

    Yang Yuan

    Full Text Available BACKGROUND: Taxonomy and phylogeny of subclass Heterodonta including Tellinoidea are long-debated issues and a complete agreement has not been reached yet. Mitochondrial (mt genomes have been proved to be a powerful tool in resolving phylogenetic relationship. However, to date, only ten complete mitochondrial genomes of Heterodonta, which is by far the most diverse major group of Bivalvia, have been determined. In this paper, we newly sequenced the complete mt genomes of six species belonging to Heterodonta in order to resolve some problematical relationships among this subclass. PRINCIPAL FINDINGS: The complete mt genomes of six species vary in size from 16,352 bp to 18,182. Hairpin-like secondary structures are found in the largest non-coding regions of six freshly sequenced mt genomes, five of which contain tandem repeats. It is noteworthy that two species belonging to the same genus show different gene arrangements with three translocations. The phylogenetic analysis of Heterodonta indicates that Sinonovacula constricta, distant from the Solecurtidae belonging to Tellinoidea, is as a sister group with Solen grandis of family Solenidae. Besides, all five species of Tellinoidea cluster together, while Sanguinolaria diphos has closer relationship with Solecurtus divaricatus, Moerella iridescens and Semele scaba rather than with Sanguinolaria olivacea. CONCLUSIONS/SIGNIFICANCE: By comparative study of gene order rearrangements and phylogenetic relationships of the five species belonging to Tellinoidea, our results support that comparisons of mt gene order rearrangements, to some extent, are a useful tool for phylogenetic studies. Based on phylogenetic analyses of multiple protein-coding genes, we prefer classifying the genus Sinonovacula within the superfamily Solenoidea and not the superfamily Tellinoidea. Besides, both gene order and sequence data agree that Sanguinolaria (Psammobiidae is not monophyletic. Nevertheless, more studies based on

  4. Prevalence and Genetic Variability in Capsid L1 Gene of Rare Human Papillomaviruses (HPV Found in Cervical Lesions of Women from North-East Brazil

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    Ana Pavla Almeida Diniz Gurgel

    2013-01-01

    Full Text Available The aim of this study was to examine the prevalence and genetic variability of the capsid L1 gene of rare HPV genotypes that were found in the cervical lesions of women from North-East Brazil. A total number of 263 patients were included in this study. HPV detection was performed using PCR followed by direct sequencing of MY09/11, as well as type-specific PCR to detect the Alpha-9 species. Epitope prediction was performed to determine whether or not the genetic variants are inserted in B-cell and T-cell epitopes. The prevalence of rare HPV types in cervical lesions was found to be 9.47%. The rare HPV genotypes that were detected were HPV-53, 54, 56, 61, 62, 66, 70, and 81. The genetic variability in the L1 gene of rare HPV types involved thirty nucleotide changes, eight of which were detected for the first time in this study. Moreover, some of these variants are embedded in B-cell or T-cell epitope regions. The results of this research suggest that rare HPV types might be involved in cervical lesions and some of these variants can be found in B-cell and T-cell epitopes. Data on the prevalence and variability of rare HPV types will assist in clarifying the role of these viruses in carcinogenesis.

  5. MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus.

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    Patricia Blanchet

    2017-08-01

    Full Text Available Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.3 contains PXDN and MYT1L. MYT1L is expressed only within the brain in humans. We hypothesized that single nucleotide variants (SNVs in MYT1L would cause a phenotype resembling deletion at 2p25.3. To examine this we sought MYT1L SNVs in exome sequencing data from 4, 296 parent-child trios. Further variants were identified through a genematcher-facilitated collaboration. We report 9 patients with MYT1L SNVs (4 loss of function and 5 missense. The phenotype of SNV carriers overlapped with that of 2p25.3 deletion carriers. To identify the transcriptomic consequences of MYT1L loss of function we used CRISPR-Cas9 to create a knockout cell line. Gene Ontology analysis in knockout cells demonstrated altered expression of genes that regulate gene expression and that are localized to the nucleus. These differentially expressed genes were enriched for OMIM disease ontology terms "mental retardation". To study the developmental effects of MYT1L loss of function we created a zebrafish knockdown using morpholinos. Knockdown zebrafish manifested loss of oxytocin expression in the preoptic neuroendocrine area. This study demonstrates that MYT1L variants are associated with syndromic obesity in humans. The mechanism is related to dysregulated expression of neurodevelopmental genes and altered development of the neuroendocrine hypothalamus.

  6. Genetic variability of microcystin biosynthesis genes in Planktothrix as elucidated from samples preserved by heat desiccation during three decades.

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    Veronika Ostermaier

    Full Text Available Historic samples of phytoplankton can provide information on the abundance of the toxigenic genotypes of cyanobacteria in dependence on increased or decreased eutrophication. The analysis of a time-series from preserved phytoplankton samples by quantitative PCR (qPCR extends observation periods considerably. The analysis of DNA from heat-desiccated samples by qPCR can be aggravated by point substitutions or the fragmentation of DNA introduced by the high temperature. In this study, we analyzed whether the heat desiccation of the cellular material of the cyanobacterium Planktothrix sp. introduced potential errors to the template DNA that is used for qPCR within (i 16S rDNA and phycocyanin genes and (ii the mcyA gene indicative of the incorporation of either dehydrobutyrine (Dhb or N-methyl-dehydroalanine (Mdha in position 7, and (ii the mcyB gene, which is indicative of homotyrosine (Hty in position 2 of the microcystin (MC molecule. Due to high temperature desiccation, the deterioration of the DNA template quality was rather due to fragmentation than due to nucleotide substitutions. By using the heat-desiccated samples of Lake Zürich, Switzerland the abundance of the Dhb, Mdha and Hty genotypes was determined during three decades (1977-2008. Despite major changes in the trophic state of the lake resulting in a major increase of the total Planktothrix population density, the proportion of these genotypes encoding the synthesis of different MC congeners showed high stability. Nevertheless, a decline of the most abundant mcyA genotype indicative of the synthesis of Dhb in position 7 of the MC molecule was observed. This decline could be related to the gradual incline in the proportion of a mutant genotype carrying a 1.8kbp deletion of this gene region. The increase of this mcyA (Dhb gene deletion mutant has been minor so far, however, and likely did not affect the overall toxicity of the population.

  7. Centimetre-scale vertical variability of phenoxy acid herbicide mineralization potential in aquifer sediment relates to the abundance of tfdA genes.

    Science.gov (United States)

    Batıoğlu-Pazarbaşı, Meriç; Bælum, Jacob; Johnsen, Anders R; Sørensen, Sebastian R; Albrechtsen, Hans-Jørgen; Aamand, Jens

    2012-05-01

    Centimetre-scale vertical distribution of mineralization potential was determined for 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA) and 2-(4-chloro-2-methylphenoxy)propanoic acid (MCPP) by 96-well microplate radiorespirometric analysis in aquifer sediment sampled just below the groundwater table. Mineralization of 2,4-D and MCPA was fastest in sediment samples taken close to the groundwater table, whereas only minor mineralization of MCPP was seen. Considerable variability was exhibited at increasing aquifer depth, more so with 2,4-D than with MCPA. This suggests that the abundance of MCPA degraders was greater than that of 2,4-D degraders, possibly due to the fact that the overlying agricultural soil had long been treated with MCPA. Mineralization of 2,4-D and MCPA was followed by increased abundance of tfdA class I and class III catabolic genes, which are known to be involved in the metabolism of phenoxy acid herbicides. tfdA class III gene copy number was approximately 100-fold greater in samples able to mineralize MCPA than in samples able to mineralize 2,4-D, suggesting that tfdA class III gene plays a greater role in the metabolism of MCPA than of 2,4-D. Degradation rate was found to correlate positively with tfdA gene copy number, as well as with the total organic carbon content of the sediment.

  8. Genetic variability of attachment (G and Fusion (F protein genes of human metapneumovirus strains circulating during 2006-2009 in Kolkata, Eastern India

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    Chawla-Sarkar Mamta

    2011-02-01

    Full Text Available Abstract Background Human metapneumovirus (hMPV is associated with the acute respiratory tract infection (ARTI in all the age groups. However, there is limited information on prevalence and genetic diversity of human metapneumovirus (hMPV strains circulating in India. Objective To study prevalence and genomic diversity of hMPV strains among ARTI patients reporting in outpatient departments of hospitals in Kolkata, Eastern India. Methods Nasal and/or throat swabs from 2309 patients during January 2006 to December 2009, were screened for the presence of hMPV by RT-PCR of nucleocapsid (N gene. The G and F genes of representative hMPV positive samples were sequenced. Results 118 of 2309 (5.11% clinical samples were positive for hMPV. The majority (≈80% of the positive cases were detected during July−November all through the study period. Genetic analysis revealed that 77% strains belong to A2 subgroup whereas rest clustered in B1 subgroup. G sequences showed higher diversity at the nucleotide and amino acid level. In contrast, less than 10% variation was observed in F gene of representative strains of all four years. Sequence analysis also revealed changes in the position of stop codon in G protein, which resulted in variable length (217-231 aa polypeptides. Conclusion The study suggests that approximately 5% of ARTI in the region were caused by hMPV. This is the first report on the genetic variability of G and F gene of hMPV strains from India which clearly shows that the G protein of hMPV is continuously evolving. Though the study partially fulfills lacunae of information, further studies from other regions are necessary for better understanding of prevalence, epidemiology and virus evolution in Indian subcontinent.

  9. Identification of the Functional Initiation Codons of a Phase-Variable Gene of Haemophilus influenzae, lic2A, with the Potential for Differential Expression▿

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    Dixon, Kevin; Bayliss, Christopher D.; Makepeace, Katherine; Moxon, E. Richard; Hood, Derek W.

    2007-01-01

    Simple sequence repeats located within reading frames mediate phase-variable ON/OFF switches in gene expression by generating frameshifts. Multiple translation initiation codons in different reading frames are found upstream of most Haemophilus influenzae tetranucleotide repeat tracts, raising the possibility of multiple active reading frames and more than two levels of gene expression for these loci. Phase variation between three levels of gene expression (strong, weak, and none) was observed when lic2A was fused to a lacZ reporter gene. The lic2A 5′ CAAT repeat tract is preceded by four 5′ ATG codons (x, y, z1, and z2) in two reading frames. Each of these initiation codons was inactivated by site-directed mutagenesis. Strong expression from frame 1 was associated with x but not y. Weak expression from frame 2 was mainly dependent on the z2 codon, and there was no expression from frame 3. Using monoclonal antibodies specific for a digalactoside epitope of lipopolysaccharide whose synthesis requires Lic2A, two levels (strong and undetectable) of antibody reactivity were detected, suggesting that weak expression of lic2A is not discernible at the phenotypic level. Inactivation of the x initiation codon resulted in loss of strong expression of the digalactoside epitope and elevated killing by human serum. The failure to detect more than two phenotypes for lic2A, despite clear evidence of weak expression from the z1/z2 initiation codons, leaves open the question of whether or not multiple initiation codons are associated with more complex patterns of phenotypic variation rather than classical phase-variable switching between two phenotypes. PMID:17098909

  10. Variable clinical expression in patients with a germline MEN1 disease gene mutation: clues to a genotype-phenotype correlation

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    Cornelis J. Lips

    2012-01-01

    Full Text Available Multiple endocrine neoplasia type 1 is an inherited endocrine tumor syndrome, predominantly characterized by tumors of the parathyroid glands, gastroenteropancreatic tumors, pituitary adenomas, adrenal adenomas, and neuroendocrine tumors of the thymus, lungs or stomach. Multiple endocrine neoplasia type 1 is caused by germline mutations of the multiple endocrine neoplasia type 1 tumor suppressor gene. The initial germline mutation, loss of the wild-type allele, and modifying genetic and possibly epigenetic and environmental events eventually result in multiple endocrine neoplasia type 1 tumors. Our understanding of the function of the multiple endocrine neoplasia type 1 gene product, menin, has increased significantly over the years. However, to date, no clear genotype-phenotype correlation has been established. In this review we discuss reports on exceptional clinical presentations of multiple endocrine neoplasia type 1, which may provide more insight into the pathogenesis of this disorder and offer clues for a possible genotype-phenotype correlation.

  11. Genetic diversity and gene flow in the morphologically variable, rare endemics Begonia dregei and Begonia homonyma (Begoniaceae).

    Science.gov (United States)

    Matolweni, L O; Balkwill, K; McLellan, T

    2000-03-01

    Begonia dregei and B. homonyma (Begoniaceae), rare plants endemic to coastal forests of eastern South Africa, are two closely related species with high levels of variation among populations in the shape of leaves. Distribution of genetic variation and genetic relatedness were investigated in 12 populations of B. dregei and seven of B. homonyma using polyacrylamide gel electrophoresis. Twelve of the 15 enzyme loci examined were polymorphic, but only seven loci were polymorphic within at least one population. Genetic diversity measures indicated that the among-population gene differentiation represents >90% of the total genetic component in both species considered individually or combined. This indicated restricted gene flow, consistent with the limited dispersal abilities of Begonia generally and the ancient separation of isolated forest patches. Genetic distances among populations are much higher than usually found within species. Allozyme data provide no support for the recognition of B. dregei and B. homonyma as distinct species.

  12. Multiple Independent Retroelement Insertions in the Promoter of a Stress Response Gene Have Variable Molecular and Functional Effects in Drosophila.

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    Miriam Merenciano

    2016-08-01

    Full Text Available Promoters are structurally and functionally diverse gene regulatory regions. The presence or absence of sequence motifs and the spacing between the motifs defines the properties of promoters. Recent alternative promoter usage analyses in Drosophila melanogaster revealed that transposable elements significantly contribute to promote diversity. In this work, we analyzed in detail one of the transposable element insertions, named FBti0019985, that has been co-opted to drive expression of CG18446, a candidate stress response gene. We analyzed strains from different natural populations and we found that besides FBti0019985, there are another eight independent transposable elements inserted in the proximal promoter region of CG18446. All nine insertions are solo-LTRs that belong to the roo family. We analyzed the sequence of the nine roo insertions and we investigated whether the different insertions were functionally equivalent by performing 5'-RACE, gene expression, and cold-stress survival experiments. We found that different insertions have different molecular and functional consequences. The exact position where the transposable elements are inserted matters, as they all showed highly conserved sequences but only two of the analyzed insertions provided alternative transcription start sites, and only the FBti0019985 insertion consistently affects CG18446 expression. The phenotypic consequences of the different insertions also vary: only FBti0019985 was associated with cold-stress tolerance. Interestingly, the only previous report of transposable elements inserting repeatedly and independently in a promoter region in D. melanogaster, were also located upstream of a stress response gene. Our results suggest that functional validation of individual structural variants is needed to resolve the complexity of insertion clusters.

  13. Phage exposure causes dynamic shifts in the expression states of specific phase-variable genes of Campylobacter jejuni

    DEFF Research Database (Denmark)

    Aidley, Jack; Holst Sørensen, Martine C.; Bayliss, Christopher D.

    2017-01-01

    Phase variation (PV) creates phenotypic heterogeneity at high frequencies and in a reversible manner. This phenomenon allows bacteria to adapt to a variety of different environments and selective pressures. In Campylobacter jejuni this reversible adaptive process is mediated by mutations in homop......Phase variation (PV) creates phenotypic heterogeneity at high frequencies and in a reversible manner. This phenomenon allows bacteria to adapt to a variety of different environments and selective pressures. In Campylobacter jejuni this reversible adaptive process is mediated by mutations...... in homopolymeric G/C tracts. Many C. jejuni-specific phages are dependent on phase-variable surface structures for successful infection. We previously identified the capsular polysaccharide (CPS) moiety, MeOPN-GalfNAc, as a receptor for phage F336 and showed that phase-variable expression of the transferase...

  14. Gene conversion events and variable degree of homogenization of rDNA loci in cultivars of Brassica napus

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    Sochorová, Jana; Coriton, Olivier; Kuderová, Alena; Lunerová, Jana; Chèvre, Anne-Marie; Kovařík, Aleš

    2017-01-01

    Background and aims Brassica napus (AACC, 2n = 38, oilseed rape) is a relatively recent allotetraploid species derived from the putative progenitor diploid species Brassica rapa (AA, 2n = 20) and Brassica oleracea (CC, 2n = 18). To determine the influence of intensive breeding conditions on the evolution of its genome, we analysed structure and copy number of rDNA in 21 cultivars of B. napus, representative of genetic diversity. Methods We used next-generation sequencing genomic approaches, Southern blot hybridization, expression analysis and fluorescence in situ hybridization (FISH). Subgenome-specific sequences derived from rDNA intergenic spacers (IGS) were used as probes for identification of loci composition on chromosomes. Key Results Most B. napus cultivars (18/21, 86 %) had more A-genome than C-genome rDNA copies. Three cultivars analysed by FISH (‘Darmor’, ‘Yudal’ and ‘Asparagus kale’) harboured the same number (12 per diploid set) of loci. In B. napus ‘Darmor’, the A-genome-specific rDNA probe hybridized to all 12 rDNA loci (eight on the A-genome and four on the C-genome) while the C-genome-specific probe showed weak signals on the C-genome loci only. Deep sequencing revealed high homogeneity of arrays suggesting that the C-genome genes were largely overwritten by the A-genome variants in B. napus ‘Darmor’. In contrast, B. napus ‘Yudal’ showed a lack of gene conversion evidenced by additive inheritance of progenitor rDNA variants and highly localized hybridization signals of subgenome-specific probes on chromosomes. Brassica napus ‘Asparagus kale’ showed an intermediate pattern to ‘Darmor’ and ‘Yudal’. At the expression level, most cultivars (95 %) exhibited stable A-genome nucleolar dominance while one cultivar (‘Norin 9’) showed co-dominance. Conclusions The B. napus cultivars differ in the degree and direction of rDNA homogenization. The prevalent direction of gene conversion (towards the A-genome) correlates

  15. Gene conversion events and variable degree of homogenization of rDNA loci in cultivars of Brassica napus.

    Science.gov (United States)

    Sochorová, Jana; Coriton, Olivier; Kuderová, Alena; Lunerová, Jana; Chèvre, Anne-Marie; Kovařík, Aleš

    2017-01-01

    Brassica napus (AACC, 2n = 38, oilseed rape) is a relatively recent allotetraploid species derived from the putative progenitor diploid species Brassica rapa (AA, 2n = 20) and Brassica oleracea (CC, 2n = 18). To determine the influence of intensive breeding conditions on the evolution of its genome, we analysed structure and copy number of rDNA in 21 cultivars of B. napus, representative of genetic diversity. We used next-generation sequencing genomic approaches, Southern blot hybridization, expression analysis and fluorescence in situ hybridization (FISH). Subgenome-specific sequences derived from rDNA intergenic spacers (IGS) were used as probes for identification of loci composition on chromosomes. Most B. napus cultivars (18/21, 86 %) had more A-genome than C-genome rDNA copies. Three cultivars analysed by FISH ('Darmor', 'Yudal' and 'Asparagus kale') harboured the same number (12 per diploid set) of loci. In B. napus 'Darmor', the A-genome-specific rDNA probe hybridized to all 12 rDNA loci (eight on the A-genome and four on the C-genome) while the C-genome-specific probe showed weak signals on the C-genome loci only. Deep sequencing revealed high homogeneity of arrays suggesting that the C-genome genes were largely overwritten by the A-genome variants in B. napus 'Darmor'. In contrast, B. napus 'Yudal' showed a lack of gene conversion evidenced by additive inheritance of progenitor rDNA variants and highly localized hybridization signals of subgenome-specific probes on chromosomes. Brassica napus 'Asparagus kale' showed an intermediate pattern to 'Darmor' and 'Yudal'. At the expression level, most cultivars (95 %) exhibited stable A-genome nucleolar dominance while one cultivar ('Norin 9') showed co-dominance. The B. napus cultivars differ in the degree and direction of rDNA homogenization. The prevalent direction of gene conversion (towards the A-genome) correlates with the direction of expression dominance indicating that gene activity may be needed for

  16. Analysis of the genetic variability of the mumps SH gene in viruses circulating in the UK between 1996 and 2005.

    Science.gov (United States)

    Cui, Aili; Myers, Richard; Xu, Wenbo; Jin, Li

    2009-01-01

    Genetic analysis (genotyping) of mumps viruses has been applied to the molecular epidemiology of mumps for over 10 years in the UK. To explore further the variation of mumps strains over time, in total, 965 sequences of the entire SH gene were analysed and compared, including 954 mumps virus strains collected in the UK between 1996 and 2005 were characterised as genotypes G2 (426), G5 (369), J (157) and F (2), which were compared with 11 F sequences found in China. Phylogenetic trees drawn for G2, G5 and J sequences showed that the diversities were greater between the sequences in earlier years (before 2001/2002) than those in later years and could be divided into two clusters within each of the three genotypes over the 10-year period. One transmission of G2, G5 and a J strain was sustained from earlier years with mutations and eventually became predominant strains. Divergences amongst the same genotype or sub-genotype was up to 4.6% for G2, 5.3% for G5 and 4.9% for J. Mutation rates per site per year based on the 316nt of SH gene were 0.94, 1.3, 0.96 and 1.86 x 10(-2) for G2, G5, J and F respectively. The ratio of d(N)/d(S) was 0.556, 0.909, 0.357 and 0.811 calculated based on the sequences of G2, G5, J and F respectively. The results revealed that the possible mumps evolution process based on the SH gene was not driven by positive selection during the 10 years between 1996 and 2005.

  17. Immunoglobulin kappa variable region gene selection during early human B cell development in health and systemic lupus erythematosus.

    Science.gov (United States)

    Hehle, Verena; Fraser, Louise D; Tahir, Romeeza; Kipling, David; Wu, Yu-Chang; Lutalo, Pamela M K; Cason, John; Choong, LeeMeng; D'Cruz, David P; Cope, Andrew P; Dunn-Walters, Deborah K; Spencer, Jo

    2015-06-01

    The unique specificity of the B cell receptor is generated by an ordered sequence of gene rearrangement events. Once IGH genes have rearranged, rearrangement at the IGK locus is initiated followed by the IGL locus if functional IGK rearrangement is not achieved. Receptor specificity can subsequently be altered by secondary light chain editing based on the features of the heavy and light chain combination. The final profile of expressed genes is not random and biases in this profile are associated with several autoimmune diseases. However, how and when biases are created is not known. To increase our understanding of the processes of selection and editing of IGK rearrangements, we compared four groups of rearrangements of IGK acquired by next generation sequencing. First, expressed rearrangements of IGK from cDNA of IGK expressing B cells. Second, productive rearrangements of IGK from DNA of the same kappa expressing B cells. Third, non-productive rearrangements of IGK from DNA of IGK and IGL expressing B cells, and fourth productively rearranged IGK from DNA of IGL expressing B cells. The latter group would have been rejected during B cell development in favour of rearrangement at the IGL locus and are therefore selected against. We saw evidence that rearranged IGK segments can be selected at a checkpoint where the decision to rearrange the IGL locus is made. In addition, our data suggest that mechanisms regulating the expression or not of IGK rearrangements may also contribute to repertoire development and also that this latter component of the selection process is defective in SLE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

    Science.gov (United States)

    Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2018-01-01

    Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

  19. Novel mutations including deletions of the entire OFD1 gene in 30 families with type I orofaciodigital syndrome: a study of the extensive clinical variability

    Science.gov (United States)

    Bisschoff, Izak J; Zeschnigk, Christine; Horn, Denise; Wellek, Brigitte; Rieß, Angelika; Wessels, Maja; Willems, Patrick; Jensen, Peter; Busche, Andreas; Bekkebraten, Jens; Chopra, Maya; Hove, Hanne Dahlgaard; Evers, Christina; Heimdal, Ketil; Kaiser, Ann-Sophie; Kunstmann, Erdmut; Robinson, Kristina Lagerstedt; Linné, Maja; Martin, Patricia; McGrath, James; Pradel, Winnie; Prescott, Trine E; Roesler, Bernd; Rudolf, Gorazd; Siebers-Renelt, Ulrike; Tyshchenko, Nataliya; Wieczorek, Dagmar; Wolff, Gerhard; Dobyns, William B.; Morris-Rosendahl, Deborah J

    2017-01-01

    OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X-linked condition with lethality in males. Mutations in OFD1 also cause X-linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X-inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability. PMID:23033313

  20. Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene

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    Gamero Miguel A

    2003-07-01

    Full Text Available Abstract Background Cerebral cavernous malformations (CCM present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members. Methods We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives. Results The phenotypes of cerebral cavernous malformations (CCMs in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA. Conclusions Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling.

  1. Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to a T494M mutation in the PRPF3 gene.

    Science.gov (United States)

    Vaclavik, Veronika; Gaillard, Marie-Claire; Tiab, L; Schorderet, Daniel F; Munier, Francis L

    2010-03-19

    To characterize the clinical, psychophysical, and electrophysiological phenotypes in a five-generation Swiss family with dominantly inherited retinitis pigmentosa caused by a T494M mutation in the Precursor mRNA-Processing factor 3 (PRPF3) gene, and to relate the phenotype to the underlying genetic mutation. Eleven affected patients were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldmann perimetry, and digital fundus photography. Some patients had autofluorescence imaging, Optical Coherence Tomography, and ISCEV-standard full-field electroretinography. All affected patients had genetic testing. The age of onset of night blindness and the severity of the progression of the disease varied between members of the family. Some patients reported early onset of night blindness at age three, with subsequent severe deterioration of visual acuity, which was 0.4 in the best eye after their fifties. The second group of patients had a later onset of night blindness, in the mid-twenties, with a milder disease progression and a visual acuity of 0.8 at age 70. Fundus autofluorescence imaging and electrophysiological and visual field abnormalities also showed some degree of varying phenotypes. The autofluorescence imaging showed a large high-density ring bilaterally. Myopia (range: -0.75 to -8) was found in 10/11 affected subjects. Fundus findings showed areas of atrophy along the arcades. A T494M change was found in exon 11 of the PRPF3 gene. The change segregates with the disease in the family. A mutation in the PRPF3 gene is rare compared to other genes causing autosomal dominant retinitis pigmentosa (ADRP). Although a T494M change has been reported, the family in our study is the first with variable expressivity. Mutations in the PRPF3 gene can cause a variable ADRP phenotype, unlike in the previously described Danish, English, and Japanese families. Our report, based on one of the largest affected

  2. Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status

    Directory of Open Access Journals (Sweden)

    Ryckman Kelli K

    2010-02-01

    Full Text Available Abstract Background The interleukin-1 (IL-1 family of cytokines is involved in the inflammatory and repair reactions of skeletal muscle during and after exercise. Specifically, plasma levels of the IL-1 receptor antagonist (IL-1ra increase dramatically after intense exercise, and accumulating evidence points to an effect of genetic polymorphisms on athletic phenotypes. Therefore, the IL-1 family cytokine genes are plausible candidate genes for athleticism. We explored whether IL-1 polymorphisms are associated with athlete status in European subjects. Methods Genomic DNA was obtained from 205 (53 professional and 152 competitive non-professional Italian athletes and 458 non-athlete controls. Two diallelic polymorphisms in the IL-1β gene (IL-1B at -511 and +3954 positions, and a variable number tandem repeats (VNTR in intron 2 of the IL-1ra gene (IL-1RN were assessed. Results We found a 2-fold higher frequency of the IL-1RN 1/2 genotype in athletes compared to non-athlete controls (OR = 1.93, 95% CI = 1.37-2.74, 41.0% vs. 26.4%, and a lower frequency of the 1/1 genotype (OR = 0.55, 95% CI = 0.40-0.77, 43.9% vs. 58.5%. Frequency of the IL-1RN 2/2 genotype did not differ between groups. No significant differences between athletes and controls were found for either -511 or +3954 IL-1B polymorphisms. However, the haplotype (-511C-(+3954T-(VNTR2 was 3-fold more frequent in athletes than in non-athletes (OR = 3.02, 95% CI = 1.16-7.87. Interestingly, the IL-1RN 1/2 genotype was more frequent in professional than in non-professional athletes (OR = 1.92, 95% CI = 1.02-3.61, 52.8% vs. 36.8%. Conclusions Our study found that variants at the IL-1ra gene associate with athletic status. This confirms the crucial role that cytokine IL-1ra plays in human physical exercise. The VNTR IL-1RN polymorphism may have implications for muscle health, performance, and/or recovery capacities. Further studies are needed to assess these specific issues. As VNTR IL-1RN

  3. Analysis of the Variability of Epstein-Barr Virus Genes in Infectious Mononucleosis: Investigation of the Potential Correlation with Biochemical Parameters of Hepatic Involvement

    Science.gov (United States)

    Lazarevic, Ivana; Stevanovic, Goran; Cirkovic, Andja; Karalic, Danijela; Cupic, Maja; Banko, Bojan; Milovanovic, Jovica; Jovanovic, Tanja

    2016-01-01

    Summary Background Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results The presence of EBV DNA in plasma samples showed correlation with patients’ necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers. PMID:28356886

  4. Genetic variability among Hymenolepis nana isolates from different geographical regions in China revealed by sequence analysis of three mitochondrial genes.

    Science.gov (United States)

    Cheng, Tian; Gao, De-Zhen; Zhu, Wei-Ning; Fang, Su-Fang; Chen, Ning; Zhu, Xing-Quan; Liu, Guo-Hua; Lin, Rui-Qing

    2016-11-01

    Hymenolepis nana is a common tapeworm that parasitizes in the small intestine of rodent animals and humans. The present study examined the sequence diversity of three mitochondrial (mt) genes namely NADH dehydrogenase subunits 5 (nad5), small subunit ribosomal RNA (rrnS), and ATPase subunit 6 (atp6) of H. nana from mice in different geographical regions of China. A part of the nad5 (pnad5), complete rrnS and atp6 genes were amplified separately from individual H. nana isolates using polymerase chain reaction (PCR) and then sequenced. The sequences of pnad5, rrnS, and atp6 were 710 bp, 704-711 bp, and 516 bp in length, respectively. The A + T contents of the sequences were 70.1-73.5% (pnad5), 70.1-71.7% (rrnS), and 76.6-77.9% (atp6). Sequence variation within H. nana was 0-1.4% for atp6, 0-1.7% for rrnS, and 0-0.7% for pnad5. The inter-specific sequence differences between H. nana and Hymenolepis diminuta were significantly higher, which was 31.6-31.7% (pnad5), 16.1-17.6% (rrnS), and 26.5-27.1% (atp6). Phylogenetic analysis based on the combined three sequences using the maximum parsimony (MP) method supported that H. nana is a species complex or "cryptic" species. These findings demonstrated clearly the usefulness of the three mtDNA sequences for population genetics and systematic studies of H. nana of human and animal health significance.

  5. Variable phenotypic penetrance of thrombosis in adult mice after tissue-selective and temporally controlled Thbd gene inactivation.

    Science.gov (United States)

    van Mens, Thijs E; Liang, Hai-Po H; Basu, Sreemanti; Hernandez, Irene; Zogg, Mark; May, Jennifer; Zhan, Min; Yang, Qiuhui; Foeckler, Jamie; Kalloway, Shawn; Sood, Rashmi; Karlson, Caren Sue; Weiler, Hartmut

    2017-06-27

    Thrombomodulin (Thbd) exerts pleiotropic effects on blood coagulation, fibrinolysis, and complement system activity by facilitating the thrombin-mediated activation of protein C and thrombin-activatable fibrinolysis inhibitor and may have additional thrombin- and protein C (pC)-independent functions. In mice, complete Thbd deficiency causes embryonic death due to defective placental development. In this study, we used tissue-selective and temporally controlled Thbd gene ablation to examine the function of Thbd in adult mice. Selective preservation of Thbd function in the extraembryonic ectoderm and primitive endoderm via the Meox2Cre-transgene enabled normal intrauterine development of Thbd-deficient (Thbd -/- ) mice to term. Half of the Thbd -/- offspring expired perinatally due to thrombohemorrhagic lesions. Surviving Thbd -/- animals only rarely developed overt thrombotic lesions, exhibited low-grade compensated consumptive coagulopathy, and yet exhibited marked, sudden-onset mortality. A corresponding pathology was seen in mice in which the Thbd gene was ablated after reaching adulthood. Supplementation of activated PC by transgenic expression of a partially Thbd-independent murine pC zymogen prevented the pathologies of Thbd -/- mice. However, Thbd -/- females expressing the PC transgene exhibited pregnancy-induced morbidity and mortality with near-complete penetrance. These findings suggest that Thbd function in nonendothelial embryonic tissues of the placenta and yolk sac affects through as-yet-unknown mechanisms the penetrance and severity of thrombosis after birth and provide novel opportunities to study the role of the natural Thbd-pC pathway in adult mice and during pregnancy.

  6. The IL-1Ra gene variable number tandem repeat variant is associated with susceptibility to temporomandibular disorders in Turkish population.

    Science.gov (United States)

    Tumer, Mehmet Kemal; Nursal, Ayse Feyda; Tekcan, Akin; Yerliyurt, Kaan; Geyko, Anastasia; Yigit, Serbulent

    2017-06-14

    Temporomandibular joint disorders (TMD) are a group of disorders involving temporomandibular joint and related structures. Interleukine-1 receptor antagonist (IL-1Ra) is an important anti-inflammatory molecule that competes with other interleukin-1 molecules. This study was designed to investigate the possible association of the IL-1Ra VNTR variant with the risk of TMD in the Turkish population. Peripheral blood samples were collected from 100 patients with TMD (23 males, 77 females) and 110 healthy individuals (35 males, 75 females). Genotyping of IL-1Ra 86 bp VNTR variant was evaluated by gel electrophoresis after polymerase chain reaction (PCR). Our results show that there is a statistically significant difference between TMD patients and control group with respect to IL-1Ra genotype distribution and allele frequencies. 1.2, 1.4, and 4.4 genotypes were more common in patients, while 2.2 and 3.3 genotypes were rarer (P<.000). Frequency of alleles 1 and 4 was higher in patient groups (P<.000), whereas alleles 2 and 3 had a lower frequency in patients with TMD (P<.000). This is the first correlation study that evaluates the association between IL-1Ra gene VNTR variant and TMD. The VNTR variant related to IL-1Ra gene showed a strong pattern of association with TMD that may have a potential impact on disease counseling and management. Larger studies with various ethnicities are needed to establish the impact of IL-1Ra VNTR variant on risk of developing TMD. © 2017 Wiley Periodicals, Inc.

  7. Analysis of genetic variability within Thelazia callipaeda (Nematoda: Thelazioidea) from Europe and Asia by sequencing and mutation scanning of the mitochondrial cytochrome c oxidase subunit 1 gene.

    Science.gov (United States)

    Otranto, D; Testini, G; De Luca, F; Hu, M; Shamsi, S; Gasser, R B

    2005-10-01

    This study investigated genetic variability within the 'eyeworm'Thelazia callipaeda (Nematoda: Thelazioidea) from Europe and Asia by polymerase chain reaction (PCR)-coupled sequencing and mutation scanning of the mitochondrial cytochrome c oxidase subunit 1 gene (cox 1). Eight different sequence variants of cox 1 (haplotypes) were determined for the 50 individual adult specimens of T. callipaeda (from dogs, foxes or cats from Italy, Germany and the Netherlands and from dogs from China and Korea). Nucleotide variation (0.3--2%) was detected at 23 of 649 positions in the cox 1. Six of these positions were invariable among all 37 individuals from Europe and among the 13 individuals from Asia (irrespective of host origin) but differed (five GA and one CT changes) between Europe and Asia. PCR-based single-strand conformation polymorphism (SSCP) analysis of the most variable portion (v-cox 1) of the cox 1 was validated (for a subset of samples) as a tool to rapidly screen for genetic (haplotypic) variability. The results for the SSCP analysis and sequencing were concordant, indicating that the mutation scanning approach provides a useful tool for investigating the population genetics and molecular ecology of T. callipaeda.

  8. Variable transcriptional responsiveness of the P2 × 3 receptor gene during CFA-induced inflammatory hyperalgesia.

    Science.gov (United States)

    Nuñez-Badinez, Paulina; Sepúlveda, Hugo; Diaz, Emilio; Greffrath, Wolfgang; Treede, Rolf-Detlef; Stehberg, Jimmy; Montecino, Martin; van Zundert, Brigitte

    2017-12-08

    The purinergic receptor P2 × 3 (P2 × 3-R) plays important roles in molecular pathways of pain, and reduction of its activity or expression effectively reduces chronic inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and cancer-induced pain can increase P2 × 3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2 × 3-R expression is unaltered or even reduced in other pain studies. The reasons for these discrepancies are unknown and might depend on the applied traumatic intervention or on intrinsic factors such as age, gender, genetic background and/or epigenetics. In this study, we sought to get insights into the molecular mechanisms responsible for inflammatory hyperalgesia by determining P2 × 3-R expression in DRG neurons of juvenile male rats that received a Complete Freund's Adjuvant (CFA) bilateral paw injection. We demonstrate that all CFA-treated rats showed inflammatory hyperalgesia, however, only a fraction (14-20%) displayed increased P2 × 3-R mRNA levels, reproducible across both sides. Immunostaining assays did not reveal significant increases in the percentage of P2 × 3-positive neurons, indicating that increased P2 × 3-R at DRG somas is not critical for inducing inflammatory hyperalgesia in CFA-treated rats. Chromatin immunoprecipitation (ChIP) assays showed a correlated (R2 = 0.671) enrichment of the transcription factor Runx1 and the epigenetic active mark histone H3 acetylation (H3Ac) at the P2 × 3-R gene promoter in a fraction of the CFA-treated rats. These results suggest that animal-specific increases in P2 × 3-R mRNA levels are likely associated with the genetic/epigenetic context of the P2 × 3-R locus that controls P2 × 3-R gene transcription by recruiting Runx1 and epigenetic co-regulators that mediate histone acetylation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. Somatic Mutation in Immunoglobulin Gene Variable Region in Patients With Chronic Lymphoid Leukemia and Its Influence on Disease Prognosis

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    Sadighi

    2016-03-01

    Full Text Available Background Chronic lymphocytic leukemia (CLL is a common blood cancer in people aged over 40. In addition to clinical and pathologic staging and blood tests, immunoglobulin variable heavy chain (IgVH mutation analysis is a relevant prognostic factor for CLL. Finding the most prevalent mutation type and conducting a molecular analysis of immunoglobulin in the majority of the patients can contribute to identifying the disease pattern. Objectives In the present study, we used molecular detection methods to find the relationship between clinical and pathologic findings with immunoglobulin heavy chain mutations in CLL patients in Iran. Patients and Methods Patients with CLL were randomly selected from patients referred to Imam Khomeini hospital, Tehran, Iran. All patients underwent a clinical staging of the disease and had flow cytometric analysis performed on their blood samples. The panels of cell surface markers used for the diagnosis of chronic lymphoid leukemia include CD19, CD3, CD23, CD10, and CD5. The diagnosis confirmed a minimum of 20% positive expression of dual CD5 and CD19 markers. Genomic DNA was then extracted from the patients’ blood and IgVH mutation analysis was conducted with pGEM-T (easy vector cloning kit followed by IgVH sequencing. Results Study patients were 42 to 80 years old, with their mean age of 62 (SE = 1.87 years. About 73% of them were male. The mean white blood cell (WBC count, lymphocytes percentage, average hemoglobin level, and platelet count were 56,000/µL, 85%, 12 g/dL, and 150,000/µL, respectively. According to their molecular analysis, 38.9% of patients were unmutated and 61.1% showed mutation in the variable heavy chain locus. The most common mutation had occurred in IgVH3 allele (66.66%. The mean overall survival rate of patients, mutated and unmutated, was, respectively, 39 (95% CI, 32 to 46 and 31 (95% CI, 26 to 36 months (P = 0.4. Binet stage had statistically significant relationship with patients

  10. Homology difference analysis of invasive mealybug species Phenacoccus solenopsis Tinsley in Southern China with COI gene sequence variability.

    Science.gov (United States)

    Wu, F Z; Ma, J; Hu, X N; Zeng, L

    2015-02-01

    The mealybug species Phenacoccus solenopsis (P. solenopsis) has caused much agricultural damage since its recent invasion in China. However, the source of this invasion remains unclear. This study uses molecular methods to clarify the relationships among different population of P. solenopsis from China, USA, Pakistan, India, and Vietnam to determine the geographic origin of the introduction of this species into China. P. solenopsis samples were collected from 25 different locations in three provinces of Southern China. Samples from the USA, Pakistan, and Vietnam were also obtained. Parts of the mitochondrial genes for cytochrome oxidase I (COI) were sequenced for each sample. Homologous DNA sequences of the samples from the USA and India were downloaded from Gen Bank. Two haplotypes were found in China. The first was from most samples from the Guangdong, Guangxi, and Hainan populations in the China and Pakistan groups, and the second from a few samples from the Guangdong, Guangxi, Hainan populations in the China, Pakistan, India, and Vietnam groups. As shown in the maximum likelihood of trees constructed using the COI sequences, these samples belonged to two clades. Phylogenetic analysis suggested that most P. solenopsis mealybugs in Southern China are probably closely related to populations in Pakistan. The variation, relationship, expansion, and probable geographic origin of P. solenopsis mealybugs in Southern China are also discussed.

  11. Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes

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    Marc Parisien

    2017-05-01

    Full Text Available Dorsal root ganglia (DRG relay sensory information to the brain, giving rise to the perception of pain, disorders of which are prevalent and burdensome. Here, we mapped expression quantitative trait loci (eQTLs in a collection of human DRGs. DRG eQTLs were enriched within untranslated regions of coding genes of low abundance, with some overlapping with other brain regions and blood cell cis-eQTLs. We confirm functionality of identified eQTLs through their significant enrichment within open chromatin and highly deleterious SNPs, particularly at the exon level, suggesting substantial contribution of eQTLs to alternative splicing regulation. We illustrate pain-related genetic association results explained by DRG eQTLs, with the strongest evidence for contribution of the human leukocyte antigen (HLA locus, confirmed using a mouse inflammatory pain model. Finally, we show that DRG eQTLs are found among hits in numerous genome-wide association studies, suggesting that this dataset will help address pain components of non-pain disorders.

  12. Variable effects of oxytetracycline on antibiotic resistance gene abundance and the bacterial community during aerobic composting of cow manure.

    Science.gov (United States)

    Qian, Xun; Sun, Wei; Gu, Jie; Wang, Xiao-Juan; Sun, Jia-Jun; Yin, Ya-Nan; Duan, Man-Li

    2016-09-05

    Livestock manure is often subjected to aerobic composting but little is known about the variation in antibiotic resistance genes (ARGs) during the composting process under different concentrations of antibiotics. This study compared the effects of three concentrations of oxytetracycline (OTC; 10, 60, and 200mg/kg) on ARGs and the succession of the bacterial community during composting. Very similar trends were observed in the relative abundances (RAs) of each ARG among the OTC treatments and the control during composting. After composting, the RAs of tetC, tetX, sul1, sul2, and intI1 increased 2-43 times, whereas those of tetQ, tetM, and tetW declined by 44-99%. OTC addition significantly increased the absolute abundances and RAs of tetC and intI1, while 200mg/kg OTC also enhanced those of tetM, tetQ, and drfA7. The bacterial community could be grouped according to the composting time under different treatments. The highest concentration of OTC had a more persistent effect on the bacterial community. In the present study, the succession of the bacterial community appeared to have a greater influence on the variation of ARGs during composting than the presence of antibiotics. Aerobic composting was not effective in reducing most of the ARGs, and thus the compost product should be considered as an important reservoir for ARGs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Identification of TENP as the Gene Encoding Chicken Egg White Ovoglobulin G2 and Demonstration of Its High Genetic Variability in Chickens.

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    Keiji Kinoshita

    Full Text Available Ovoglobulin G2 (G2 has long been known as a major protein constituent of chicken egg white. However, little is known about the biochemical properties and biological functions of G2 because the gene encoding G2 has not been identified. Therefore, the identification of the gene encoding G2 and an analysis of its genetic variability is an important step toward the goal of understanding the biological functions of the G2 protein and its utility in poultry production. To identify and characterize the gene encoding G2, we separated G2 from egg white using electrophoresis on a non-denaturing polyacrylamide gel. Two polymorphic forms of G2 protein (G2A and G2B, with different mobilities (fast and slow respectively, were detected by staining. The protein band corresponding to G2B was electro-eluted from the native gel, re-electrophoresed under denaturing conditions and its N-terminal sequence was determined by Edman degradation following transfer onto a membrane. Sequencing of the 47 kDa G2B band revealed it to be identical to TENP (transiently expressed in neural precursors, also known as BPI fold-containing family B, member 2 (BPIFB2, a protein with strong homology to a bacterial permeability-increasing protein family (BPI in mammals. Full-length chicken TENP cDNA sequences were determined for 78 individuals across 29 chicken breeds, lines, and populations, and consequently eleven non-synonymous substitutions were detected in the coding region. Of the eleven non-synonymous substitutions, A329G leading to Arg110Gln was completely associated with the noted differential electrophoretic mobility of G2. Specifically G2B, with a slower mobility is encoded by A329 (Arg110, whereas G2A, with a faster mobility, is encoded by G329 (Gln110. The sequence data, derived from the coding region, also revealed that the gene encoding G2 demonstrates significant genetic variability across different chicken breeds/lines/populations. These variants, and how they correlate

  14. Identification of TENP as the Gene Encoding Chicken Egg White Ovoglobulin G2 and Demonstration of Its High Genetic Variability in Chickens.

    Science.gov (United States)

    Kinoshita, Keiji; Shimogiri, Takeshi; Ibrahim, Hisham R; Tsudzuki, Masaoki; Maeda, Yoshizane; Matsuda, Yoichi

    2016-01-01

    Ovoglobulin G2 (G2) has long been known as a major protein constituent of chicken egg white. However, little is known about the biochemical properties and biological functions of G2 because the gene encoding G2 has not been identified. Therefore, the identification of the gene encoding G2 and an analysis of its genetic variability is an important step toward the goal of understanding the biological functions of the G2 protein and its utility in poultry production. To identify and characterize the gene encoding G2, we separated G2 from egg white using electrophoresis on a non-denaturing polyacrylamide gel. Two polymorphic forms of G2 protein (G2A and G2B), with different mobilities (fast and slow respectively), were detected by staining. The protein band corresponding to G2B was electro-eluted from the native gel, re-electrophoresed under denaturing conditions and its N-terminal sequence was determined by Edman degradation following transfer onto a membrane. Sequencing of the 47 kDa G2B band revealed it to be identical to TENP (transiently expressed in neural precursors), also known as BPI fold-containing family B, member 2 (BPIFB2), a protein with strong homology to a bacterial permeability-increasing protein family (BPI) in mammals. Full-length chicken TENP cDNA sequences were determined for 78 individuals across 29 chicken breeds, lines, and populations, and consequently eleven non-synonymous substitutions were detected in the coding region. Of the eleven non-synonymous substitutions, A329G leading to Arg110Gln was completely associated with the noted differential electrophoretic mobility of G2. Specifically G2B, with a slower mobility is encoded by A329 (Arg110), whereas G2A, with a faster mobility, is encoded by G329 (Gln110). The sequence data, derived from the coding region, also revealed that the gene encoding G2 demonstrates significant genetic variability across different chicken breeds/lines/populations. These variants, and how they correlate with egg

  15. Analysis of genetic variability within Argulus japonicus from representatives of Africa, Middle East, and Asia revealed by sequences of three mitochondrial DNA genes.

    Science.gov (United States)

    Wadeh, Hicham; Alsarakibi, Muhamd; Li, Guoqing

    2010-08-01

    This study investigated the genetic variability within fish louse Argulus japonicus (Crustacea: Branchiura) from Africa, Middle East, and Asia by polymerase chain reaction in three mitochondrial DNA (mtDNA) regions, namely, cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunits 1 and 4 (nad1 and nad4). Six different sequences from a portion of the cox1 gene (pcox1) and a portion of the nad1 and nad4 genes (pnad1 and pnad4) for ten adult specimens from infected fish in China, Egypt, and Syria were amplified separately from individual and the amplicons were subjected to direct sequencing. A + T percentages were 68.8-69% for pcox1, 77.1-77.6% for pnad1, and 60.4-60.9% for pnad4. Among all the collected parasites, A. japonicus sequence variations were 0.0-1.9% for cox1, 0.0-2.3% for nad1, and 0.0-0.8% for nad4. In rivers, sequence variations among all individuals were 0.4-0.8% for cox1, 1.0-2.3% for nad1, and 0.4-0.8% for nad4, while sequence variations among all the collected parasites in fish farms were 0.6-1.9% for cox1, 0.0-1.7% for nad1, and 0.2-0.6% for nad4. The nad1 was the most variable gene among selected markers, while nad4 was a more conserved gene than cox1. All isolates of A. japonicus were sister to Argulus americanus in phylogenetic tree and they grouped together in one sub-clade, while isolates from China and Egypt fish farms were closely clustered together. However, moderate genetic drift and slight mutation could be observed among A. japonicus individuals. These findings demonstrated the convenience and attributes of the three selected mtDNA sequences for population genetic studies of A. japonicus where nad1 is a new and reliable marker to detect the sequence variation among A. japonicus individuals.

  16. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region.

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    Paula Stewart

    Full Text Available Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE during the bovine spongiform encephalopathy (BSE epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD remains an open question. Variation in the host-encoded prion protein (PrP(C largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo and pine marten (Martes martes were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus and mountain lion (Puma concolor from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.

  17. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region.

    Science.gov (United States)

    Stewart, Paula; Campbell, Lauren; Skogtvedt, Susan; Griffin, Karen A; Arnemo, Jon M; Tryland, Morten; Girling, Simon; Miller, Michael W; Tranulis, Michael A; Goldmann, Wilfred

    2012-01-01

    Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrP(C)) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C) protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo) and pine marten (Martes martes) were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus) and mountain lion (Puma concolor) from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.

  18. Variable responses of two VlMYBA gene promoters to ABA and ACC in Kyoho grape berries.

    Science.gov (United States)

    Zhai, Xiawan; Zhang, Yushu; Kai, Wenbin; Liang, Bin; Jiang, Li; Du, Yangwei; Wang, Juan; Sun, Yufei; Leng, Ping

    2017-04-01

    The VlMYBA subfamily of transcription factors has been known to be the functional regulators in anthocyanin biosynthesis in red grapes. In this study, the expressions of the VlMYBA1-2 and VlMYBA 2 genes, and the responses of the VlMYBA1-2/2 promoters to ABA and ACC treatments in Kyoho grape berries are examined through quantitative real-time PCR analysis and the transient expression assay. The results show that the expressions of VlMYBA1-2/2 increase dramatically after véraison and reach their highest levels when the berries are nearly fully ripe. Exogenous ABA promotes the expressions of VlMYBA1-2/2, whereas the ACC treatment increases the expression of VlMYBA2, however, it has no effect on VlMYBA1-2. The ABA treatment has a faster and stronger effect on berry pigmentation than ACC does. The VlMYBA1-2 promoter sequence contains two ABA response elements (ABRE) but no ethylene response element (ERE), whereas the VlMYBA2 promoter sequence contains two ABRE and one ERE in the upstream region of the start codon. The VlMYBA2 promoter can be activated by both ABA (more effective) and ACC, whereas the VlMYBA1-2 promoter can be activated by ABA only. In sum, ABA can promote the coloring of Kyoho grape by the promotion of VlMYBA1-2/2 transcriptions via activating the response of their promoters to ABA, whereas ethylene only regulates VlMYBA2 through the response activation of its promoter to ACC which partially enhances the coloring. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Interleukin-1 Receptor Antagonist and Interleukin-4 Genes Variable Number Tandem Repeats Are Associated with Adiposity in Malaysian Subjects

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    Yung-Yean Kok

    2017-01-01

    Full Text Available Interleukin-1 receptor antagonist (IL1RA intron 2 86 bp repeat and interleukin-4 (IL4 intron 3 70 bp repeat are variable number tandem repeats (VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians. The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher overall adiposity, relative to those having the I/I genotype or I allele, respectively, even after controlling for ethnicity [Odds Ratio (OR of I/II genotype = 12.21 (CI = 2.54, 58.79; p=0.002; II allele = 5.78 (CI = 1.73, 19.29; p=0.004]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p=0.03]. Individuals with IL1RA II allele had significantly higher TBF than those with I allele (31.79±2.52 versus 23.51±0.40; p=0.005. Taken together, IL1RA intron 2 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

  20. A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO).

    Science.gov (United States)

    Berardo, Andres; Coku, Jorida; Kurt, Bulent; DiMauro, Salvatore; Hirano, Michio

    2010-03-01

    We describe a 62-year-old woman with chronic progressive external ophthalmoplegia (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNA(Ile) gene (MTTI). This is the first mutation at position 44 in the variable loop (V loop) of any mitochondrial tRNA. The muscle biopsy revealed 10% ragged-red/ragged-blue fibers and 25% cytochrome c oxidase (COX)-deficient fibers. No deletions or duplications were detected by Southern blot analysis. The 4302A>G transition was present only in the patient's muscle and single-fiber analysis revealed significantly higher levels of the mutation in COX-deficient than in normal fibers. Like tRNA(Leu(UUR)), tRNA(Ile) appears to be a "hot spot" for mtDNA mutations causing CPEO. Copyright 2010 Elsevier B.V. All rights reserved.

  1. The adverse impact of obesity on heart rate variability is modified by a NFE2L2 gene variant: The SAPALDIA cohort.

    Science.gov (United States)

    Adam, Martin; Imboden, Medea; Schaffner, Emmanuel; Boes, Eva; Kronenberg, Florian; Pons, Marco; Bettschart, Robert; Barthelemy, Jean-Claude; Schindler, Christian; Probst-Hensch, Nicole

    2017-02-01

    Overweight has been associated with an increase in inflammatory markers and with an imbalance in the autonomic nervous system, such as a decrease in heart rate variability (HRV). In this study we aimed to investigate the modifying effect of a genetic variation in a major anti-inflammatory marker gene, NFE2L2, on the relationship between overweight and HRV. We analyzed participants of the SAPALDIA cohort aged 50years and older, twice in 2002/2003 (N=1472) and 2010/2011 (N=1235). We included persons with valid genotype data, who underwent ambulatory 24-h electrocardiogram monitoring, and reported on medical history and lifestyle. The association between HRV and BMI, measured as standard deviation of normal-to-normal intervals (SDNN) by BMI and the modifying effect of the cardiovascular health-related NFE2L2 gene variant rs2364723 were tested, applying multivariable mixed linear regression models. We found study participants with overweight (BMI>25) over two follow-up surveys 10years apart to have a negative association between SDNN, calculated as geometric means, with BMI. The examined NFE2L2 variant sustainably modified (pinteraction=0.014) the found inverse association between a BMI increment and SDNN, causing a stronger decrement in SDNN for participants with the CC genotype (-20.7%; 95%-confidence interval: -12.33 to -28.28) compared with participants carrying the GC (-7.43; 95%CI: -3.56 to -11.15) or GG (-11.26%; 95%CI: -7.68 to -14.7) genotype, estimated for the difference from the 90(th) to the 10(th) percentile of BMI by the NFE2L2 variant. Our results are consistent with the hypothesis that overweight decreases heart rate variability through inflammatory processes. Copyright © 2016 Swiss Tropical and Public Health Institute. Published by Elsevier Ireland Ltd.. All rights reserved.

  2. Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI.

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    Kyung Woo Park

    Full Text Available Paraoxonase (PON is a high-density-lipoprotein (HDL associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation.A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR, and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months.PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61% and those with RR-genotype (521 patients, 39%. After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55-87.0, but not repeat revascularization (HR 1.12, 95% CI: 0.78-1.61. The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342 but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027. The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS patients compared with non-ACS patients.PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C.

  3. Associations of air pollution exposure with blood pressure and heart rate variability are modified by oxidative stress genes: A repeated-measures panel among elderly urban residents.

    Science.gov (United States)

    Kim, Kyoung-Nam; Kim, Jin Hee; Jung, Kweon; Hong, Yun-Chul

    2016-03-25

    Oxidative stress has been suggested as a major cause of elevated blood pressure (BP) and reduced heart rate variability (HRV) due to air pollution. We hypothesized that the associations of air pollution exposure with BP and HRV are modified by oxidative stress gene polymorphisms. Between 2008 and 2010, we conducted up to 5 surveys of 547 elderly participants, measured their BP and HRV, and genotyped 47 single nucleotide polymorphisms (SNPs) in 18 oxidative stress genes. Linear mixed models were constructed to evaluate the associations of particulate matter ≤10 μm, nitrogen dioxide, and sulfur dioxide with BP and HRV, as well as the modifications of these associations by the genotyped SNPs. Single-SNP analyses revealed interactions between air pollution and 15 SNPs (for BP) and 33 SNPs (for HRV) (all, P for interaction pollution exposure with BP and HRV were modified by the genetic risk scores (P for interaction pollution with BP and HRV are mediated by oxidative stress pathways.

  4. Genetic variability and evolutionary implications of RNA silencing suppressor genes in RNA1 of sweet potato chlorotic stunt virus isolates infecting sweetpotato and related wild species.

    Science.gov (United States)

    Tugume, Arthur K; Amayo, Robert; Weinheimer, Isabel; Mukasa, Settumba B; Rubaihayo, Patrick R; Valkonen, Jari P T

    2013-01-01

    The bipartite single-stranded RNA genome of Sweet potato chlorotic stunt virus (SPCSV, genus Crinivirus; Closteroviridae) encodes a Class 1 RNase III (RNase3), a putative hydrophobic protein (p7) and a 22-kDa protein (p22) from genes located in RNA1. RNase3 and p22 suppress RNA silencing, the basal antiviral defence mechanism in plants. RNase3 is sufficient to render sweetpotato (Ipomoea batatas) virus-susceptible and predisposes it to development of severe diseases following infection with unrelated virus. The incidence, strains and gene content of SPCSV infecting wild plant species have not been studied. Thirty SPCSV isolates were characterized from 10 wild Ipomoea species, Hewittia sublobata or Lepistemon owariensis (family Convolvulaceae) in Uganda and compared with 34 local SPCSV isolates infecting sweetpotatoes. All isolates belonged to the East African (EA) strain of SPCSV and contained RNase3 and p7, but p22 was not detected in six isolates. The three genes showed only limited genetic variability and the proteins were under purifying selection. SPCSV isolates lacking p22 synergized with Sweet potato feathery mottle virus (SPFMV, genus potyvirus; Potyviridae) and caused severe symptoms in co-infected sweetpotato plants. One SPCSV isolate enhanced accumulation of SPFMV, but no severe symptoms developed. A new whitefly-transmitted virus (KML33b) encoding an RNase3 homolog (<56% identity to SPCSV RNase3) able to suppresses sense-mediated RNA silencing was detected in I. sinensis. SPCSV isolates infecting wild species and sweetpotato in Uganda were genetically undifferentiated, suggesting inter-species transmission of SPCSV. Most isolates in Uganda contained p22, unlike SPCSV isolates characterized from other countries and continents. Enhanced accumulation of SPFMV and increased disease severity were found to be uncoupled phenotypic outcomes of RNase3-mediated viral synergism in sweetpotato. A second virus encoding an RNase3-like RNA silencing suppressor was

  5. The DUB/USP17 deubiquitinating enzymes: A gene family within a tandemly repeated sequence, is also embedded within the copy number variable Beta-defensin cluster

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    Scott Christopher J

    2010-04-01

    Full Text Available Abstract Background The DUB/USP17 subfamily of deubiquitinating enzymes were originally identified as immediate early genes induced in response to cytokine stimulation in mice (DUB-1, DUB-1A, DUB-2, DUB-2A. Subsequently we have identified a number of human family members and shown that one of these (DUB-3 is also cytokine inducible. We originally showed that constitutive expression of DUB-3 can block cell proliferation and more recently we have demonstrated that this is due to its regulation of the ubiquitination and activity of the 'CAAX' box protease RCE1. Results Here we demonstrate that the human DUB/USP17 family members are found on both chromosome 4p16.1, within a block of tandem repeats, and on chromosome 8p23.1, embedded within the copy number variable beta-defensin cluster. In addition, we show that the multiple genes observed in humans and other distantly related mammals have arisen due to the independent expansion of an ancestral sequence within each species. However, it is also apparent when sequences from humans and the more closely related chimpanzee are compared, that duplication events have taken place prior to these species separating. Conclusions The observation that the DUB/USP17 genes, which can influence cell growth and survival, have evolved from an unstable ancestral sequence which has undergone multiple and varied duplications in the species examined marks this as a unique family. In addition, their presence within the beta-defensin repeat raises the question whether they may contribute to the influence of this repeat on immune related conditions.

  6. Phase variable O antigen biosynthetic genes control expression of the major protective antigen and bacteriophage receptor in Vibrio cholerae O1.

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    Kimberley D Seed

    2012-09-01

    Full Text Available The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage.

  7. Teaching Gene Technology in an Outreach Lab: Students' Assigned Cognitive Load Clusters and the Clusters' Relationships to Learner Characteristics, Laboratory Variables, and Cognitive Achievement

    Science.gov (United States)

    Scharfenberg, Franz-Josef; Bogner, Franz X.

    2013-02-01

    This study classified students into different cognitive load (CL) groups by means of cluster analysis based on their experienced CL in a gene technology outreach lab which has instructionally been designed with regard to CL theory. The relationships of the identified student CL clusters to learner characteristics, laboratory variables, and cognitive achievement were examined using a pre-post-follow-up design. Participants of our day-long module Genetic Fingerprinting were 409 twelfth-graders. During the module instructional phases (pre-lab, theoretical, experimental, and interpretation phases), we measured the students' mental effort (ME) as an index of CL. By clustering the students' module-phase-specific ME pattern, we found three student CL clusters which were independent of the module instructional phases, labeled as low-level, average-level, and high-level loaded clusters. Additionally, we found two student CL clusters that were each particular to a specific module phase. Their members reported especially high ME invested in one phase each: within the pre-lab phase and within the interpretation phase. Differentiating the clusters, we identified uncertainty tolerance, prior experience in experimentation, epistemic interest, and prior knowledge as relevant learner characteristics. We found relationships to cognitive achievement, but no relationships to the examined laboratory variables. Our results underscore the importance of pre-lab and interpretation phases in hands-on teaching in science education and the need for teachers to pay attention to these phases, both inside and outside of outreach laboratory learning settings.

  8. Bacterial community structure of mangrove sediments in relation to environmental variables accessed by 16S rRNA gene-denaturing gradient gel electrophoresis fingerprinting

    Directory of Open Access Journals (Sweden)

    Yanying Zhang

    2009-09-01

    Full Text Available Bacterial community structure and the relationship between environmental variables and microbial communities in the surface sediments of tropical mangrove ecosystems were investigated in Sanya, Hainan Island, China. Profiles of bacterial communities were generated using culture-independent PCR-denaturing gradient gel electrophoresis (DGGE, and the results were interpreted with multivariate statistical analysis. Findings suggested that microbial communities varied with sample collection sites and seasons. The samples collected from the same sample sites at the same time had more similar microbial communities except samples SH3 and AB5, which also had unique sediment quality. Canonical correspondence analysis (CCA revealed that the organic carbon concentration of the sediments accounted for a significant amount of the variability in the bacterial community composition. Phylogenetic analysis was used to identify the major groups of the predominant bacterial phylotypes. 16S rRNA gene-V3 fragments from 17 individual DGGE bands were sequenced and the corresponding bacteria were found in mangrove sediments for the first time based on BLAST results. Predominant bacterial phylotypes clustered with various taxonomic groups, including Proteobacteria, Bacteroidetes, Gemmatimonadetes, Actinobacteria and Firmicutes.

  9. Genetic variability and evolutionary implications of RNA silencing suppressor genes in RNA1 of sweet potato chlorotic stunt virus isolates infecting sweetpotato and related wild species.

    Directory of Open Access Journals (Sweden)

    Arthur K Tugume

    Full Text Available BACKGROUND: The bipartite single-stranded RNA genome of Sweet potato chlorotic stunt virus (SPCSV, genus Crinivirus; Closteroviridae encodes a Class 1 RNase III (RNase3, a putative hydrophobic protein (p7 and a 22-kDa protein (p22 from genes located in RNA1. RNase3 and p22 suppress RNA silencing, the basal antiviral defence mechanism in plants. RNase3 is sufficient to render sweetpotato (Ipomoea batatas virus-susceptible and predisposes it to development of severe diseases following infection with unrelated virus. The incidence, strains and gene content of SPCSV infecting wild plant species have not been studied. METHODOLOGY/PRINCIPAL FINDINGS: Thirty SPCSV isolates were characterized from 10 wild Ipomoea species, Hewittia sublobata or Lepistemon owariensis (family Convolvulaceae in Uganda and compared with 34 local SPCSV isolates infecting sweetpotatoes. All isolates belonged to the East African (EA strain of SPCSV and contained RNase3 and p7, but p22 was not detected in six isolates. The three genes showed only limited genetic variability and the proteins were under purifying selection. SPCSV isolates lacking p22 synergized with Sweet potato feathery mottle virus (SPFMV, genus potyvirus; Potyviridae and caused severe symptoms in co-infected sweetpotato plants. One SPCSV isolate enhanced accumulation of SPFMV, but no severe symptoms developed. A new whitefly-transmitted virus (KML33b encoding an RNase3 homolog (<56% identity to SPCSV RNase3 able to suppresses sense-mediated RNA silencing was detected in I. sinensis. CONCLUSIONS/SIGNIFICANCE: SPCSV isolates infecting wild species and sweetpotato in Uganda were genetically undifferentiated, suggesting inter-species transmission of SPCSV. Most isolates in Uganda contained p22, unlike SPCSV isolates characterized from other countries and continents. Enhanced accumulation of SPFMV and increased disease severity were found to be uncoupled phenotypic outcomes of RNase3-mediated viral synergism in

  10. Molecular analysis of immunoglobulin variable genes supports a germinal center experienced normal counterpart in primary cutaneous diffuse large B-cell lymphoma, leg-type.

    Science.gov (United States)

    Pham-Ledard, Anne; Prochazkova-Carlotti, Martina; Deveza, Mélanie; Laforet, Marie-Pierre; Beylot-Barry, Marie; Vergier, Béatrice; Parrens, Marie; Feuillard, Jean; Merlio, Jean-Philippe; Gachard, Nathalie

    2017-07-26

    Immunophenotype of primary cutaneous diffuse large B-cell lymphoma, leg-type (PCLBCL-LT) suggests a germinal center-experienced B lymphocyte (BCL2+ MUM1+ BCL6+/-). As maturation history of B-cell is "imprinted" during B-cell development on the immunoglobulin gene sequence, we studied the structure and sequence of the variable part of the genes (IGHV, IGLV, IGKV), immunoglobulin surface expression and features of class switching in order to determine the PCLBCL-LT cell of origin. Clonality analysis with BIOMED2 protocol and VH leader primers was done on DNA extracted from frozen skin biopsies on retrospective samples from 14 patients. The clonal DNA IGHV sequence of the tumor was aligned and compared with the closest germline sequence and homology percentage was calculated. Superantigen binding sites were studied. Features of selection pressure were evaluated with the multinomial Lossos model. A functional monoclonal sequence was observed in 14 cases as determined for IGHV (10), IGLV (2) or IGKV (3). IGV mutation rates were high (>5%) in all cases but one (median:15.5%), with superantigen binding sites conservation. Features of selection pressure were identified in 11/12 interpretable cases, more frequently negative (75%) than positive (25%). Intraclonal variation was detected in 3 of 8 tumor specimens with a low rate of mutations. Surface immunoglobulin was an IgM in 12/12 cases. FISH analysis of IGHM locus, deleted during class switching, showed heterozygous IGHM gene deletion in half of cases. The genomic PCR analysis confirmed the deletions within the switch μ region. IGV sequences were highly mutated but functional, with negative features of selection pressure suggesting one or more germinal center passage(s) with somatic hypermutation, but superantigen (SpA) binding sites conservation. Genetic features of class switch were observed, but on the non functional allele and co-existing with primary isotype IgM expression. These data suggest that cell-of origin is

  11. Benefits of gene flow are mediated by individual variability in self-compatibility in small isolated populations of an endemic plant species.

    Science.gov (United States)

    Frye, Christopher T; Neel, Maile C

    2017-07-01

    Many rare and endemic species experience increased rates of self-fertilization and mating among close relatives as a consequence of existing in small populations within isolated habitat patches. Variability in self-compatibility among individuals within populations may reflect adaptation to local demography and genetic architecture, inbreeding, or drift. We use experimental hand-pollinations under natural field conditions to assess the effects of gene flow in 21 populations of the central Appalachian endemic Trifolium virginicum that varied in population size and degree of isolation. We quantified the effects of distance from pollen source on pollination success and fruit set. Rates of self-compatibility varied dramatically among maternal plants, ranging from 0% to 100%. This variation was unrelated to population size or degree of isolation. Nearly continuous variation in the success of selfing and near-cross-matings via hand pollination suggests that T. virginicum expresses pseudo-self-fertility, whereby plants carrying the same S-allele mate successfully by altering the self-incompatibility reaction. However, outcrossing among populations produced significantly higher fruit set than within populations, an indication of drift load. These results are consistent with strong selection acting to break down self-incompatibility in these small populations and/or early-acting inbreeding depression expressed upon selfing.

  12. Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

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    Trino Baptista

    2015-06-01

    Full Text Available Objective:Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD, but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I.Methods:The available relatives of the same family were interviewed (DSM-IV-R and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS, leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs for the leptin receptor and promoter and PPAR-γ2 genes. The frequency of MS was compared with that recorded in the local general population.Results:Ninety-three relatives of three adults with BD were evaluated (30 aged 18 years. The frequency of MS was similar to that of the general population. Significantly higher frequencies of abnormal glucose, total and low density cholesterol (LDL-c levels (all p < 0.05, waist circumference (p = 0.057, and leptin and insulin resistance values (in adults only were observed in the family. Adults with the QQ genotype of the leptin receptor displayed higher LDL-c levels than carriers of the R allele.Conclusions:The associations among BD consanguinity, familial hypercholesterolemia, and leptin receptor SNPs reported herein should be replicated and extended in other pedigrees.

  13. Low Variability and Stable Frequency of Common Haplotypes of the TP53 Gene Region in Colorectal Cancer Patients in a Slovak Population.

    Science.gov (United States)

    Škereňová, Mária; Halašová, Erika; Matáková, Tatiana; Jesenská, Ľubica; Jurečeková, Jana; Šarlinová, Miroslava; Čierny, Daniel; Dobrota, Dušan

    2017-04-01

    To test the association between common TP53 haplotypes and colorectal cancer (CRC) development. A total of 277 CRC patients and 167 healthy volunteers were included in the study. Common TP53 haplotypes were estimated from eight single-nucleotide polymorphisms (SNPs) (rs1614984, rs77697176, rs12947788, rs1800372, rs2909430, rs1042522, rs17878362 and rs11652704). Stepwise haplotype trend regression showed the haplotype-regressor cccgaRDa as a possible predictive marker. The rare haplotype cccgaRDa was identified in 10 CRC cases and 3 controls. Although it is approximately twice as common in CRC (odds ratio (OR)=2.068; 95% confidence interval (CI)=0.471-9.069), the cccgaRDa haplotype frequency is low in the studied groups. Results of our study suggest that the common TP53 variability is relatively low (only 3 haplotypes occurred above 10%). The haplotype background of TP53 gene is relative stable and despite low haplotype-regressor cccgaRDa frequency it shows to be a possible predictive parameter for CRC development. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Molecular characterization of GPR50 gene and study of its comparative genetic variability in sheep breeds adapted to different thermo-contrasting climatic regimens

    Science.gov (United States)

    Saxena, Vijay Kumar; Kumar, Davendra; Naqvi, S. M. K.

    2017-04-01

    GPR50, formerly known as a melatonin-related receptor, is one of the three subtypes of melatonin receptor subfamily, together with MTNR1A and MTNR1B. GPR50, despite its high identity with the melatonin receptor family, does not bind melatonin and is considered to be an ortholog of MTNR1C in mammals. GPR50-expressing cells have been found in the dorsomedial nucleus of the hypothalamus, the periventricular nucleus, and the median eminence. Genetic and functional evidence have been recently investigated linking GPR50 to adaptive thermogenesis and torpor, but still, it is an orphan receptor and is yet to be studied conclusively. The aims of the study were to characterize the GPR50 gene of sheep and to study the sequence variability of the gene in Indian sheep breeds of two different thermo-varied agroclimatic conditions. Genomic DNA isolation was done and a 791-bp sequence was amplified using self-designed primers and SNP profiling done out of samples of all the breeds to study the relative frequency of SNPs in each of the breed. Five important non-synonymous mutations were observed in the various breeds studied. T698G, G1097A, G1270A, G1318A, and C1334G lead to the following substitution: valine by glycine, arginine by glutamine, threonine by alanine, isoleucine by valine, and serine by cytosine, respectively. Two synonymous mutations (T663G and C888T) were also observed in some of the studied breeds. G1270A and C888T were the most prevalent SNPs observed in nearly all of the breeds. C888T SNPs were observed in higher prevalence in Chokla, Marwari, and Magra in comparison to Gaddi and Bharat Merino. A PolyPhen-2 analysis, which is used to assess the potential damaging nature of an SNP, revealed that mutation T698G and G1270A were benign while G1097A, G1318A, and C1334G were damaging with a score of 0.987, 0.993, and 0.739, respectively. A 3-D homology model of the protein was prepared using c4zwjA (UniProt sequence ID) as a template using the online version of Phyre2

  15. Interleukin-17A Gene Variability in Patients with Type 1 Diabetes Mellitus and Chronic Periodontitis: Its Correlation with IL-17 Levels and the Occurrence of Periodontopathic Bacteria.

    Science.gov (United States)

    Borilova Linhartova, Petra; Kastovsky, Jakub; Lucanova, Svetlana; Bartova, Jirina; Poskerova, Hana; Vokurka, Jan; Fassmann, Antonin; Kankova, Katerina; Izakovicova Holla, Lydie

    2016-01-01

    Interleukin-17 contributes to the pathogenesis of type 1 diabetes mellitus (T1DM) and chronic periodontitis (CP). We analyzed IL-17A -197A/G and IL-17F +7488C/T polymorphisms in T1DM and CP and determined their associations with IL-17 production and occurrence of periopathogens. Totally 154 controls, 125 T1DM, and 244 CP patients were genotyped using 5' nuclease TaqMan(®) assays. Bacterial colonization was investigated by a DNA-microarray kit. Production of IL-17 after in vitro stimulation of mononuclear cells by mitogens and bacteria was examined by the Luminex system. Although no differences in the allele/genotype frequencies between patients with CP and T1DM + CP were found, the IL-17A -197 A allele increased the risk of T1DM (P < 0.05). Levels of HbA1c were significantly elevated in carriers of the A allele in T1DM patients (P < 0.05). Production of IL-17 by mononuclear cells of CP patients (unstimulated/stimulated by Porphyromonas gingivalis) was associated with IL-17A A allele (P < 0.05). IL-17A polymorphism increased the number of Tannerella forsythia and Treponema denticola in patients with CP and T1DM + CP, respectively (P < 0.05). IL-17A gene variability may influence control of T1DM and the "red complex" bacteria occurrence in patients with CP and T1DM + CP. Our findings demonstrated the functional relevance of the IL-17A polymorphism with higher IL-17 secretion in individuals with A allele.

  16. Association of STin2 Variable Number of Tandem Repeat (VNTR) Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects

    Science.gov (United States)

    Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Peng, Dangwei; Liang, Chaozhao

    2016-01-01

    Background The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). Material/Methods We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. Results The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31–0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. Conclusions Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers. PMID:27713390

  17. Global analysis of genetic variations in a 56-bp variable number of tandem repeat polymorphisms within the human deoxyribonuclease I gene.

    Science.gov (United States)

    Fujihara, Junko; Yasuda, Toshihiro; Iida, Reiko; Ueki, Misuzu; Sano, Rie; Kominato, Yoshihiko; Inoue, Ken; Kimura-Kataoka, Kaori; Takeshita, Haruo

    2015-07-01

    A 56-bp variable number of tandem repeat polymorphism is confirmed in intron 4 of the human deoxyribonuclease I (DNase I) gene (HumDN1). The purpose of the present study was to document global ethnic variations of allelic frequencies in HumDN1 VNTR polymorphisms. In this study, HumDN1 VNTR polymorphisms in 11 worldwide populations were examined by polymerase chain reaction and compared with those reported previously. Fifteen genotypes were identified in these 11 populations. Novel genotypes were found: 1/2 was observed in Ghanaians and mestizos, 3/6 was in Tamangs, 4/6 was in Tibetans and Nahuas, 6/6 was in Sinhalese. The African population showed the highest frequency for the HumDN1(∗)3 allele. Among Asian populations, the different genotype distribution was observed. The predominant allele in Mongolian, Korean, Japanese, and Chinese populations was HumDN1(∗)3, followed by HumDN1(∗)4, and then HumDN1(∗)5. In Chinese from South China, Tamangs, and Sinhalese, HumDN1(∗)4 and HumDN1(∗)5 were predominant. The allele frequency for HumDN1(∗)4 was high in three Mexican populations, but a significant difference was observed between Nahuas and Huicoles. Germans and Turks showed a similar distribution. This study is the first to show the existence of a certain genetic heterogeneity in the worldwide distribution of HumDN1 VNTR polymorphism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Four patients with speech delay, seizures and variable corpus callosum thickness sharing a 0.440 Mb deletion in region 1q44 containing the HNRPU gene

    NARCIS (Netherlands)

    Caliebe, Almuth; Kroes, Hester Y.; van der Smagt, Jasper J.; Martin-Subero, Jose I.; Toennies, Holger; van 't Slot, Ruben; Nievelstein, Rutger A. J.; Muhle, Hiltrud; Stephani, Ulrich; Alfke, Karsten; Stefanova, Irina; Hellenbroich, Yorck; Gillessen-Kaesbach, Gabriele; Hochstenbach, Ron; Siebert, Reiner; Poot, Martin

    2010-01-01

    Structural genome aberrations are frequently associated with highly variable congenital phenotypes involving mental retardation and developmental delay. Although some of these aberrations may result in recognizable phenotypes, a high degree of phenotypic variability often complicates a comprehensive

  19. Effect of Genetic Variability in the CYP4F2, CYP4F11, and CYP4F12 Genes on Liver mRNA Levels and Warfarin Response

    Directory of Open Access Journals (Sweden)

    J. E. Zhang

    2017-05-01

    Full Text Available Genetic polymorphisms in the gene encoding cytochrome P450 (CYP 4F2, a vitamin K oxidase, affect stable warfarin dose requirements and time to therapeutic INR. CYP4F2 is part of the CYP4F gene cluster, which is highly polymorphic and exhibits a high degree of linkage disequilibrium, making it difficult to define causal variants. Our objective was to examine the effect of genetic variability in the CYP4F gene cluster on expression of the individual CYP4F genes and warfarin response. mRNA levels of the CYP4F gene cluster were quantified in human liver samples (n = 149 obtained from a well-characterized liver bank and fine mapping of the CYP4F gene cluster encompassing CYP4F2, CYP4F11, and CYP4F12 was performed. Genome-wide association study (GWAS data from a prospective cohort of warfarin-treated patients (n = 711 was also analyzed for genetic variations across the CYP4F gene cluster. In addition, SNP-gene expression in human liver tissues and interactions between CYP4F genes were explored in silico using publicly available data repositories. We found that SNPs in CYP4F2, CYP4F11, and CYP4F12 were associated with mRNA expression in the CYP4F gene cluster. In particular, CYP4F2 rs2108622 was associated with increased CYP4F2 expression while CYP4F11 rs1060467 was associated with decreased CYP4F2 expression. Interestingly, these CYP4F2 and CYP4F11 SNPs showed similar effects with warfarin stable dose where CYP4F11 rs1060467 was associated with a reduction in daily warfarin dose requirement (∼1 mg/day, Pc = 0.017, an effect opposite to that previously reported with CYP4F2 (rs2108622. However, inclusion of either or both of these SNPs in a pharmacogenetic algorithm consisting of age, body mass index (BMI, gender, baseline clotting factor II level, CYP2C9∗2 rs1799853, CYP2C9∗3 rs1057910, and VKORC1 rs9923231 improved warfarin dose variability only by 0.5–0.7% with an improvement in dose prediction accuracy of ∼1–2%. Although there is complex

  20. Genes del receptor variable beta de células T en células circulantes de pacientes con lupus eritematoso generalizado y sus familiares sanos.

    Science.gov (United States)

    Jakez-Ocampo, Juan; Paulín-Vera, Carmen María; Rivadeneyra-Espinoza, Liliana; Gómez-Martín, Diana; Carrillo-Maravilla, Eduardo; Lima, Guadalupe; Vargas-Rojas, María Inés; Pérez-Romano, Beatriz; Calva-Cevenini, Gabriella; García-Carrasco, Mario; Ruiz-Argüelles, Alejandro; Llorente, Luis

    2018-01-01

    Se investigó la proporción de la expresión génica del receptor variable beta de células T (Vβ TCR) en linfocitos periféricos CD3+ en pacientes con lupus eritematoso generalizado (LEG) familiar y no familiar. El repertorio de Vβ TCR se estudió en 14 familias que presentaban más de un miembro con LEG. El uso de Vβ TCR en pacientes con LEG (n = 27) se comparó con el de los miembros sanos de estas familias (n = 47), con 37 pacientes con LEG esporádico y con 15 controles sanos. La expresión del repertorio de Vβ TCR se estudió por citometría de flujo multiparamétrica utilizando un arreglo de 24 diferentes anticuerpos monoclonales específicos de genes familiares para Vβ TCR. Se encontró el mismo perfil de expresión en las comparaciones entre los casos de LEG esporádico y familiar, así como en los consanguíneos sanos de las familias multicasos, que incluía una expresión incrementada de Vβ 5.2, Vβ 11 y Vβ 16, y una menor expresión de Vβ 3, Vβ4, Vβ 7.1 y Vβ 7. De manera interesante, solo Vβ 17 se expresó de modo diferente entre casos familiares y esporádicos de LEG. Igualmente, la expresión incrementada de Vβ 9 fue el distintivo entre los casos de LEG familiar (casos y consanguíneos sanos) y los controles sanos. Estos resultados refuerzan la noción de que el perfil final del repertorio Vβ TCR observado en LEG familiar y no familiar parece surgir de la interacción de factores genéticos, ambientales e inmunorreguladores, además de que pueden explicar las alteraciones inmunitarias que se observan en los consanguíneos sanos de pacientes con LEG.

  1. Centimetre-scale vertical variability of phenoxy acid herbicide mineralization potential in aquifer sediment relates to the abundance of tfdA genes

    DEFF Research Database (Denmark)

    Pazarbasi, Meric Batioglu; Bælum, Jacob; Johnsen, Anders R.

    2012-01-01

    are known to be involved in the metabolism of phenoxy acid herbicides. tfdA class III gene copy number was approximately 100-fold greater in samples able to mineralize MCPA than in samples able to mineralize 2,4-D, suggesting that tfdA class III gene plays a greater role in the metabolism of MCPA than of 2...

  2. X-Linked Lymphoproliferative Syndrome and Common Variable Immunodeficiency May Not Be Differentiated by SH2D1A and XIAP/BIRC4 Genes Sequence Analysis

    Directory of Open Access Journals (Sweden)

    Nesrin Gulez

    2011-01-01

    Full Text Available The X-linked lymphoproliferative syndrome (XLP is a rare, inherited immunodeficiency characterized by recurrent episodes of hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, and/or lymphomas. Recently, X-linked inhibitor of apoptosis (XIAP/BIRC4 gene defects, in families with XLP but without SH2D1A gene defects, has been defined. The distinction from primary immunodeficiencies with a defined genetic cause is mandatory. A six-year-old male patient was admitted with the complaints of persistent general lymphadenopathy, for two years had fever, bilateral cervical multiple microlymphadenopathy, hepatic/splenic enlargement with laboratory findings as decreased serum immunoglobulins, negative EBV VCA IgM (viral capsid antigen and anti-EBV EA (antibody to early D antigen, positive EBV VCA IgG (viral capsid antigen and EBV EBNA (antibody to nuclear antigen. SH2D1A gene analysis was negative. XIAP/BIRC4 sequencing revealed two novel single nucleotide variants (exon 7, 1978G > A, and 1996T > A in the 3′UTR of the gene in both patient and mother which were not disease causing. XIAP protein expression was found to be normal. The clinical and laboratory resemblance, no gene mutations, and normal XIAP protein expression led us to think that there may be another responsible gene for XLP. The patient will to be followed up as CVID until he presents new diagnostic signs or until the identification of a new gene.

  3. A novel 'splice site' HCN4 Gene mutation, c.1737+1 G>T, causes familial bradycardia, reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability.

    Science.gov (United States)

    Hategan, Lidia; Csányi, Beáta; Ördög, Balázs; Kákonyi, Kornél; Tringer, Annamária; Kiss, Orsolya; Orosz, Andrea; Sághy, László; Nagy, István; Hegedűs, Zoltán; Rudas, László; Széll, Márta; Varró, András; Forster, Tamás; Sepp, Róbert

    2017-08-15

    The most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome. A novel c.1737+1 G>T 'splice-site' HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart ratesite' HCN4 gene mutation, c.1737+1 G>T, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. High variability in complementarity-determining regions compensates for a low number of V gene families in the lambda light chain locus of the platypus

    National Research Council Canada - National Science Library

    Johansson, Jeannette; Salazar, Janice N; Aveskogh, Maria; Munday, Barry; Miller, Robert D; Hellman, Lars

    2005-01-01

    Based on the analysis of a panel of variable (V) region sequences from the Australian duck-billed platypus and the Australian short beaked echidna, the monotremes were found to express a highly diversified Vlambda repertoire...

  5. Increased chromosomal breakage in Tourette syndrome predicts the possibility of variable multiple gene involvement in spectrum phenotypes: Preliminary findings and hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Gericke, G.S.; Simonic, I.; Cloete, E.; Buckle, C. [Univ. of Pretoria (South Africa)] [and others

    1995-10-09

    Increased chromosomal breakage was found in 12 patients with DSM-IV Tourette syndrome (TS) as compared with 10 non-TS control individuals with respect to untreated, modified RPM1-, and BrdU treated lymphocyte cultures (P < 0.001 in each category). A hypothesis is proposed that a major TS gene is probably connected to genetic instability, and associated chromosomal marker sites may be indicative of the localization of secondary genes whose altered expression could be responsible for associated comorbid conditions. This concept implies that genes influencing higher brain functions may be situated at or near highly recombigenic areas allowing enhanced amplification, duplication and recombination following chromosomal strand breakage. Further studies on a larger sample size are required to confirm the findings relating to chromosomal breakage and to analyze the possible implications for a paradigmatic shift in linkage strategy for complex disorders by focusing on areas at or near unstable chromosomal marker sites. 32 refs., 1 tab.

  6. Genes encoding 4-Cys antimicrobial peptides in wheat Triticum kiharae Dorof. et Migush.: multimodular structural organization, instraspecific variability, distribution and role in defence.

    Science.gov (United States)

    Utkina, Lyubov L; Andreev, Yaroslav A; Rogozhin, Eugene A; Korostyleva, Tatyana V; Slavokhotova, Anna A; Oparin, Peter B; Vassilevski, Alexander A; Grishin, Eugene V; Egorov, Tsezi A; Odintsova, Tatyana I

    2013-08-01

    A novel family of antifungal peptides was discovered in the wheat Triticum kiharae Dorof. et Migusch. Two members of the family, designated Tk-AMP-X1 and Tk-AMP-X2, were completely sequenced and shown to belong to the α-hairpinin structural family of plant peptides with a characteristic C1XXXC2-X(n)-C3XXXC4 motif. The peptides inhibit the spore germination of several fungal pathogens in vitro. cDNA and gene cloning disclosed unique structure of genes encoding Tk-AMP-X peptides. They code for precursor proteins of unusual multimodular structure, consisting of a signal peptide, several α-hairpinin (4-Cys) peptide domains with a characteristic cysteine pattern separated by linkers and a C-terminal prodomain. Three types of precursor proteins, with five, six or seven 4-Cys peptide modules, were found in wheat. Among the predicted family members, several peptides previously isolated from T. kiharae seeds were identified. Genes encoding Tk-AMP-X precursors have no introns in the protein-coding regions and are upregulated by fungal pathogens and abiotic stress, providing conclusive evidence for their role in stress response. A combined PCR-based and bioinformatics approach was used to search for related genes in the plant kingdom. Homologous genes differing in the number of peptide modules were discovered in phylogenetically-related Triticum and Aegilops species, including polyploid wheat genome donors. Association of the Tk-AMP-X genes with A, B/G or D genomes of hexaploid wheat was demonstrated. Furthermore, Tk-AMP-X-related sequences were shown to be widespread in the Poaceae family among economically important crops, such as barley, rice and maize. © 2013 FEBS.

  7. ALG11--a new variable DNA marker for sponge phylogeny: comparison of phylogenetic performances with the 18S rDNA and the COI gene.

    Science.gov (United States)

    Belinky, Frida; Szitenberg, Amir; Goldfarb, Itay; Feldstein, Tamar; Wörheide, Gert; Ilan, Micha; Huchon, Dorothée

    2012-06-01

    Phylogenetic relationships within sponge classes are highly debated. The low phylogenetic signal observed with some current molecular data can be attributed to the use of few markers, usually slowly-evolving, such as the nuclear rDNA genes and the mitochondrial COI gene. In this study, we conducted a bioinformatics search for a new molecular marker. We sought a marker that (1) is likely to have no paralogs; (2) evolves under a fast evolutionary rate; (3) is part of a continuous exonic region; and (4) is flanked by conserved regions. Our search suggested the nuclear ALG11 as a potential suitable marker. We next demonstrated that this marker can indeed be used for solving phylogenetic relationships within sponges. Specifically, we successfully amplified the ALG11 gene from DNA samples of representatives from all four sponge classes as well as from several cnidarian classes. We also amplified the 18S rDNA and the COI gene for these species. Finally, we analyzed the phylogenetic performance of ALG11 to solve sponge relationships compared to and in combination with the nuclear 18S rDNA and the COI mtDNA genes. Interestingly, the ALG11 marker seems to be superior to the widely-used COI marker. Our work thus indicates that the ALG11 marker is a relevant marker which can complement and corroborate the phylogenetic inferences observed with nuclear ribosomal genes. This marker is also expected to contribute to resolving evolutionary relationships of other apparently slow-evolving animal phyla, such as cnidarians. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Variability of the mc1r gene in melanic and non-melanic Podarcis lilfordi and Podarcis pityusensis from the Balearic archipelago.

    Directory of Open Access Journals (Sweden)

    Joana M Buades

    Full Text Available The association between polymorphism at the mc1r locus and colour variation was studied in two wall lizard species (Podarcis lilfordi and P. pityusensis from the Balearic archipelago. Podarcis lilfordi comprises several deep mitochondrial lineages, the oldest of which originated in the Pliocene, while much shallower mitochondrial lineages are found in P. pityusensis. Here, we examined whether specific substitutions were associated with the melanic colouration found in islet populations of these species. Homologous nuclear sequences covering most of the mc1r gene were obtained from 73 individuals from melanic and non-melanic Podarcis from different populations (the entire gene was also sequenced in six selected individuals. MtDNA gene trees were also constructed and used as a framework to assess mc1r diversity. Mc1r showed greater polymorphism in P. lilfordi than in P. pityusensis. However, we observed no substitutions that were common to all melanic individuals across the two species. Only one significant association was detected in the mc1r partial sequence, but this was a synonymous A/G mutation with A alleles being more abundant in melanic populations. In addition, there were no associations between the main dominant phenotypes (green and brown, blue and yellow spots and ventral colour and synonymous or non-synonymous substitutions in the mc1r gene. There was no statistical evidence of selection on mc1r. This study suggests no relationship between mc1r polymorphism and colour variation in Balearic Podarcis.

  9. Variability of the mc1r gene in melanic and non-melanic Podarcis lilfordi and Podarcis pityusensis from the Balearic archipelago.

    Science.gov (United States)

    Buades, Joana M; Rodríguez, Virginia; Terrasa, Bàrbara; Pérez-Mellado, Valentin; Brown, Richard P; Castro, Jose A; Picornell, Antònia; Ramon, M M

    2013-01-01

    The association between polymorphism at the mc1r locus and colour variation was studied in two wall lizard species (Podarcis lilfordi and P. pityusensis) from the Balearic archipelago. Podarcis lilfordi comprises several deep mitochondrial lineages, the oldest of which originated in the Pliocene, while much shallower mitochondrial lineages are found in P. pityusensis. Here, we examined whether specific substitutions were associated with the melanic colouration found in islet populations of these species. Homologous nuclear sequences covering most of the mc1r gene were obtained from 73 individuals from melanic and non-melanic Podarcis from different populations (the entire gene was also sequenced in six selected individuals). MtDNA gene trees were also constructed and used as a framework to assess mc1r diversity. Mc1r showed greater polymorphism in P. lilfordi than in P. pityusensis. However, we observed no substitutions that were common to all melanic individuals across the two species. Only one significant association was detected in the mc1r partial sequence, but this was a synonymous A/G mutation with A alleles being more abundant in melanic populations. In addition, there were no associations between the main dominant phenotypes (green and brown, blue and yellow spots and ventral colour) and synonymous or non-synonymous substitutions in the mc1r gene. There was no statistical evidence of selection on mc1r. This study suggests no relationship between mc1r polymorphism and colour variation in Balearic Podarcis.

  10. Antimicrobial susceptibility, risk factors and prevalence of bla cefotaximase, temoneira, and sulfhydryl variable genes among Escherichia coli in community-acquired pediatric urinary tract infection

    Directory of Open Access Journals (Sweden)

    Kallyadan V Nisha

    2017-01-01

    Conclusion: ESBL-producing E. coli from community-acquired pediatric UTI carries more than one type of beta-lactamase coding genes correlating their increased antibiotic resistance. Aggressive infection control policy, routine screening for detecting ESBL isolates in clinical samples, and antimicrobial stewardship are the keys to prevent their dissemination in community settings.

  11. Childhood allergic rhinitis, traffic-related air pollution, and variability in the GSTP1, TNF, TLR2, and TLR4 genes : Results from the TAG Study

    NARCIS (Netherlands)

    Fuertes, Elaine; Brauer, Michael; MacIntyre, Elaina; Bauer, Mario; Bellander, Tom; von Berg, Andrea; Berdel, Dietrich; Brunekreef, Bert; Chan-Yeung, Moira; Gehring, Ulrike; Herbarth, Olf; Hoffmann, Barbara; Kerkhof, Marjan; Kluemper, Claudia; Koletzko, Sibylle; Kozyrskyj, Anita; Kull, Inger; Heinrich, Joachim; Melen, Erik; Pershagen, Goran; Postma, Dirkje; Tiesler, Carla M. T.; Carlsten, Chris

    Background: Associations between traffic-related air pollution (TRAP) and allergic rhinitis remain inconsistent, possibly because of unexplored gene-environment interactions. Objective: In a pooled analysis of 6 birth cohorts (N-total = 15,299), we examined whether TRAP and genetic polymorphisms

  12. Linear poly(amido amine)s with secondary and tertiary amino groups and variable amounts of disulfide linkages: synthesis and in vitro gene transfer properties

    NARCIS (Netherlands)

    Lin, C.; Zhong, Zhiyuan; Lok, Martin C.; Jiang, Xulin; Hennink, Wim E.; Feijen, Jan; Engbersen, Johannes F.J.

    2006-01-01

    A group of novel poly(amido amine) homo- and copolymers (PAAs) containing secondary and tertiary amine groups in their main chain and different structures in the bisacrylamide segments were synthesized and evaluated as non-viral gene delivery vectors. Among these, also the disulfide-containing

  13. [Molecular criteria in insects systematics: bar-coding gene COI range of variability as a taxonomic criterion for genus, tribe, and subfamily, with Chironominae and Orthocladiinae midges (Chironomidae, Diptera) as a case study].

    Science.gov (United States)

    Polukonova, N V; Demin, A G; Miuge, N S

    2013-01-01

    Contemporary systematics of insects is based mainly on morphological traits. However, their usage is limited both by high variability and complications in comparisons of remote taxa due to low number of common traits. In whole, this leads to a somewhat subjective view when elaborating the system. Unlike morphological ones, molecular traits of taxa, revealed by use of marker genes such as gene cytochrome-c-oxidase I (COI), are less variable and more uniform, which allows them to be used as a criterion of genus, tribe, and subfamily for a wide range of organisms. Application of molecular criteria appears to be all the more important when constructing the system for groups of organisms with high morphological and specific diversity, such as midges (Chironomidae, Diptera). Last years, the DNA-sequence of gene COI is becoming widely used for species identification as a bar-coding one. Its use as a criterion for taxa of super-species level is hampered by its high nucleotide variability. We established the bounds of COI nucleotide and aminoacid divergence between midge species of Chironominae subfamily belonging to the same genus, same tribe, different tribes, as well as between species of Chironominae and Orthocladiinae subfamilies. It is shown that the level of aminoacid divergence reflects molecular boundaries of genus and tribe better than nucleotide one. It can be stated that if the level of aminoacid divergence falls within the limits from 0 to 1.7% then a pair of species compared belongs to the same genus; if it falls within the limits from 1.7 to 4.0% then they belong to the same tribe; within the limits from 4.6 to 6.3%--to different tribes; if it exceeds 7.9%--to different subfamilies. The accuracy of identification when using these ranges turns out to be not less than 75%. In this regard, bounds of COI sequence aminoacid divergence may be used as taxonomic criteria for midge genus, tribe or subfamily.

  14. Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis.

    Science.gov (United States)

    Li, Aihong; Rue, Montse; Zhou, Jianbiao; Wang, Hongjun; Goldwasser, Meredith A; Neuberg, Donna; Dalton, Virginia; Zuckerman, David; Lyons, Cheryl; Silverman, Lewis B; Sallan, Stephen E; Gribben, John G

    2004-06-15

    Sequence analysis of the immunoglobulin heavy chain genes (IgH) has demonstrated preferential usage of specific variable (V), diversity (D), and joining (J) genes at different stages of B-cell development and in B-cell malignancies, and this has provided insight into B-cell maturation and selection. Knowledge of the association between rearrangement patterns based on updated databases and clinical characteristics of pediatric acute lymphoblastic leukemia (ALL) is limited. We analyzed 381 IgH sequences identified at presentation in 317 children with B-lineage ALL and assessed the V(H)D(H)J(H) gene utilization profiles. The D(H)J(H)-proximal V(H) segments and the D(H)2 gene family were significantly overrepresented. Only 21% of V(H)-J(H) joinings were potentially productive, a finding associated with a trend toward an increased risk of relapse. These results suggest that physical location at the V(H) locus is involved in preferential usage of D(H)J(H)-proximal V(H) segments whereas D(H) and J(H) segment usage is governed by position-independent molecular mechanisms. Molecular pathophysiology appears relevant to clinical outcome in patients who have only productive rearrangements, and specific rearrangement patterns are associated with differences in the tumor biology of childhood ALL.

  15. Caracterización de variables cinemáticas de la marcha humana mediante un sistema computarizado de captura de imágenes subacuáticas: parámetros angulares de rodilla

    OpenAIRE

    Mauricio Hernando Valencia; José Henry Osorio

    2014-01-01

    Antecedentes. El proceso de ejecución de las terapias en el agua, realizadas en varios centros de rehabilitación en el entorno nacional e internacional, requiere de un sistema de medición. Objetivo. Validar la posibilidad de cuantificar las variables cinemáticas de la marcha humana, en individuos sanos, usando video fotogrametría como sistema computarizado de captura de imágenes subacuáticas con registro en plano sagital. Materiales y métodos. Mediante un sistema robótico que consta de un sis...

  16. The association between dopamine receptor (DRD4) gene polymorphisms and second language learning style and behavioral variability in undergraduate students in Turkey.

    Science.gov (United States)

    Maras Atabay, Meltem; Safi Oz, Zehra; Kurtman, Elvan

    2014-08-01

    The dopamine D4 receptor gene (DRD4) encodes a receptor for dopamine, a chemical messenger used in the brain. One variant of the DRD4 gene, the 7R allele, is believed to be associated with attention deficit hyperactivity disorder (ADHD). The aim of this study was to investigate the relationships between repeat polymorphisms in dopamine DRD4 and second language learning styles such as visual (seeing), tactile (touching), auditory (hearing), kinesthetic (moving) and group/individual learning styles, as well as the relationships among DRD4 gene polymorphisms and ADHD in undergraduate students. A total of 227 students between the ages of 17-21 years were evaluated using the Wender Utah rating scale and DSM-IV diagnostic criteria for ADHD. Additionally, Reid's perceptual learning style questionnaire for second language learning style was applied. In addition, these students were evaluated for social distress factors using the list of Threatening Events (TLE); having had no TLE, having had just one TLE or having had two or more TLEs within the previous 6 months before the interview. For DRD4 gene polymorphisms, DNA was extracted from whole blood using the standard phenol/chloroform method and genotyped using polymerase chain reaction. Second language learners with the DRD4.7+ repeats showed kinaesthetic and auditory learning styles, while students with DRD4.7-repeats showed visual, tactile and group learning, and also preferred the more visual learning styles [Formula: see text]. We also demonstrated that the DRD4 polymorphism significantly affected the risk effect conferred by an increasing level of exposure to TLE.

  17. Analysis of the Variability of Epstein-Barr Virus Genes in Infectious Mononucleosis: Investigation of the Potential Correlation with Biochemical Parameters of Hepatic Involvement

    Directory of Open Access Journals (Sweden)

    Banko Ana

    2016-09-01

    Full Text Available Background: Primary Epstein-Barr virus (EBV infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM, during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters.

  18. L-Asparaginase from Streptomyces griseus NIOT-VKMA29: optimization of process variables using factorial designs and molecular characterization of L-asparaginase gene

    Science.gov (United States)

    Meena, Balakrishnan; Anburajan, Lawrance; Sathish, Thadikamala; Vijaya Raghavan, Rangamaran; Dharani, Gopal; Valsalan Vinithkumar, Nambali; Kirubagaran, Ramalingam

    2015-07-01

    Marine actinobacteria are known to be a rich source for novel metabolites with diverse biological activities. In this study, a potential extracellular L-asparaginase was characterised from the Streptomyces griseus NIOT-VKMA29. Box-Behnken based optimization was used to determine the culture medium components to enhance the L-asparaginase production. pH, starch, yeast extract and L-asparagine has a direct correlation for enzyme production with a maximum yield of 56.78 IU mL-1. A verification experiment was performed to validate the experiment and more than 99% validity was established. L-Asparaginase biosynthesis gene (ansA) from Streptomyces griseus NIOT-VKMA29 was heterologously expressed in Escherichia coli M15 and the enzyme production was increased threefold (123 IU mL-1) over the native strain. The ansA gene sequences reported in this study encloses several base substitutions with that of reported sequences in GenBank, resulting in altered amino acid sequences of the translated protein.

  19. Ashtekar variables

    Science.gov (United States)

    Ashtekar, Abhay

    2015-05-01

    In the spirit of Scholarpedia, this invited article is addressed to students and younger researchers. It provides the motivation and background material, a summary of the main physical ideas, mathematical structures and results, and an outline of applications of the connection variables for general relativity. These variables underlie both the canonical/Hamiltonian and the spinfoam/path integral approaches in loop quantum gravity.

  20. Variability Bugs:

    DEFF Research Database (Denmark)

    Melo, Jean

    2017-01-01

    be exploited. Variability bugs are not confined to any particular type of bug, error-prone feature, or location. In addition to introducing an exponential number of program variants, variability increases the complexity of bugs due to unintended feature interactions, hidden features, combinations of layers...... and bug finding, but not terribly so. This is positive and consistent with the existence of highly-configurable software systems with hundreds, even thousands, of features, testifying that developers in the trenches are able to deal with variability.......Many modern software systems are highly configurable. They embrace variability to increase adaptability and to lower cost. To implement configurable software, developers often use the C preprocessor (CPP), which is a well-known technique, mainly in industry, to deal with variability in code...

  1. Response of CYP1A Gene expression in fish liver of catfish (Ariopsis felis) from Gulf of Mexico and their relationship with the genetic variability.

    Science.gov (United States)

    Zapata-Perez, Omar; Sanchez-Teyer, Lorenzo F; Perez-Nunez, Maria T; Arroyo-Herrera, Ana L; Moreno, Adriana Quiroz; Albores-Medina, Arnulfo

    2010-01-01

    We determined the hepatic Cytochrome P4501A (CYP1A) mRNA and Ethoxyresorufin-O-deethylase (EROD) activities in the fish, Ariopsis felis, from highly polluted to relatively pristine regions in the southwest Gulf of Mexico and their relationship with the genetic polymorphisms of the same fish. We hypothesized that a high genetic variation reflects interindividual variability in levels of CYP1A mRNA underlying the pathway culminating in EROD induction caused by the environmental contaminants. Catfish from Laguna de Mecoacan exhibited marked induction of CYP1A mRNA and high levels of hepatic EROD activities, whereas fish from Laguna de Celestun showed no induction of CYP1A mRNA and moderately low levels of EROD activities. In contrast, the similarity index considering all samples varied from 0.4 to 0.87, showing a wide range of variation. A dendrogram showed a clear grouping of fish collected from the Laguna de Terminos, Rio Coatzacoalcos and Laguna de Celestun, with discrete subgroups according to region. In contrast, fish from Laguna de Mecoacan were grouped together completely separate from the rest of the fish. Despite the low number of fish from Mecoacan (a high bootstrap support was observed in this group), the results indicated a significant genetic variability in comparison with the other ecosystems included. The differential level of expression of CYP1A and the EROD activity observed among the ecosystems analyzed could be due to the high range of genetic variation, with special emphasis on fish collected in Mecoacan where it is possible to find a subspecies of Ariopsis felis.

  2. Uropathogenic Escherichia coli pathogenicity islands and other ExPEC virulence genes may contribute to the genome variability of enteroinvasive E. coli.

    Science.gov (United States)

    da Silva, Laís Cristina; de Mello Santos, Ana Carolina; Silva, Rosa Maria

    2017-03-16

    Enteroinvasive Escherichia coli (EIEC) may be the causative agent of part of those million cases of diarrhea illness reported worldwide every year and attributable to Shigella. That is because both enteropathogens have many common characteristics that difficult their identification either by traditional microbiological methods or by molecular tools used in the clinical laboratory settings. While Shigella has been extensively studied, EIEC remains barely characterized at the molecular level. Recent EIEC important outbreaks, apparently generating more life-threatening cases, have prompted us to screen EIEC for virulence traits usually related to extraintestinal pathogenic E. coli (ExPEC). That could explain the appearance of EIEC strains presenting higher virulence potential. EIEC strains were distributed mainly in three phylogroups in a serogroup-dependent manner. Serogroups O124, O136, O144, and O152 were exclusively classified in phylogroup A; O143 in group E; and O28ac and O29 in group B1. Only two serogroups showed diverse phylogenetic origin as follows: O164 was assigned to groups A, B1, C, and B2 (one strain each), and O167 in groups E (five strains), and A (one strain) (Table 1). Eleven of 20 virulence genes (VGs) searched were detected, and the majority of the 19 different VGs combinations found were serogroup-specific. Uropathogenic E. coli (UPEC) PAI genetic markers were detected in all EIEC strains. PAIs I J96 and II CFT073 were the most frequent (92.1 and 80.4%, respectively). PAI IV 536 was restricted to some serogroups from phylogroups A, B1 and E. PAI I CFT073 was uniquely detected in phylogroups B2 and E. A total of 45 (88%) strains presented multiple PAI markers (two to four). PAIs I J96 and II CFT073 were found together in 80% of strains. EIEC is a DEC pathovar that presents VGs and pathogenicity island genetic markers typically associated with ExPEC, especially UPEC. These features are distributed in a phylogenetic and serogroup-dependent manner

  3. High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID

    Directory of Open Access Journals (Sweden)

    Wynn Thomas A

    2005-07-01

    interpretation of altered gene expression patterns in Common Variable Immune Deficiency (CVID. High-Throughput GoMiner will be useful in a wide range of applications, including the study of time-courses, evaluation of multiple drug treatments, comparison of multiple gene knock-outs or knock-downs, and screening of large numbers of chemical derivatives generated from a promising lead compound.

  4. Large-scale mitochondrial COI gene sequence variability reflects the complex colonization history of the invasive soft-shell clam, Mya arenaria (L.) (Bivalvia)

    Science.gov (United States)

    Lasota, Rafal; Pierscieniak, Karolina; Garcia, Pascale; Simon-Bouhet, Benoit; Wolowicz, Maciej

    2016-11-01

    The aim of the study was to determine genetic diversity in the soft-shell clam Mya arenaria on a wide geographical scale using mtDNA COI gene sequences. Low levels of genetic diversity was found, which can most likely be explained by a bottleneck effect during Pleistocene glaciations and/or selection. The geographical genetic structuring of the studied populations was also very low. The star-like phylogeny of the haplotypes indicates a relatively recent, rapid population expansion following the glaciation period and repeated expansion following the founder effect(s) after the initial introduction of the soft-shell clam to Europe. North American populations are characterized by the largest number of haplotypes, including rare ones, as expected for native populations. Because of the founder effect connected with initial and repeated expansion events, European populations have significantly lower numbers of haplotypes in comparison with those of North America. We also observed subtle differentiations among populations from the North and Baltic seas. The recently founded soft-shell clam population in the Black Sea exhibited the highest genetic similarity to Baltic populations, which confirmed the hypothesis that M. arenaria was introduced to the Gulf of Odessa from the Baltic Sea. The most enigmatic results were obtained for populations from the White Sea, which were characterized by high genetic affinity with American populations.

  5. Variability in the leptin, leptin receptor and heart fatty acid binding protein genes in relationship with meat quality traits in pigs

    Directory of Open Access Journals (Sweden)

    Renata Mikolášová

    2005-01-01

    Full Text Available The leptin (LEP-HinfI, leptin receptor (LEPR-HpaII and heart fatty acid binding protein (H-FABP-HinfI genes and their genotypes combination (LEP-HinfI *LEPR-HpaII were tested for associations with the pH1, pH24, myoglobin content (mg/100 g, intramuscular fat content (% and remission (%. The genotypes were determined in Large White, Landrace and Duroc breeds (n = 106, 56 and 4, respectively. The allele frequencies were: LEP-HinfI: C = 0.133 T = 0.867; LEPR-HpaII: A = 0.331 B = 0.669; H-FABP-HinfI: H = 0.745 h = 0.255. The populations of breeds were in the genetic equilibrium according to the χ2 test in the tested loci. The combinations of LEP-HinfI and LEPR-HpaII were significantly associated with the pH24 and remission. The H-FABP-HinfI locus was significantly associated with intramuscular fat content.

  6. Caracterización de variables cinemáticas de la marcha humana mediante un sistema computarizado de captura de imágenes subacuáticas: parámetros angulares de rodilla

    Directory of Open Access Journals (Sweden)

    Mauricio Hernando Valencia

    2014-01-01

    Full Text Available Antecedentes. El proceso de ejecución de las terapias en el agua, realizadas en varios centros de rehabilitación en el entorno nacional e internacional, requiere de un sistema de medición. Objetivo. Validar la posibilidad de cuantificar las variables cinemáticas de la marcha humana, en individuos sanos, usando video fotogrametría como sistema computarizado de captura de imágenes subacuáticas con registro en plano sagital. Materiales y métodos. Mediante un sistema robótico que consta de un sistema de cadena y una plataforma móvil en el piso del tanque de marcha, que ajusta la posición final de la cámara submarina, se realizó análisis de la marcha y posterior cálculo de los ángulos articulares en ambiente acuático de cuatro individuos voluntarios. Resultados. El ángulo filtrado de flexión de la rodilla durante la fase de balanceo en el ciclo de marcha subacuática es mayor en el género masculino (52,2±9,7 que en el femenino (45,6±7,0. El ángulo filtrado de flexión de la rodilla durante la fase de apoyo en el ciclo de marcha subacuática es mayor en el género masculino (1,6±1,5 que en el femenino (0,1±0,01. Conclusiones. Se pueden cuantificar las variables cinemáticas de la marcha humana (parámetros angulares de la rodilla, en individuos sanos, usando video fotogrametría como sistema computarizado de captura de imágenes subacuáticas, en el tanque de marcha.

  7. Chapter 2: Genetic Variability in Nuclear Ribosomal and Chloroplast DNA in Utah (Juniperus Osteosperma) and Western (J. Occidentalis) Juniper (Cupressaceae): Evidence for Interspecific Gene Flow1

    Energy Technology Data Exchange (ETDEWEB)

    Terry, Randall G.; Tausch, Robin J.; Nowak, Robert S.

    1998-02-14

    Early studies of evolutionary change in chloroplast DNA indicated limited variability within species. This finding has been attributed to relatively low rates of sequence evolution and has been maintained as justification for the lack of intraspecific sampling in studies examining, relationships at the species level and above. However, documentation of intraspecific variation in cpDNA has become increasingly common and has been attributed in many cases to ''chloroplast capture'' following genetic exchange across species boundaries. Rleseberg and Wendel (1993) list 37 cases of proposed hybridization in plants that include intraspecific variation in cpDNA, 24 (65%) of which they considered to be probable instances of introgression. Rieseberg (1995) suspected that a review of the literature at that time would reveal over 100 cases of intraspecific variation in CPDNA that could be attributed to hybridization and introgression. That intraspecific variation in cpDNA is potentially indicative of hybridization is founded on the expectation that slowly evolving loci or genomes will produce greater molecular variation between than within species. In cases where a species is polymorphic for CPDNA and at least one of the molecular variants is diagnostic for a second species, interspecific hybridization is a plausible explanation. Incongruence between relationships suggested by cpDNA variation and those supported by other types of data (e.g., morphology or molecular data from an additional locus) provides additional support for introgression. One aspect of hybridization in both animals and plants that has become increasingly evident is incongruence in the phylogenetic and geographic distribution of cytoplasmic and nuclear markers. In most cases cytoplasmic introgression appears to be more pervasive than nuclear exchange. This discordance appears attributable to several factors including differences in the mutation rate, number of effective alleles, and modes

  8. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  9. Diversidad genética de la región variable de los genes msp1a y msp4 en cepas de Anaplasma marginale de México

    Directory of Open Access Journals (Sweden)

    Rafael Jiménez Ocampo

    2012-01-01

    Full Text Available La anaplasmosis es de difícil control debido a la diversidad genética de la rickettsia. La proteína Msp1a, compuesta de repetidos variables de entre 23 y 31 aminoácidos en su región variable y la proteína Msp4, son dos de las proteínas de superficie más estudiadas en A. marginale y han sido ampliamente usadas como marcadores genéticos en la caracterización de cepas de A. marginale de diferentes orígenes geográficos. En este trabajo se analizaron, la región variable de la proteína Msp1a y la proteína Msp4 de 10 cepas mexicanas. En el caso de Msp1a, se observó un patrón de segregación que contiene los repetidos (alpha, beta, beta, gama en diferentes modalidades a lo largo de aislamientos del Golfo de México, principalmente en zonas de estabilidad enzoótica, mientras que la máxima variabilidad se presentó en Tamaulipas, en aislamientos de un brote de la enfermedad, es decir en zonas de inestabilidad. La diversidad observada no es tan extensa como se esperaba y, misma que se puede explicar por la presión que el sistema inmune del hospedero ejerce contra la rickettsia y los mecanismos de esta última para evadirla. En el caso de la proteína Msp4, la secuencia fue altamente conservada tanto en nucleótidos como en aminoácidos para los aislados en estudio, aunque, se observan diferencias con lo previamente reportado en México para este marcador.

  10. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  11. Variable liver fat concentration as a proxy for body fat mobilization postpartum has minor effects on insulin-induced changes in hepatic gene expression related to energy metabolism in dairy cows.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Bruckmaier, R M; Röntgen, M; Kuhla, B; Hammon, H M

    2017-02-01

    A and IGF1 tended to be lower in LLFC than in HLFC. Administration of insulin, albeit at a supraphysiological dose, was associated with inhibition of gene expression related to glucose production and β-oxidation, but we observed variable effects in the degree of insulin depression of individual genes. Insulin status is important for regulation of nutrient partitioning, but different LFC pp had very little influence on changes in hepatic gene expression following administration of insulin. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  12. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  13. Complex variables

    CERN Document Server

    Taylor, Joseph L

    2011-01-01

    The text covers a broad spectrum between basic and advanced complex variables on the one hand and between theoretical and applied or computational material on the other hand. With careful selection of the emphasis put on the various sections, examples, and exercises, the book can be used in a one- or two-semester course for undergraduate mathematics majors, a one-semester course for engineering or physics majors, or a one-semester course for first-year mathematics graduate students. It has been tested in all three settings at the University of Utah. The exposition is clear, concise, and lively

  14. Pattern dystrophy with high intrafamilial variability associated with Y141C mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal injections.

    Science.gov (United States)

    Vaclavik, Veronika; Tran, Hoai V; Gaillard, Marie-Claire; Schorderet, Daniel F; Munier, Francis L

    2012-10-01

    To identify disease causing mutation in three generations of a Swiss family with pattern dystrophy and high intrafamilial variability of phenotype. To assess the effect of intravitreal ranibizumab injections in the treatment of subfoveal choroidal neovascularization associated with pattern dystrophy in one patient. Affected family members were ascertained for phenotypic and genotypic characterization. Ophthalmic evaluations included fundus photography, autofluorescence imaging, optical coherence tomography, and International Society for Clinical Electrophysiology of Vision standard full-field electroretinography. When possible family members had genetic testing. The proband presented with choroidal neovascularization and had intravitreal injections as needed according to visual acuity and optical coherence tomography. Proband had a multifocal type pattern dystrophy, and his choroidal neovascularization regressed after four intravitreal injections. The vision improved from 0.8 to 1.0, and optical coherence tomography showed complete anatomical restoration. A butterfly-shaped pattern was observed in her cousin, whereas a fundus pulverulentus pattern was seen in a second cousin. Aunt had a multifocal atrophic appearance, simulating geographic atrophy in age-related macular degeneration. The Y141C mutation was identified in the peripherin/RDS gene and segregated with disease in the family. This is the first report of marked intrafamilial variation of pattern dystrophy because of peripherin/RDS Y141C mutation. Intravitreal ranibizumab injections might be a valuable treatment for associated subfoveal choroidal neovascularization.

  15. Using gene expression noise to understand gene regulation

    NARCIS (Netherlands)

    Munsky, B.; Neuert, G.; van Oudenaarden, A.

    2012-01-01

    Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

  16. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.

    1998-01-01

    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

  17. Score test variable screening.

    Science.gov (United States)

    Zhao, Sihai Dave; Li, Yi

    2014-12-01

    Variable screening has emerged as a crucial first step in the analysis of high-throughput data, but existing procedures can be computationally cumbersome, difficult to justify theoretically, or inapplicable to certain types of analyses. Motivated by a high-dimensional censored quantile regression problem in multiple myeloma genomics, this article makes three contributions. First, we establish a score test-based screening framework, which is widely applicable, extremely computationally efficient, and relatively simple to justify. Secondly, we propose a resampling-based procedure for selecting the number of variables to retain after screening according to the principle of reproducibility. Finally, we propose a new iterative score test screening method which is closely related to sparse regression. In simulations we apply our methods to four different regression models and show that they can outperform existing procedures. We also apply score test screening to an analysis of gene expression data from multiple myeloma patients using a censored quantile regression model to identify high-risk genes. © 2014, The International Biometric Society.

  18. Housekeeping Gene Sequencing and Multilocus Variable-Number Tandem-Repeat Analysis To Identify Subpopulations within Pseudomonas syringae pv. maculicola and Pseudomonas syringae pv. tomato That Correlate with Host Specificity

    Science.gov (United States)

    Gironde, S.

    2012-01-01

    Pseudomonas syringae pv. maculicola causes bacterial spot on Brassicaceae worldwide, and for the last 10 years severe outbreaks have been reported in the Loire Valley, France. P. syringae pv. maculicola resembles P. syringae pv. tomato in that it is also pathogenic for tomato and causes the same types of symptoms. We used a collection of 106 strains of P. syringae to characterize the relationships between P. syringae pv. maculicola and related pathovars, paying special attention to P. syringae pv. tomato. Phylogenetic analysis of gyrB and rpoD gene sequences showed that P. syringae pv. maculicola, which causes diseases in Brassicaceae, forms six genetic lineages within genomospecies 3 of P. syringae strains as defined by L. Gardan et al. (Int. J. Syst. Bacteriol. 49[Pt 2]:469–478, 1999), whereas P. syringae pv. tomato forms two distinct genetic lineages. A multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) conducted with eight minisatellite loci confirmed the genetic structure obtained with rpoD and gyrB sequence analyses. These results provide promising tools for fine-scale epidemiological studies on diseases caused by P. syringae pv. maculicola and P. syringae pv. tomato. The two pathovars had distinct host ranges; only P. syringae pv. maculicola strains were pathogenic for Brassicaceae. A subpopulation of P. syringae pv. maculicola strains that are pathogenic for Pto-expressing tomato plants were shown to lack avrPto1 and avrPtoB or to contain a disrupted avrPtoB homolog. Taking phylogenetic and pathological features into account, our data suggest that the DC3000 strain belongs to P. syringae pv. maculicola. This study shows that P. syringae pv. maculicola and P. syringae pv. tomato appear multiclonal, as they did not diverge from a single common ancestral group within the ancestral P. syringae genomospecies 3, and suggests that pathovar specificity within P. syringae may be due to independent genetic events. PMID:22389364

  19. Genetic variability of a population of Aedes aegypti from Paraná, Brazil, using the mitochondrial ND4 gene Variabilidade genética de uma população de Aedes aegypti do Paraná, Brasil, usando o gene mitocondrial ND4

    Directory of Open Access Journals (Sweden)

    Adriana L. Twerdochlib

    2012-06-01

    Full Text Available Genetic variability of a population of Aedes aegypti from Paraná, Brazil, using the mitochondrial ND4 gene. To analyze the genetic variability of populations of Aedes aegypti, 156 samples were collected from 10 municipalities in the state of Paraná, Brazil. A 311 base pairs (bp region of the NADH dehydrogenase subunit 4 (ND4 mitochondrial gene was examined. An analysis of this fragment identified eight distinct haplotypes. The mean genetic diversity was high (h = 0.702; p = 0.01556. AMOVA analysis indicated that most of the variation (67% occurred within populations and the F ST value (0.32996 was highly significant. F ST values were significant in most comparisons among cities. The isolation by distance was not significant (r = -0.1216 and p = 0, 7550, indicating that genetic distance is not related to geographic distance. Neighbor-joining analysis showed two genetically distinct groups within Paraná. The DNA polymorphism and AMOVA data indicate a decreased gene flow in populations from Paraná, which can result in increased vectorial competence.Variabilidade genética de uma população de Aedes aegypti do Paraná, Brasil, usando o gene mitocondrial ND4. Para analisar a variabilidade genética de populações de Aedes aegypti, 156 amostras foram coletadas em dez cidades do estado do Paraná, Brasil. Foi examinada a distribuição dos 311 pares de base do gene que codifica a subunidade 4 da enzima NADH desidrogenase. Pela amplificação e o sequenciamento deste fragmento foram identificados 8 haplótipos distintos. Os valores de diversidade genética foram altos (h = 0.702; p = 0.01556. A análise de AMOVA indicou que a maior variação ocorreu dentro das populações com um valor de FST de 0.32996 altamente significativo. Valores de FST foram significativos na maior das comparações entre as cidades. O isolamento por distância não foi significativo (r = -0.1216 e p = 0.755, indicando que a distância genética não está relacionada a

  20. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  1. Mechanisms of Disease and Clinical Features of Mutations of the Gene for Mitofusin 2: An Important Cause of Hereditary Peripheral Neuropathy with Striking Clinical Variability in Children and Adults

    Science.gov (United States)

    Ouvrier, Robert; Grew, Simon

    2010-01-01

    Mitofusin 2, a large transmembrane GTPase located in the outer mitochondrial membrane, promotes membrane fusion and is involved in the maintenance of the morphology of axonal mitochondria. Mutations of the gene encoding mitofusin 2 ("MFN2") have recently been identified as the cause of approximately one-third of dominantly inherited cases of the…

  2. Variable importance in latent variable regression models

    NARCIS (Netherlands)

    Kvalheim, O.M.; Arneberg, R.; Bleie, O.; Rajalahti, T.; Smilde, A.K.; Westerhuis, J.A.

    2014-01-01

    The quality and practical usefulness of a regression model are a function of both interpretability and prediction performance. This work presents some new graphical tools for improved interpretation of latent variable regression models that can also assist in improved algorithms for variable

  3. Classifying variability modeling techniques

    NARCIS (Netherlands)

    Sinnema, Marco; Deelstra, Sybren

    Variability modeling is important for managing variability in software product families, especially during product derivation. In the past few years, several variability modeling techniques have been developed, each using its own concepts to model the variability provided by a product family. The

  4. Estimación de variables biofísicas del pastizal en un ecosistema de dehesa a partir de espectro-radiometría de campo e imágenes hiperespectrales aeroportadas

    Directory of Open Access Journals (Sweden)

    J. R. Melendo-Vega

    2017-06-01

    Full Text Available Este trabajo aborda la estimación de variables biofísicas de un pastizal de dehesa a partir de información óptica generada por sensores próximos y remotos. Las variables de contenido de humedad del combustible (FMC, contenido de agua del dosel (CWC, índice de área foliar (LAI, materia seca (Cm y biomasa superficial (AGB fueron estimadas en laboratorio a partir de muestras de vegetación tomadas simultáneamente a la adquisición de datos hiperespectrales del sensor Compact Airbone Spectrographic Imager (CASI y del espectro-radiómetro de campo ASD FieldSpec® 3. A partir de la información espectral se han calculado diversos índices extraídos de la literatura y se han analizado las relaciones lineales existentes con las variables biofísicas medidas en campo. Los resultados muestran relaciones consistentes entre las variables biofísicas y los índices espectrales, especialmente en el caso de los índices basados en bandas del infrarrojo medio de onda corta (SWIR y del red-edge, poniendo de manifiesto la importancia de estas regiones en la estimación de variables biofísicas en cubiertas de pastizal. Se han obteniendo coeficientes de determinación (R2 superiores a 0,91 y un error cuadrático medio relativo (RRMSE de 21,4%, para los índices espectrales calculados con datos ASD; y R2 de 0,91 y RRMSE de 15,5% para los índices espectrales calculados con datos CASI. .

  5. A Bayesian approach to gene-gene and gene-environment interactions in chronic fatigue syndrome.

    Science.gov (United States)

    Lin, Eugene; Hsu, Sen-Yen

    2009-01-01

    In the study of genomics, it is essential to address gene-gene and gene-environment interactions for describing the complex traits that involves disease-related mechanisms. In this work, our goal is to detect gene-gene and gene-environment interactions resulting from the analysis of chronic fatigue syndrome patients' genetic and demographic factors including SNPs, age, gender and BMI. We employed the dataset that was original to the previous study by the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Research Group. To investigate gene-gene and gene-environment interactions, we implemented a Bayesian based method for identifying significant interactions between factors. Here, we employed a two-stage Bayesian variable selection methodology based on Markov Chain Monte Carlo approaches. By applying our Bayesian based approach, NR3C1 was found in the significant two-locus gene-gene effect model, as well as in the significant two-factor gene-environment effect model. Furthermore, a significant gene-environment interaction was identified between NR3C1 and gender. These results support the hypothesis that NR3C1 and gender may play a role in biological mechanisms associated with chronic fatigue syndrome. We demonstrated that our Bayesian based approach is a promising method to assess the gene-gene and gene-environment interactions in chronic fatigue syndrome patients by using genetic factors, such as SNPs, and demographic factors such as age, gender and BMI.

  6. Technical variability is greater than biological variability in a microarray experiment but both are outweighed by changes induced by stimulation.

    Directory of Open Access Journals (Sweden)

    Penelope A Bryant

    Full Text Available INTRODUCTION: A central issue in the design of microarray-based analysis of global gene expression is that variability resulting from experimental processes may obscure changes resulting from the effect being investigated. This study quantified the variability in gene expression at each level of a typical in vitro stimulation experiment using human peripheral blood mononuclear cells (PBMC. The primary objective was to determine the magnitude of biological and technical variability relative to the effect being investigated, namely gene expression changes resulting from stimulation with lipopolysaccharide (LPS. METHODS AND RESULTS: Human PBMC were stimulated in vitro with LPS, with replication at 5 levels: 5 subjects each on 2 separate days with technical replication of LPS stimulation, amplification and hybridisation. RNA from samples stimulated with LPS and unstimulated samples were hybridised against common reference RNA on oligonucleotide microarrays. There was a closer correlation in gene expression between replicate hybridisations (0.86-0.93 than between different subjects (0.66-0.78. Deconstruction of the variability at each level of the experimental process showed that technical variability (standard deviation (SD 0.16 was greater than biological variability (SD 0.06, although both were low (SD<0.1 for all individual components. There was variability in gene expression both at baseline and after stimulation with LPS and proportion of cell subsets in PBMC was likely partly responsible for this. However, gene expression changes after stimulation with LPS were much greater than the variability from any source, either individually or combined. CONCLUSIONS: Variability in gene expression was very low and likely to improve further as technical advances are made. The finding that stimulation with LPS has a markedly greater effect on gene expression than the degree of variability provides confidence that microarray-based studies can be used to

  7. Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function

    DEFF Research Database (Denmark)

    Ek, J; Grarup, N; Urhammer, S A

    2001-01-01

    , and 46 type 2 diabetic patients with an impaired beta-cell function by combined single-strand conformation polymorphism (SSCP) and heteroduplex analysis. Analysis of the promoter and nine exons including intron-exon boundaries of the HNF-1beta gene revealed one novel silent polymorphism and three...... glucose tolerant control subjects (NS). No difference in insulin secretion during an OGTT was seen between carriers of the different IVS6+26T-->C genotypes among the 229 middle-aged control subjects, nor among 302 glucose tolerant 60-year-old Danish Caucasians. Mutation analysis of the four exons...

  8. Types of biological variables.

    Science.gov (United States)

    Mayya, Shreemathi S; Monteiro, Ashma D; Ganapathy, Sachit

    2017-06-01

    Identification and description of variables used in any study is a necessary component in biomedical research. Statistical analyses rely on the type of variables that are involved in the study. In this short article, we introduce the different types of biological variables. A researcher has to be familiar with the type of variable he/she is dealing with in his/her research to decide about appropriate graphs/diagrams, summary measures and statistical analysis.

  9. Variable mechanical ventilation

    OpenAIRE

    Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini Jr.,Luiz Alberto; Friedman, Gilberto

    2017-01-01

    Objective To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Methods Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE?, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". Results A total of 36 studies were selected. ...

  10. Latent variable theory

    NARCIS (Netherlands)

    Borsboom, D.

    2008-01-01

    This paper formulates a metatheoretical framework for latent variable modeling. It does so by spelling out the difference between observed and latent variables. This difference is argued to be purely epistemic in nature: We treat a variable as observed when the inference from data structure to

  11. Amplification variable factor amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2007-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ; SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and

  12. Amplification variable factor amplifier

    NARCIS (Netherlands)

    Akitsugu, O.; Nauta, Bram

    2006-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ; SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and

  13. Allan-Herndon-Dudley syndrome (AHDS) in two consecutive generations caused by a missense MCT8 gene mutation. Phenotypic variability with the presence of normal serum T3 levels.

    Science.gov (United States)

    Boccone, Loredana; Dessì, Valentina; Meloni, Antonella; Loudianos, Georgios

    2013-04-01

    Allan-Herndon-Dudley syndrome (AHDS), an X linked condition, is characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia in combination with altered TH levels, in particular, high serum T3 levels. Mutations in the MCT8 gene coding for the monocarboxylate thyroid hormone transporter 8 have been associated with AHDS. Here we describe a family with the presence of a MCT8 gene mutation, p.A224T, in three consecutive generations. In two generations its presence was detected in the hemizygous state in two males with neurological abnormalities including mental retardation, axial hypotonia, hypertonia of arms and legs and athetoid movements. One of them presented normal thyroid hormone levels. Mutation was also detected, although in the heterozygous state, in three females showing thyroid hormone levels in the normal range. Our results show the difficulty of distinguishing AHDS from patients with X-linked intellectual disability solely on the basis of clinical features and biochemical tests, and we advise screening for MCT8 mutations in either young or older patients with severe intellectual disability, axial hypotonia/dystonia, poor head control, spastic paraplegia, and athetoid movements even when they have normal thyroid hormone profiles. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. A pocket of variability in Pinus rigida

    Science.gov (United States)

    F. Thomas Ledig; John H. Fryer

    1971-01-01

    Steady state gene frequencies around a pocket of differential fitness have been formulated by Hanson (1966) in a generalization of the work of Haldane (1948). A pocket of differential fitness would result in a pocket-of-variability, assuming that the radius of the area of contrasting fitness was large in relation to the vagility of the organism. Conversely, the absence...

  15. Three duplication events and variable molecular evolution ...

    Indian Academy of Sciences (India)

    Three duplication events and variable molecular evolution characteristics involved in multiple GGPS genes of six Solanaceae species. FENG LI CHUNYANG WEI CHAN QIAO ZHENXI CHEN PENG WANG PAN WEI RAN WANG LIFENG JIN JUN YANG FUCHENG LIN ZHAOPENG LUO. RESEARCH NOTE Volume 95 Issue ...

  16. gene structure, gene expression

    Indian Academy of Sciences (India)

    Primer 5.0 software. To adjust for RNA quality and diffe- rences in cDNA concentration, we amplified actin as an internal control with the following primers: PtActin-F (5′-TG. AAGGAGAAACTTGCGTAT-3′) and PtActin-R (5′-GCA. CAATGTTACCGTACAGAT-3′). These genes were ampli- fied from first-strand cDNA using ...

  17. Variable mechanical ventilation

    Science.gov (United States)

    Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini Jr., Luiz Alberto; Friedman, Gilberto

    2017-01-01

    Objective To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Methods Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". Results A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Conclusion Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation. PMID:28444076

  18. Variable mechanical ventilation.

    Science.gov (United States)

    Fontela, Paula Caitano; Prestes, Renata Bernardy; Forgiarini, Luiz Alberto; Friedman, Gilberto

    2017-01-01

    To review the literature on the use of variable mechanical ventilation and the main outcomes of this technique. Search, selection, and analysis of all original articles on variable ventilation, without restriction on the period of publication and language, available in the electronic databases LILACS, MEDLINE®, and PubMed, by searching the terms "variable ventilation" OR "noisy ventilation" OR "biologically variable ventilation". A total of 36 studies were selected. Of these, 24 were original studies, including 21 experimental studies and three clinical studies. Several experimental studies reported the beneficial effects of distinct variable ventilation strategies on lung function using different models of lung injury and healthy lungs. Variable ventilation seems to be a viable strategy for improving gas exchange and respiratory mechanics and preventing lung injury associated with mechanical ventilation. However, further clinical studies are necessary to assess the potential of variable ventilation strategies for the clinical improvement of patients undergoing mechanical ventilation.

  19. The nebular variables

    CERN Document Server

    Glasby, John S

    1974-01-01

    The Nebular Variables focuses on the nebular variables and their characteristics. Discussions are organized by type of nebular variable, namely, RW Aurigae stars, T Orionis stars, T Tauri stars, and peculiar nebular objects. Topics range from light variations of the stars to their spectroscopic and physical characteristics, spatial distribution, interaction with nebulosity, and evolutionary features. This volume is divided into four sections and consists of 25 chapters, the first of which provides general information on nebular variables, including their stellar associations and their classifi

  20. INTER-EXAMINER VARIABILITY

    African Journals Online (AJOL)

    Background: The traditional clinical examination has fallen into disfavour on account of considerable inter-examiner variability. The OSCE is gaining popularity as it is perceived to be less prone to this. Objective: To establish whether inter-examiner variability is still a significant factor for the undergraduate orthopaedic ...

  1. Software variability management

    NARCIS (Netherlands)

    Bosch, J; Nord, RL

    2004-01-01

    During recent years, the amount of variability that has to be supported by a software artefact is growing considerably and its management is evolving into a major challenge during development, usage, and evolution of software artefacts. Successful management of variability in software leads to

  2. Microinertia and internal variables

    CERN Document Server

    Berezovski, A

    2015-01-01

    The origin of microinertia of micromorphic theories is investigated from the point of view of non-equilibrium thermodynamics. In the framework of dual internal variables microinertia stems from a thermodynamic equation of state related to the internal variable with the properties of mechanical momentum.

  3. Variable volume combustor

    Science.gov (United States)

    Ostebee, Heath Michael; Ziminsky, Willy Steve; Johnson, Thomas Edward; Keener, Christopher Paul

    2017-01-17

    The present application provides a variable volume combustor for use with a gas turbine engine. The variable volume combustor may include a liner, a number of micro-mixer fuel nozzles positioned within the liner, and a linear actuator so as to maneuver the micro-mixer fuel nozzles axially along the liner.

  4. Rapidly variable relatvistic absorption

    Science.gov (United States)

    Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.

    2017-10-01

    I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.

  5. Eternity Variables to Simulate Specifications

    NARCIS (Netherlands)

    Hesselink, WH; Boiten, EA; Moller, B

    2002-01-01

    Simulation of specifications is introduced as a unification and generalization of refinement mappings, history variables, forward simulations, prophecy variables, and backward simulations. Eternity variables are introduced as a more powerful alternative for prophecy variables and backward

  6. Perspective: Is Random Monoallelic Expression a Contributor to Phenotypic Variability of Autosomal Dominant Disorders?

    National Research Council Canada - National Science Library

    Baoheng Gui; Jesse Slone; Taosheng Huang

    2017-01-01

    Several factors have been proposed as contributors to interfamilial and intrafamilial phenotypic variability in autosomal dominant disorders, including allelic variation, modifier genes, environmental...

  7. Gene Locater

    DEFF Research Database (Denmark)

    Anwar, Muhammad Zohaib; Sehar, Anoosha; Rehman, Inayat-Ur

    2012-01-01

    UNLABELLED: Locating genes on a chromosome is important for understanding the gene function and its linkage and recombination. Knowledge of gene positions on chromosomes is necessary for annotation. The study is essential for disease genetics and genomics, among other aspects. Currently available...... software's for calculating recombination frequency is mostly limited to the range and flexibility of this type of analysis. GENE LOCATER is a fully customizable program for calculating recombination frequency, written in JAVA. Through an easy-to-use interface, GENE LOCATOR allows users a high degree...

  8. Variable-Rate Premiums

    Data.gov (United States)

    Pension Benefit Guaranty Corporation — These interest rates are used to value vested benefits for variable rate premium purposes as described in PBGC's regulation on Premium Rates (29 CFR Part 4006) and...

  9. Software Testing Requires Variability

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak

    2003-01-01

    Software variability is the ability of a software system or artefact to be changed, customized or configured for use in a particular context. Variability in software systems is important from a number of perspectives. Some perspectives rightly receive much attention due to their direct economic i...... impact in software production. As is also apparent from the call for papers these perspectives focus on qualities such as reuse, adaptability, and maintainability.......Software variability is the ability of a software system or artefact to be changed, customized or configured for use in a particular context. Variability in software systems is important from a number of perspectives. Some perspectives rightly receive much attention due to their direct economic...

  10. Variable Attitude Test Stand

    Data.gov (United States)

    Federal Laboratory Consortium — The Variable Attitude Test Stand designed and built for testing of the V-22 tilt rotor aircraft propulsion system, is used to evaluate the effect of aircraft flight...

  11. Calculus of one variable

    CERN Document Server

    Grossman, Stanley I

    1986-01-01

    Calculus of One Variable, Second Edition presents the essential topics in the study of the techniques and theorems of calculus.The book provides a comprehensive introduction to calculus. It contains examples, exercises, the history and development of calculus, and various applications. Some of the topics discussed in the text include the concept of limits, one-variable theory, the derivatives of all six trigonometric functions, exponential and logarithmic functions, and infinite series.This textbook is intended for use by college students.

  12. Genomic variation in Salmonella enterica core genes for epidemiological typing

    DEFF Research Database (Denmark)

    Leekitcharoenphon, Pimlapas; Lukjancenko, Oksana; Rundsten, Carsten Friis

    2012-01-01

    time. The core genes-the genes that are conserved in all (or most) members of a genus or species-are potentially good candidates for investigating genomic variation in phylogeny and epidemiology. Results: We identify a set of 2,882 core genes clusters based on 73 publicly available Salmonella enterica...... confidence. The core genes can be divided into two categories: a few highly variable genes and a larger set of conserved core genes, with low variance. For the most variable core genes, the variance in amino acid sequences is higher than for the corresponding nucleotide sequences, suggesting...

  13. Biasogram: visualization of confounding technical bias in gene expression data

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Szallasi, Zoltan Imre; Eklund, Aron Charles

    2013-01-01

    Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors...... such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined...... by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may...

  14. Response variables for evaluation of the effectiveness of conservation corridors.

    Science.gov (United States)

    Gregory, Andrew J; Beier, Paul

    2014-06-01

    Many studies have evaluated effectiveness of corridors by measuring species presence in and movement through small structural corridors. However, few studies have assessed whether these response variables are adequate for assessing whether the conservation goals of the corridors have been achieved or considered the costs or lag times involved in measuring the response variables. We examined 4 response variables-presence of the focal species in the corridor, interpatch movement via the corridor, gene flow, and patch occupancy--with respect to 3 criteria--relevance to conservation goals, lag time (fewest generations at which a positive response to the corridor might be evident with a particular variable), and the cost of a study when applying a particular variable. The presence variable had the least relevance to conservation goals, no lag time advantage compared with interpatch movement, and only a moderate cost advantage over interpatch movement or gene flow. Movement of individual animals between patches was the most appropriate response variable for a corridor intended to provide seasonal migration, but it was not an appropriate response variable for corridor dwellers, and for passage species it was only moderately relevant to the goals of gene flow, demographic rescue, and recolonization. Response variables related to gene flow provided a good trade-off among cost, relevance to conservation goals, and lag time. Nonetheless, the lag time of 10-20 generations means that evaluation of conservation corridors cannot occur until a few decades after a corridor has been established. Response variables related to occupancy were most relevant to conservation goals, but the lag time and costs to detect corridor effects on occupancy were much greater than the lag time and costs to detect corridor effects on gene flow. © 2014 Society for Conservation Biology.

  15. Neuroanatomical variability of religiosity.

    Science.gov (United States)

    Kapogiannis, Dimitrios; Barbey, Aron K; Su, Michael; Krueger, Frank; Grafman, Jordan

    2009-09-28

    We hypothesized that religiosity, a set of traits variably expressed in the population, is modulated by neuroanatomical variability. We tested this idea by determining whether aspects of religiosity were predicted by variability in regional cortical volume. We performed structural magnetic resonance imaging of the brain in 40 healthy adult participants who reported different degrees and patterns of religiosity on a survey. We identified four Principal Components of religiosity by Factor Analysis of the survey items and associated them with regional cortical volumes measured by voxel-based morphometry. Experiencing an intimate relationship with God and engaging in religious behavior was associated with increased volume of R middle temporal cortex, BA 21. Experiencing fear of God was associated with decreased volume of L precuneus and L orbitofrontal cortex BA 11. A cluster of traits related with pragmatism and doubting God's existence was associated with increased volume of the R precuneus. Variability in religiosity of upbringing was not associated with variability in cortical volume of any region. Therefore, key aspects of religiosity are associated with cortical volume differences. This conclusion complements our prior functional neuroimaging findings in elucidating the proximate causes of religion in the brain.

  16. Classifying TDSS Stellar Variables

    Science.gov (United States)

    Amaro, Rachael Christina; Green, Paul J.; TDSS Collaboration

    2017-01-01

    The Time Domain Spectroscopic Survey (TDSS), a subprogram of SDSS-IV eBOSS, obtains classification/discovery spectra of point-source photometric variables selected from PanSTARRS and SDSS multi-color light curves regardless of object color or lightcurve shape. Tens of thousands of TDSS spectra are already available and have been spectroscopically classified both via pipeline and by visual inspection. About half of these spectra are quasars, half are stars. Our goal is to classify the stars with their correct variability types. We do this by acquiring public multi-epoch light curves for brighter stars (rclassifications and parameters in the Catalina Surveys Periodic Variable Star Catalog. Variable star classifications include RR Lyr, close eclipsing binaries, CVs, pulsating white dwarfs, and other exotic systems. The key difference between our catalog and others is that along with the light curves, we will be using TDSS spectra to help in the classification of variable type, as spectra are rich with information allowing estimation of physical parameters like temperature, metallicity, gravity, etc. This work was supported by the SDSS Research Experience for Undergraduates program, which is funded by a grant from Sloan Foundation to the Astrophysical Research Consortium.

  17. Does habitat variability really promote metabolic network modularity?

    Science.gov (United States)

    Takemoto, Kazuhiro

    2013-01-01

    The hypothesis that variability in natural habitats promotes modular organization is widely accepted for cellular networks. However, results of some data analyses and theoretical studies have begun to cast doubt on the impact of habitat variability on modularity in metabolic networks. Therefore, we re-evaluated this hypothesis using statistical data analysis and current metabolic information. We were unable to conclude that an increase in modularity was the result of habitat variability. Although horizontal gene transfer was also considered because it may contribute for survival in a variety of environments, closely related to habitat variability, and is known to be positively correlated with network modularity, such a positive correlation was not concluded in the latest version of metabolic networks. Furthermore, we demonstrated that the previously observed increase in network modularity due to habitat variability and horizontal gene transfer was probably due to a lack of available data on metabolic reactions. Instead, we determined that modularity in metabolic networks is dependent on species growth conditions. These results may not entirely discount the impact of habitat variability and horizontal gene transfer. Rather, they highlight the need for a more suitable definition of habitat variability and a more careful examination of relationships of the network modularity with horizontal gene transfer, habitats, and environments.

  18. Resiliencia y variables sociodemograficas

    OpenAIRE

    Calero Martinez, Edgar David

    2015-01-01

    En el presente trabajo se aborda la definición de una de las variables dentro de lo que se denomina Capital psicológico positivo, la Resiliencia, sus principales características y algunas de las variables socio demográficas que en el estudio pretenden ver el nivel de relación existente entre cada una de ellas (indirecta o directamente) en el proceso resiliente de una persona para posteriores discusiones y su implicación dentro de la gestión empresarial y sus direcciones futuras.

  19. Validation and Variability

    DEFF Research Database (Denmark)

    Carusi, Annamaria

    2014-01-01

    as inter-subject variability. This need is simultaneously social and epistemic: social as systems biologists attempt to engage with the interests and concerns of clinicians and others in applied medical research; epistemic as they attempt to develop new strategies to cope with variability in the validation...... of the computational models typical of systems biology. This paper describes one attempt to develop such a strategy: a trial with a population of models approach in the context of cardiac electrophysiology. I discuss the development of this approach against the background of ongoing tensions between mathematically...

  20. Applied complex variables

    CERN Document Server

    Dettman, John W

    1965-01-01

    Analytic function theory is a traditional subject going back to Cauchy and Riemann in the 19th century. Once the exclusive province of advanced mathematics students, its applications have proven vital to today's physicists and engineers. In this highly regarded work, Professor John W. Dettman offers a clear, well-organized overview of the subject and various applications - making the often-perplexing study of analytic functions of complex variables more accessible to a wider audience. The first half of Applied Complex Variables, designed for sequential study, is a step-by-step treatment of fun

  1. Internal variables in thermoelasticity

    CERN Document Server

    Berezovski, Arkadi

    2017-01-01

    This book describes an effective method for modeling advanced materials like polymers, composite materials and biomaterials, which are, as a rule, inhomogeneous. The thermoelastic theory with internal variables presented here provides a general framework for predicting a material’s reaction to external loading. The basic physical principles provide the primary theoretical information, including the evolution equations of the internal variables. The cornerstones of this framework are the material representation of continuum mechanics, a weak nonlocality, a non-zero extra entropy flux, and a consecutive employment of the dissipation inequality. Examples of thermoelastic phenomena are provided, accompanied by detailed procedures demonstrating how to simulate them.

  2. Terrestrial Carbon Cycle Variability.

    Science.gov (United States)

    Baldocchi, Dennis; Ryu, Youngryel; Keenan, Trevor

    2016-01-01

    A growing literature is reporting on how the terrestrial carbon cycle is experiencing year-to-year variability because of climate anomalies and trends caused by global change. As CO 2 concentration records in the atmosphere exceed 50 years and as satellite records reach over 30 years in length, we are becoming better able to address carbon cycle variability and trends. Here we review how variable the carbon cycle is, how large the trends in its gross and net fluxes are, and how well the signal can be separated from noise. We explore mechanisms that explain year-to-year variability and trends by deconstructing the global carbon budget. The CO 2 concentration record is detecting a significant increase in the seasonal amplitude between 1958 and now. Inferential methods provide a variety of explanations for this result, but a conclusive attribution remains elusive. Scientists have reported that this trend is a consequence of the greening of the biosphere, stronger northern latitude photosynthesis, more photosynthesis by semi-arid ecosystems, agriculture and the green revolution, tropical temperature anomalies, or increased winter respiration. At the global scale, variability in the terrestrial carbon cycle can be due to changes in constituent fluxes, gross primary productivity, plant respiration and heterotrophic (microbial) respiration, and losses due to fire, land use change, soil erosion, or harvesting. It remains controversial whether or not there is a significant trend in global primary productivity (due to rising CO 2 , temperature, nitrogen deposition, changing land use, and preponderance of wet and dry regions). The degree to which year-to-year variability in temperature and precipitation anomalies affect global primary productivity also remains uncertain. For perspective, interannual variability in global gross primary productivity is relatively small (on the order of 2 Pg-C y -1 ) with respect to a large and uncertain background (123 +/- 4 Pg-C y -1 ), and

  3. Complex variables I essentials

    CERN Document Server

    Solomon, Alan D

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Complex Variables I includes functions of a complex variable, elementary complex functions, integrals of complex functions in the complex plane, sequences and series, and poles and r

  4. Biological Sampling Variability Study

    Energy Technology Data Exchange (ETDEWEB)

    Amidan, Brett G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hutchison, Janine R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-11-08

    There are many sources of variability that exist in the sample collection and analysis process. This paper addresses many, but not all, sources of variability. The main focus of this paper was to better understand and estimate variability due to differences between samplers. Variability between days was also studied, as well as random variability within each sampler. Experiments were performed using multiple surface materials (ceramic and stainless steel), multiple contaminant concentrations (10 spores and 100 spores), and with and without the presence of interfering material. All testing was done with sponge sticks using 10-inch by 10-inch coupons. Bacillus atrophaeus was used as the BA surrogate. Spores were deposited using wet deposition. Grime was coated on the coupons which were planned to include the interfering material (Section 3.3). Samples were prepared and analyzed at PNNL using CDC protocol (Section 3.4) and then cultured and counted. Five samplers were trained so that samples were taken using the same protocol. Each sampler randomly sampled eight coupons each day, four coupons with 10 spores deposited and four coupons with 100 spores deposited. Each day consisted of one material being tested. The clean samples (no interfering materials) were run first, followed by the dirty samples (coated with interfering material). There was a significant difference in recovery efficiency between the coupons with 10 spores deposited (mean of 48.9%) and those with 100 spores deposited (mean of 59.8%). There was no general significant difference between the clean and dirty (containing interfering material) coupons or between the two surface materials; however, there was a significant interaction between concentration amount and presence of interfering material. The recovery efficiency was close to the same for coupons with 10 spores deposited, but for the coupons with 100 spores deposited, the recovery efficiency for the dirty samples was significantly larger (65

  5. Proper elimination of latent variables

    NARCIS (Netherlands)

    Polderman, Jan W.

    1997-01-01

    We consider behaviors in which we distinguish two types of variables, manifest variables, the variables that are of interest to the user and latent variables, the variables that are introduced to obtain a first representation. The problem is to find a representation of the manifest behavior, that

  6. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  7. Gene circuit analysis of the terminal gap gene huckebein.

    Directory of Open Access Journals (Sweden)

    Maksat Ashyraliyev

    2009-10-01

    Full Text Available The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.

  8. Spatial Variability of Rainfall

    DEFF Research Database (Denmark)

    Jensen, N.E.; Pedersen, Lisbeth

    2005-01-01

    As a part of a Local Area Weather Radar (LAWR) calibration exercise 15 km south of Århus, Denmark, the variability in accumulated rainfall within a single radar pixel (500 by 500 m) was measured using nine high-resolution rain gauges. The measured values indicate up to a 100% variation between ne...

  9. Variability in GPS sources

    NARCIS (Netherlands)

    Jauncey, DL; King, EA; Bignall, HE; Lovell, JEJ; Kedziora-Chudczer, L; Tzioumis, AK; Tingay, SJ; Macquart, JP; McCulloch, PM

    2003-01-01

    Flux density monitoring data at 2.3 and 8.4 GHz is presented for a sample of 33 southern hemisphere GPS sources, drawn from the 2.7 GHz Parkes survey. This monitoring data, together with VLBI monitoring data, shows that a small fraction of these sources, similar to10%, vary. Their variability falls

  10. Classes of Instructional Variables.

    Science.gov (United States)

    Reigeluth, Charles M.; Merrill, M. David

    1979-01-01

    Describes three classes of variables which should be considered when one is designing instructional materials, doing research on instruction, or developing better methods of instruction, and proposes a classification scheme which is summarized in the last of the 13 figures that illustrate the article. A blbliography is included. (Author/RAO)

  11. Variable rate irrigation

    Science.gov (United States)

    Systems are available to producers to make variable-rate applications of defoliants, fertilizer, lime, pesticides, plant growth regulators, and seed. These systems could potentially offer cost savings to a producer; however, the full potential of the benefits and savings cannot be realized if water ...

  12. Variable gravity research facility

    Science.gov (United States)

    Allan, Sean; Ancheta, Stan; Beine, Donna; Cink, Brian; Eagon, Mark; Eckstein, Brett; Luhman, Dan; Mccowan, Daniel; Nations, James; Nordtvedt, Todd

    1988-01-01

    Spin and despin requirements; sequence of activities required to assemble the Variable Gravity Research Facility (VGRF); power systems technology; life support; thermal control systems; emergencies; communication systems; space station applications; experimental activities; computer modeling and simulation of tether vibration; cost analysis; configuration of the crew compartments; and tether lengths and rotation speeds are discussed.

  13. Typhoon Structural Variability,

    Science.gov (United States)

    1985-10-01

    1980: An analytical model of the wind and pressure profiles in hurricanes. Mort . KUa. Rev., 108, 8, 1212-1218. Holland, G. J., and R. T. Merrill, 1984...Recipient’s Acce..sion No. SHEET ATS-391 4. Title and Subit le 5. Report Date Typhoon Structural Variability October, 1985 6. 7. Author(s) S. Performing

  14. Variable thrust cartridge

    Science.gov (United States)

    Taleyarkhan, Rusi P.

    2000-11-07

    The present invention is a variable thrust cartridge comprising a water-molten aluminum reaction chamber from which a slug is propelled. The cartridge comprises a firing system that initiates a controlled explosion from the reaction chamber. The explosive force provides a thrust to a slug, preferably contained within the cartridge.

  15. Variability and component composition

    NARCIS (Netherlands)

    T. van der Storm (Tijs)

    2004-01-01

    textabstractIn component-based product populations, feature models have to be described at the component level to be able to benefit from a product family approach. As a consequence, composition of components becomes very complex. We describe how component-level variability can be managed in the

  16. Variable speed generators

    CERN Document Server

    Boldea, Ion

    2005-01-01

    With the deregulation of electrical energy production and distribution, says Boldea (Polytechnical Institute, Timisoara, Romania) producers are looking for ways to tailor their electricity for different markets. Variable-speed electric generators are serving that purpose, up to the 400 megavolt ampere unit size, in Japan since 1996 and Germany sinc

  17. All Those Independent Variables.

    Science.gov (United States)

    Meacham, Merle L.

    This paper presents a case study of a sixth grade remedial math class which illustrates the thesis that only the "experimental attitude," not the "experimental method," is appropriate in the classroom. The thesis is based on the fact that too many independent variables exist in a classroom situation to allow precise measurement. The case study…

  18. Genetics of wide compatible gene and variability studies in rice ...

    Indian Academy of Sciences (India)

    production and productivity on a sustainable basis. Exploita- tion of heterosis in rice has resulted in release of several hybrids for commercial cultivation in India. One of ... However, rice being the staple food of. Indians, improving its productivity has become a critically important issue (Subbaiah et al. 2011). Knowledge on ...

  19. Phenotypic effects of genetic variability in human clock genes on ...

    Indian Academy of Sciences (India)

    2008-12-31

    Dec 31, 2008 ... all cause clear and reproducible effects in terms of free- running circadian period. It is probably fair to ... have been shown to have free-running circadian rhythms in spite of being surrounded by the nonvisual ..... BMAL1 is necessary for fertility and proper testosterone pro- duction in mice. J. Biol. Rhythms 23 ...

  20. A Bayesian Semiparametric Approach to Learning About Gene-Gene Interactions in Case-Control Studies

    OpenAIRE

    Bhattacharya, Durba; Bhattacharya, Sourabh

    2014-01-01

    Gene-gene interactions are often regarded as playing significant roles in influencing variabilities of complex traits. Although much research has been devoted to this area, to date a comprehensive statistical model that adequately addresses the highly dependent structures associated with the interactions between the genes, multiple loci of every gene, various and unknown number of sub-populations that the subjects arise from, seem to be lacking. In this paper, we propose and develop a novel B...

  1. Phylogenetic analysis of gene expression.

    Science.gov (United States)

    Dunn, Casey W; Luo, Xi; Wu, Zhijin

    2013-11-01

    Phylogenetic analyses of gene expression have great potential for addressing a wide range of questions. These analyses will, for example, identify genes that have evolutionary shifts in expression that are correlated with evolutionary changes in morphological, physiological, and developmental characters of interest. This will provide entirely new opportunities to identify genes related to particular phenotypes. There are, however, 3 key challenges that must be addressed for such studies to realize their potential. First, data on gene expression must be measured from multiple species, some of which may be field-collected, and parameterized in such a way that they can be compared across species. Second, it will be necessary to develop comparative phylogenetic methods suitable for large multidimensional datasets. In most phylogenetic comparative studies to date, the number n of independent observations (independent contrasts) has been greater than the number p of variables (characters). The behavior of comparative methods for these classic problems is now well understood under a wide variety of conditions. In studies of gene expression, and in studies based on other high-throughput tools, the number n of samples is dwarfed by the number p of variables. The estimated covariance matrices will be singular, complicating their analysis and interpretation, and prone to spurious results. Third, new approaches are needed to investigate the expression of the many genes whose phylogenies are not congruent with species phylogenies due to gene loss, gene duplication, and incomplete lineage sorting. Here we outline general considerations of project design for phylogenetic analyses of gene expression and suggest solutions to these three categories of challenges. These topics are relevant to high-throughput phenotypic data well beyond gene expression.

  2. Technological Capability's Predictor Variables

    Directory of Open Access Journals (Sweden)

    Fernanda Maciel Reichert

    2011-03-01

    Full Text Available The aim of this study was to identify the factors that influence in configuration of the technological capability of companies in sectors with medium-low technological intensity. To achieve the goal proposed in this article a survey was carried out. Based on the framework developed by Lall (1992 which classifies firms in basic, intermediate and advanced level of technological capability; it was found that the predominant technological capability is intermediate, with 83.7% of respondent companies (plastics companies in Brazil. It is believed that the main contribution of this study is the finding that the dependent variable named “Technological Capability” can be explained at a rate of 65% by six variables: development of new processes; selection of the best equipment supplier; sales of internally developed new technology to third parties; design and manufacture of equipment; study of the work methods and perform inventory control; and improvement of product quality.

  3. Complex variable HVPT

    Energy Technology Data Exchange (ETDEWEB)

    Killingbeck, John P [Mathematics Department, University of Hull, Hull HU6 7RX (United Kingdom); Grosjean, Alain [Laboratoire d' Astrophysique de l' Observatoire de Besancon (CNRS, UPRES-A 6091), 41 bis Avenue de l' Observatoire, BP 1615, 25010 Besancon Cedex (France); Jolicard, Georges [Laboratoire d' Astrophysique de l' Observatoire de Besancon (CNRS, UPRES-A 6091), 41 bis Avenue de l' Observatoire, BP 1615, 25010 Besancon Cedex (France)

    2004-08-13

    Complex variable hypervirial perturbation theory is applied to the case of oscillator and Coulomb potentials perturbed by a single term potential of the form Vx{sup n} or Vr{sup n}, respectively. The trial calculations reported show that this approach can produce accurate complex energies for resonant states via a simple and speedy calculation and can also be useful in studies of PT symmetry and tunnelling resonance effects. (addendum)

  4. Spreading with variable viscosity

    OpenAIRE

    Foit, J.J.

    1997-01-01

    Ausbreitung mit variabler Viskosität Die isotherme Ausbreitung eines Volumenstromes, , in Form von dünnen Schichten kann mit Hilfe selbstähnlicher Lösungen beschrieben werden (Huppert). Für die axialsymmetrische Ausbreitung eines konstanten Volumens mit einer variablen Viskosität von der Form existieren ebenfalls selbstähnliche Lösungen (Sakimoto, Zuber). Dieses Ergebnis wird auf den Fall einer eindimensionalen und einer axialsymmetrischen Ausbreitung für alle , erweitert.

  5. Historical Variable Star Catalogs

    OpenAIRE

    Pagnotta, Ashley; Graur, Or; Murray, Zachary; Kruk, Julia; Christie-Dervaux, Lucien; Chen, Dong Yi

    2015-01-01

    Slides from my talk during one of the Historical Astronomy Division sessions at AAS 225 in Seattle, WA (January 2015). A brief history of the variable star catalogs Henrietta Swan Leavitt and Cecilia Payne-Gaposchkin assembled at Harvard, and the update to them that some of our students at AMNH have done.(Figshare only previews the first few slides. Download the PDF to see all of them!)

  6. Score test variable screening

    OpenAIRE

    Zhao, Sihai Dave; Li, Yi

    2014-01-01

    Variable screening has emerged as a crucial first step in the analysis of high-throughput data, but existing procedures can be computationally cumbersome, difficult to justify theoretically, or inapplicable to certain types of analyses. Motivated by a high-dimensional censored quantile regression problem in multiple myeloma genomics, this paper makes three contributions. First, we establish a score test-based screening framework, which is widely applicable, extremely computationally efficient...

  7. Short Timescale Variability In The Faint Sky Variability Survey

    NARCIS (Netherlands)

    Morales-Rueda, L.; Groot, P.J.; Augusteijn, T.; Nelemans, G.A.; Vreeswijk, P.M.; Besselaar, E.J.M. van den

    2006-01-01

    We present the V band variability analysis of the point sources in the Faint Sky Variability Survey on time scales from 24 minutes to tens of days. We find that about one percent of the point sources down to V = 24 are variables. We discuss the variability detection probabilities for each field

  8. Short timescale variability in the faint sky variability survey

    NARCIS (Netherlands)

    Morales-Rueda, L.; Groot, P.J.; Augusteijn, T.; Nelemans, G.A.; Vreeswijk, P.M.; Besselaar, E.J.M. van den

    2006-01-01

    We present the V-band variability analysis of the Faint Sky Variability Survey (FSVS). The FSVS combines colour and time variability information, from timescales of 24 minutes to tens of days, down to V = 24. We find that �1% of all point sources are variable along the main sequence reaching �3.5%

  9. Population effects and variability.

    Science.gov (United States)

    Dorne, Jean Lou; Amzal, Billy; Bois, Frédéric; Crépet, Amélie; Tressou, Jessica; Verger, Philippe

    2012-01-01

    Chemical risk assessment for human health requires a multidisciplinary approach through four steps: hazard identification and characterization, exposure assessment, and risk characterization. Hazard identification and characterization aim to identify the metabolism and elimination of the chemical (toxicokinetics) and the toxicological dose-response (toxicodynamics) and to derive a health-based guidance value for safe levels of exposure. Exposure assessment estimates human exposure as the product of the amount of the chemical in the matrix consumed and the consumption itself. Finally, risk characterization evaluates the risk of the exposure to human health by comparing the latter to with the health-based guidance value. Recently, many research efforts in computational toxicology have been put together to characterize population variability and uncertainty in each of the steps of risk assessment to move towards more quantitative and transparent risk assessment. This chapter focuses specifically on modeling population variability and effects for each step of risk assessment in order to provide an overview of the statistical and computational tools available to toxicologists and risk assessors. Three examples are given to illustrate the applicability of those tools: derivation of pathway-related uncertainty factors based on population variability, exposure to dioxins, dose-response modeling of cadmium.

  10. Gene Therapy

    Science.gov (United States)

    ... or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and ...

  11. Regularization by External Variables

    DEFF Research Database (Denmark)

    Bossolini, Elena; Edwards, R.; Glendinning, P. A.

    2016-01-01

    Regularization was a big topic at the 2016 CRM Intensive Research Program on Advances in Nonsmooth Dynamics. There are many open questions concerning well known kinds of regularization (e.g., by smoothing or hysteresis). Here, we propose a framework for an alternative and important kind of regula...... of regularization, by external variables that shadow either the state or the switch of the original system. The shadow systems are derived from and inspired by various applications in electronic control, predator-prey preference, time delay, and genetic regulation....

  12. Atmospheric Infrared Radiance Variability.

    Science.gov (United States)

    1981-05-27

    ATMOSPHERIC VARIABILITY ON INFRARED RADIANCE PREDICTIONS - T. C. Degges 53 5. ATMOSPHERIC STRUCTURE - C.H. HLmphrey, C.R. Philbrick, S.M. Silverman , T.F. Tuan...variations similar to those shown in Figure 2. In arctic and subarctic regions, sudden warmings and coolings of the winter stratosphere and mesosphere... Silverman \\Jr I",rre. (;.L~~sIalmratorN Hanscom Air Force Base, Manss. T.F. Tuan Universitv of Cincinnati Cincinnati, (tio M. Anapol S.S.G.. Inc. Waltham

  13. Variable camshaft timing system

    Energy Technology Data Exchange (ETDEWEB)

    Butterfield, R.P.; Smith, F.R.

    1989-09-05

    This patent describes an improvement in a variable camshaft timing system for an internal combustion engine having intake and exhaust valves and a camshaft for each of the intake and exhaust valves, an intake sprocket and an exhaust sprocket keyed to their respective camshaft, only one of the camshafts being directly driven by an engine crankshaft, and a timing chain engaging both sprockets. The improvement comprising a single bracket carrying at least one idler sprocket engaging the timing chain, the bracket being mounted for movement to alter the timing relationship between the intake and exhaust sprockets.

  14. Complex variables II essentials

    CERN Document Server

    Solomon, Alan D

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Complex Variables II includes elementary mappings and Mobius transformation, mappings by general functions, conformal mappings and harmonic functions, applying complex functions to a

  15. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

    Science.gov (United States)

    Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  16. Identification of human HK genes and gene expression regulation study in cancer from transcriptomics data analysis.

    Science.gov (United States)

    Chen, Meili; Xiao, Jingfa; Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer.

  17. Glycemic variability: Clinical implications

    Directory of Open Access Journals (Sweden)

    Surabhi Venkata Satya Krishna

    2013-01-01

    Full Text Available Glycemic control and its benefits in preventing microvascular diabetic complications are convincingly proved by various prospective trials. Diabetes control and complications trial (DCCT had reported variable glycated hemoglobin (HbA1C as a cause of increased microvascular complications in conventional glycemic control group versus intensive one. However, in spite of several indirect evidences, its link with cardiovascular events or macrovascular complications is still not proved. Glycemic variability (GV is one more tool to explain relation between hyperglycemia and increased cardiovascular risk in diabetic patients. In fact GV along with fasting blood sugar, postprandial blood sugar, HbA1C, and quality of life has been proposed to form glycemic pentad, which needs to be considered in diabetes management. Postprandial spikes in blood glucose as well as hypoglycemic events, both are blamed for increased cardiovascular events in Type 2 diabetics. GV includes both these events and hence minimizing GV can prevent future cardiovascular events. Modern diabetes management modalities including improved sulfonylureas, glucagon like peptide-1 (GLP-1-based therapy, newer basal insulins, and modern insulin pumps address the issue of GV effectively. This article highlights mechanism, clinical implications, and measures to control GV in clinical practice.

  18. Variable Valve Actuation

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey Gutterman; A. J. Lasley

    2008-08-31

    Many approaches exist to enable advanced mode, low temperature combustion systems for diesel engines - such as premixed charge compression ignition (PCCI), Homogeneous Charge Compression Ignition (HCCI) or other HCCI-like combustion modes. The fuel properties and the quantity, distribution and temperature profile of air, fuel and residual fraction in the cylinder can have a marked effect on the heat release rate and combustion phasing. Figure 1 shows that a systems approach is required for HCCI-like combustion. While the exact requirements remain unclear (and will vary depending on fuel, engine size and application), some form of substantially variable valve actuation is a likely element in such a system. Variable valve actuation, for both intake and exhaust valve events, is a potent tool for controlling the parameters that are critical to HCCI-like combustion and expanding its operational range. Additionally, VVA can be used to optimize the combustion process as well as exhaust temperatures and impact the after treatment system requirements and its associated cost. Delphi Corporation has major manufacturing and product development and applied R&D expertise in the valve train area. Historical R&D experience includes the development of fully variable electro-hydraulic valve train on research engines as well as several generations of mechanical VVA for gasoline systems. This experience has enabled us to evaluate various implementations and determine the strengths and weaknesses of each. While a fully variable electro-hydraulic valve train system might be the 'ideal' solution technically for maximum flexibility in the timing and control of the valve events, its complexity, associated costs, and high power consumption make its implementation on low cost high volume applications unlikely. Conversely, a simple mechanical system might be a low cost solution but not deliver the flexibility required for HCCI operation. After modeling more than 200 variations of

  19. Variability of chromosome number and morphology and gymnosperm improvement

    OpenAIRE

    Tucović Aleksandar; Šijačić-Nikolić Mirjana; Vilotić Dragica

    2004-01-01

    The causes of monotypic and polytypic variability of the gymnosperm chromosome complex were studied. The development of karyogram and idiograms of the species should be applied in the aim of upgrading the breeding method and technique. The study of the chromosome variability depends on the knowledge on gene function at the level of chromosome and at the level of genome, i.e. at the supra-chromosome level.

  20. Chatter Prediction for Variable Pitch and Variable Helix Milling

    Directory of Open Access Journals (Sweden)

    Yong Wang

    2015-01-01

    Full Text Available Regenerative chatter is a self-excited vibration that can occur during milling, which shortens the lifetime of the tool and results in unacceptable surface quality. In this paper, an improved semidiscretization method for modeling and simulation with variable pitch and variable helix milling is proposed. Because the delay between each flute varies along the axial depth of the tool in milling, the cutting tool is discrete into some axial layers to simplify calculation. A comparison of the predicted and observed performance of variable pitch and variable helix against uniform pitch and uniform helix milling is presented. It is shown that variable pitch and variable helix milling can obtain larger stable cutting area than uniform pitch and uniform helix milling. Thus, it is concluded that variable pitch and variable helix milling are an effective way for suppressing chatter.

  1. Variable cycle engine

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, A.P.; Sprunger, E.V.

    1980-09-16

    A variable cycle turboshaft engine includes a remote fan system and respective high and low pressure systems for selectively driving the fan system in such a manner as to provide VTOL takeoff capability and minimum specific fuel consumption (SFC) at cruise and loiter conditions. For takeoff the fan system is primarily driven by the relatively large low pressure system whose combustor receives the motive fluid from a core bypass duct and, for cruise and loiter conditions, the fan system is driven by both a relatively small high pressure core and the low pressure system with its combustor inoperative. A mixer is disposed downstream of the high pressure system for mixing the relatively cold air from the bypass duct and the relatively hot air from the core prior to its flow to the low pressure turbine.

  2. Variable Amplitude Fatigue

    Science.gov (United States)

    Ranganathan, Narayanaswami; Joly, Damien; Leroy, René

    Fatigue crack growth behavior of selected aluminum alloys under variable amplitude loading is discussed in this study, based principally on experimental observations. The tests include single overloads tests in different environments, block load tests and tests using an aircraft wing loading spectrum. It is shown that conditions favoring a planar slip behavior lead to very high delays as opposed to conditions leading to multiple slip behavior. The Aluminium Liithium alloy studied here, has the best fatigue crack growth resistance in almost all test conditions studied here as compared to other conventional alloys. Under the spectrum loading studied here, the same alloy exhibits a change in micromechanism leading to a four fould acceleration of growth rates. Acceptable life predictions can be made, by taking into account this crack acceleration effect.

  3. RNA-seq: technical variability and sampling

    Science.gov (United States)

    2011-01-01

    Background RNA-seq is revolutionizing the way we study transcriptomes. mRNA can be surveyed without prior knowledge of gene transcripts. Alternative splicing of transcript isoforms and the identification of previously unknown exons are being reported. Initial reports of differences in exon usage, and splicing between samples as well as quantitative differences among samples are beginning to surface. Biological variation has been reported to be larger than technical variation. In addition, technical variation has been reported to be in line with expectations due to random sampling. However, strategies for dealing with technical variation will differ depending on the magnitude. The size of technical variance, and the role of sampling are examined in this manuscript. Results In this study three independent Solexa/Illumina experiments containing technical replicates are analyzed. When coverage is low, large disagreements between technical replicates are apparent. Exon detection between technical replicates is highly variable when the coverage is less than 5 reads per nucleotide and estimates of gene expression are more likely to disagree when coverage is low. Although large disagreements in the estimates of expression are observed at all levels of coverage. Conclusions Technical variability is too high to ignore. Technical variability results in inconsistent detection of exons at low levels of coverage. Further, the estimate of the relative abundance of a transcript can substantially disagree, even when coverage levels are high. This may be due to the low sampling fraction and if so, it will persist as an issue needing to be addressed in experimental design even as the next wave of technology produces larger numbers of reads. We provide practical recommendations for dealing with the technical variability, without dramatic cost increases. PMID:21645359

  4. Reference gene screening for analyzing gene expression across goat tissue.

    Science.gov (United States)

    Zhang, Yu; Zhang, Xiao-Dong; Liu, Xing; Li, Yun-Sheng; Ding, Jian-Ping; Zhang, Xiao-Rong; Zhang, Yun-Hai

    2013-12-01

    Real-time quantitative PCR (qRT-PCR) is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2) in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  5. Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2013-12-01

    Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  6. Evolution of the Vertebrate Resistin Gene Family.

    Directory of Open Access Journals (Sweden)

    Qingda Hu

    Full Text Available Resistin (encoded by Retn was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish, but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions.

  7. Gait Variability and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Michael J. Socie

    2013-01-01

    Full Text Available Gait variability, that is, fluctuations in movement during walking, is an indicator of walking function and has been associated with various adverse outcomes such as falls. In this paper, current research concerning gait variability in persons with multiple sclerosis (MS is discussed. It is well established that persons with MS have greater gait variability compared to age and gender matched controls without MS. The reasons for the increase in gait variability are not completely understood. Evidence indicates that disability level, assistive device use, attentional requirement, and fatigue are related to gait variability in persons with MS. Future research should address the time-evolving structure (i.e., temporal characteristics of gait variability, the clinical importance of gait variability, and underlying mechanisms that drive gait variability in individuals with MS.

  8. Modeling Shared Variables in VHDL

    DEFF Research Database (Denmark)

    Madsen, Jan; Brage, Jens P.

    1994-01-01

    A set of concurrent processes communicating through shared variables is an often used model for hardware systems. This paper presents three modeling techniques for representing such shared variables in VHDL, depending on the acceptable constraints on accesses to the variables. Also a set...... of guidelines for handling atomic updates of multiple shared variables is given. 1 Introduction It is often desirable to partition a computational system into discrete functional units which cooperates to....

  9. Strong Decomposition of Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jørgensen, Jørgen; Kagan, Abram M.; Pitt, Loren D.

    2007-01-01

    A random variable X is stongly decomposable if X=Y+Z where Y=Φ(X) and Z=X-Φ(X) are independent non-degenerated random variables (called the components). It is shown that at least one of the components is singular, and we derive a necessary and sufficient condition for strong decomposability...... of a discrete random variable....

  10. THE VARIABILITY OF INTERLANGUAGE USE

    African Journals Online (AJOL)

    www

    This pattern of linguistic behaviour is called "non-systematic variability". In this article, the phenomenon of this variability in L2 knowledge is investigated. The existing body of knowledge about L2 acquisition provides ample proof that L2 learners are characteristically variable in their interlanguage use. The question arises ...

  11. Preservice Teachers' Understanding of Variable

    Science.gov (United States)

    Brown, Sue; Bergman, Judy

    2013-01-01

    This study examines the research on middle school students' understanding of variables and explores preservice elementary and middle school teachers' knowledge of variables. According to research studies, middle school students have limited understanding of variables. Many studies have examined the performance of middle school students and offered…

  12. Integration i flere variable

    DEFF Research Database (Denmark)

    Markvorsen, Steen

    2010-01-01

    Denne note handler om parameterfremstillinger for kurver, flader og rumlige områder og om integration af funktioner på sådanne geometriske objekter. Formålet er primært at opstille og motivere de generelle definitioner og beregninger af henholdsvis kurve- \\, flade- \\, og rum-integraler. Udgangspu......Denne note handler om parameterfremstillinger for kurver, flader og rumlige områder og om integration af funktioner på sådanne geometriske objekter. Formålet er primært at opstille og motivere de generelle definitioner og beregninger af henholdsvis kurve- \\, flade- \\, og rum......-integralerne. Undervejs introduceres \\texttt{Integrator8}. Det er en pakke med Maple procedurer, som er udviklet specielt med henblik på eksempelbaseret visuel læring af de indledende integrationsbegreber og deres mangfoldige anvendelser. Vi giver eksempler på, hvordan integration i flere variable anvendes til beregning...... og forståelse af rumfang, vægt, massemidtpunkter, inertimomenter, kraftmomenter, etc. Flowkurverne for et givet vektorfelt i rummet kan findes og visualiseres med \\texttt{Integrator8}. De vigtige begreber divergens og rotation for et vektorfelt fremtræder derved som naturlige størrelser til...

  13. Variables moderadoras del estres

    Directory of Open Access Journals (Sweden)

    María Cristina Richaud de Minzi

    1999-01-01

    Full Text Available El objetivo del presente trabajo es analizar la influenciadel estilo atribucional, la confianza interpersonal y el soporte social sobre la percepción de la amenaza. Se administraron la Escala de Estilo Atribucional; la Manheim Interview 01 Social Support, la Escala de Confianza Interpersonal; y el Inventario de Situaciones y Respuestas de Ansiedad, a 260 sujetos de ambos sexos, de 30 años de edad promedio, de nivel socioeconómico medio, residentes en la ciudad de Buenos Aires. El soporte social no demostró influencia significativa sobre la percepción de la amenaza. Con respecto a la influencia del estilo atribucional se puede decir que las personas indefensas perciben más amenaza, especialmente expresada como ansiedad cognitiva y, en menor grado, como ansiedad motora o conductual. La confianza interpersonal demostró ser una variable importante en la percepción de la amenaza. Los sujetos que presentaron alta desconfianza hacia las personas de su entorno perciben un mundo amenazante, que se manifiesta como ansiedad cognitiva, fisiológica y motora o conductual.

  14. Hydrostatic continuously variable transmission

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, T.; Saito, M.; Matsuto, T.; Nakajima, Y.; Sakakibara, K.; Yakigaya, N.; Nakamura, K.

    1989-05-09

    A hydrostatic continuously variable transmission is described, comprising: a swashplate type hydraulic pump having a pump swashplate and annularly arranged pump plungers whose suction and discharge strokes are provided by the pump swashplate; a swashplate type hydraulic motor having a motor swashplate and annularly arranged motor plungers whose expansion and shrinkage strokes are provided by the motor swashplate; and a hydraulic closed circuit formed between the hydraulic pump and the hydraulic motor. The transmission has at least one of a relationship that a middle point of a discharge region of the hydraulic pump is angularly delayed at a given angle in a direction of rotation of the hydraulic pump relative to a tilting axis of the pump swashplate and a relationship that a middle point of an expansion region of the hydraulic motor is angularly advanced at a given angle in a direction of rotation of the hydraulic motor relative to a tilting axis of the motor swashplate, wherein the transmission has at least one of a relationship that a suction region of the hydraulic pump is set at an angle larger than that of the discharge region thereof and a relationship that a shrinkage region of the hydraulic motor is set at an angle larger than that of the expansion region of the motor.

  15. Variable subsistence indemnity

    CERN Document Server

    1999-01-01

    At its meeting on 9 December 1998, the Finance Committee approved, with effect from 1st January 1999, adjustments to the Variable Subsistence Indemnity according to the rates published by the United Nations Organization given in document CERN/FC/4113. This decision maintained the reference method in force since 1983. The Management now proposes to adjust the CERN rates of indemnities, with effect from 1st January 2000, on the basis of the United Nations 1999 rates, as shown for typical destinations in the table contained in this document. Although a precise estimate of the cost effect for duty travel is difficult to achieve due to currency exchange values, it is probable that this will remain unchanged if calculated in Swiss francs. The Management also proposes to formalise the practice of paying a lower subsistence indemnity than the approved basic amount, wherever feasible for events such as group duty travel to conferences or similar events, as discussed at the Finance Committee in December 1998. An amendm...

  16. Variable angle correlation spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Kyo [Univ. of California, Berkeley, CA (United States)

    1994-05-01

    In this dissertation, a novel nuclear magnetic resonance (NMR) technique, variable angle correlation spectroscopy (VACSY) is described and demonstrated with 13C nuclei in rapidly rotating samples. These experiments focus on one of the basic problems in solid state NMR: how to extract the wealth of information contained in the anisotropic component of the NMR signal while still maintaining spectral resolution. Analysis of the anisotropic spectral patterns from poly-crystalline systems reveal information concerning molecular structure and dynamics, yet in all but the simplest of systems, the overlap of spectral patterns from chemically distinct sites renders the spectral analysis difficult if not impossible. One solution to this problem is to perform multi-dimensional experiments where the high-resolution, isotropic spectrum in one dimension is correlated with the anisotropic spectral patterns in the other dimensions. The VACSY technique incorporates the angle between the spinner axis and the static magnetic field as an experimental parameter that may be incremented during the course of the experiment to help correlate the isotropic and anisotropic components of the spectrum. The two-dimensional version of the VACSY experiments is used to extract the chemical shift anisotropy tensor values from multi-site organic molecules, study molecular dynamics in the intermediate time regime, and to examine the ordering properties of partially oriented samples. The VACSY technique is then extended to three-dimensional experiments to study slow molecular reorientations in a multi-site polymer system.

  17. Genealogy and gene trees.

    Science.gov (United States)

    Rasmuson, Marianne

    2008-02-01

    Heredity can be followed in persons or in genes. Persons can be identified only a few generations back, but simplified models indicate that universal ancestors to all now living persons have occurred in the past. Genetic variability can be characterized as variants of DNA sequences. Data are available only from living persons, but from the pattern of variation gene trees can be inferred by means of coalescence models. The merging of lines backwards in time leads to a MRCA (most recent common ancestor). The time and place of living for this inferred person can give insights in human evolutionary history. Demographic processes are incorporated in the model, but since culture and customs are known to influence demography the models used ought to be tested against available genealogy. The Icelandic data base offers a possibility to do so and points to some discrepancies. Mitochondrial DNA and Y chromosome patterns give a rather consistent view of human evolutionary history during the latest 100 000 years but the earlier epochs of human evolution demand gene trees with longer branches. The results of such studies reveal as yet unsolved problems about the sources of our genome.

  18. Genetic Variability in Soybean (Glycine max L.) for Low Soil ...

    African Journals Online (AJOL)

    Abush Tesfaye

    1Jimma Research Center, P.O.Box 192, Jimma, Ethiopia, 2Jomo Kenyatta University of and Technology,. Department of Horticulture ... Assessment of the genetic variability of soybean genotypes under low soil phosphorus (P) .... coefficient of variations, broad sense heritability, genetic advance were analyzed using. Genes ...

  19. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Science.gov (United States)

    Zhou, Xiaobo; Wang, Xiaodong; Dougherty, Edward R.

    2004-12-01

    A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  20. Gene Prediction Using Multinomial Probit Regression with Bayesian Gene Selection

    Directory of Open Access Journals (Sweden)

    Wang Xiaodong

    2004-01-01

    Full Text Available A critical issue for the construction of genetic regulatory networks is the identification of network topology from data. In the context of deterministic and probabilistic Boolean networks, as well as their extension to multilevel quantization, this issue is related to the more general problem of expression prediction in which we want to find small subsets of genes to be used as predictors of target genes. Given some maximum number of predictors to be used, a full search of all possible predictor sets is combinatorially prohibitive except for small predictors sets, and even then, may require supercomputing. Hence, suboptimal approaches to finding predictor sets and network topologies are desirable. This paper considers Bayesian variable selection for prediction using a multinomial probit regression model with data augmentation to turn the multinomial problem into a sequence of smoothing problems. There are multiple regression equations and we want to select the same strongest genes for all regression equations to constitute a target predictor set or, in the context of a genetic network, the dependency set for the target. The probit regressor is approximated as a linear combination of the genes and a Gibbs sampler is employed to find the strongest genes. Numerical techniques to speed up the computation are discussed. After finding the strongest genes, we predict the target gene based on the strongest genes, with the coefficient of determination being used to measure predictor accuracy. Using malignant melanoma microarray data, we compare two predictor models, the estimated probit regressors themselves and the optimal full-logic predictor based on the selected strongest genes, and we compare these to optimal prediction without feature selection.

  1. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  2. Gene Ontology

    Directory of Open Access Journals (Sweden)

    Gaston K. Mazandu

    2012-01-01

    Full Text Available The wide coverage and biological relevance of the Gene Ontology (GO, confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.

  3. Spatial variability of groundwater recharge - I. Is it really variable?

    OpenAIRE

    De Silva, RP

    2004-01-01

    The spatial variability of recharge is an important consideration in estimating recharge especially as all methods of estimating it are 'point' estimates and in most places recharge varies in space. This paper along with the accompanying paper attempts to find a suitable answer to the question of taking this variability into account in estimating groundwater recharge. This paper attempts to determine if recharge is actually varying in space and that this is 'true' variability and that it is n...

  4. Variable Sampling Mapping

    Science.gov (United States)

    Smith, Jeffrey, S.; Aronstein, David L.; Dean, Bruce H.; Lyon, Richard G.

    2012-01-01

    The performance of an optical system (for example, a telescope) is limited by the misalignments and manufacturing imperfections of the optical elements in the system. The impact of these misalignments and imperfections can be quantified by the phase variations imparted on light traveling through the system. Phase retrieval is a methodology for determining these variations. Phase retrieval uses images taken with the optical system and using a light source of known shape and characteristics. Unlike interferometric methods, which require an optical reference for comparison, and unlike Shack-Hartmann wavefront sensors that require special optical hardware at the optical system's exit pupil, phase retrieval is an in situ, image-based method for determining the phase variations of light at the system s exit pupil. Phase retrieval can be used both as an optical metrology tool (during fabrication of optical surfaces and assembly of optical systems) and as a sensor used in active, closed-loop control of an optical system, to optimize performance. One class of phase-retrieval algorithms is the iterative transform algorithm (ITA). ITAs estimate the phase variations by iteratively enforcing known constraints in the exit pupil and at the detector, determined from modeled or measured data. The Variable Sampling Mapping (VSM) technique is a new method for enforcing these constraints in ITAs. VSM is an open framework for addressing a wide range of issues that have previously been considered detrimental to high-accuracy phase retrieval, including undersampled images, broadband illumination, images taken at or near best focus, chromatic aberrations, jitter or vibration of the optical system or detector, and dead or noisy detector pixels. The VSM is a model-to-data mapping procedure. In VSM, fully sampled electric fields at multiple wavelengths are modeled inside the phase-retrieval algorithm, and then these fields are mapped to intensities on the light detector, using the properties

  5. HOW NORMAL IS VARIABLE, OR HOW VARIABLE IS NORMAL

    NARCIS (Netherlands)

    TOUWEN, BCL

    Variability is an important property of the central nervous system, and it shows characteristic changes during infancy and childhood. The large amount of variations in the performance of sensomotor functions in infancy is called indiscriminate or primary variability. During toddling age the child

  6. Variable Speed Rotor System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Variable speed rotors will give helicopters several advantages: higher top speed, greater fuel efficiency, momentary emergency over-power, resonance detuning...

  7. The Hubble Catalog of Variables

    Directory of Open Access Journals (Sweden)

    Sokolovsky K.

    2017-01-01

    Full Text Available We aim to construct an exceptionally deep (V ≲ 27 catalog of variable objects in selected Galactic and extragalactic fields visited multiple times by the Hubble Space Telescope (HST. While HST observations of some of these fields were searched for specific types of variables before (most notably, the extragalactic Cepheids, we attempt a systematic study of the population of variable objects of all types at the magnitude range not easily accessible with ground-based telescopes. The variability timescales that can be probed range from hours to years depending on how often a particular field has been visited. For source extraction and cross-matching of sources between visits we rely on the Hubble Source Catalog which includes 107 objects detected with WFPC2, ACS, and WFC3 HST instruments. The lightcurves extracted from the HSC are corrected for systematic effects by applying local zero-point corrections and are screened for bad measurements. For each lightcurve we compute variability indices sensitive to a broad range of variability types. The indices characterize the overall lightcurve scatter and smoothness. Candidate variables are selected as having variability index values significantly higher than expected for objects of similar brightness in the given set of observations. The Hubble Catalog of Variables will be released in 2018.

  8. Gene regulatory networks and the role of robustness and stochasticity in the control of gene expression

    Science.gov (United States)

    MacNeil, Lesley T.; Walhout, Albertha J.M.

    2011-01-01

    In any given cell, thousands of genes are expressed and work in concert to ensure the cell's function, fitness, and survival. Each gene, in turn, must be expressed at the proper time and in the proper amounts to ensure the appropriate functional outcome. The regulation and expression of some genes are highly robust; their expression is controlled by invariable expression programs. For instance, developmental gene expression is extremely similar in a given cell type from one individual to another. The expression of other genes is more variable: Their levels are noisy and are different from cell to cell and from individual to individual. This can be highly beneficial in physiological responses to outside cues and stresses. Recent advances have enabled the analysis of differential gene expression at a systems level. Gene regulatory networks (GRNs) involving interactions between large numbers of genes and their regulators have been mapped onto graphic diagrams that are used to visualize the regulatory relationships. The further characterization of GRNs has already uncovered global principles of gene regulation. Together with synthetic network biology, such studies are starting to provide insights into the transcriptional mechanisms that cause robust versus stochastic gene expression and their relationships to phenotypic robustness and variability. Here, we discuss GRNs and their topological properties in relation to transcriptional and phenotypic outputs in development and organismal physiology. PMID:21324878

  9. Variability in human body size

    Science.gov (United States)

    Annis, J. F.

    1978-01-01

    The range of variability found among homogeneous groups is described and illustrated. Those trends that show significantly marked differences between sexes and among a number of racial/ethnic groups are also presented. Causes of human-body size variability discussed include genetic endowment, aging, nutrition, protective garments, and occupation. The information is presented to aid design engineers of space flight hardware and equipment.

  10. Students' Misconceptions about Random Variables

    Science.gov (United States)

    Kachapova, Farida; Kachapov, Ilias

    2012-01-01

    This article describes some misconceptions about random variables and related counter-examples, and makes suggestions about teaching initial topics on random variables in general form instead of doing it separately for discrete and continuous cases. The focus is on post-calculus probability courses. (Contains 2 figures.)

  11. Phonological Variability in Canadian English.

    Science.gov (United States)

    de Wolf, Gaelan Dodds

    A study compared salient variables of Canadian English from two concurrent sociodialectal surveys, one for Ottawa, Ontario and one for Vancouver, British Columbia. Using the Labovian model of phonological variation in association with sociological parameters and other linguistic variables within each specific area, the analysis investigated four…

  12. A process variability control chart

    NARCIS (Netherlands)

    Riaz, M.; Does, R.J.M.M.

    2009-01-01

    In this study a Shewhart type control chart namely the Vt chart, is proposed for improvedmonitoring of the process variability of a quality characteristic of interest Y . The proposed control chart is based on the ratio type estimator of the variance using a single auxiliary variable X. It is

  13. Speed control variable rate irrigation

    Science.gov (United States)

    Speed control variable rate irrigation (VRI) is used to address within field variability by controlling a moving sprinkler’s travel speed to vary the application depth. Changes in speed are commonly practiced over areas that slope, pond or where soil texture is predominantly different. Dynamic presc...

  14. A candidate gene survey of quantitative trait loci affecting chemical composition in tomato fruit

    National Research Council Canada - National Science Library

    L. Bermúdez; U. Urias; D. Milstein; L. Kamenetzky; R. Asis; A. R. Fernie; M. A. Van Sluys; F. Carrari; M. Rossi

    2008-01-01

    In tomato, numerous wild-related species have been demonstrated to be untapped sources of valuable genetic variability, including pathogen-resistance genes, nutritional, and industrial quality traits...

  15. Association between oral variables and heart rate variability.

    Science.gov (United States)

    Santana, Milana Drumond Ramos; de Souza, Ana Cecilia Amorim; de Abreu, Luiz Carlos; Valenti, Vitor E

    2013-12-27

    The heart rate variability is a useful method to assess cardiac autonomic modulation in patients undergoing dental procedures, because knowledge of physiological conditions provides greater security to the professional as well as the possibility of a better plan treatment to patient benefit. The aim of our study was to describe the association between cardiac autonomic control and dental variables. We consulted the databases Medline, SciELO, Lilacs and Cochrane, using the terms "autonomic", "dentistry", "heart rate variability", "cardiovascular physiology." The selected studies indicated a strong relationship between dental variables and HRV. There was an association between malocclusion, TMD, dental procedures cirugia and low HRV. Thus, they become more studies that relate to HRV in dental science, especially in clinical practice.

  16. Variable pixel size ionospheric tomography

    Science.gov (United States)

    Zheng, Dunyong; Zheng, Hongwei; Wang, Yanjun; Nie, Wenfeng; Li, Chaokui; Ao, Minsi; Hu, Wusheng; Zhou, Wei

    2017-06-01

    A novel ionospheric tomography technique based on variable pixel size was developed for the tomographic reconstruction of the ionospheric electron density (IED) distribution. In variable pixel size computerized ionospheric tomography (VPSCIT) model, the IED distribution is parameterized by a decomposition of the lower and upper ionosphere with different pixel sizes. Thus, the lower and upper IED distribution may be very differently determined by the available data. The variable pixel size ionospheric tomography and constant pixel size tomography are similar in most other aspects. There are some differences between two kinds of models with constant and variable pixel size respectively, one is that the segments of GPS signal pay should be assigned to the different kinds of pixel in inversion; the other is smoothness constraint factor need to make the appropriate modified where the pixel change in size. For a real dataset, the variable pixel size method distinguishes different electron density distribution zones better than the constant pixel size method. Furthermore, it can be non-chided that when the effort is spent to identify the regions in a model with best data coverage. The variable pixel size method can not only greatly improve the efficiency of inversion, but also produce IED images with high fidelity which are the same as a used uniform pixel size method. In addition, variable pixel size tomography can reduce the underdetermined problem in an ill-posed inverse problem when the data coverage is irregular or less by adjusting quantitative proportion of pixels with different sizes. In comparison with constant pixel size tomography models, the variable pixel size ionospheric tomography technique achieved relatively good results in a numerical simulation. A careful validation of the reliability and superiority of variable pixel size ionospheric tomography was performed. Finally, according to the results of the statistical analysis and quantitative comparison, the

  17. Systems Biophysics of Gene Expression

    Science.gov (United States)

    Vilar, Jose M.G.; Saiz, Leonor

    2013-01-01

    Gene expression is a process central to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges to the use of traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including precision and flexibility of the transcriptional responses. PMID:23790365

  18. Symmetrization of binary random variables

    OpenAIRE

    Kagan, Abram; Mallows, Colin L.; Shepp, Larry A.; Vanderbei, Robert J.; Vardi, Yehuda

    1999-01-01

    A random variable [math] is called an independent symmetrizer of a given random variable [math] if (a) it is independent of [math] and (b) the distribution of [math] is symmetric about [math] . In cases where the distribution of [math] is symmetric about its mean, it is easy to see that the constant random variable [math] is a minimum-variance independent symmetrizer. Taking [math] to have the same distribution as [math] clearly produces a symmetric sum, but it may not be of minimum variance....

  19. Solar Variability and Planetary Climates

    CERN Document Server

    Calisesi, Y; Gray, L; Langen, J; Lockwood, M

    2007-01-01

    Variations in solar activity, as revealed by variations in the number of sunspots, have been observed since ancient times. To what extent changes in the solar output may affect planetary climates, though, remains today more than ever a subject of controversy. In 2000, the SSSI volume on Solar Variability and Climate reviewed the to-date understanding of the physics of solar variability and of the associated climate response. The present volume on Solar Variability and Planetary Climates provides an overview of recent advances in this field, with particular focus at the Earth's middle and lower atmosphere. The book structure mirrors that of the ISSI workshop held in Bern in June 2005, the collection of invited workshop contributions and of complementary introductory papers synthesizing the current understanding in key research areas such as middle atmospheric processes, stratosphere-troposphere dynamical coupling, tropospheric aerosols chemistry, solar storm influences, solar variability physics, and terrestri...

  20. Mirador - Climate Variability and Change

    Data.gov (United States)

    National Aeronautics and Space Administration — Earth Science data access made simple. NASA's role in climate variability study is centered around providing the global scale observational data sets on oceans and...

  1. External bulb variable volume maser

    Science.gov (United States)

    Reinhardt, V. S.; Cervenka, P. O. (Inventor)

    1978-01-01

    A maser functioning as a frequency standard stable to one part in 10 to the 14th power includes a variable volume, constant surface area storage bulb having a fixed volume portion located in a resonant cavity from which the frequency standard is derived. A variable volume portion of the bulb, exterior to the resonant cavity, has a maximum volume on the same order of magnitude as the fixed volume bulb portion. The cavity has a length to radius ratio of at least 3:1 so that the operation is attained without the need for a feedback loop. A baffle plate, between the fixed and variable volume bulb portions, includes apertures for enabling hydrogen atoms to pass between the two bulb portions and is an electromagnetic shield that prevents coupling of the electromagnetic field of the cavity into the variable volume bulb portion.

  2. Variability of Colletotrichum spp in common bean.

    Science.gov (United States)

    Mota, S F; Barcelos, Q L; Dias, M A; Souza, E A

    2016-04-07

    The Colletotrichum genus presents large genetic variability, as demonstrated by the occurrence of several pathogenic races and phenotypic traits. The objective of this study was to characterize 22 strains of C. lindemuthianum and Colletotrichum spp recovered from anthracnose lesions and bean scab, and to verify the relationship between species of the Colletotrichum genus, which inhabit anthracnose and scab lesions. Colony morphology, conidium size, the presence of septa, germination, sporulation, and mycelium growth rates, were analyzed in addition to the presence of mating-type genes, IRAP markers, and pathogenicity. Strains of Colletotrichum spp presented wide variation for all evaluated traits, indicating the presence of different species. Pathogenicity tests verified that the severity of the disease caused by strains of Colletotrichum spp must be evaluated 17 days after inoculation. Molecular analysis showed that only the C. lindemuthianum strains were grouped by the IRAP markers. For the physiological traits, we observed that C. lindemuthianum mycelium growth is slower than that of Colletotrichum spp strains. The information generated in this study confirms variability in the evaluated species of Colletotrichum and may direct future basic and applied studies aiming to control these diseases in common bean.

  3. Application of Gene Shaving and Mixture Models to Cluster Microarray Gene Expression Data

    Directory of Open Access Journals (Sweden)

    S. Wen

    2007-01-01

    Full Text Available Researchers are frequently faced with the analysis of microarray data of a relatively large number of genes using a small number of tissue samples. We examine the application of two statistical methods for clustering such microarray expression data: EMMIX-GENE and GeneClust. EMMIX-GENE is a mixture-model based clustering approach, designed primarily to cluster tissue samples on the basis of the genes. GeneClust is an implementation of the gene shaving methodology, motivated by research to identify distinct sets of genes for which variation in expression could be related to a biological property of the tissue samples. We illustrate the use of these two methods in the analysis of Affymetrix oligonucleotide arrays of well-known data sets from colon tissue samples with and without tumors, and of tumor tissue samples from patients with leukemia. Although the two approaches have been developed from different perspectives, the results demonstrate a clear correspondence between gene clusters produced by GeneClust and EMMIX-GENE for the colon tissue data. It is demonstrated, for the case of ribosomal proteins and smooth muscle genes in the colon data set, that both methods can classify genes into co-regulated families. It is further demonstrated that tissue types (tumor and normal can be separated on the basis of subtle distributed patterns of genes. Application to the leukemia tissue data produces a division of tissues corresponding closely to the external classification, acute myeloid leukemia (AML and acute lymphoblastic leukaemia (ALL, for both methods. In addition, we also identify genes specifi c for the subgroup of ALL-T cell samples. Overall, we find that the gene shaving method produces gene clusters at great speed; allows variable cluster sizes and can incorporate partial or full supervision; and finds clusters of genes in which the gene expression varies greatly over the tissue samples while maintaining a high level of coherence between the

  4. Computational tools and algorithms for designing customized synthetic genes

    National Research Council Canada - National Science Library

    Gould, Nathan; Hendy, Oliver; Papamichail, Dimitris

    2014-01-01

    ... that is encoded in nucleic and amino acids. To aid this goal, a large number of software tools of variable sophistication have been implemented, enabling the design of synthetic genes for sequence optimization based on rationally defined properties...

  5. The winds of cataclysmic variables

    Energy Technology Data Exchange (ETDEWEB)

    Mauche, C.W. [Lawrence Livermore National Lab., CA (United States). Lab. for Experimental Astrophysics; Raymond, J.C. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States)

    1994-02-16

    The authors present an observational and theoretical review of the winds of cataclysmic variables (CVs). Specifically, they consider the related problems of the geometry and mass-loss rate of the winds of CVs, their ionization state and variability, and the results from studies of eclipsing CVs. Finally, they consider the properties of accretion disk wind models. Some of these models predict substantial angular momentum loss, which could affect both disk structure and binary evolution.

  6. Ordering variable for parton showers

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Zoltán [DESY,Notkestrasse 85, 22607 Hamburg (Germany); Soper, Davison E. [Institute of Theoretical Science, University of Oregon,Eugene, OR 97403-5203 (United States)

    2014-06-30

    The parton splittings in a parton shower are ordered according to an ordering variable, for example the transverse momentum of the daughter partons relative to the direction of the mother, the virtuality of the splitting, or the angle between the daughter partons. We analyze the choice of the ordering variable and conclude that one particular choice has the advantage of factoring softer splittings from harder splittings graph by graph in a physical gauge.

  7. Ordering variable for parton showers

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Zoltan [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Soper, Davison E. [Oregon Univ., Eugene, OR (United States). Inst. of Theoretical Science

    2014-01-15

    The parton splittings in a parton shower are ordered according to an ordering variable, for example the transverse momentum of the daughter partons relative to the direction of the mother, the virtuality of the splitting, or the angle between the daughter partons. We analyze the choice of the ordering variable and conclude that one particular choice has the advantage of factoring softer splittings from harder splittings graph by graph in a physical gauge.

  8. Decomposing global crop yield variability

    Science.gov (United States)

    Ben-Ari, Tamara; Makowski, David

    2014-11-01

    Recent food crises have highlighted the need to better understand the between-year variability of agricultural production. Although increasing future production seems necessary, the globalization of commodity markets suggests that the food system would also benefit from enhanced supplies stability through a reduction in the year-to-year variability. Here, we develop an analytical expression decomposing global crop yield interannual variability into three informative components that quantify how evenly are croplands distributed in the world, the proportion of cultivated areas allocated to regions of above or below average variability and the covariation between yields in distinct world regions. This decomposition is used to identify drivers of interannual yield variations for four major crops (i.e., maize, rice, soybean and wheat) over the period 1961-2012. We show that maize production is fairly spread but marked by one prominent region with high levels of crop yield interannual variability (which encompasses the North American corn belt in the USA, and Canada). In contrast, global rice yields have a small variability because, although spatially concentrated, much of the production is located in regions of below-average variability (i.e., South, Eastern and South Eastern Asia). Because of these contrasted land use allocations, an even cultivated land distribution across regions would reduce global maize yield variance, but increase the variance of global yield rice. Intermediate results are obtained for soybean and wheat for which croplands are mainly located in regions with close-to-average variability. At the scale of large world regions, we find that covariances of regional yields have a negligible contribution to global yield variance. The proposed decomposition could be applied at any spatial and time scales, including the yearly time step. By addressing global crop production stability (or lack thereof) our results contribute to the understanding of a key

  9. Investigation of load reduction for a variable speed, variable pitch, and variable coning wind turbine

    Energy Technology Data Exchange (ETDEWEB)

    Pierce, K. [Univ. of Utah, Salt Lake City, UT (United States)

    1997-12-31

    A two bladed, variable speed and variable pitch wind turbine was modeled using ADAMS{reg_sign} to evaluate load reduction abilities of a variable coning configuration as compared to a teetered rotor, and also to evaluate control methods. The basic dynamic behavior of the variable coning turbine was investigated and compared to the teetered rotor under constant wind conditions as well as turbulent wind conditions. Results indicate the variable coning rotor has larger flap oscillation amplitudes and much lower root flap bending moments than the teetered rotor. Three methods of control were evaluated for turbulent wind simulations. These were a standard IPD control method, a generalized predictive control method, and a bias estimate control method. Each control method was evaluated for both the variable coning configuration and the teetered configuration. The ability of the different control methods to maintain the rotor speed near the desired set point is evaluated from the RMS error of rotor speed. The activity of the control system is evaluated from cycles per second of the blade pitch angle. All three of the methods were found to produce similar results for the variable coning rotor and the teetered rotor, as well as similar results to each other.

  10. Estimating peer effects in longitudinal dyadic data using instrumental variables.

    Science.gov (United States)

    O'Malley, A James; Elwert, Felix; Rosenquist, J Niels; Zaslavsky, Alan M; Christakis, Nicholas A

    2014-09-01

    The identification of causal peer effects (also known as social contagion or induction) from observational data in social networks is challenged by two distinct sources of bias: latent homophily and unobserved confounding. In this paper, we investigate how causal peer effects of traits and behaviors can be identified using genes (or other structurally isomorphic variables) as instrumental variables (IV) in a large set of data generating models with homophily and confounding. We use directed acyclic graphs to represent these models and employ multiple IV strategies and report three main identification results. First, using a single fixed gene (or allele) as an IV will generally fail to identify peer effects if the gene affects past values of the treatment. Second, multiple fixed genes/alleles, or, more promisingly, time-varying gene expression, can identify peer effects if we instrument exclusion violations as well as the focal treatment. Third, we show that IV identification of peer effects remains possible even under multiple complications often regarded as lethal for IV identification of intra-individual effects, such as pleiotropy on observables and unobservables, homophily on past phenotype, past and ongoing homophily on genotype, inter-phenotype peer effects, population stratification, gene expression that is endogenous to past phenotype and past gene expression, and others. We apply our identification results to estimating peer effects of body mass index (BMI) among friends and spouses in the Framingham Heart Study. Results suggest a positive causal peer effect of BMI between friends. © 2014 The Authors. Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  11. Variable Selection via Partial Correlation.

    Science.gov (United States)

    Li, Runze; Liu, Jingyuan; Lou, Lejia

    2017-07-01

    Partial correlation based variable selection method was proposed for normal linear regression models by Bühlmann, Kalisch and Maathuis (2010) as a comparable alternative method to regularization methods for variable selection. This paper addresses two important issues related to partial correlation based variable selection method: (a) whether this method is sensitive to normality assumption, and (b) whether this method is valid when the dimension of predictor increases in an exponential rate of the sample size. To address issue (a), we systematically study this method for elliptical linear regression models. Our finding indicates that the original proposal may lead to inferior performance when the marginal kurtosis of predictor is not close to that of normal distribution. Our simulation results further confirm this finding. To ensure the superior performance of partial correlation based variable selection procedure, we propose a thresholded partial correlation (TPC) approach to select significant variables in linear regression models. We establish the selection consistency of the TPC in the presence of ultrahigh dimensional predictors. Since the TPC procedure includes the original proposal as a special case, our theoretical results address the issue (b) directly. As a by-product, the sure screening property of the first step of TPC was obtained. The numerical examples also illustrate that the TPC is competitively comparable to the commonly-used regularization methods for variable selection.

  12. Bayesian Variable Selection in High Dimensional Survival Time Cancer Genomic Datasets using Nonlocal Priors

    OpenAIRE

    Nikooienejad, Amir; Wang, Wenyi; Johnson, Valen E.

    2017-01-01

    Variable selection in high dimensional cancer genomic studies has become very popular in the past decade, due to the interest in discovering significant genes pertinent to a specific cancer type. Censored survival data is the main data structure in such studies and performing variable selection for such data type requires certain methodology. With recent developments in computational power, Bayesian methods have become more attractive in the context of variable selection. In this article we i...

  13. tRNA genes protect a reporter gene from epigenetic silencing in mouse cells.

    Science.gov (United States)

    Ebersole, Thomas; Kim, Jung-Hyun; Samoshkin, Alexander; Kouprina, Natalay; Pavlicek, Adam; White, Robert J; Larionov, Vladimir

    2011-08-15

    It is a well-established fact that the tRNA genes in yeast can function as chromatin barrier elements. However, so far there is no experimental evidence that tRNA and other Pol III-transcribed genes exhibit barrier activity in mammals. This study utilizes a recently developed reporter gene assay to test a set of Pol III-transcribed genes and gene clusters with variable promoter and intergenic regions for their ability to prevent heterochromatin-mediated reporter gene silencing in mouse cells. The results show that functional copies of mouse tRNA genes are effective barrier elements. The number of tRNA genes as well as their orientation influence barrier function. Furthermore, the DNA sequence composition of intervening and flanking regions affects barrier activity of tRNA genes. Barrier activity was maintained for much longer time when the intervening and flanking regions of tRNA genes were replaced by AT-rich sequences, suggesting a negative role of DNA methylation in the establishment of a functional barrier. Thus, our results suggest that tRNA genes are essential elements in establishment and maintenance of chromatin domain architecture in mammalian cells.

  14. An atlas of gene expression and gene co-regulation in the human retina.

    Science.gov (United States)

    Pinelli, Michele; Carissimo, Annamaria; Cutillo, Luisa; Lai, Ching-Hung; Mutarelli, Margherita; Moretti, Maria Nicoletta; Singh, Marwah Veer; Karali, Marianthi; Carrella, Diego; Pizzo, Mariateresa; Russo, Francesco; Ferrari, Stefano; Ponzin, Diego; Angelini, Claudia; Banfi, Sandro; di Bernardo, Diego

    2016-07-08

    The human retina is a specialized tissue involved in light stimulus transduction. Despite its unique biology, an accurate reference transcriptome is still missing. Here, we performed gene expression analysis (RNA-seq) of 50 retinal samples from non-visually impaired post-mortem donors. We identified novel transcripts with high confidence (Observed Transcriptome (ObsT)) and quantified the expression level of known transcripts (Reference Transcriptome (RefT)). The ObsT included 77 623 transcripts (23 960 genes) covering 137 Mb (35 Mb new transcribed genome). Most of the transcripts (92%) were multi-exonic: 81% with known isoforms, 16% with new isoforms and 3% belonging to new genes. The RefT included 13 792 genes across 94 521 known transcripts. Mitochondrial genes were among the most highly expressed, accounting for about 10% of the reads. Of all the protein-coding genes in Gencode, 65% are expressed in the retina. We exploited inter-individual variability in gene expression to infer a gene co-expression network and to identify genes specifically expressed in photoreceptor cells. We experimentally validated the photoreceptors localization of three genes in human retina that had not been previously reported. RNA-seq data and the gene co-expression network are available online (http://retina.tigem.it). © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Special Issue: Gene Conversion in Duplicated Genes

    Directory of Open Access Journals (Sweden)

    Hideki Innan

    2011-06-01

    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  16. Atmospheric variables as driving variables of agricultural and forest ecosystems

    Directory of Open Access Journals (Sweden)

    Luigi Mariani

    Full Text Available Atmospheric variables, which represent meteorology if seen in their instantaneous behavior or climatology if seen in their long time behavior, can be considered among the main driving variables of agricultural and forest ecosystems. In other words meteo-climatic variables determine productivity and quality and territorial specificity of agroforestry productions. On the base of this premise some significant examples are shown in order to describe how different modeling approaches (empirical and mechanistic can improve our degree of description of phenomena and the rationality of our approach to management of agro-ecosystem. The need of strict linkage among agrometeorology and other physical and biological sciences referred to agro-forestry ecosystems is also discussed.

  17. Crank drive for variable compression ratio; Kurbeltrieb fuer variable Verdichtung

    Energy Technology Data Exchange (ETDEWEB)

    Bollig, C. [FEV Motorentechnik GmbH und Co. KG, Aachen (Germany); Habermann, K.; Marckwardt, H.; Yapici, K.I. [Technische Hochschule Aachen (Germany). Lehrstuhl fuer Angewandte Thermodynamik (LAT)

    1997-11-01

    In a research project at the Institute of Applied Thermodynamics (LAT) of the University of Aachen (RWTH) between April 1995 and October 1996, a variable compression ratio was realised on a specially prepared FEV Single Cylinder Research Engine and investigated in terms of combustion and tribological behaviour. On the basis of an invention by the FEV Motorentechnik, the variable compression ratio was realised with a variable crankdrive. This technology allows a variable compression ratio across a wide range. In combination with High Pressure Supercharging, F.E. concept for S.I. engines results in a fuel saving potential of up to 30%. Equipped with well-known Three-Way-Catalyst (TWC) technology, it is capable of meeting future low emission standards. To achieve a weight-optimised design of the conrod, FEM analyses have been conducted. The primary goal of the test bench investigation was to obtain information about the influence of the unconventional piston movement during combustion as well as about the tribological behaviour of the variable crankdrive. (orig.) [Deutsch] Innerhalb eines Forschungsprojektes am Lehrstuhl fuer Angewandte Thermodynamik der RWTH-Aachen (LAT) wurde im Zeitraum April 1995 bis Oktober 1996 ein variables Verdichtungsverhaeltnis an einem speziell praeparierten FEV-Einzylinder-Ottomotor umgesetzt und brennverfahrenstechnisch wie auch tribologisch im Pruefstandsbetrieb untersucht. Basierend auf einer Erfindung der FEV Motorentechnik wurde das veraenderliche Verdichtungsverhaeltnis mit einem variablen Kurbeltrieb realisiert. Diese Technik ermoeglicht eine Variabilitaet der Verdichtung in einem grossen Bereich. In Verbindung mit Hochaufladung kann so ein ottomotorisches Verbrauchskonzept mit einem Einsparpotential von bis zu 30% dargestellt werden, das unter Beibehaltung der {lambda}=1-Technik zukuenftige Abgasnormen erfuellen kann. Die Eignung des variablen Kurbeltriebs zur Realisierung einer veraenderlichen Verdichtung konnte in der

  18. The cataclysmic variable AE Aquarii: orbital variability in V band

    Science.gov (United States)

    Zamanov, R.; Latev, G.

    2017-07-01

    We present 62.7 hours observations of the cataclysmic variable AE Aqr in Johnson V band. These are non-published archive electro-photometric data obtained during the time period 1993 to 1999. We construct the orbital variability in V band and obtain a Fourier fit to the double-wave quiescent light curve. The strongest flares in our data set are in phase interval 0.6 - 0.8. The data can be downloaded from http://www.astro.bas.bg/~rz/DATA/AEAqr.elphot.dat.

  19. Variable order variable stepsize algorithm for solving nonlinear Duffing oscillator

    Science.gov (United States)

    Fadly Nurullah Rasedee, Ahmad; Ishak, Norizarina; Raihana Hamzah, Siti; Ijam, Hazizah Mohd; Suleiman, Mohamed; Bibi Ibrahim, Zarina; Sathar, Mohammad Hasan Abdul; Ainna Ramli, Nur; Shuhada Kamaruddin, Nur

    2017-09-01

    Nonlinear phenomena in science and engineering such as a periodically forced oscillator with nonlinear elasticity are often modeled by the Duffing oscillator (Duffing equation). The Duffling oscillator is a type of nonlinear higher order differential equation. In this research, a numerical approximation for solving the Duffing oscillator directly is introduced using a variable order stepsize (VOS) algorithm coupled with a backward difference formulation. By selecting the appropriate restrictions, the VOS algorithm provides a cost efficient computational code without affecting its accuracy. Numerical results have demonstrated the advantages of a variable order stepsize algorithm over conventional methods in terms of total steps and accuracy.

  20. Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression

    OpenAIRE

    Casanova, Emily L.; Sharp, Julia L.; Chakraborty, Hrishikesh; Sumi, Nahid Sultana; Casanova, Manuel F.

    2016-01-01

    Background Intellectual disability (ID), autism, and epilepsy share frequent yet variable comorbidities with one another. In order to better understand potential genetic divergence underlying this variable risk, we studied genes responsible for monogenic IDs, grouped according to their autism and epilepsy comorbidities. Methods Utilizing 465 different forms of ID with known molecular origins, we accessed available genetic databases in conjunction with gene ontology (GO) to determine whether t...

  1. a canvas for disease gene exploration

    Indian Academy of Sciences (India)

    2008-04-09

    Apr 9, 2008 ... well as from published literature. Selection of genes and genomic region. This study was aimed at understanding variability in SNPs across diverse individual ..... (b) Representation of system structure-derived membership information on the linguistic map of India. Blue, brown, green and pink backgrounds ...

  2. Polymorphisms in human muscarinic receptor subtype genes

    NARCIS (Netherlands)

    Michel, Martin C.; Teitsma, Christine A.

    2012-01-01

    A wide range of polymorphisms have been reported in muscarinic receptor subtype genes, mostly in M₁ and M₂ and, to a lesser extent, M₃ receptors. Most studies linking such genetic variability to phenotype have been performed for brain functions, but a more limited amount of information is also

  3. All varieties of encoding variability are not created equal: Separating variable processing from variable tasks

    Science.gov (United States)

    Huff, Mark J.; Bodner, Glen E.

    2014-01-01

    Whether encoding variability facilitates memory is shown to depend on whether item-specific and relational processing are both performed across study blocks, and whether study items are weakly versus strongly related. Variable-processing groups studied a word list once using an item-specific task and once using a relational task. Variable-task groups’ two different study tasks recruited the same type of processing each block. Repeated-task groups performed the same study task each block. Recall and recognition were greatest in the variable-processing group, but only with weakly related lists. A variable-processing benefit was also found when task-based processing and list-type processing were complementary (e.g., item-specific processing of a related list) rather than redundant (e.g., relational processing of a related list). That performing both item-specific and relational processing across trials, or within a trial, yields encoding-variability benefits may help reconcile decades of contradictory findings in this area. PMID:25018583

  4. Candidate Gene Identification of Flowering Time Genes in Cotton

    Directory of Open Access Journals (Sweden)

    Corrinne E. Grover

    2015-07-01

    Full Text Available Flowering time control is critically important to all sexually reproducing angiosperms in both natural ecological and agronomic settings. Accordingly, there is much interest in defining the genes involved in the complex flowering-time network and how these respond to natural and artificial selection, the latter often entailing transitions in day-length responses. Here we describe a candidate gene analysis in the cotton genus , which uses homologs from the well-described flowering network to bioinformatically and phylogenetically identify orthologs in the published genome sequence from Ulbr., one of the two model diploid progenitors of the commercially important allopolyploid cottons, L. and L. Presence and patterns of expression were evaluated from 13 aboveground tissues related to flowering for each of the candidate genes using allopolyploid as a model. Furthermore, we use a comparative context to determine copy number variability of each key gene family across 10 published angiosperm genomes. Data suggest a pattern of repeated loss of duplicates following ancient whole-genome doubling events in diverse lineages. The data presented here provide a foundation for understanding both the parallel evolution of day-length neutrality in domesticated cottons and the flowering-time network, in general, in this important crop plant.

  5. Cortical evolution in mammals: the bane and beauty of phenotypic variability.

    Science.gov (United States)

    Krubitzer, Leah A; Seelke, Adele M H

    2012-06-26

    Evolution by natural selection, the unifying theory of all biological sciences, provides a basis for understanding how phenotypic variability is generated at all levels of organization from genes to behavior. However, it is important to distinguish what is the target of selection vs. what is transmitted across generations. Physical traits, behaviors, and the extended phenotype are all selected features of an individual, but genes that covary with different aspects of the targets of selection are inherited. Here we review the variability in cortical organization, morphology, and behavior that have been observed across species and describe similar types of variability within species. We examine sources of variability and the constraints that limit the types of changes that evolution has and can produce. Finally, we underscore the importance of how genes and genetic regulatory networks are deployed and interact within an individual, and their relationship to external, physical forces within the environment that shape the ultimate phenotype.

  6. Sparse estimation for structural variability

    Directory of Open Access Journals (Sweden)

    Singh Rohit

    2011-04-01

    Full Text Available Abstract Background Proteins are dynamic molecules that exhibit a wide range of motions; often these conformational changes are important for protein function. Determining biologically relevant conformational changes, or true variability, efficiently is challenging due to the noise present in structure data. Results In this paper we present a novel approach to elucidate conformational variability in structures solved using X-ray crystallography. We first infer an ensemble to represent the experimental data and then formulate the identification of truly variable members of the ensemble (as opposed to those that vary only due to noise as a sparse estimation problem. Our results indicate that the algorithm is able to accurately distinguish genuine conformational changes from variability due to noise. We validate our predictions for structures in the Protein Data Bank by comparing with NMR experiments, as well as on synthetic data. In addition to improved performance over existing methods, the algorithm is robust to the levels of noise present in real data. In the case of Human Ubiquitin-conjugating enzyme Ubc9, variability identified by the algorithm corresponds to functionally important residues implicated by mutagenesis experiments. Our algorithm is also general enough to be integrated into state-of-the-art software tools for structure-inference.

  7. Continuous-variable supraquantum nonlocality

    Science.gov (United States)

    Ketterer, Andreas; Laversanne-Finot, Adrien; Aolita, Leandro

    2018-01-01

    Supraquantum nonlocality refers to correlations that are more nonlocal than allowed by quantum theory but still physically conceivable in postquantum theories, in the sense of respecting the basic no-faster-than-light communication principle. While supraquantum correlations are relatively well understood for finite-dimensional systems, little is known in the infinite-dimensional case. Here, we study supraquantum nonlocality for bipartite systems with two measurement settings and infinitely many outcomes per subsystem. We develop a formalism for generic no-signaling black-box measurement devices with continuous outputs in terms of probability measures, instead of probability distributions, which involves a few technical subtleties. We show the existence of a class of supraquantum Gaussian correlations, which violate the Tsirelson bound of an adequate continuous-variable Bell inequality. We then introduce the continuous-variable version of the celebrated Popescu-Rohrlich (PR) boxes, as a limiting case of the above-mentioned Gaussian ones. Finally, we characterize the geometry of the set of continuous-variable no-signaling correlations. Namely, we show that that the convex hull of the continuous-variable PR boxes is dense in the no-signaling set. We also show that these boxes are extreme in the set of no-signaling behaviors and provide evidence suggesting that they are indeed the only extreme points of the no-signaling set. Our results lay the grounds for studying generalized-probability theories in continuous-variable systems.

  8. Entropy as a collective variable

    Science.gov (United States)

    Parrinello, Michele

    Sampling complex free energy surfaces that exhibit long lived metastable states separated by kinetic bottlenecks is one of the most pressing issues in the atomistic simulations of matter. Not surprisingly many solutions to this problem have been suggested. Many of them are based on the identification of appropriate collective variables that span the manifold of the slow varying modes of the system. While much effort has been put in devising and even constructing on the fly appropriate collective variables there is still a cogent need of introducing simple, generic, physically transparent, and yet effective collective variables. Motivated by the physical observation that in many case transitions between one metastable state and another result from a trade off between enthalpy and entropy we introduce appropriate collective variables that are able to represent in a simple way these two physical properties. We use these variables in the context of the recently introduced variationally enhanced sampling and apply it them with success to the simulation of crystallization from the liquid and to conformational transitions in protein. Department of Chemistry and Applied Biosciences, ETH Zurich, and Facolta' di Informatica, Istituto di Scienze Computazionali, Universita' della Svizzera Italiana, Via G. Buffi 13, 6900 Lugano, Switzerland.

  9. Statistical variability of hydro-meteorological variables as indicators ...

    African Journals Online (AJOL)

    The aim of this study is to examine the variability patterns of rainfall and actual evapotranspiration during two climatic scenarios as an insight in climatic response to global warming. The comparison between evapotranspiration during the periods (1943-1977) and (1978-2012) at the five studied weather stations revealed a ...

  10. Cardinality-dependent Variability in Orthogonal Variability Models

    DEFF Research Database (Denmark)

    Mærsk-Møller, Hans Martin; Jørgensen, Bo Nørregaard

    2012-01-01

    During our work on developing and running a software product line for eco-sustainable greenhouse-production software tools, which currently have three products members we have identified a need for extending the notation of the Orthogonal Variability Model (OVM) to support what we refer...

  11. Evaluating codon bias perspective in barbiturase gene using ...

    African Journals Online (AJOL)

    GC3 of synonymously variable codons, RSCU, NC and CAI were estimated with statistical softwares. Examination of DNA composition along with codon usage was done to reveal dynamics of gene evolution and expression of this enzyme. Keywords: Codon usage, barbiturase gene, multivariate statistical analysis

  12. Time as a dynamical variable

    Science.gov (United States)

    Thron, Christopher

    2017-01-01

    Since the time of Galileo, the equations of physics have expressed dynamical variables such as particle position or electromagnetic field strength as functions of time. In this paper, we argue that this assumption reflects observational bias, and that there are many good reasons for viewing time also as a dynamical variable. We hypothesize that the spacetime universe is an outcome of a process, rather than a process unfolding in time. This new viewpoint gives rise to a physical interpretation of the wavefunction as a complex vibrational amplitude in a non-spacetime independent variable. It resolves quantum mechanical paradoxes involving wavefunction entanglement, and gives a much simpler solution to the problem of wavefunction collapse than the many-worlds interpretation. The Born rule is also shown to be a natural consequence. We also show that small deviations from conventional quantum probabilities are predicted.

  13. Variable geometry Darrieus wind machine

    Science.gov (United States)

    Pytlinski, J. T.; Serrano, D.

    1983-08-01

    A variable geometry Darrieus wind machine is proposed. The lower attachment of the blades to the rotor can move freely up and down the axle allowing the blades of change shape during rotation. Experimental data for a 17 m. diameter Darrieus rotor and a theoretical model for multiple streamtube performance prediction were used to develop a computer simulation program for studying parameters that affect the machine's performance. This new variable geometry concept is described and interrelated with multiple streamtube theory through aerodynamic parameters. The computer simulation study shows that governor behavior of a Darrieus turbine can not be attained by a standard turbine operating within normally occurring rotational velocity limits. A second generation variable geometry Darrieus wind turbine which uses a telescopic blade is proposed as a potential improvement on the studied concept.

  14. Gene co-expression network analysis identifies porcine genes associated with variation in Salmonella shedding

    OpenAIRE

    Kommadath, Arun; Bao, Hua; Arantes, Adriano S.; Plastow, Graham S; Tuggle, Christopher K.; Bearson, Shawn MD; Luo Guan, Le; Stothard, Paul

    2014-01-01

    Background Salmonella enterica serovar Typhimurium is a gram-negative bacterium that can colonise the gut of humans and several species of food producing farm animals to cause enteric or septicaemic salmonellosis. While many studies have looked into the host genetic response to Salmonella infection, relatively few have used correlation of shedding traits with gene expression patterns to identify genes whose variable expression among different individuals may be associated with differences in ...

  15. Complex variable methods in elasticity

    CERN Document Server

    England, A H

    2003-01-01

    The plane strain and generalized plane stress boundary value problems of linear elasticity are the focus of this graduate-level text, which formulates and solves these problems by employing complex variable theory. The text presents detailed descriptions of the three basic methods that rely on series representation, Cauchy integral representation, and the solution via continuation. Its five-part treatment covers functions of a complex variable, the basic equations of two-dimensional elasticity, plane and half-plane problems, regions with circular boundaries, and regions with curvilinear bounda

  16. A process variability control chart

    OpenAIRE

    Riaz, M.; Does, R.J.M.M.

    2009-01-01

    In this study a Shewhart type control chart namely the Vt chart, is proposed for improvedmonitoring of the process variability of a quality characteristic of interest Y . The proposed control chart is based on the ratio type estimator of the variance using a single auxiliary variable X. It is assumed that (Y, X) follows a bivariate normal distribution. The design structure of the Vt chart is developed for Phase-I quality control and its comparison is made with those of the S2 chart (a well-kn...

  17. Genetic components of litter size variability in sheep

    Directory of Open Access Journals (Sweden)

    Chevalet Claude

    2001-05-01

    Full Text Available Abstract Classical selection for increasing prolificacy in sheep leads to a concomitant increase in its variability, even though the objective of the breeder is to maximise the frequency of an intermediate litter size rather than the frequency of high litter sizes. For instance, in the Lacaune sheep breed raised in semi-intensive conditions, ewes lambing twins represent the economic optimum. Data for this breed, obtained from the national recording scheme, were analysed. Variance components were estimated in an infinitesimal model involving genes controlling the mean level as well as its environmental variability. Large heritability was found for the mean prolificacy, but a high potential for increasing the percentage of twins at lambing while reducing the environmental variability of prolificacy is also suspected. Quantification of the response to such a canalising selection was achieved.

  18. Mouse histocompatibility-related genes are not conserved in other mammals.

    OpenAIRE

    Rogers, J.H.

    1985-01-01

    In addition to the genes for classical H-2 antigens, the H-2 complex of the mouse contains numerous homologous genes belonging to several distinct families. It is not known whether they have any functions. To address this question, I have investigated whether these genes are separately conserved in evolution. Subcloned 5' gene segments, encoding the variable domains, were used as hybridisation probes on genomic DNA blots of various mammals. Only the largest gene family, which includes the cla...

  19. QB1 - Stochastic Gene Regulation

    Energy Technology Data Exchange (ETDEWEB)

    Munsky, Brian [Los Alamos National Laboratory

    2012-07-23

    Summaries of this presentation are: (1) Stochastic fluctuations or 'noise' is present in the cell - Random motion and competition between reactants, Low copy, quantization of reactants, Upstream processes; (2) Fluctuations may be very important - Cell-to-cell variability, Cell fate decisions (switches), Signal amplification or damping, stochastic resonances; and (3) Some tools are available to mode these - Kinetic Monte Carlo simulations (SSA and variants), Moment approximation methods, Finite State Projection. We will see how modeling these reactions can tell us more about the underlying processes of gene regulation.

  20. Reference Gene Selection for Quantitative PCR Studies in Sheep Neutrophils

    Directory of Open Access Journals (Sweden)

    Jean A. Hall

    2013-05-01

    Full Text Available Reference genes are essential for studying mRNA expression with quantitative PCR (qPCR. We investigated 11 potential neutrophil reference genes (RPL19, GAPDH, ACTB, B2M, HPRT, G6PD, TFRC, PGK1, YWHAZ, SDHA and GYPC for sheep under disease conditions of foot rot (FR and with or without Se supplementation. Initial screening was based on gene expression level (<28 Cq cycles and variability (SD < 1.5 Cq cycles and excluded TFRC, GYPC and HPRT from further analysis. Expression stability of the remaining genes was evaluated using four software programs: geNorm, NormFinder, BestKeeper and the comparative delta Cq method. The neutrophil reference genes, G6PD, YWHAZ, GAPDH, RPL19 and SDHA, consistently ranked among the top five most stable genes under these experimental conditions. The SDHA gene expression was not stable in FR-diseased sheep receiving Se treatment and, thus, cannot be recommended as a reference gene. The commonly used genes, PGK1, ACTB and B2M, were not reliable reference genes, underscoring the need to validate neutrophil reference genes under different experimental conditions. Multiple references genes rather than a single gene may provide more robust and reliable results. The best pair of reference genes was SDHA/G6PD in healthy sheep and GADPH/YWHAZ in FR-diseased sheep.

  1. Noise minimization in eukaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

    2004-01-15

    All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

  2. Complex Variables throughout the Curriculum

    Science.gov (United States)

    D'Angelo, John P.

    2017-01-01

    We offer many specific detailed examples, several of which are new, that instructors can use (in lecture or as student projects) to revitalize the role of complex variables throughout the curriculum. We conclude with three primary recommendations: revise the syllabus of Calculus II to allow early introductions of complex numbers and linear…

  3. On colorings of variable words

    OpenAIRE

    Tyros, Konstantinos

    2014-01-01

    In this note, we prove that the base case of the Graham--Rothschild Theorem, i.e., the one that considers colorings of the ($1$-dimensional) variable words, admits bounds in the class $\\mathcal{E}^5$ of Grzegorczyk's hierarchy.

  4. UXOR Hunting among Algol Variables

    Science.gov (United States)

    Poxon, M.

    2015-06-01

    The class of variable typified by UX Orionis (UXORs or UXors) are young stars characterised by aperiodic or semiperiodic fades from maximum. This has led to several of the class being formerly catalogued as Algol-type eclipsing binaries (EAs), which can show superficially similar light variations. With this in view, I propose a campaign to search for more UX Ori type stars.

  5. Cataclysmic Variables in the Backyard

    Science.gov (United States)

    Patterson, J.

    2012-06-01

    (Abstract only) The last decade has seen plummeting prices and significant advances in CCD-camera and smart-telescope technology, reaching all the way to the humblest of telescopes. There are now thousands of well-equipped amateur astronomers interested in using their telescopes for research, and many hundreds already doing so in coordinated campaigns. Variable star science has benefited tremendously. Since it's always dark and always clear somewhere, coordinated photometry can accumulate nearly 24-hour coverage - and since the observers own their telescopes, very long campaigns are feasible, with little worry about weather. I'll describe one network of observers, the Center for Backyard Astrophysics (CBA). The telescope apertures are 20-50 cm, enabling good signal-to-noise and time resolution down to V=18. We organize campaigns of time-series photometry of cataclysmic variables (novae, dwarf novae, magnetic variables, some X-ray binaries) - and routinely achieve thousand-hour campaigns with no significant aliasing, since the telescopes are distributed around the world. This enables sensitive searches for periodic signals, extending even to long time scales (months). We now produce most of the world's supply of accretion-disk precession periods, and keep close watch on all the other clocks in cataclysmic variables (orbit, white-dwarf rotation and pulsation, and quasiperiodic oscillations).

  6. Operating Reserves and Variable Generation

    Energy Technology Data Exchange (ETDEWEB)

    Ela, E.; Milligan, M.; Kirby, B.

    2011-08-01

    This report tries to first generalize the requirements of the power system as it relates to the needs of operating reserves. It also includes a survey of operating reserves and how they are managed internationally in system operations today and then how new studies and research are proposing they may be managed in the future with higher penetrations of variable generation.

  7. Marginality and Variability in Esperanto.

    Science.gov (United States)

    Brent, Edmund

    This paper discusses Esperanto as a planned language and refutes three myths connected to it, namely, that Esperanto is achronical, atopical, and apragmatic. The focus here is on a synchronic analysis. Synchronic variability is studied with reference to the structuralist determination of "marginality" and the dynamic linguistic…

  8. Several topics in complex variables

    NARCIS (Netherlands)

    Smit, I.M.

    2015-01-01

    This thesis is based on three articles in the field of Several Complex Variables. The first article, which is joint work with M. El Kadiri, defines and studies the concept of maximality for plurifinely plurisubharmonic functions. Its main result is that a finite plurifinely plurisubharmonic function

  9. Variable rules meet Impoverishment theory

    DEFF Research Database (Denmark)

    Parrott, Jeffrey K.; Nevins, Andrew

    2010-01-01

    This paper revives the sociolinguistic notion of ‘variable rules’ (Labov 1969, Cedergren and Sankoff 1974, Guy 1991) as a specific and restricted mechanism within the theoretical framework of Distributed Morphology (Halle and Marantz 1993, Embick and Noyer 2007). We propose that intra-individual ...

  10. Compact plasmonic variable optical attenuator

    DEFF Research Database (Denmark)

    Leosson, Kristjan; Rosenzveig, Tiberiu; Hermannsson, Pétur Gordon

    2008-01-01

    We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators operating in the 1525-1625 nm wavelength range. The devices have a footprint as low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and full modulation bandwidth of 1 kHz. The polarization...

  11. Extraction Methods, Variability Encountered in

    NARCIS (Netherlands)

    Bodelier, P.L.E.; Nelson, K.E.

    2014-01-01

    Synonyms Bias in DNA extractions methods; Variation in DNA extraction methods Definition The variability in extraction methods is defined as differences in quality and quantity of DNA observed using various extraction protocols, leading to differences in outcome of microbial community composition

  12. Lectures on several complex variables

    CERN Document Server

    Gauthier, Paul M

    2014-01-01

    This monograph provides a concise, accessible snapshot of key topics in several complex variables, including the Cauchy Integral Formula, sequences of holomorphic functions, plurisubharmonic functions, the Dirichlet problem, and meromorphic functions.  Based on a course given at Université de Montréal, this brief introduction covers areas of contemporary importance that are not mentioned in most treatments of the subject, such as modular forms, which are essential for Wiles' theorem and the unification of quantum theory and general relativity.   Also covered is the Riemann manifold of a function, which generalizes the Riemann surface of a function of a single complex variable and is a topic that is well-known in one complex variable, but rarely treated in several variables.  Many details, which are intentionally left out, as well as many theorems are stated as problems, providing students with carefully structured instructive exercises.   Prerequisites for use of this book are functions of one complex ...

  13. A Nonlinear Model for Gene-Based Gene-Environment Interaction

    Directory of Open Access Journals (Sweden)

    Jian Sa

    2016-06-01

    Full Text Available A vast amount of literature has confirmed the role of gene-environment (G×E interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction.

  14. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...

  15. Variability of brain anatomy for three common mouse strains.

    Science.gov (United States)

    Scholz, Jan; LaLiberté, Christine; van Eede, Matthijs; Lerch, Jason P; Henkelman, Mark

    2016-11-15

    The way in which brain structures express different morphologies is not fully understood. Here we investigate variability in brain anatomy using ex vivo MRI of three common laboratory mouse strains: in two inbred strains (C57BL/6 and 129S6) and one outbred strain (CD-1). We use Generalised Procrustes Analysis (GPA) to estimate modes of anatomical variability. We find three distinct bilateral modes of anatomical surface variability associated with the motor cortex, the anterior somatosensory, the retrosplenial and the entorhinal cortex. The modes of variability that are associated with the motor cortex and anterior somatosensory cortex are predominantly due to genetic, i.e. strain differences. Next, we specifically test if a particular strain is more variable. We find that only the mode associated with motor cortex size has a slightly larger variance in the outbred CD-1 mice compared to the two inbred strains. This suggests that the hypothesis that outbred strains are more variable in general is not true for brain anatomy and the use of outbred CD-1 mice does probably not come at the price of increased variability. Further, we show that the first two principal components distinguish between the three strains with 91% accuracy. This indicates that neuroanatomical strain differences are captured by considerably fewer dimensions than necessary for atlas-based or voxel-wise testing. Statistical comparisons based on shape models could thus be a powerful complement to traditional atlas and voxel-based methods at detecting gene-related brain differences in mice. Finally, we find that the principal components of individual brain structures are correlated, suggesting a tightly coupled network of interdependent developmental trajectories. These results raise the question to what degree neuroanatomical variability is directly genetically determined or the result of experience and epigenetic mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Statistical significance of variables driving systematic variation in high-dimensional data

    Science.gov (United States)

    Chung, Neo Christopher; Storey, John D.

    2015-01-01

    Motivation: There are a number of well-established methods such as principal component analysis (PCA) for automatically capturing systematic variation due to latent variables in large-scale genomic data. PCA and related methods may directly provide a quantitative characterization of a complex biological variable that is otherwise difficult to precisely define or model. An unsolved problem in this context is how to systematically identify the genomic variables that are drivers of systematic variation captured by PCA. Principal components (PCs) (and other estimates of systematic variation) are directly constructed from the genomic variables themselves, making measures of statistical significance artificially inflated when using conventional methods due to over-fitting. Results: We introduce a new approach called the jackstraw that allows one to accurately identify genomic variables that are statistically significantly associated with any subset or linear combination of PCs. The proposed method can greatly simplify complex significance testing problems encountered in genomics and can be used to identify the genomic variables significantly associated with latent variables. Using simulation, we demonstrate that our method attains accurate measures of statistical significance over a range of relevant scenarios. We consider yeast cell-cycle gene expression data, and show that the proposed method can be used to straightforwardly identify genes that are cell-cycle regulated with an accurate measure of statistical significance. We also analyze gene expression data from post-trauma patients, allowing the gene expression data to provide a molecularly driven phenotype. Using our method, we find a greater enrichment for inflammatory-related gene sets compared to the original analysis that uses a clinically defined, although likely imprecise, phenotype. The proposed method provides a useful bridge between large-scale quantifications of systematic variation and gene

  17. Selection of reliable reference genes for gene expression studies in peach using real-time PCR

    Directory of Open Access Journals (Sweden)

    Zhou Jun

    2009-07-01

    Full Text Available Abstract Background RT-qPCR is a preferred method for rapid and reliable quantification of gene expression studies. Appropriate application of RT-qPCR in such studies requires the use of reference gene(s as an internal control to normalize mRNA levels between different samples for an exact comparison of gene expression level. However, recent studies have shown that no single reference gene is universal for all experiments. Thus, the identification of high quality reference gene(s is of paramount importance for the interpretation of data generated by RT-qPCR. Only a few studies on reference genes have been done in plants and none in peach (Prunus persica L. Batsch. Therefore, the present study was conducted to identify suitable reference gene(s for normalization of gene expression in peach. Results In this work, eleven reference genes were investigated in different peach samples using RT-qPCR with SYBR green. These genes are: actin 2/7 (ACT, cyclophilin (CYP2, RNA polymerase II (RP II, phospholipase A2 (PLA2, ribosomal protein L13 (RPL13, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, 18S ribosomal RNA (18S rRNA, tubblin beta (TUB, tubblin alpha (TUA, translation elongation factor 2 (TEF2 and ubiquitin 10 (UBQ10. All eleven reference genes displayed a wide range of Cq values in all samples, indicating that they expressed variably. The stability of these genes except for RPL13 was determined by three different descriptive statistics, geNorm, NormFinder and BestKeeper, which produced highly comparable results. Conclusion Our study demonstrates that expression stability varied greatly between genes studied in peach. Based on the results from geNorm, NormFinder and BestKeeper analyses, for all the sample pools analyzed, TEF2, UBQ10 and RP II were found to be the most suitable reference genes with a very high statistical reliability, and TEF2 and RP II for the other sample series, while 18S rRNA, RPL13 and PLA2 were unsuitable as internal controls

  18. Sylvatic plague reduces genetic variability in black-tailed prairie dogs.

    Science.gov (United States)

    Trudeau, Kristie M; Britten, Hugh B; Restani, Marco

    2004-04-01

    Small, isolated populations are vulnerable to loss of genetic diversity through in-breeding and genetic drift. Sylvatic plague due to infection by the bacterium Yersinia pestis caused an epizootic in the early 1990s resullting in declines and extirpations of many black-tailed prairie dog (Cynomys ludovicianus) colonies in north-central Montana, USA. Plague-induced population bottlenecks may contribute to significant reductions in genetic variability. In contrast, gene flow maintains genetic variability within colonies. We investigated the impacts of the plague epizootic and distance to nearest colony on levels of genetic variability in six prairie dog colonies sampled between June 1999 and July 2001 using 24 variable randomly amplified polymorphic DNA (RAPD) markers. Number of effective alleles per locus (n(e)) and gene diversity (h) were significantly decreased in the three colonies affected by plague that were recovering from the resulting bottlenecks compared with the three colonies that did not experience plague. Genetic variability was not significantly affected by geographic distance between colonies. The majority of variance in gene fieqnencies was found within prairie clog colonies. Conservation of genetic variability in black-tailed prairie dogs will require the preservation of both large and small colony complexes and the gene flow amonog them.

  19. Soil variability in engineering applications

    Science.gov (United States)

    Vessia, Giovanna

    2014-05-01

    Natural geomaterials, as soils and rocks, show spatial variability and heterogeneity of physical and mechanical properties. They can be measured by in field and laboratory testing. The heterogeneity concerns different values of litho-technical parameters pertaining similar lithological units placed close to each other. On the contrary, the variability is inherent to the formation and evolution processes experienced by each geological units (homogeneous geomaterials on average) and captured as a spatial structure of fluctuation of physical property values about their mean trend, e.g. the unit weight, the hydraulic permeability, the friction angle, the cohesion, among others. The preceding spatial variations shall be managed by engineering models to accomplish reliable designing of structures and infrastructures. Materon (1962) introduced the Geostatistics as the most comprehensive tool to manage spatial correlation of parameter measures used in a wide range of earth science applications. In the field of the engineering geology, Vanmarcke (1977) developed the first pioneering attempts to describe and manage the inherent variability in geomaterials although Terzaghi (1943) already highlighted that spatial fluctuations of physical and mechanical parameters used in geotechnical designing cannot be neglected. A few years later, Mandelbrot (1983) and Turcotte (1986) interpreted the internal arrangement of geomaterial according to Fractal Theory. In the same years, Vanmarcke (1983) proposed the Random Field Theory providing mathematical tools to deal with inherent variability of each geological units or stratigraphic succession that can be resembled as one material. In this approach, measurement fluctuations of physical parameters are interpreted through the spatial variability structure consisting in the correlation function and the scale of fluctuation. Fenton and Griffiths (1992) combined random field simulation with the finite element method to produce the Random

  20. NASA's atmospheric variability experiments /AVE/

    Science.gov (United States)

    Hill, K.; Turner, R. E.

    1977-01-01

    A series of seven mesoscale experiments were conducted under the NASA program, Atmospheric Variability Experiments (AVE). Rawinsonde, satellite, aircraft, and ground observations were recorded during specially selected meteorological periods lasting from 1 to 3 days. Details are presented for each AVE relative to observation times, experiment size and location, and significant weather. Some research results based on the use of these AVE data are referenced. These include contributions to regional numerical prediction; relations between wind shears, instability, and thunderstorm motion and development; relations between moisture and temperature and the probability of convection; retrieval of tropospheric temperature profiles from cloud-contaminated satellite data; variation of convection intensity as a result of atmospheric variability; and effects of cloud rotation on their trajectories.

  1. Continuous-Variable Entanglement Swapping

    Directory of Open Access Journals (Sweden)

    Kevin Marshall

    2015-05-01

    Full Text Available We present a very brief overview of entanglement swapping as it relates to continuous-variable quantum information. The technical background required is discussed and the natural link to quantum teleportation is established before discussing the nature of Gaussian entanglement swapping. The limitations of Gaussian swapping are introduced, along with the general applications of swapping in the context of to quantum communication and entanglement distribution. In light of this, we briefly summarize a collection of entanglement swapping schemes which incorporate a non-Gaussian ingredient and the benefits of such schemes are noted. Finally, we motivate the need to further study and develop such schemes by highlighting requirements of a continuous-variable repeater.

  2. Variable immune molecules in invertebrates.

    Science.gov (United States)

    Cerenius, Lage; Söderhäll, Kenneth

    2013-12-01

    Recently it has become evident that invertebrates may mount a highly variable immune response that is dependent on which pathogen is involved. The molecular mechanisms behind this diversity are beginning to be unravelled and in several invertebrate taxa immune proteins exhibiting a broad range of diversity have been found. In some cases, evidence has been gathered suggesting that this molecular diversity translates into the ability of an affected invertebrate to mount a defence that is specifically aimed at a particular pathogen.

  3. Reproducing Kernels and Variable Bandwidth

    Directory of Open Access Journals (Sweden)

    R. Aceska

    2012-01-01

    Full Text Available We show that a modulation space of type ( is a reproducing kernel Hilbert space (RKHS. In particular, we explore the special cases of variable bandwidth spaces Aceska and Feichtinger (2011 with a suitably chosen weight to provide strong enough decay in the frequency direction. The reproducing kernel property is valid even if ( does not coincide with any of the classical Sobolev spaces because unbounded bandwidth (globally is allowed. The reproducing kernel will be described explicitly.

  4. AEROSOL VARIABILITY OBSERVED WITH RPAS

    Directory of Open Access Journals (Sweden)

    B. Altstädter

    2013-08-01

    Full Text Available To observe the origin, vertical and horizontal distribution and variability of aerosol particles, and especially ultrafine particles recently formed, we plan to employ the remotely piloted aircraft system (RPAS Carolo-P360 "ALADINA" of TU Braunschweig. The goal of the presented project is to investigate the vertical and horizontal distribution, transport and small-scale variability of aerosol particles in the atmospheric boundary layer using RPAS. Two additional RPAS of type MASC of Tübingen University equipped with turbulence instrumentation add the opportunity to study the interaction of the aerosol concentration with turbulent transport and exchange processes of the surface and the atmosphere. The combination of different flight patterns of the three RPAS allows new insights in atmospheric boundary layer processes. Currently, the different aerosol sensors are miniaturized at the Leibniz Institute for Tropospheric Research, Leipzig and together with the TU Braunschweig adapted to fit into the RPAS. Moreover, an additional meteorological payload for measuring temperature, humidity and turbulence properties is constructed by Tübingen University. Two condensation particle counters determine the total aerosol number with a different lower detection threshold in order to investigate the horizontal and vertical aerosol variability and new particle formation (aerosol particles of some nm diameter. Further the aerosol size distribution in the range from about 0.300 to ~5 μm is given by an optical particle counter.

  5. Simulating solar power plant variability :

    Energy Technology Data Exchange (ETDEWEB)

    Lave, Matthew Samuel; Ellis, Abraham; Stein, Joshua.

    2013-06-01

    It is important to be able to accurately simulate the variability of solar PV power plants for grid integration studies. We aim to inform integration studies of the ease of implementation and application-specific accuracy of current PV power plant output simulation methods. This report reviews methods for producing simulated high-resolution (sub-hour or even sub-minute) PV power plant output profiles for variability studies and describes their implementation. Two steps are involved in the simulations: estimation of average irradiance over the footprint of a PV plant and conversion of average irradiance to plant power output. Six models are described for simulating plant-average irradiance based on inputs of ground-measured irradiance, satellite-derived irradiance, or proxy plant measurements. The steps for converting plant-average irradiance to plant power output are detailed to understand the contributions to plant variability. A forthcoming report will quantify the accuracy of each method using application-specific validation metrics.

  6. Aerosol Variability Observed with Rpas

    Science.gov (United States)

    Altstädter, B.; Lampert, A.; Scholtz, A.; Bange, J.; Platis, A.; Hermann, M.; Wehner, B.

    2013-08-01

    To observe the origin, vertical and horizontal distribution and variability of aerosol particles, and especially ultrafine particles recently formed, we plan to employ the remotely piloted aircraft system (RPAS) Carolo-P360 "ALADINA" of TU Braunschweig. The goal of the presented project is to investigate the vertical and horizontal distribution, transport and small-scale variability of aerosol particles in the atmospheric boundary layer using RPAS. Two additional RPAS of type MASC of Tübingen University equipped with turbulence instrumentation add the opportunity to study the interaction of the aerosol concentration with turbulent transport and exchange processes of the surface and the atmosphere. The combination of different flight patterns of the three RPAS allows new insights in atmospheric boundary layer processes. Currently, the different aerosol sensors are miniaturized at the Leibniz Institute for Tropospheric Research, Leipzig and together with the TU Braunschweig adapted to fit into the RPAS. Moreover, an additional meteorological payload for measuring temperature, humidity and turbulence properties is constructed by Tübingen University. Two condensation particle counters determine the total aerosol number with a different lower detection threshold in order to investigate the horizontal and vertical aerosol variability and new particle formation (aerosol particles of some nm diameter). Further the aerosol size distribution in the range from about 0.300 to ~5 μm is given by an optical particle counter.

  7. Evolution of stress-regulated gene expression in duplicate genes of Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Cheng Zou

    2009-07-01

    Full Text Available Due to the selection pressure imposed by highly variable environmental conditions, stress sensing and regulatory response mechanisms in plants are expected to evolve rapidly. One potential source of innovation in plant stress response mechanisms is gene duplication. In this study, we examined the evolution of stress-regulated gene expression among duplicated genes in the model plant Arabidopsis thaliana. Key to this analysis was reconstructing the putative ancestral stress regulation pattern. By comparing the expression patterns of duplicated genes with the patterns of their ancestors, duplicated genes likely lost and gained stress responses at a rapid rate initially, but the rate is close to zero when the synonymous substitution rate (a proxy for time is > approximately 0.8. When considering duplicated gene pairs, we found that partitioning of putative ancestral stress responses occurred more frequently compared to cases of parallel retention and loss. Furthermore, the pattern of stress response partitioning was extremely asymmetric. An analysis of putative cis-acting DNA regulatory elements in the promoters of the duplicated stress-regulated genes indicated that the asymmetric partitioning of ancestral stress responses are likely due, at least in part, to differential loss of DNA regulatory elements; the duplicated genes losing most of their stress responses were those that had lost more of the putative cis-acting elements. Finally, duplicate genes that lost most or all of the ancestral responses are more likely to have gained responses to other stresses. Therefore, the retention of duplicates that inherit few or no functions seems to be coupled to neofunctionalization. Taken together, our findings provide new insight into the patterns of evolutionary changes in gene stress responses after duplication and lay the foundation for testing the adaptive significance of stress regulatory changes under highly variable biotic and abiotic environments.

  8. Evolution of V genes from the TRV loci of mammals.

    Science.gov (United States)

    Olivieri, David N; Gambón-Cerdá, Santiago; Gambón-Deza, Francisco

    2015-07-01

    Information concerning the evolution of T lymphocyte receptors (TCR) can be deciphered from that part of the molecule that recognizes antigen presented by major histocompatibility complex (MHC), namely the variable (V) regions. The genes that code for these variable regions are found within the TCR loci. Here, we describe a study of the evolutionary origin of V genes that code for the α and β chains of the TCR loci of mammals. In particular, we demonstrate that most of the 35 TRAV and 25 TRBV conserved genes found in Primates are also found in other Eutheria, while in Marsupials, Monotremes, and Reptiles, these genes diversified in a different manner. We also show that in mammals, all TRAV genes are derived from five ancestral genes, while all TRBV genes originate from four such genes. In Reptiles, the five TRAV and three out of the four TRBV ancestral genes exist, as well as other V genes not found in mammals. We also studied the TRGV and TRDV loci from all mammals, and we show a relationship of the TRDV to the TRAV locus throughout evolutionary time.

  9. The rules of gene expression in plants: organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana.

    Science.gov (United States)

    Aceituno, Felipe F; Moseyko, Nick; Rhee, Seung Y; Gutiérrez, Rodrigo A

    2008-09-23

    Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8) with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant capable of restraining the capacity of a gene to respond to

  10. The rules of gene expression in plants: Organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Gutiérrez Rodrigo A

    2008-09-01

    Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant

  11. Positive selection in the leucine-rich repeat domain of Gro1 genes in ...

    Indian Academy of Sciences (India)

    In potato, the gene Gro1-4 confers resistance to Globodera rostochiensis. The investigation of variablity in different copies of this gene represents a good model for the verification of positive selection mechanisms. Two datasets of Gro1 LRR sequences were constructed, one derived from the Gro1-4 gene, belonging to ...

  12. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  13. Components of genetic variability of ear length of silage maize

    Directory of Open Access Journals (Sweden)

    Sečanski Mile

    2006-01-01

    Full Text Available The objective of this study was to evaluate following parameters of the ear length of silage maize: variability of inbred lines and their diallel hybrids, superior-parent heterosis and genetic components of variability and habitability on the basis of a diallel set. The analysis of genetic variance shows that the additive component (D was lower than the dominant (H1 and H2 genetic variances, while the frequency of dominant genes (u for this trait was greater than the frequency of recessive genes (v Furthermore, this is also confirmed by the dominant to recessive genes ratio in parental inbreeds for the ear length (Kd/Kr> 1, which is greater than unity during both investigation years. The calculated value of the average degree of dominance √H1/D is greater than unity, pointing out to superdominance in inheritance of this trait in both years of investigation, which is also confirmed by the results of Vr/Wr regression analysis of inheritance of the ear length. As a presence of the non-allelic interaction was established it is necessary to study effects of epitasis as it can have a greater significance in certain hybrids. A greater value of dominant than additive variance resulted in high broad-sense habitability for ear length in both investigation years.

  14. Andoyer construction for Hill and Delaunay variables

    Science.gov (United States)

    Laskar, Jacques

    2017-08-01

    Andoyer variables are well known for the study of rotational dynamics. These variables were derived by Andoyer through a procedure that can be also used to obtain the Hill variables of the Kepler problem. Andoyer construction can also forecast the Delaunay variables which canonicity is then obtained without the use of a generating function.

  15. Andoyer construction for Hill and Delaunay variables

    OpenAIRE

    Laskar, Jacques

    2014-01-01

    Andoyer variables are well known for the study of rotational dynamics. These variables were derived by Andoyer through a procedure that can be also used to obtain the Hill variables of the Kepler problem. Andoyer construction can also forecast the Delaunay variables which canonicity is then obtained without the use of a generating function.

  16. An evaluation of FIA's stand age variable

    Science.gov (United States)

    John D. Shaw

    2015-01-01

    The Forest Inventory and Analysis Database (FIADB) includes a large number of measured and computed variables. The definitions of measured variables are usually well-documented in FIA field and database manuals. Some computed variables, such as live basal area of the condition, are equally straightforward. Other computed variables, such as individual tree volume,...

  17. Genomic environment of variant surface antigen genes of Trypanosoma equiperdum.

    Science.gov (United States)

    Raibaud, A; Gaillard, C; Longacre, S; Hibner, U; Buck, G; Bernardi, G; Eisen, H

    1983-01-01

    Expression of variant antigen genes in Trypanosoma equiperdum is accompanied by the duplication of a silent basic copy gene and the transposition of the copy to an expression site elsewhere in the genome. We have analyzed the genomic locations of both the basic and expression-linked copies of the T. equiperdum gene for variable surface glycoprotein VSG-1. Both copies are situated proximal to termini in both extracted DNA and in chromatin. The regions between the VSG-1 genes and the termini have a very high buoyant density in CsCl and contain an unidentified nucleoside that replaces deoxycytidine. Images PMID:6308614

  18. Genomic environment of variant surface antigen genes of Trypanosoma equiperdum.

    OpenAIRE

    Raibaud, A; Gaillard, C; Longacre, S; Hibner, U; Buck, G; Bernardi, G; Eisen, H

    1983-01-01

    Expression of variant antigen genes in Trypanosoma equiperdum is accompanied by the duplication of a silent basic copy gene and the transposition of the copy to an expression site elsewhere in the genome. We have analyzed the genomic locations of both the basic and expression-linked copies of the T. equiperdum gene for variable surface glycoprotein VSG-1. Both copies are situated proximal to termini in both extracted DNA and in chromatin. The regions between the VSG-1 genes and the termini ha...

  19. Motor Integrated Variable Speed Drives

    OpenAIRE

    Singh, Yash Veer

    2015-01-01

    A new trend in the variable speed drives (VSDs) is to develop fully integrated systems, which lead to low-cost products with shorter design cycles. Motor Integrated design of VSDs will reduce cable length to connect drive with machine windings and installation time for end user. The electric drives are expected to have minimum effect on grid and motor connected to it, i.e. currents drawn from grid should be within specified limits and currents injecting in to machine should not overheat the m...

  20. Gibbs Variable Selection using BUGS

    Directory of Open Access Journals (Sweden)

    Ioannis Ntzoufras

    2002-09-01

    Full Text Available In this paper we discuss and present in detail the implementation of Gibbs variable selection as defined by Dellaportas et al. (2000, 2002 using the BUGS software (Spiegelhalter et al. , 1996a,b,c. The specification of the likelihood, prior and pseudo-prior distributions of the parameters as well as the prior term and model probabilities are described in detail. Guidance is also provided for the calculation of the posterior probabilities within BUGS environment when the number of models is limited. We illustrate the application of this methodology in a variety of problems including linear regression, log-linear and binomial response models.

  1. SYSTEMATICALLY MISCLASSIFIED BINARY DEPENDENT VARIABLES.

    Science.gov (United States)

    Tennekoon, Vidhura; Rosenman, Robert

    When a binary dependent variable is misclassified, that is, recorded in the category other than where it really belongs, probit and logit estimates are biased and inconsistent. In some cases the probability of misclassification may vary systematically with covariates, and thus be endogenous. In this paper we develop an estimation approach that corrects for endogenous misclassification, validate our approach using a simulation study, and apply it to the analysis of a treatment program designed to improve family dynamics. Our results show that endogenous misclassification could lead to potentially incorrect conclusions unless corrected using an appropriate technique.

  2. Variable Density Turbulence Tunnel Facility

    OpenAIRE

    Bodenschatz, Eberhard; Bewley, Gregory P.; Nobach, Holger; Sinhuber, Michael; Xu, Haitao

    2014-01-01

    The Variable Density Turbulence Tunnel (VDTT) at the Max Planck Institute for Dynamics and Self-Organization in G\\"ottingen, Germany produces very high turbulence levels at moderate flow velocities, low power consumption and adjustable kinematic viscosity between $10^{-4} m^2/s$ and $10^{-7} m^2/s$. The Reynolds number can be varied by changing the pressure or flow rate of the gas or by using different non-flammable gases including air. The highest kinematic viscosities, and hence lowest Reyn...

  3. Lateralidad y variables de personalidad

    OpenAIRE

    Claudia Brusasca; Mabel Labiano; José Portellano-Pérez

    2011-01-01

    El objetivo del presente trabajo fue realizar una medición de lateralidad en una muestra de individuos de la región de Cuyo, Argentina, analizando las asociaciones entre lateralidad (diestros-zurdos) y variables de personalidad (control-neuroticismo; introversión-extroversión). Se conformó una muestra no aleatoria de 197 individuos (100 sujetos de sexo femenino y 97 de sexo masculino), con un rango de edad entre 18 y 55 años (M= 28,14; DE= 9,77). Se aplicaron los siguientes instrumentos: ...

  4. Continuously-Variable Vernier Scale

    Science.gov (United States)

    Miller, Irvin M.

    1989-01-01

    Easily fabricated device increases precision in reading graphical data. Continuously-variable vernier scale (CV VS) designed to provide greater accuracy to scientists and technologists in reading numerical values from graphical data. Placed on graph and used to interpolate coordinate value of point on curve or plotted point on figure within division on each coordinate axis. Requires neither measurement of line segments where projection of point intersects division nor calculation to quantify projected value. Very flexible device constructed with any kind of scale. Very easy to use, requiring no special equipment of any kind, and saves considerable amount of time if numerous points to be evaluated.

  5. Genes and Hearing Loss

    Science.gov (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as ...

  6. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A

    2009-06-01

    Full Text Available Gene regulatory processes lead to differential gene expression and are referred to as epigenetic phenomena; these are ubiquitous processes in the biological world. These reversible heritable changes concern DNA and RNA, their interactions...

  7. Polydactyly and genes

    National Research Council Canada - National Science Library

    Phadke, Shubha R; Sankar, V H

    2010-01-01

    .... A lot of information about genes involved in development is available now. Genetics of hand development and genes involved in polydactyly syndromes is discussed in this article as a prototype to know about genetics of malformations...

  8. Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy

    Directory of Open Access Journals (Sweden)

    Claudia Gonzaga-Jauregui

    2015-08-01

    Full Text Available Charcot-Marie-Tooth (CMT disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼45% (17/37 of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity.

  9. Evolution of gene expression after gene amplification.

    Science.gov (United States)

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim

    2015-04-24

    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat-maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a γ-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Classification and prediction of port variables

    Energy Technology Data Exchange (ETDEWEB)

    Molina Serrano, B.

    2016-07-01

    Many variables are included in planning and management of port terminals. They can beeconomic, social, environmental and institutional. Agent needs to know relationshipbetween these variables to modify planning conditions. Use of Bayesian Networks allowsfor classifying, predicting and diagnosing these variables. Bayesian Networks allow forestimating subsequent probability of unknown variables, basing on know variables.In planning level, it means that it is not necessary to know all variables because theirrelationships are known. Agent can know interesting information about how port variablesare connected. It can be interpreted as cause-effect relationship. Bayesian Networks can beused to make optimal decisions by introduction of possible actions and utility of theirresults.In proposed methodology, a data base has been generated with more than 40 port variables.They have been classified in economic, social, environmental and institutional variables, inthe same way that smart port studies in Spanish Port System make. From this data base, anetwork has been generated using a non-cyclic conducted grafo which allows for knowingport variable relationships - parents-children relationships-. Obtained network exhibits thateconomic variables are – in cause-effect terms- cause of rest of variable typologies.Economic variables represent parent role in the most of cases. Moreover, whenenvironmental variables are known, obtained network allows for estimating subsequentprobability of social variables.It has been concluded that Bayesian Networks allow for modeling uncertainty in aprobabilistic way, even when number of variables is high as occurs in planning andmanagement of port terminals. (Author)

  11. Life-cycle modification in open oceans accounts for genome variability in a cosmopolitan phytoplankton

    Science.gov (United States)

    von Dassow, Peter; John, Uwe; Ogata, Hiroyuki; Probert, Ian; Bendif, El Mahdi; Kegel, Jessica U; Audic, Stéphane; Wincker, Patrick; Da Silva, Corinne; Claverie, Jean-Michel; Doney, Scott; Glover, David M; Flores, Daniella Mella; Herrera, Yeritza; Lescot, Magali; Garet-Delmas, Marie-José; de Vargas, Colomban

    2015-01-01

    Emiliania huxleyi is the most abundant calcifying plankton in modern oceans with substantial intraspecific genome variability and a biphasic life cycle involving sexual alternation between calcified 2N and flagellated 1N cells. We show that high genome content variability in Emiliania relates to erosion of 1N-specific genes and loss of the ability to form flagellated cells. Analysis of 185 E. huxleyi strains isolated from world oceans suggests that loss of flagella occurred independently in lineages inhabiting oligotrophic open oceans over short evolutionary timescales. This environmentally linked physiogenomic change suggests life cycling is not advantageous in very large/diluted populations experiencing low biotic pressure and low ecological variability. Gene loss did not appear to reflect pressure for genome streamlining in oligotrophic oceans as previously observed in picoplankton. Life-cycle modifications might be common in plankton and cause major functional variability to be hidden from traditional taxonomic or molecular markers. PMID:25461969

  12. Life-cycle modification in open oceans accounts for genome variability in a cosmopolitan phytoplankton.

    Science.gov (United States)

    von Dassow, Peter; John, Uwe; Ogata, Hiroyuki; Probert, Ian; Bendif, El Mahdi; Kegel, Jessica U; Audic, Stéphane; Wincker, Patrick; Da Silva, Corinne; Claverie, Jean-Michel; Doney, Scott; Glover, David M; Flores, Daniella Mella; Herrera, Yeritza; Lescot, Magali; Garet-Delmas, Marie-José; de Vargas, Colomban

    2015-06-01

    Emiliania huxleyi is the most abundant calcifying plankton in modern oceans with substantial intraspecific genome variability and a biphasic life cycle involving sexual alternation between calcified 2N and flagellated 1N cells. We show that high genome content variability in Emiliania relates to erosion of 1N-specific genes and loss of the ability to form flagellated cells. Analysis of 185 E. huxleyi strains isolated from world oceans suggests that loss of flagella occurred independently in lineages inhabiting oligotrophic open oceans over short evolutionary timescales. This environmentally linked physiogenomic change suggests life cycling is not advantageous in very large/diluted populations experiencing low biotic pressure and low ecological variability. Gene loss did not appear to reflect pressure for genome streamlining in oligotrophic oceans as previously observed in picoplankton. Life-cycle modifications might be common in plankton and cause major functional variability to be hidden from traditional taxonomic or molecular markers.

  13. How Genes Evolve

    Indian Academy of Sciences (India)

    evolutionary history of duplicated genes within a given lineage. The timings of gene duplication events can be inferred ... evolutionary history of the creatures in which various globin genes are found, the timings of the ..... But I cannot find heart to give any part of my life for money-making purposes ... : In 1901, one of the large ...

  14. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  15. Microelectrofluidic iris for variable aperture

    Science.gov (United States)

    Chang, Jong-hyeon; Jung, Kyu-Dong; Lee, Eunsung; Choi, Minseog; Lee, Seungwan

    2012-03-01

    This paper presents a variable aperture design based on the microelectrofluidic technology which integrates electrowetting and microfluidics. The proposed microelectrofluidic iris (MEFI) consists of two immiscible fluids and two connected surface channels formed by three transparent plates and two spacers between them. In the initial state, the confined aqueous ring makes two fluidic interfaces, on which the Laplace pressure is same, in the hydrophobic surface channels. When a certain voltage is applied between the dielectric-coated control electrode beneath the three-phase contact line (TCL) and the reference electrode for grounding the aqueous, the contact angle changes on the activated control electrode. At high voltage over the threshold, the induced positive pressure difference makes the TCLs on the 1st channel advance to the center and the aperture narrow. If there is no potential difference between the control and reference electrodes, the pressure difference becomes negative. It makes the TCLs on the 1st channel recede and the aperture widen to the initial state. It is expected that the proposed MEFI is able to be widely used because of its fast response, circular aperture, digital operation, high aperture ratio, and possibility to be miniaturized for variable aperture.

  16. CONSTRUCTING ACCOUNTING UNCERTAINITY ESTIMATES VARIABLE

    Directory of Open Access Journals (Sweden)

    Nino Serdarevic

    2012-10-01

    Full Text Available This paper presents research results on the BIH firms’ financial reporting quality, utilizing empirical relation between accounting conservatism, generated in created critical accounting policy choices, and management abilities in estimates and prediction power of domicile private sector accounting. Primary research is conducted based on firms’ financial statements, constructing CAPCBIH (Critical Accounting Policy Choices relevant in B&H variable that presents particular internal control system and risk assessment; and that influences financial reporting positions in accordance with specific business environment. I argue that firms’ management possesses no relevant capacity to determine risks and true consumption of economic benefits, leading to creation of hidden reserves in inventories and accounts payable; and latent losses for bad debt and assets revaluations. I draw special attention to recent IFRS convergences to US GAAP, especially in harmonizing with FAS 130 Reporting comprehensive income (in revised IAS 1 and FAS 157 Fair value measurement. CAPCBIH variable, resulted in very poor performance, presents considerable lack of recognizing environment specifics. Furthermore, I underline the importance of revised ISAE and re-enforced role of auditors in assessing relevance of management estimates.

  17. Phenotypic variability in Patau syndrome.

    Science.gov (United States)

    Caba, Lavinia; Rusu, Cristina; Butnariu, Lacramioara; Panzaru, Monica; Braha, Elena; Volosciuc, M; Popescu, Roxana; Gramescu, Mihaela; Bujoran, C; Martiniuc, Violeta; Covic, M; Gorduza, E V

    2013-01-01

    Patau syndrome has an incidence of 1/10.000-20.000, the clinical diagnosis being suggested by the triad cleft lip and palate, microphthalmia/anophthalmia and postaxial polydactyly. Most frequent cytogenetic abnormality is free and homogeneous trisomy 13 (80.0%), rarely being detected trisomy mosaics or Robertsonian translocations. The objective of the study was to identify phenotypic features of trisomy 13. The retrospective study was conducted on a trial group of 14 cases diagnosed cytogenetically with trisomy 13 between January 2000 and December 2012 at lasi Medical Genetics Centre. Of the 14 cases, 3 were evaluated pathologically (two aborted foetuses and one stillborn), 8 cases were detected in the neonatal period, and 3 in infancy. Clinical diagnosis was supported by the identification of a model of abnormal development, mainly characterized by: maxillary cleft (lip and palate--5 cases; lip--1 case), ocular abnormalities (microphthalmia/anophthalmia--7 cases; cyclopia--1 case), postaxial polydactyly (7 cases), scalp defects (6 cases), congenital heart anomalies (10 cases, 6 patients with atrial septal defect), complete holoprosencephaly (4 cases), ear abnormalities (11 cases), broad nasal root (10 cases). An important issue in confirming the phenotypic variability of Patau syndrome is that the classic clinical triad was identified only in one case. Patau syndrome is a disease with variable expression and is characterized by a pattern of abnormal prenatal development characterized by facial dysmorphia, polydactyly and severe birth defects (heart, brain) that generate an increased in utero and perinatal mortality.

  18. Somatic mosaicism and variable penetrance in doublecortin-associated migration disorders.

    Science.gov (United States)

    Aigner, L; Uyanik, G; Couillard-Despres, S; Ploetz, S; Wolff, G; Morris-Rosendahl, D; Martin, P; Eckel, U; Spranger, S; Otte, J; Woerle, H; Holthausen, H; Apheshiotis, N; Fluegel, D; Winkler, J

    2003-01-28

    X-linked isolated lissencephaly sequence (XLIS) and subcortical band heterotopia (SBH) are allelic disorders caused by mutations in the doublecortin (DCX) gene. This genetic analysis of seven families revealed four novel mutations in the DCX gene. The authors detected a high rate of somatic mosaicism in male and female patients with variable penetrance of bilateral SBH including nonpenetrance in a heterozygous woman. In addition, the authors implemented prenatal diagnosis in a family with SBH/XLIS.

  19. Analysis of variable sites between two complete South China tiger (Panthera tigris amoyensis) mitochondrial genomes.

    Science.gov (United States)

    Zhang, Wenping; Yue, Bisong; Wang, Xiaofang; Zhang, Xiuyue; Xie, Zhong; Liu, Nonglin; Fu, Wenyuan; Yuan, Yaohua; Chen, Daqing; Fu, Danghua; Zhao, Bo; Yin, Yuzhong; Yan, Xiahui; Wang, Xinjing; Zhang, Rongying; Liu, Jie; Li, Maoping; Tang, Yao; Hou, Rong; Zhang, Zhihe

    2011-10-01

    In order to investigate the mitochondrial genome of Panthera tigris amoyensis, two South China tigers (P25 and P27) were analyzed following 15 cymt-specific primer sets. The entire mtDNA sequence was found to be 16,957 bp and 17,001 bp long for P25 and P27 respectively, and this difference in length between P25 and P27 occurred in the number of tandem repeats in the RS-3 segment of the control region. The structural characteristics of complete P. t. amoyensis mitochondrial genomes were also highly similar to those of P. uncia. Additionally, the rate of point mutation was only 0.3% and a total of 59 variable sites between P25 and P27 were found. Out of the 59 variable sites, 6 were located in 6 different tRNA genes, 6 in the 2 rRNA genes, 7 in non-coding regions (one located between tRNA-Asn and tRNA-Tyr and six in the D-loop), and 40 in 10 protein-coding genes. COI held the largest amount of variable sites (9 sites) and Cytb contained the highest variable rate (0.7%) in the complete sequences. Moreover, out of the 40 variable sites located in 10 protein-coding genes, 12 sites were nonsynonymous.

  20. MicroRNA expression variability in human cervical tissues.

    Directory of Open Access Journals (Sweden)

    Patrícia M Pereira

    Full Text Available MicroRNAs (miRNAs are short (approximately 22 nt non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL and 9 low-grade squamous intraepithelial lesion (LSIL samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.

  1. INTRINSIC REGULATION OF HEMOGLOBIN EXPRESSION BY VARIABLE SUBUNIT INTERFACE STRENGTHS

    Science.gov (United States)

    Manning, James M.; Popowicz, Anthony M.; Padovan, Julio C.; Chait, Brian T.; Manning, Lois R.

    2012-01-01

    SUMMARY The expression of the six types of human hemoglobin subunits over time is currently considered to be regulated mainly by transcription factors that bind to upstream control regions of the gene (the “extrinsic” component of regulation). Here we describe how subunit pairing and further assembly to tetramers in the liganded state is influenced by the affinity of subunits for one another (the “intrinsic” component of regulation). The adult hemoglobin dimers have the strongest subunit interfaces and the embryonic hemoglobins are the weakest with fetal hemoglobins of intermediate strength, corresponding to the temporal order of their expression. These variable subunit binding strengths and the attenuating effects of acetylation contribute to the differences with which these hemoglobin types form functional O2-binding tetramers consistent with gene switching. PMID:22129306

  2. Genetic structure and molecular variability of potato virus M populations.

    Science.gov (United States)

    Tabasinejad, Fatemeh; Jafarpour, Behrooz; Zakiaghl, Mohammad; Siampour, Majid; Rouhani, Hamid; Mehrvar, Mohsen

    2014-08-01

    To investigate the genetic diversity of potato virus M (PVM; genus Carlavirus, family Betaflexiviridae), the complete nucleotide sequence of the coat protein gene of 30 PVM isolates from a major potato-growing region in Iran were determined. Phylogenetic analysis of these Iranian PVM isolates together with those available in the GenBank database suggested two divergent evolutionary lineages that did not reflect the origin of the isolates, and these were designated as PVM-o and PVM-d. Examination of the genetic variability of the coat protein of Iranian isolates and their counterparts whose sequences are available in the Genbank database revealed 16 genotype groups in the PVM population. Analysis of the synonymous-tononsynonymous ratio showed strong purifying selection in the CP gene in the genotype groups of divergent clades.

  3. Gene expression patterns of invertase gene families and modulation of the inhibitor gene in tomato sucrose metabolism.

    Science.gov (United States)

    Zhang, Y L; Zhang, A H; Jiang, J

    2013-01-24

    Patterns of gene expression in the different types of sucrose metabolism in the tomato are highly variable and heritable. This genetic variation causes considerable functional differences. We examined the patterns of expression of invertase (Inv) gene families and an invertase inhibitor (INH) gene involved in elongating roots, hypocotyls, and fruit of the tomato (Lycopersicon esculentum cv. Micro-Tom and L. chmielewskii) through a real-time quantitative PCR analysis. We found that the Lin6 gene plays an important role in the vegetative growth stage. Lin5 and Lin7 did not express in Micro-Tom, but did express in L. chmielewskii. Overall relative expression levels of sucrose Inv gene families were significantly lower in L. chmielewskii during the reproductive growth stage than in Micro-Tom, being up to hundreds of times lower. It was not expressed in the dissepiment in L. chmielewskii. We suggest that differences in sucrose accumulation in tomato fruit is mainly due to differentially expressed invertase gene families at the later fruit growth stages.

  4. Joubert syndrome: large clinical variability and a unique neuroimaging aspect

    Energy Technology Data Exchange (ETDEWEB)

    Leao, Emilia Katiane Embirucu; Lima, Marcilia Martyn; Kok, Fernando; Parizotto, Juliana [University of Sao Paulo (USP), Sao Paulo, SP (Brazil). Clinical Hospital. Dept. of Child Neurology; Maia Junior, Otacilio de Oliveira [University of Sao Paulo (USP), Sao Paulo, SP (Brazil). Clinical Hospital. Dept. of Child Ophthalmology

    2010-04-15

    Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g. pigmentary retinopathy, oculomotor apraxia and nystagmus), renal cysts and hepatic fibrosis. Respiratory abnormalities, as apnoea and hyperpnoea, may be present, as well as mental retardation. At least seven JS loci have been determined and five genes identified. Herein, we report five children, belonging to independent families, with JS: they shared the same typical MRI abnormality, known as molar tooth sign, but had an otherwise quite variable phenotype, regarding mostly their cognitive performance, visual abilities and extra-neurological compromise. (author)

  5. Gene therapy in periodontics

    Science.gov (United States)

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-01-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ‘the use of genes as medicine’. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone. PMID:23869119

  6. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  7. Modelling prokaryote gene content

    Directory of Open Access Journals (Sweden)

    Edward Susko

    2006-01-01

    Full Text Available The patchy distribution of genes across the prokaryotes may be caused by multiple gene losses or lateral transfer. Probabilistic models of gene gain and loss are needed to distinguish between these possibilities. Existing models allow only single genes to be gained and lost, despite the empirical evidence for multi-gene events. We compare birth-death models (currently the only widely-used models, in which only one gene can be gained or lost at a time to blocks models (allowing gain and loss of multiple genes within a family. We analyze two pairs of genomes: two E. coli strains, and the distantly-related Archaeoglobus fulgidus (archaea and Bacillus subtilis (gram positive bacteria. Blocks models describe the data much better than birth-death models. Our models suggest that lateral transfers of multiple genes from the same family are rare (although transfers of single genes are probably common. For both pairs, the estimated median time that a gene will remain in the genome is not much greater than the time separating the common ancestors of the archaea and bacteria. Deep phylogenetic reconstruction from sequence data will therefore depend on choosing genes likely to remain in the genome for a long time. Phylogenies based on the blocks model are more biologically plausible than phylogenies based on the birth-death model.

  8. Microvillous inclusion disease: ultrastructural variability.

    Science.gov (United States)

    Iancu, Theodore C; Mahajnah, Muhammad; Manov, Irena; Shaoul, Ron

    2007-01-01

    Microvillous inclusion disease (MVID) is a congenital, usually neonatal, autosomal recessive condition manifested by severe, prolonged secretory diarrhea. Intestinal biopsies reveal extensive microvilli abnormalities, typical inclusions and vesicles mainly of the apical-luminal enterocytes and colonocytes. Although diagnosis can be suspected by special stains of the mucosa (PAS, CD10), the definitive diagnosis, recommended in view of potential intestinal transplantation, requires electron microscopy. In view of the marked variability of ultrastructural changes, extensive illustration is considered valuable for diagnosis. While the pathogenesis is still unknown, a number of images illustrate the suspected "arrested-trafficking" hypothesis of microvillous abnormalities. Others micrographs support the "engulfing" mechanism of inclusion formation. The electron micrographs should help ultrastructural diagnosis in this heterogeneous disease and can confirm diagnosis even in the absence of the typical inclusions.

  9. AMXP Pulse variability wih NICER

    Science.gov (United States)

    Bult, Peter

    2017-08-01

    Accreting millisecond X-ray pulsars show a diverse scope variability, including coherent pulsations from the stellar surface and quasi-periodic oscillations attributed to the accretion flow. Because the pulsations are ultimately powered by accreting material, it may be expected that these periodic and quasi-periodic signals show coupled behavior. Observing and characterizing such coupling then gives a unique view of the flow of matter in the closest vicinity of the neutron star surface. In this contribution I will present recently developed specialized methods that can detect such coupling, and discuss how high quality X-ray observations by NICER may enable pulse amplitude modulation studies, and their potential to constrain the physics of accretion.

  10. Quantum computation and hidden variables

    CERN Document Server

    Aristov, V V

    2010-01-01

    Many physicists limit oneself to an instrumentalist description of quantum phenomena and ignore the problems of foundation and interpretation of quantum mechanics. This instrumentalist approach results to "specialization barbarism" and mass delusion concerning the problem, how a quantum computer can be made. The idea of quantum computation can be described within the limits of quantum formalism. But in order to understand how this idea can be put into practice one should realize the question: "What could the quantum formalism describe?", in spite of the absence of an universally recognized answer. Only a realization of this question and the undecided problem of quantum foundations allows to see in which quantum systems the superposition and EPR correlation could be expected. Because of the "specialization barbarism" many authors are sure that Bell proved full impossibility of any hidden-variables interpretation. Therefore it is important to emphasize that in reality Bell has restricted to validity limits of t...

  11. Earth\\'s Mass Variability

    CERN Document Server

    Mawad, Ramy

    2014-01-01

    The perturbation of the Earth caused by variability of mass of Earth as additional reason with gravity of celestial bodies and shape of the Earth. The Earth eating and collecting matters from space and loss or eject matters to space through its flying in the space around the Sun. The source of the rising in the global sea level is not closed in global warming and icebergs, but the outer space is the additional important source for this rising. The Earth eats waters from space in unknown mechanism. The mass of the Earth become greater in November i.e. before transit apoapsis two months, and become latter in February i.e. after transit apoapsis to two months.

  12. Motor Integrated Variable Speed Drives

    DEFF Research Database (Denmark)

    Singh, Yash Veer

    A new trend in the variable speed drives (VSDs) is to develop fully integrated systems, which lead to low-cost products with shorter design cycles. Motor Integrated design of VSDs will reduce cable length to connect drive with machine windings and installation time for end user. The electric drives...... are expected to have minimum effect on grid and motor connected to it, i.e. currents drawn from grid should be within specified limits and currents injecting in to machine should not overheat the machine windings to avoid insulation failure due to harmonics. It is also necessary that electric drives should...... when it comes to the development of any kind of power converter topology for power electronic applications. Concerning the use of a power converter in motor integrated VSDs, the first two mentioned aspects receive an even greater im-portance. Power converter design for integrated drives poses a host...

  13. Variable-bias coin tossing

    Science.gov (United States)

    Colbeck, Roger; Kent, Adrian

    2006-03-01

    Alice is a charismatic quantum cryptographer who believes her parties are unmissable; Bob is a (relatively) glamorous string theorist who believes he is an indispensable guest. To prevent possibly traumatic collisions of self-perception and reality, their social code requires that decisions about invitation or acceptance be made via a cryptographically secure variable-bias coin toss (VBCT). This generates a shared random bit by the toss of a coin whose bias is secretly chosen, within a stipulated range, by one of the parties; the other party learns only the random bit. Thus one party can secretly influence the outcome, while both can save face by blaming any negative decisions on bad luck. We describe here some cryptographic VBCT protocols whose security is guaranteed by quantum theory and the impossibility of superluminal signaling, setting our results in the context of a general discussion of secure two-party computation. We also briefly discuss other cryptographic applications of VBCT.

  14. Benchmarking heart rate variability toolboxes.

    Science.gov (United States)

    Vest, Adriana N; Li, Qiao; Liu, Chengyu; Nemati, Shamim; Shah, Amit; Clifford, Gari D

    Heart rate variability (HRV) metrics hold promise as potential indicators for autonomic function, prediction of adverse cardiovascular outcomes, psychophysiological status, and general wellness. Although the investigation of HRV has been prevalent for several decades, the methods used for preprocessing, windowing, and choosing appropriate parameters lack consensus among academic and clinical investigators. A comprehensive and open-source modular program is presented for calculating HRV implemented in Matlab with evidence-based algorithms and output formats. We compare our software with another widely used HRV toolbox written in C and available through PhysioNet.org. Our findings show substantially similar results when using high quality electrocardiograms (ECG) free from arrhythmias. Our software shows equivalent performance alongside an established predecessor and includes validated tools for performing preprocessing, signal quality, and arrhythmia detection to help provide standardization and repeatability in the field, leading to fewer errors in the presence of noise or arrhythmias. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Continuously variable focal length lens

    Science.gov (United States)

    Adams, Bernhard W; Chollet, Matthieu C

    2013-12-17

    A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

  16. Habitat variability does not generally promote metabolic network modularity in flies and mammals.

    Science.gov (United States)

    Takemoto, Kazuhiro

    2016-01-01

    The evolution of species habitat range is an important topic over a wide range of research fields. In higher organisms, habitat range evolution is generally associated with genetic events such as gene duplication. However, the specific factors that determine habitat variability remain unclear at higher levels of biological organization (e.g., biochemical networks). One widely accepted hypothesis developed from both theoretical and empirical analyses is that habitat variability promotes network modularity; however, this relationship has not yet been directly tested in higher organisms. Therefore, I investigated the relationship between habitat variability and metabolic network modularity using compound and enzymatic networks in flies and mammals. Contrary to expectation, there was no clear positive correlation between habitat variability and network modularity. As an exception, the network modularity increased with habitat variability in the enzymatic networks of flies. However, the observed association was likely an artifact, and the frequency of gene duplication appears to be the main factor contributing to network modularity. These findings raise the question of whether or not there is a general mechanism for habitat range expansion at a higher level (i.e., above the gene scale). This study suggests that the currently widely accepted hypothesis for habitat variability should be reconsidered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Intraindividual Variability in Serum Micronutrients

    Science.gov (United States)

    Shvetsov, Yurii B.; Hernandez, Brenda Y.; Wong, Sze H.; Wilkens, Lynne R.; Franke, Adrian A.; Goodman, Marc T.

    2009-01-01

    Background: Although serum measures of micronutrients are more specific than questionnaires in quantifying nutritional status, the reliability of serum measures depends on between- and within-person variability of circulating micronutrient levels. The extent to which multiple samples per person might improve reliability is useful information for planning studies and interpreting results. Methods: We analyzed levels of 25 micronutrients in serum samples taken from 381 Hawaii women at 4-month intervals. For all subjects and for subjects at the low and high end of the micronutrient distributions, we calculated inter- and intraindividual variability, reliability coefficients, and the number of measurements required to limit attenuation in estimated parameters (ie, to keep estimates close to their true values). Results: For 18 of the 25 micronutrients, a single measurement provided an estimate within 20% of the true value. For regression coefficients, 2 measurements were needed to limit attenuation to no more than 20% for nearly half of the micronutrients. To achieve no more than 10% attenuation, the number of measurements required ranged from 2 to 10 for correlation and from 3 to 20 for regression coefficients. To achieve no more than 5% attenuation, the corresponding ranges were 3 to 21 for correlation and 6 to 42 regression coefficients. In general, more measurements were required for adequate characterization of subjects with relatively high levels of micronutrients than for subjects with lower levels. Conclusions: Our analysis suggests that 2 or 3 blood measurements are enough to limit attenuation of regression coefficients within 20% of the true value for most carotenoids and tocopherols. For 10% attenuation or less, 4 or more micronutrient measurements may be needed. PMID:18813024

  18. Strategies in Gene Therapy for Glioblastoma

    Science.gov (United States)

    Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S.

    2013-01-01

    Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy. PMID:24202446

  19. Strategies in Gene Therapy for Glioblastoma

    Directory of Open Access Journals (Sweden)

    Mariano S. Viapiano

    2013-10-01

    Full Text Available Glioblastoma (GBM is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.

  20. Strategies in Gene Therapy for Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Kwiatkowska, Aneta; Nandhu, Mohan S.; Behera, Prajna; Chiocca, E. Antonio; Viapiano, Mariano S., E-mail: mviapiano@partners.org [Department of Neurosurgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2013-10-22

    Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.