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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. Genetic Variants Contribute to Gene Expression Variability in Humans

    Science.gov (United States)

    Hulse, Amanda M.; Cai, James J.

    2013-01-01

    Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

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

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    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.

  4. 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

  5. Quantifying intrinsic and extrinsic variability in stochastic gene expression models.

    Science.gov (United States)

    Singh, Abhyudai; Soltani, Mohammad

    2013-01-01

    Genetically identical cell populations exhibit considerable intercellular variation in the level of a given protein or mRNA. Both intrinsic and extrinsic sources of noise drive this variability in gene expression. More specifically, extrinsic noise is the expression variability that arises from cell-to-cell differences in cell-specific factors such as enzyme levels, cell size and cell cycle stage. In contrast, intrinsic noise is the expression variability that is not accounted for by extrinsic noise, and typically arises from the inherent stochastic nature of biochemical processes. Two-color reporter experiments are employed to decompose expression variability into its intrinsic and extrinsic noise components. Analytical formulas for intrinsic and extrinsic noise are derived for a class of stochastic gene expression models, where variations in cell-specific factors cause fluctuations in model parameters, in particular, transcription and/or translation rate fluctuations. Assuming mRNA production occurs in random bursts, transcription rate is represented by either the burst frequency (how often the bursts occur) or the burst size (number of mRNAs produced in each burst). Our analysis shows that fluctuations in the transcription burst frequency enhance extrinsic noise but do not affect the intrinsic noise. On the contrary, fluctuations in the transcription burst size or mRNA translation rate dramatically increase both intrinsic and extrinsic noise components. Interestingly, simultaneous fluctuations in transcription and translation rates arising from randomness in ATP abundance can decrease intrinsic noise measured in a two-color reporter assay. Finally, we discuss how these formulas can be combined with single-cell gene expression data from two-color reporter experiments for estimating model parameters.

  6. Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

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    Lun Yang

    Full Text Available 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.

  7. 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.

  8. A Bayesian variable selection procedure for ranking overlapping gene sets

    DEFF Research Database (Denmark)

    Skarman, Axel; Mahdi Shariati, Mohammad; Janss, Luc

    2012-01-01

    Background Genome-wide expression profiling using microarrays or sequence-based technologies allows us to identify genes and genetic pathways whose expression patterns influence complex traits. Different methods to prioritize gene sets, such as the genes in a given molecular pathway, have been de...

  9. 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…

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

    Indian Academy of Sciences (India)

    2008-12-31

    Dec 31, 2008 ... Circadian rhythm-related sleep disorders have also been ..... cause or an effect of the scant attention that has been paid to the Bmal2 gene, no re- .... When sleep de- prived, PER35 homozygotes exhibited much greater deficit.

  11. Cloning, sequencing and variability analysis of the gap gene from Mycoplasma hominis

    DEFF Research Database (Denmark)

    Mygind, Tina; Jacobsen, Iben Søgaard; Melkova, Renata

    2000-01-01

    The gap gene encodes the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The gene was cloned and sequenced from the Mycoplasma hominis type strain PG21(T). The intraspecies variability was investigated by inspection of restriction fragment length polymorphism (RFLP) patterns...... after polymerase chain reaction (PCR) amplification of the gap gene from 15 strains and furthermore by sequencing of part of the gene in eight strains. The M. hominis gap gene was found to vary more than the Escherichia coli counterpart, but the variation at nucleotide level gave rise to only a few...

  12. Dissecting Time- from Tumor-Related Gene Expression Variability in Bilateral Breast Cancer

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    Maurizio Callari

    2018-01-01

    Full Text Available Metachronous (MBC and synchronous bilateral breast tumors (SBC are mostly distinct primaries, whereas paired primaries and their local recurrences (LRC share a common origin. Intra-pair gene expression variability in MBC, SBC, and LRC derives from time/tumor microenvironment-related and tumor genetic background-related factors and pairs represents an ideal model for trying to dissect tumor-related from microenvironment-related variability. Pairs of tumors derived from women with SBC (n = 18, MBC (n = 11, and LRC (n = 10 undergoing local-regional treatment were profiled for gene expression; similarity between pairs was measured using an intraclass correlation coefficient (ICC computed for each gene and compared using analysis of variance (ANOVA. When considering biologically unselected genes, the highest correlations were found for primaries and paired LRC, and the lowest for MBC pairs. By instead limiting the analysis to the breast cancer intrinsic genes, correlations between primaries and paired LRC were enhanced, while lower similarities were observed for SBC and MBC. Focusing on stromal-related genes, the ICC values decreased for MBC and were significantly different from SBC. These findings indicate that it is possible to dissect intra-pair gene expression variability into components that are associated with genetic origin or with time and microenvironment by using specific gene subsets.

  13. Cloning, sequencing and variability analysis of the gap gene from Mycoplasma hominis

    DEFF Research Database (Denmark)

    Mygind, Tina; Jacobsen, Iben Søgaard; Melkova, Renata

    2000-01-01

    The gap gene encodes the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The gene was cloned and sequenced from the Mycoplasma hominis type strain PG21(T). The intraspecies variability was investigated by inspection of restriction fragment length polymorphism (RFLP) patterns...... after polymerase chain reaction (PCR) amplification of the gap gene from 15 strains and furthermore by sequencing of part of the gene in eight strains. The M. hominis gap gene was found to vary more than the Escherichia coli counterpart, but the variation at nucleotide level gave rise to only a few...... amino acid substitutions. To verify that the gene was expressed in M. hominis, a polyclonal antibody was produced and tested against whole cell protein from 15 strains. The enzyme was expressed in all strains investigated as a 36-kDa protein. All strains except type strain PG21(T) showed reaction...

  14. Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women's Cancers.

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    Thomas E Bartlett

    Full Text Available We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221, which validates in two independent data sets from Mayo Clinic (n = 198 and TCGA (n = 358, with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes.

  15. Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women's Cancers.

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    Bartlett, Thomas E; Jones, Allison; Goode, Ellen L; Fridley, Brooke L; Cunningham, Julie M; Berns, Els M J J; Wik, Elisabeth; Salvesen, Helga B; Davidson, Ben; Trope, Claes G; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin

    2015-01-01

    We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes.

  16. Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures

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    Liu Yufeng

    2011-01-01

    Full Text Available Abstract Background Multiple breast cancer gene expression profiles have been developed that appear to provide similar abilities to predict outcome and may outperform clinical-pathologic criteria; however, the extent to which seemingly disparate profiles provide additive prognostic information is not known, nor do we know whether prognostic profiles perform equally across clinically defined breast cancer subtypes. We evaluated whether combining the prognostic powers of standard breast cancer clinical variables with a large set of gene expression signatures could improve on our ability to predict patient outcomes. Methods Using clinical-pathological variables and a collection of 323 gene expression "modules", including 115 previously published signatures, we build multivariate Cox proportional hazards models using a dataset of 550 node-negative systemically untreated breast cancer patients. Models predictive of pathological complete response (pCR to neoadjuvant chemotherapy were also built using this approach. Results We identified statistically significant prognostic models for relapse-free survival (RFS at 7 years for the entire population, and for the subgroups of patients with ER-positive, or Luminal tumors. Furthermore, we found that combined models that included both clinical and genomic parameters improved prognostication compared with models with either clinical or genomic variables alone. Finally, we were able to build statistically significant combined models for pathological complete response (pCR predictions for the entire population. Conclusions Integration of gene expression signatures and clinical-pathological factors is an improved method over either variable type alone. Highly prognostic models could be created when using all patients, and for the subset of patients with lymph node-negative and ER-positive breast cancers. Other variables beyond gene expression and clinical-pathological variables, like gene mutation status or DNA

  17. Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

    1987-01-01

    The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

  18. Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay

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    Amel Al-Murrani

    2012-01-01

    Full Text Available The contactin-associated protein-like 2 (CNTNAP2 gene is highly expressed in the frontal lobe circuits in the developing human brain. Mutations in this gene have been associated with several neurodevelopmental disorders such as autism and specific language impairment. Here we describe a 450 kb deletion within the CNTNAP2 gene that is maternally inherited in two male siblings, but with a variable clinical phenotype. This variability is described in the context of a limited number of other cases reported in the literature. The in-frame intragenic deletion removes a critical domain of the CNTNAP2 protein, and this case also highlights the challenges of correlating genotype and phenotype.

  19. Amino-Terminal Microdeletion within the CNTNAP2 Gene Associated with Variable Expressivity of Speech Delay

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    Al-Murrani, Amel; Ashton, Fern; Aftimos, Salim; George, Alice M.; Love, Donald R.

    2012-01-01

    The contactin-associated protein-like 2 (CNTNAP2) gene is highly expressed in the frontal lobe circuits in the developing human brain. Mutations in this gene have been associated with several neurodevelopmental disorders such as autism and specific language impairment. Here we describe a 450 kb deletion within the CNTNAP2 gene that is maternally inherited in two male siblings, but with a variable clinical phenotype. This variability is described in the context of a limited number of other cases reported in the literature. The in-frame intragenic deletion removes a critical domain of the CNTNAP2 protein, and this case also highlights the challenges of correlating genotype and phenotype. PMID:23074684

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

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    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

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

    Science.gov (United States)

    Cameron, Jessie M; Levandovskiy, Valeriy; Roberts, Wendy; Anagnostou, Evdokia; Scherer, Stephen; Loh, Alvin; Schulze, Andreas

    2017-07-31

    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 spectrum

  2. 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.

  3. Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays

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    Spitznagel Edward

    2003-11-01

    Full Text Available Abstract Background The assessment of data reproducibility is essential for application of microarray technology to exploration of biological pathways and disease states. Technical variability in data analysis largely depends on signal intensity. Within that context, the reproducibility of individual probe sets has not been hitherto addressed. Results We used an extraordinarily large replicate data set derived from human placental trophoblast to analyze probe-specific contribution to variability of gene expression. We found that signal variability, in addition to being signal-intensity dependant, is probe set-specific. Importantly, we developed a novel method to quantify the contribution of this probe set-specific variability. Furthermore, we devised a formula that incorporates a priori-computed, replicate-based information on probe set- and intensity-specific variability in determination of expression changes even without technical replicates. Conclusion The strategy of incorporating probe set-specific variability is superior to analysis based on arbitrary fold-change thresholds. We recommend its incorporation to any computation of gene expression changes using high-density DNA microarrays. A Java application implementing our T-score is available at http://www.sadovsky.wustl.edu/tscore.html.

  4. Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency.

    OpenAIRE

    Volanakis, J E; Zhu, Z B; Schaffer, F M; Macon, K J; Palermos, J; Barger, B O; Go, R; Campbell, R D; Schroeder, H W; Cooper, M D

    1992-01-01

    We have proposed that significant subsets of individuals with IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) may represent polar ends of a clinical spectrum reflecting a single underlying genetic defect. This proposal was supported by our finding that individuals with these immunodeficiencies have in common a high incidence of C4A gene deletions and C2 rare gene alleles. Here we present our analysis of the MHC haplotypes of 12 IgA-D and 19 CVID individuals from 21 families...

  5. 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.

  6. Bayesian nonparametric variable selection as an exploratory tool for discovering differentially expressed genes.

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    Shahbaba, Babak; Johnson, Wesley O

    2013-05-30

    High-throughput scientific studies involving no clear a priori hypothesis are common. For example, a large-scale genomic study of a disease may examine thousands of genes without hypothesizing that any specific gene is responsible for the disease. In these studies, the objective is to explore a large number of possible factors (e.g., genes) in order to identify a small number that will be considered in follow-up studies that tend to be more thorough and on smaller scales. A simple, hierarchical, linear regression model with random coefficients is assumed for case-control data that correspond to each gene. The specific model used will be seen to be related to a standard Bayesian variable selection model. Relatively large regression coefficients correspond to potential differences in responses for cases versus controls and thus to genes that might 'matter'. For large-scale studies, and using a Dirichlet process mixture model for the regression coefficients, we are able to find clusters of regression effects of genes with increasing potential effect or 'relevance', in relation to the outcome of interest. One cluster will always correspond to genes whose coefficients are in a neighborhood that is relatively close to zero and will be deemed least relevant. Other clusters will correspond to increasing magnitudes of the random/latent regression coefficients. Using simulated data, we demonstrate that our approach could be quite effective in finding relevant genes compared with several alternative methods. We apply our model to two large-scale studies. The first study involves transcriptome analysis of infection by human cytomegalovirus. The second study's objective is to identify differentially expressed genes between two types of leukemia. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Evaluation of tools for highly variable gene discovery from single-cell RNA-seq data.

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    Yip, Shun H; Sham, Pak Chung; Wang, Junwen

    2018-02-21

    Traditional RNA sequencing (RNA-seq) allows the detection of gene expression variations between two or more cell populations through differentially expressed gene (DEG) analysis. However, genes that contribute to cell-to-cell differences are not discoverable with RNA-seq because RNA-seq samples are obtained from a mixture of cells. Single-cell RNA-seq (scRNA-seq) allows the detection of gene expression in each cell. With scRNA-seq, highly variable gene (HVG) discovery allows the detection of genes that contribute strongly to cell-to-cell variation within a homogeneous cell population, such as a population of embryonic stem cells. This analysis is implemented in many software packages. In this study, we compare seven HVG methods from six software packages, including BASiCS, Brennecke, scLVM, scran, scVEGs and Seurat. Our results demonstrate that reproducibility in HVG analysis requires a larger sample size than DEG analysis. Discrepancies between methods and potential issues in these tools are discussed and recommendations are made.

  8. Variable number of tandem repeats of 9 Plasmodium vivax genes among Southeast Asian isolates.

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    Wang, Bo; Nyunt, Myat Htut; Yun, Seung-Gyu; Lu, Feng; Cheng, Yang; Han, Jin-Hee; Ha, Kwon-Soo; Park, Won Sun; Hong, Seok-Ho; Lim, Chae-Seung; Cao, Jun; Sattabongkot, Jetsumon; Kyaw, Myat Phone; Cui, Liwang; Han, Eun-Taek

    2017-06-01

    The variable number of tandem repeats (VNTRs) provides valuable information about both the functional and evolutionary aspects of genetic diversity. Comparative analysis of 3 Plasmodium falciparum genomes has shown that more than 9% of its open reading frames (ORFs) harbor VNTRs. Although microsatellites and VNTR genes of P. vivax were reported, the VNTR polymorphism of genes has not been examined widely. In this study, 230 P. vivax genes were analyzed for VNTRs by SERV, and 33 kinds of TR deletions or insertions from 29 P. vivax genes (12.6%) were found. Of these, 9 VNTR fragments from 8 P. vivax genes were used for PCR amplification and sequence analysis to examine the genetic diversity among 134 isolates from four Southeast Asian countries (China, Republic of Korea, Thailand, and Myanmar) with different malaria endemicity. We confirmed the existence of extensive polymorphism of VNTR fragments in field isolates. This detection provides several suitable markers for analysis of the molecular epidemiology of P. vivax field isolates. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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.

  10. Molecular characterization, tissue expression and sequence variability of the barramundi (Lates calcarifer myostatin gene

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    Smith-Keune Carolyn

    2008-02-01

    Full Text Available Abstract Background Myostatin (MSTN is a member of the transforming growth factor-β superfamily that negatively regulates growth of skeletal muscle tissue. The gene encoding for the MSTN peptide is a consolidate candidate for the enhancement of productivity in terrestrial livestock. This gene potentially represents an important target for growth improvement of cultured finfish. Results Here we report molecular characterization, tissue expression and sequence variability of the barramundi (Lates calcarifer MSTN-1 gene. The barramundi MSTN-1 was encoded by three exons 379, 371 and 381 bp in length and translated into a 376-amino acid peptide. Intron 1 and 2 were 412 and 819 bp in length and presented typical GT...AG splicing sites. The upstream region contained cis-regulatory elements such as TATA-box and E-boxes. A first assessment of sequence variability suggested that higher mutation rates are found in the 5' flanking region with several SNP's present in this species. A putative micro RNA target site has also been observed in the 3'UTR (untranslated region and is highly conserved across teleost fish. The deduced amino acid sequence was conserved across vertebrates and exhibited characteristic conserved putative functional residues including a cleavage motif of proteolysis (RXXR, nine cysteines and two glycosilation sites. A qualitative analysis of the barramundi MSTN-1 expression pattern revealed that, in adult fish, transcripts are differentially expressed in various tissues other than skeletal muscles including gill, heart, kidney, intestine, liver, spleen, eye, gonad and brain. Conclusion Our findings provide valuable insights such as sequence variation and genomic information which will aid the further investigation of the barramundi MSTN-1 gene in association with growth. The finding for the first time in finfish MSTN of a miRNA target site in the 3'UTR provides an opportunity for the identification of regulatory mutations on the

  11. 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.

  12. 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.

  13. EPSPS variability, gene expression, and enzymatic activity in glyphosate-resistant biotypes of Digitaria insularis.

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    Galeano, E; Barroso, A A M; Vasconcelos, T S; López-Rubio, A; Albrecht, A J P; Victoria Filho, R; Carrer, H

    2016-08-12

    Weed resistance to herbicides is a natural phenomenon that exerts selection on individuals in a population. In Brazil, glyphosate resistance was recently detected in Digitaria insularis. The objective of this study was to elucidate mechanisms of weed resistance in this plant, including genetic variability, allelism, amino acid substitutions, gene expression, and enzymatic activity levels. Most of these have not previously been studied in this species. D. insularis DNA sequences were used to analyze genetic variability. cDNA from resistant and susceptible plants was used to identify mutations, alleles, and 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) expression, using real-time quantitative reverse transcription-polymerase chain reaction. In addition, EPSPS activity was measured. We found a decrease in genetic variability between populations related to glyphosate application. Substitutions from proline to threonine and tyrosine to cysteine led to a decrease in EPSPS affinity for the glyphosate. In addition, the EPSPS enzymatic activity was slightly higher in resistant plants, whereas EPSPS gene expression was almost identical in both biotypes, suggesting feedback regulation at different levels. To conclude, our results suggest new molecular mechanisms used by D. insularis to increase glyphosate resistance.

  14. A new efficient statistical test for detecting variability in the gene expression data.

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    Mathur, Sunil; Dolo, Samuel

    2008-08-01

    DNA microarray technology allows researchers to monitor the expressions of thousands of genes under different conditions. The detection of differential gene expression under two different conditions is very important in microarray studies. Microarray experiments are multi-step procedures and each step is a potential source of variance. This makes the measurement of variability difficult because approach based on gene-by-gene estimation of variance will have few degrees of freedom. It is highly possible that the assumption of equal variance for all the expression levels may not hold. Also, the assumption of normality of gene expressions may not hold. Thus it is essential to have a statistical procedure which is not based on the normality assumption and also it can detect genes with differential variance efficiently. The detection of differential gene expression variance will allow us to identify experimental variables that affect different biological processes and accuracy of DNA microarray measurements.In this article, a new nonparametric test for scale is developed based on the arctangent of the ratio of two expression levels. Most of the tests available in literature require the assumption of normal distribution, which makes them inapplicable in many situations, and it is also hard to verify the suitability of the normal distribution assumption for the given data set. The proposed test does not require the assumption of the distribution for the underlying population and hence makes it more practical and widely applicable. The asymptotic relative efficiency is calculated under different distributions, which show that the proposed test is very powerful when the assumption of normality breaks down. Monte Carlo simulation studies are performed to compare the power of the proposed test with some of the existing procedures. It is found that the proposed test is more powerful than commonly used tests under almost all the distributions considered in the study. A

  15. Recommended Reference Genes for Quantitative PCR Analysis in Soybean Have Variable Stabilities during Diverse Biotic Stresses.

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    Raman Bansal

    Full Text Available For real-time reverse transcription-PCR (qRT-PCR in soybean, reference genes in different tissues, developmental stages, various cultivars, and under stress conditions have been suggested but their usefulness for research on soybean under various biotic stresses occurring in North-Central U.S. is not known. Here, we investigated the expression stabilities of ten previously recommended reference genes (ABCT, CYP, EF1A, FBOX, GPDH, RPL30, TUA4, TUB4, TUA5, and UNK2 in soybean under biotic stress from Bean pod mottle virus (BPMV, powdery mildew (PMD, soybean aphid (SBA, and two-spotted spider mite (TSSM. BPMV, PMD, SBA, and TSSM are amongst the most common pest problems on soybean in North-Central U.S. and other regions. Reference gene stability was determined using three software algorithms (geNorm, NormFinder, BestKeeper and a web-based tool (RefFinder. Reference genes showed variability in their expression as well as stability across various stressors and the best reference genes were stress-dependent. ABCT and FBOX were found to be the most stable in soybean under both BPMV and SBA stress but these genes had only minimal to moderate stability during PMD and TSSM stress. Expression of TUA4 and CYP was found to be most stable during PMD stress; TUB4 and TUA4 were stable under TSSM stress. Under various biotic stresses on soybean analyzed, GPDH expression was found to be consistently unstable. For all biotic stressors on soybean, we obtained pairwise variation (V2/3 values less than 0.15 which suggested that combined use of the two most stable reference genes would be sufficient for normalization. Further, we demonstrated the utility of normalizing the qRT-PCR data for target genes using the most stable reference genes validated in current study. Following of the recommendations from our current study will enable an accurate and reliable normalization of qRT-PCR data in soybean under biotic stress.

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

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    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.

  17. The importance of immune gene variability (MHC in evolutionary ecology and conservation

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    Sommer Simone

    2005-10-01

    Full Text Available Abstract Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs. However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC. MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I

  18. Defect in IgV gene somatic hypermutation in common variable immuno-deficiency syndrome.

    Science.gov (United States)

    Levy, Y; Gupta, N; Le Deist, F; Garcia, C; Fischer, A; Weill, J C; Reynaud, C A

    1998-10-27

    Common Variable Immuno-Deficiency (CVID) is the most common symptomatic primary antibody-deficiency syndrome, but the basic immunologic defects underlying this syndrome are not well defined. We report here that among eight patients studied (six CVID and two hypogammaglobulinemic patients with recurrent infections), there is in two CVID patients a dramatic reduction in Ig V gene somatic hypermutation with 40-75% of IgG transcripts totally devoid of mutations in the circulating memory B cell compartment. Functional assays of the T cell compartment point to an intrinsic B cell defect in the process of antibody affinity maturation in these two cases.

  19. 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.

  20. 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

  1. 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

  2. Expression patterns of the aquaporin gene family during renal development: influence of genetic variability.

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    Parreira, Kleber S; Debaix, Huguette; Cnops, Yvette; Geffers, Lars; Devuyst, Olivier

    2009-08-01

    High-throughput analyses have shown that aquaporins (AQPs) belong to a cluster of genes that are differentially expressed during kidney organogenesis. However, the spatiotemporal expression patterns of the AQP gene family during tubular maturation and the potential influence of genetic variation on these patterns and on water handling remain unknown. We investigated the expression patterns of all AQP isoforms in fetal (E13.5 to E18.5), postnatal (P1 to P28), and adult (9 weeks) kidneys of inbred (C57BL/6J) and outbred (CD-1) mice. Using quantitative polymerase chain reaction (PCR), we evidenced two mRNA patterns during tubular maturation in C57 mice. The AQPs 1-7-11 showed an early (from E14.5) and progressive increase to adult levels, similar to the mRNA pattern observed for proximal tubule markers (Megalin, NaPi-IIa, OAT1) and reflecting the continuous increase in renal cortical structures during development. By contrast, AQPs 2-3-4 showed a later (E15.5) and more abrupt increase, with transient postnatal overexpression. Most AQP genes were expressed earlier and/or stronger in maturing CD-1 kidneys. Furthermore, adult CD-1 kidneys expressed more AQP2 in the collecting ducts, which was reflected by a significant delay in excreting a water load. The expression patterns of proximal vs. distal AQPs and the earlier expression in the CD-1 strain were confirmed by immunoblotting and immunostaining. These data (1) substantiate the clustering of important genes during tubular maturation and (2) demonstrate that genetic variability influences the regulation of the AQP gene family during tubular maturation and water handling by the mature kidney.

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

    Science.gov (United States)

    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.

  4. 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

  5. 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 (P<0.05, two-tailed Mann-Whitney U test). The results suggest that there may be at least two groups of P. multocida in sheep - a genetically homogeneous group that resides in the respiratory tract and a genetically heterogeneous group that is the predominant cause of disease.

  6. 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

  7. Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder.

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    Galimberti, Daniela; Prunas, Cecilia; Paoli, Riccardo A; Dell'Osso, Bernardo; Fenoglio, Chiara; Villa, Chiara; Palazzo, Carlotta; Cigliobianco, Michela; Camuri, Giulia; Serpente, Maria; Scarpini, Elio; Altamura, A Carlo

    2014-11-01

    Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]. Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure

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    Moyer, E. L.; Al-Shayeb, B.; Baer, L. A.; Ronca, A. E.

    2016-01-01

    Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hyper-gravity demonstrated significantly increased (8-15%) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported a similar outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes and the plasma of animals treated with our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats.

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

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

    2014-02-01

    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 (Capsicum 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 Capsium 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. Copyright © 2013. Published by Elsevier Ireland Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Genetic variability of Echinococcus granulosus based on the mitochondrial 16S ribosomal RNA gene.

    Science.gov (United States)

    Wang, Ning; Wang, Jiahai; Hu, Dandan; Zhong, Xiuqin; Jiang, Zhongrong; Yang, Aiguo; Deng, Shijin; Guo, Li; Tsering, Dawa; Wang, Shuxian; Gu, Xiaobin; Peng, Xuerong; Yang, Guangyou

    2015-06-01

    Echinococcus granulosus is the etiological agent of cystic echinococcosis, a major zoonotic disease of both humans and animals. In this study, we assessed genetic variability and genetic structure of E. granulosus in the Tibet plateau, using the complete mitochondrial 16 S ribosomal RNA gene for the first time. We collected and sequenced 62 isolates of E. granulosus from 3 populations in the Tibet plateau. A BLAST analysis indicated that 61 isolates belonged to E. granulosus sensu stricto (genotypes G1-G3), while one isolate belonged to E. canadensis (genotype G6). We detected 16 haplotypes with a haplotype network revealing a star-like expansion, with the most common haplotype occupying the center of the network. Haplotype diversity and nucleotide diversity were low, while negative values were observed for Tajima's D and Fu's Fs. AMOVA results and Fst values revealed that the three geographic populations were not genetically differentiated. Our results suggest that a population bottleneck or population expansion has occurred in the past, and that this explains the low genetic variability of E. granulosus in the Tibet Plateau.

  12. Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements

    International Nuclear Information System (INIS)

    Schroeder, H.W. Jr.; Walter, M.A.; Hofker, M.H.; Ebens, A.; Van Dijk, K.W.; Liao, L.C.; Cox, D.W.; Milner, E.C.B.; Perlmutter, R.M.

    1988-01-01

    Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (V H ), diversity (D H ), and joining (J H ) region gene segments appears preferentially in the human fetal repertoire. The authors report here that one of these early-expressed V H elements (termed V H 6) is the most 3' V H gene segment, positioned 77 kilobases on the 5' side of the J H locus and immediately adjacent to a set of previously described D H sequences. In addition to providing a physical map linking human V H , D H , and J H elements, these results support the view that the programmed development of the antibody V H repertoire is determined in part by the chromosomal position of these gene segments

  13. Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women’s Cancers

    Science.gov (United States)

    Bartlett, Thomas E.; Jones, Allison; Goode, Ellen L.; Fridley, Brooke L.; Cunningham, Julie M.; Berns, Els M. J. J.; Wik, Elisabeth; Salvesen, Helga B.; Davidson, Ben; Trope, Claes G.; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin

    2015-01-01

    We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes. PMID:26629914

  14. 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.

  15. T-cell receptor variable genes and genetic susceptibility to celiac disease: an association and linkage study.

    Science.gov (United States)

    Roschmann, E; Wienker, T F; Gerok, W; Volk, B A

    1993-12-01

    Genetic susceptibility of celiac disease is primarily associated with a particular combination of and HLA-DQA1/DQB1 gene; however, this does not fully account for the genetic predisposition. Therefore, the aim of this study was to examine whether T-cell receptor (TCR) genes may be susceptibility genes in celiac disease. HLA class II typing was performed by polymerase chain reaction amplification in combination with sequence-specific oligonucleotide hybridization. TCR alpha (TCRA), TCR gamma (TCRG), and TCR beta (TCRB) loci were investigated by restriction fragment length polymorphism analysis. Allelic frequencies of TCRA, TCRG, and TCRB variable genes were compared between patients with celiac disease (n = 53) and control patients (n = 67), and relative risk (RR) estimates were calculated. The RR was 1.67 for allele C1 at TCRA1, 3.35 for allele D2 at TCRA2, 1.66 for allele B2 at TCRG, and 1.35 for allele B at TCRB, showing no significant association. Additionally, linkage analysis was performed in 23 families. The logarithm of odd scores for celiac disease vs. the TCR variable genes at TCRA, TCRG, and TCRB showed no significant linkage. These data suggest that the analyzed TCR variable gene segments V alpha 1.2, V gamma 11, and V beta 8 do not play a major role in susceptibility to celiac disease.

  16. Comparative Genetic Variability in HIV-1 Subtype C vpu Gene in Early Age Groups of Infants.

    Science.gov (United States)

    Sharma, Uma; Gupta, Poonam; Gupta, Sunil; Venkatesh, S; Husain, Mohammad

    2018-01-01

    Identifying the genetic variability in vertically transmitted viruses in early infancy is important to understand the disease progression. Being important in HIV-1 disease pathogenesis, vpu gene, isolated from young infants was investigated to understand the viral characteristics. Blood samples were obtained from 80 HIV-1 positive infants, categorized in two age groups; acute (6-18 months). A total of 77 PCR positive samples, amplified for vpu gene, were sequenced and analyzed. 73 isolates belonged to subtype C. Analysis of heterogeneity of amino acid sequences in infant groups showed that in the sequences of acute age group both insertions and deletions were present while in the early age group only deletions were present. In the acute age group, a deletion of 3 residues (RAE) in the first alfa helix in one sequence and insertions of 1-2 residues (DM, GH, G and H) in the second alfa helix in 4 sequences were observed. In the early age group, deletion of 2 residues (VN) in the cytoplasmic tail region in 2 sequences was observed. Length of the amino terminal was observed to be gradually increasing with the increasing age of the infants. Protein Variation Effect Analyzer software showed that deleterious mutations were more in the acute than the early age group. Entropy analysis revealed that heterogeneity of the residues was comparatively higher in the sequences of acute than the early age group. Mutations observed in the helixes may affect the conformation and lose the ability to degrade CD4 receptors. Heterogeneity was decreasing with the increasing ages of the infants, indicating positive selection for robust virion survival. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Interleukin 6 variable number of tandem repeats (VNTR) gene polymorphism in centenarians.

    Science.gov (United States)

    Capurso, C; Solfrizzi, V; D'Introno, A; Colacicco, A M; Capurso, S A; Semeraro, C; Capurso, A; Panza, F

    2007-11-01

    Recent population-based studies identified the magnitude of interleukin 6 (IL6) serum levels as a marker for functional disability, and a predictor of disability and mortality among the elderly. We investigated whether there was evidence in Southern Italy of an association between the IL6 gene variable number of tandem repeats (VNTR) polymorphism and extreme longevity, and tested for the possible interaction of apolipoprotein E (APOE) alleles with the IL6 VNTR alleles. Four alleles coding for variants of four different lengths have been identified: allele A [760 base pairs (bp)], allele B (680 bp), allele C (640 bp), and allele D (610 bp). IL6 VNTR and APOE allele and genotype frequencies were studied in a total of 61 centenarians and 94 middle-aged subjects from Southern Italy. The IL6 VNTR allele B was overrepresented in the younger control group compared with centenarians (odds ratio: 0.56, 95% confidence interval: 0.35-0.88, Bonferroni p-value VNTR alleles and APOE alleles on the odds ratios to reach extreme longevity were evaluated for the smallest number of subjects in centenarians and younger controls. Our findings suggested that the presence of the IL6 VNTR allele B could be detrimental for reaching extreme longevity.

  18. Insights into variability of actinorhodopsin genes of the LG1 cluster in two different freshwater habitats.

    Directory of Open Access Journals (Sweden)

    Jitka Jezberová

    Full Text Available Actinorhodopsins (ActRs are recently discovered proteorhodopsins present in Actinobacteria, enabling them to adapt to a wider spectrum of environmental conditions. Frequently, a large fraction of freshwater bacterioplankton belongs to the acI lineage of Actinobacteria and codes the LG1 type of ActRs. In this paper we studied the genotype variability of the LG1 ActRs. We have constructed two clone libraries originating from two environmentally different habitats located in Central Europe; the large alkaline lake Mondsee (Austria and the small humic reservoir Jiřická (the Czech Republic. The 75 yielded clones were phylogenetically analyzed together with all ActR sequences currently available in public databases. Altogether 156 sequences were analyzed and 13 clusters of ActRs were distinguished. Newly obtained clones are distributed over all three LG1 subgroups--LG1-A, B and C. Eighty percent of the sequences belonged to the acI lineage (LG1-A ActR gene bearers further divided into LG1-A1 and LG1-A2 subgroups. Interestingly, the two habitats markedly differed in genotype composition with no identical sequence found in both samples of clones. Moreover, Jiřická reservoir contained three so far not reported clusters, one of them LG1-C related, presenting thus completely new, so far undescribed, genotypes of Actinobacteria in freshwaters.

  19. Tools to Minimize Inter-Laboratory Variability in Vitellogenin Gene Expression Monitoring Programs

    Data.gov (United States)

    U.S. Environmental Protection Agency — All data files are in excel format. Files with names CSU are different mesocosms qPCR data results for vitellogen gene and 18s a house keeping gene. Data files...

  20. Progranulin gene variability and plasma levels in bipolar disorder and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Daniela Galimberti

    Full Text Available Basing on the assumption that frontotemporal lobar degeneration (FTLD, schizophrenia and bipolar disorder (BPD might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN in a German population of patients with schizophrenia (n = 271 or BPD (n = 237 as compared with 574 age-, gender- and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls.A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR:0.63, 95%CI:0.49-0.80, rs4792938 (30.7 versus 39.7%, P = 0.005, OR: 0.70, 95%CI: 0.55-0.89 and rs5848 (30.3 versus 36.8, P = 0.007, OR: 0.71, 95%CI: 0.56-0.91. Mean±SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69±3.97 and 116.14±5.80 ng/ml, respectively, versus 180.81±18.39 ng/ml P<0.001 and were not correlated with age.In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results.

  1. Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Kim, Bung-Nyun; Kim, Jae-Won; Cummins, Tarrant D R; Bellgrove, Mark A; Hawi, Ziarih; Hong, Soon-Beom; Yang, Young-Hui; Kim, Hyo-Jin; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

    2013-06-01

    Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time

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

    African Journals Online (AJOL)

    These polymorphisms were confirmed by direct sequencing. The comparative gene sequence analysis in cattle and buffalo breeds revealed 18 single nucleotide polymorphisms (SNPs) across different loci. Eight SNPs were detected in the bovine growth hormone receptor (GHR) gene, of which four were found in the ...

  3. Incidence of temonera, sulphuhydryl variables and cefotaximase genes associated with ?-lactamase producing escherichia coli in clinical isolates

    OpenAIRE

    Isaiah, Ibeh Nnana; Nche, Bikwe Thomas; Nwagu, Ibeh Georgina; Nwagu, Ibeh Isaiah

    2011-01-01

    Background: The occurrence of the different types of Extended spectrum beta Lactamase producing Escherichia coli with the, Sulphurhydryl variable, Temonera and the Cefotaximase have been on the rise Aim: The study was to determine the prevalence of extended spectrum beta lactamase gene resistance across the clinical isolates of hospitalized patients. Materials and Method: Three hundred and fifty isolates of Escherichia coli were received from different clinical specimens. The susceptibility p...

  4. 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 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 for multiple comparisons). In conclusion, alleles of the VNTR are expressed at the

  5. 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.

  6. 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.

  7. 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.

  8. The evolution of highly variable immunity genes across a passerine bird radiation.

    Science.gov (United States)

    O'Connor, E A; Strandh, M; Hasselquist, D; Nilsson, J-Å; Westerdahl, H

    2016-02-01

    To survive, individuals must be able to recognize and eliminate pathogens. The genes of the major histocompatibility complex (MHC) play an essential role in this process in vertebrates as their diversity affects the repertoire of pathogens that can be recognized by the immune system. Emerging evidence suggests that birds within the parvorder Passerida possess an exceptionally high number of MHC genes. However, this has yet to be directly investigated using a consistent framework, and the question of how this MHC diversity has evolved has not been addressed. We used next-generation sequencing to investigate how MHC class I gene copy number and sequence diversity varies across the Passerida radiation using twelve species chosen to represent the phylogenetic range of this group. Additionally, we performed phylogenetic analyses on this data to identify, for the first time, the evolutionary model that best describes how MHC class I gene diversity has evolved within Passerida. We found evidence of multiple MHC class I genes in every family tested, with an extremely broad range in gene copy number across Passerida. There was a strong phylogenetic signal in MHC gene copy number and diversity, and these traits appear to have evolved through a process of Brownian motion in the species studied, that is following the pattern of genetic drift or fluctuating selection, as opposed to towards a single optimal value or through evolutionary 'bursts'. By characterizing MHC class I gene diversity across Passerida in a systematic framework, this study provides a first step towards understanding this huge variation. © 2016 John Wiley & Sons Ltd.

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes.

    NARCIS (Netherlands)

    Menko, F.H.; Kneepkens, C.M.; Leeuw, N. de; Peeters, E.A.; Maldergem, L. van; Kamsteeg, E.J.; Davidson, R.; Rozendaal, L.; Lasham, C.A.; Peeters-Scholte, C.M.; Jansweijer, M.C.E.; Hilhorst-Hofstee, Y.; Gille, J.J.P.; Heins, Y.M.; Nieuwint, A.W.; Sistermans, E.A.

    2008-01-01

    Infantile juvenile polyposis is a rare disease with severe gastrointestinal symptoms and a grave clinical course. Recently, 10q23 microdeletions involving the PTEN and BMPR1A genes were found in four patients with infantile juvenile polyposis. It was hypothesized that a combined and synergistic

  14. Variability and repertoire size of T-cell receptor V alpha gene segments.

    Science.gov (United States)

    Becker, D M; Pattern, P; Chien, Y; Yokota, T; Eshhar, Z; Giedlin, M; Gascoigne, N R; Goodnow, C; Wolf, R; Arai, K

    The immune system of higher organisms is composed largely of two distinct cell types, B lymphocytes and T lymphocytes, each of which is independently capable of recognizing an enormous number of distinct entities through their antigen receptors; surface immunoglobulin in the case of the former, and the T-cell receptor (TCR) in the case of the latter. In both cell types, the genes encoding the antigen receptors consist of multiple gene segments which recombine during maturation to produce many possible peptides. One striking difference between B- and T-cell recognition that has not yet been resolved by the structural data is the fact that T cells generally require a major histocompatibility determinant together with an antigen whereas, in most cases, antibodies recognize antigen alone. Recently, we and others have found that a series of TCR V beta gene sequences show conservation of many of the same residues that are conserved between heavy- and light-chain immunoglobulin V regions, and these V beta sequences are predicted to have an immunoglobulin-like secondary structure. To extend these studies, we have isolated and sequenced eight additional alpha-chain complementary cDNA clones and compared them with published sequences. Analyses of these sequences, reported here, indicate that V alpha regions have many of the characteristics of V beta gene segments but differ in that they almost always occur as cross-hybridizing gene families. We conclude that there may be very different selective pressures operating on V alpha and V beta sequences and that the V alpha repertoire may be considerably larger than that of V beta.

  15. Variable Copy Number, Intra-Genomic Heterogeneities and Lateral Transfers of the 16S rRNA Gene in Pseudomonas

    Science.gov (United States)

    Bodilis, Josselin; Nsigue-Meilo, Sandrine; Besaury, Ludovic; Quillet, Laurent

    2012-01-01

    Even though the 16S rRNA gene is the most commonly used taxonomic marker in microbial ecology, its poor resolution is still not fully understood at the intra-genus level. In this work, the number of rRNA gene operons, intra-genomic heterogeneities and lateral transfers were investigated at a fine-scale resolution, throughout the Pseudomonas genus. In addition to nineteen sequenced Pseudomonas strains, we determined the 16S rRNA copy number in four other Pseudomonas strains by Southern hybridization and Pulsed-Field Gel Electrophoresis, and studied the intra-genomic heterogeneities by Denaturing Gradient Gel Electrophoresis and sequencing. Although the variable copy number (from four to seven) seems to be correlated with the evolutionary distance, some close strains in the P. fluorescens lineage showed a different number of 16S rRNA genes, whereas all the strains in the P. aeruginosa lineage displayed the same number of genes (four copies). Further study of the intra-genomic heterogeneities revealed that most of the Pseudomonas strains (15 out of 19 strains) had at least two different 16S rRNA alleles. A great difference (5 or 19 nucleotides, essentially grouped near the V1 hypervariable region) was observed only in two sequenced strains. In one of our strains studied (MFY30 strain), we found a difference of 12 nucleotides (grouped in the V3 hypervariable region) between copies of the 16S rRNA gene. Finally, occurrence of partial lateral transfers of the 16S rRNA gene was further investigated in 1803 full-length sequences of Pseudomonas available in the databases. Remarkably, we found that the two most variable regions (the V1 and V3 hypervariable regions) had probably been laterally transferred from another evolutionary distant Pseudomonas strain for at least 48.3 and 41.6% of the 16S rRNA sequences, respectively. In conclusion, we strongly recommend removing these regions of the 16S rRNA gene during the intra-genus diversity studies. PMID:22545126

  16. Expression of activation-induced cytidine deaminase gene in B lymphocytes of patients with common variable immunodeficiency.

    Science.gov (United States)

    Abolhassani, Hassan; Farrokhi, Amir Salek; Pourhamdi, Shabnam; Mohammadinejad, Payam; Sadeghi, Bamdad; Moazzeni, Seyed-Mohammad; Aghamohammadi, Asghar

    2013-08-01

    Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by reduced serum level of IgG, IgA or IgM and recurrent bacterial infections. Class switch recombination (CSR) as a critical process in immunoglobulin production is defective in a group of CVID patients. Activation-induced cytidine deaminase (AID) protein is an important molecule involving CSR process. The aim of this study was to investigate the AID gene mRNA production in a group of CVID patients indicating possible role of this molecule in this disorder. Peripheral blood mononuclear cells (PBMC) of 29 CVID patients and 21 healthy controls were isolated and stimulated by CD40L and IL-4 to induce AID gene expression. After 5 days AID gene mRNA production was investigated by real time polymerase chain reaction. AID gene was expressed in all of the studied patients. However the mean density of extracted AID mRNA showed higher level in CVID patients (230.95±103.04 ng/ml) rather than controls (210.00±44.72 ng/ml; P=0.5). CVID cases with lower level of AID had decreased total level of IgE (P=0.04) and stimulated IgE production (P=0.02); while cases with increased level of AID presented higher level of IgA (P=0.04) and numbers of B cells (P=0.02) and autoimmune disease (P=0.02). Different levels of AID gene expression may have important roles in dysregulation of immune system and final clinical presentation in CVID patients. Therefore investigating the expression of AID gene can help in classifying CVID patients.

  17. Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia.

    Science.gov (United States)

    Novakovic, Boris; Evain-Brion, Danièle; Murthi, Padma; Fournier, Thiery; Saffery, Richard

    2017-06-01

    placental development and function.-Novakovic, B., Evain-Brion, D., Murthi, P., Fournier, T., Saffery, R. Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia. © FASEB.

  18. Gene expression in response to Cotton Leaf Curl Virus infection in Gossypium hirsutum under variable environmental conditions

    Directory of Open Access Journals (Sweden)

    Rehman Iqra

    2017-01-01

    Full Text Available Cotton Leaf Curl Disease (CLCuD is one of the threatening constrains of cotton production in Pakistan for which no adequate remedy is available until now. Local variety of Gossypium hirsutum (FH-142 was grown in field and infected naturally by CLCuV under variable range of temperature and humidity. Plants showed thickening of veins in lower leaf surface at 34°C and 60% relative humidity at 15days post infection (dpi and curling of leaf margins at 33°C with 58% relative humidity at 30dpi. Remarkable leaf darkening was observed with reduced boll formation at 45dpi at 26°C and 41% relative humidity. Enation developed, severe thickening and curling of leaves intensified and plants showed dwarf growth at 60dpi at 24°C with 52% relative humidity. PCR amplification of Rep associated gene confirmed the presence of CLCuD-associated begomovirus in the infected samples. Quantitative RT-PCR confirmed the amplification and differential expression of a number of pathogen stress responsive genes at different levels of temperature and humidity. This observation predicts that Cotton Leaf Curl Virus (CLCuV interacts with several host genes that are upregulated to make plants susceptible or suppress other genes to overcome host defense responses.

  19. Using Variable Precision Rough Set for Selection and Classification of Biological Knowledge Integrated in DNA Gene Expression

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    Calvo-Dmgz D.

    2012-12-01

    Full Text Available DNA microarrays have contributed to the exponential growth of genomic and experimental data in the last decade. This large amount of gene expression data has been used by researchers seeking diagnosis of diseases like cancer using machine learning methods. In turn, explicit biological knowledge about gene functions has also grown tremendously over the last decade. This work integrates explicit biological knowledge, provided as gene sets, into the classication process by means of Variable Precision Rough Set Theory (VPRS. The proposed model is able to highlight which part of the provided biological knowledge has been important for classification. This paper presents a novel model for microarray data classification which is able to incorporate prior biological knowledge in the form of gene sets. Based on this knowledge, we transform the input microarray data into supergenes, and then we apply rough set theory to select the most promising supergenes and to derive a set of easy interpretable classification rules. The proposed model is evaluated over three breast cancer microarrays datasets obtaining successful results compared to classical classification techniques. The experimental results shows that there are not significat differences between our model and classical techniques but it is able to provide a biological-interpretable explanation of how it classifies new samples.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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

    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....

  4. Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus

    DEFF Research Database (Denmark)

    Hansen, L; Jensen, J N; Ekstrøm, C T

    2001-01-01

    Phosphatase and tensin homologue deleted from chromosome ten (PTEN) has recently been characterized as a novel member in the expanding network of proteins regulating the intracellular effects of insulin. By dephosphorylation of phosphatidyl-inositol-(3, 4, 5)-trisphosphate (PIP3) the PTEN protein...... regulates the insulin-dependent phosphoinositide 3-kinase (PI3K) signalling cassette and accordingly might function as a regulator of insulin sensitivity in skeletal muscle and adipose tissue. In this study we tested PTEN as a candidate gene for insulin resistance and late-onset Type II (non...

  5. Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature.

    Science.gov (United States)

    Thomas, N Simon; Harvey, John F; Bunyan, David J; Rankin, Julia; Grigelioniene, Giedre; Bruno, Damien L; Tan, Tiong Y; Tomkins, Susan; Hastings, Robert

    2009-07-01

    Deletions of the SHOX gene are well documented and cause disproportionate short stature and variable skeletal abnormalities. In contrast interstitial SHOX duplications limited to PAR1 appear to be very rare and the clinical significance of the only case report in the literature is unclear. Mapping of this duplication has now shown that it includes the entire SHOX gene but little flanking sequence and so will not encompass any of the long-range enhancers required for SHOX transcription. We now describe the clinical and molecular characterization of three additional cases. The duplications all included the SHOX coding sequence but varied in the amount of flanking sequence involved. The probands were ascertained for a variety of reasons: hypotonia and features of Asperger syndrome, Leri-Weill dyschondrosteosis (LWD), and a family history of cleft palate. However, the presence of a duplication did not correlate with any of these features or with evidence of skeletal abnormality. Remarkably, the proband with LWD had inherited both a SHOX deletion and a duplication. The effect of the duplications on stature was variable: height appeared to be elevated in some carriers, particularly in those with the largest duplications, but was still within the normal range. SHOX duplications are likely to be under ascertained and more cases need to be identified and characterized in detail in order to accurately determine their phenotypic consequences.

  6. Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene.

    Science.gov (United States)

    Eisenkraft, Arik; Pode-Shakked, Ben; Goldstein, Nurit; Shpirer, Zvi; van Bokhoven, Hans; Anikster, Yair

    2015-01-01

    Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish descent, in which the index patient presented with a persistent scalp skin lesion, dystrophic nails and light thin hair. Further evaluation revealed over 10 affected individuals in the kindred, over four generations, exhibiting varying degrees of ectodermal involvement. Analysis of the TP63 gene from four of the patients and from two healthy individuals of the same family was performed. Gene sequencing of the patients revealed a nonsense mutation leading to a premature termination codon (PTC) (p.Gln16X). The same mutation was found in all tested affected individuals in the family, but gave rise to marked phenotypic variability with minor clinical manifestations in some individuals, underscoring the clinical heterogeneity associated with the recently described PTC-causing mutations.

  7. 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

  8. 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

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

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    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.

  10. 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...... 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...

  11. Variability of the caprine whey protein genes and their association with milk yield, composition and renneting properties in the Sarda breed: 2. The BLG gene.

    Science.gov (United States)

    Dettori, Maria Luisa; Pazzola, Michele; Pira, Emanuela; Puggioni, Ornella; Vacca, Giuseppe Massimo

    2015-11-01

    The variability of the promoter region and the 3'UTR (exon-7) of the BLG gene, encoding the β-lactoglobulin, was investigated by sequencing in 263 lactating Sarda goats in order to assess its association with milk traits. Milk traits included: milk yield, fat, total protein and lactose content, pH, daily fat and protein yield (DFPY), freezing point, milk energy, somatic cell count, total microbial mesophilic count, rennet coagulation time (RCT), curd firming rate (k20) and curd firmness (a30). A total of 7 polymorphic sites were detected and the sequence analysed was given accession number KM817769. Only three SNPs (c.-381C>T, c.-323C>T and c.*420C>A) had minor allele frequency higher than 0.05. The effects of farm, stage of lactation and the interaction farm × stage of lactation significantly influenced all the milk traits (P T and c.*420C>A (P T (P < 0.001). The c.-381TT homozygous goats showed lower pH, RCT and k20 than c.-381CT (P < 0.05). In conclusion the polymorphism of the goat BLG gene did not affect the total protein content of the Sarda goat milk, and only weakly influenced RCT and k20. On the other hand, an interesting effect on milk yields and DFPY emerged in two SNPs. This information might be useful in dairy goat breeding programs.

  12. Functional Versatility of AGY Serine Codons in Immunoglobulin Variable Region Genes

    Directory of Open Access Journals (Sweden)

    Thiago Detanico

    2016-11-01

    Full Text Available In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ag often arise by somatic hypermutation (SHM that converts AGT and AGC (AGY Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase (AID, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in anti-viral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses, and found that mutations producing Arg codons in anti-viral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with antigen (Ag. In many cases, mutations producing codons for these alternative amino acids in anti-viral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which 2/3rds of random mutations generate codons for these key residues. Finally, by directly analyzing x-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via somatic hypermutation occurred more often at AGY than at any other codon group. Thus, preservation of

  13. 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

  14. Nucleotide variability in the 5-enolpyruvylshikimate-3-phosphate synthase gene from Eleusine indica (L.) Gaertn.

    Science.gov (United States)

    Chong, J L; Wickneswari, R; Ismail, B S; Salmijah, S

    2008-02-01

    This study reports the results of the partial DNA sequence analysis of the 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant (R) and glyphosate-susceptible (S) biotypes of Eleusine indica (L.) Gaertn from Peninsular Malaysia. Sequencing results revealed point mutation at nucleotide position 875 in the R biotypes of Bidor, Chaah and Temerloh. In the Chaah R population, substitution of cytosine (C) to adenine (A) resulted in the change of threonine (Thr106) to proline (Pro106) and from C to thymidine (T) in the Bidor R population, leading to serine (Ser106) from Pro106. As for the Temerloh R, C was substituted by T resulting in the change of Pro106 to Ser106. A new mutation previously undetected in the Temerloh R was revealed with C being substituted with A, resulting in the change of Pro106 to Thr106 indicating multiple founding events rather than to the spread of a single resistant allele. There was no point mutation recorded at nucleotide position 875 previously demonstrated to play a pivotal role in conferring glyphosate resistance to E. indica for the Lenggeng, Kuala Selangor, Melaka R populations. Thus, there may be another resistance mechanism yet undiscovered in the resistant Lenggeng, Kuala Selangor and Melaka populations.

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

    Science.gov (United States)

    Krishnan, Neeraja M; Seligmann, Hervé; Rao, Basuthkar J

    2008-01-28

    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. 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. 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 strategies. These converge with increasing domestication levels of

  16. Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability.

    Science.gov (United States)

    Aller, E; Jaijo, T; Oltra, S; Alió, J; Galán, F; Nájera, C; Beneyto, M; Millán, J M

    2004-12-01

    Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is named clarin-1 and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening for mutations in clarin-1 gene among our series of Usher syndrome Spanish patients. Clarin-1 has been found to be responsible for the disease in only two families: the first one is a previously reported family homozygous for Y63X mutation and the second one, described here, is homozygous for C40G. This accounts for 1.7% of Usher syndrome Spanish families. It is noticeable that, whereas C40G family is clinically compatible with Usher syndrome type III due to the progression of the hearing loss, Y63X family could be diagnosed as Usher syndrome type I because the hearing impairment is profound and stable. Thus, we consider that the progression of hearing loss is not the definitive key parameter to distinguish Usher syndrome type III from Usher syndrome type I and Usher syndrome type II.

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

    Science.gov (United States)

    Eves-van den Akker, Sebastian; Lilley, Catherine J; Jones, John T; Urwin, Peter E

    2014-09-01

    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.

  18. 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.

  19. FLO1 is a variable green beard gene that drives biofilm-like cooperation in budding yeast

    Science.gov (United States)

    Smukalla, Scott; Caldara, Marina; Pochet, Nathalie; Beauvais, Anne; Guadagnini, Stephanie; Yan, Chen; Vinces, Marcelo D.; Jansen, An; Prevost, Marie Christine; Latgé, Jean-Paul; Fink, Gerald R.; Foster, Kevin R.; Verstrepen, Kevin J.

    2008-01-01

    Summary The budding yeast, Saccharomyces cerevisiae, has emerged as an archetype of eukaryotic cell biology. Here we show that S. cerevisiae is also a model for the evolution of cooperative behavior by revisiting flocculation, a self-adherence phenotype lacking in most laboratory strains. Expression of the gene FLO1 in the laboratory strain S288C restores flocculation, an altered physiological state, reminiscent of bacterial biofilms. Flocculation protects the FLO1-expressing cells from multiple stresses, including antimicrobials and ethanol. Furthermore, FLO1+ cells avoid exploitation by non-expressing flo1 cells by self/non-self recognition: FLO1+ cells preferentially stick to one another, regardless of genetic relatedness across the rest of the genome. Flocculation, therefore, is driven by one of a few known “green beard genes”, which direct cooperation towards other carriers of the same gene. Moreover, FLO1 is highly variable among strains both in expression and in sequence, suggesting that flocculation in S. cerevisiae is a dynamic, rapidly-evolving social trait. PMID:19013280

  20. Incidence of temonera, sulphuhydryl variables and cefotaximase genes associated with β-lactamase producing escherichia coli in clinical isolates

    Science.gov (United States)

    Isaiah, Ibeh Nnana; Nche, Bikwe Thomas; Nwagu, Ibeh Georgina; Nwagu, Ibeh Isaiah

    2011-01-01

    Background: the occurrence of the different types of Extended spectrum beta Lactamase producing Escherichia coli with the, Sulphurhydryl variable, Temonera and the Cefotaximase have been on the rise Aim: The study was to determine the prevalence of extended spectrum beta lactamase gene resistance across the clinical isolates of hospitalized patients. Materials and Method: Three hundred and fifty isolates of Escherichia coli were received from different clinical specimens. The susceptibility profile of the isolates against 10 different antibiotics was examined, the MICs (Minimum Inhibitory Concentration) for ceftazidime were also determined using micro-broth dilution assay. Isolates showing MIC ≥ 6 μg/ml for ceftazidime were screened for ESBL (PCT)phenotypic confirmatory test and subjected to PCR (polymerase chain reaction) to further. Results: By disk diffusion test, there was resistance to ceftazidime and cefotaxime were 180(51.4%) and 120 (34.2%) respectively. However, all strains were susceptible to imipenem. 250 isolates showed MICs≥ 6 μg/ml for ceftazidime of which 180 (72%) were positive for extended spectrum beta lactamase. The prevalence of Sulphurhydryl variable, Temonera and the Cefotaximase among these isolates were 17.1%, 6.6% and 17%, respectively. Conclusion: For the identification of extended spectrum beta lactamase producing isolates it is recommended that clinical laboratories adopt simple test based on Cinical laboratory standard institute recommendation for confirming extended spectrum beta lactamase production in enterobacteriacea species. PMID:22363078

  1. Transcription of the var genes from a freshly-obtained field isolate of Plasmodium falciparum shows more variable switching patterns than long laboratory-adapted isolates.

    Science.gov (United States)

    Ye, Run; Zhang, Dongmei; Chen, Biaobang; Zhu, Yongqiang; Zhang, Yilong; Wang, Shengyue; Pan, Weiqing

    2015-02-07

    Antigenic variation in Plasmodium falciparum involves switching among multicopy var gene family and is responsible for immune evasion and the maintenance of chronic infections. Current understanding of var gene expression and switching patterns comes from experiments conducted on long laboratory-adapted strains, with little known about their wild counterparts. Genome sequencing was used to obtain 50 var genes from a parasite isolated from the China-Myanmar border. Four clones with different dominant var genes were cultured in vitro in replicates for 50 generations. Transcription of the individual var gene was detected by real-time PCR and then the switching process was analysed. The expression of multicopy var genes is mutually exclusive in clones of a wild P. falciparum isolate. The activation of distinct primary dominant var genes leads to different and favoured switching patterns in the four clones. The on/off rates of individual var genes are variable and the choice of subsequent dominant var genes are random, which results in the different switching patterns among replicates of each clonal wild P. falciparum isolate with near identical initial transcription profiles. This study suggests that the switching patterns of var genes are abundant, which consist of both conserved and random parts.

  2. 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...

  3. Robust variable selection method for nonparametric differential equation models with application to nonlinear dynamic gene regulatory network analysis.

    Science.gov (United States)

    Lu, Tao

    2016-01-01

    The gene regulation network (GRN) evaluates the interactions between genes and look for models to describe the gene expression behavior. These models have many applications; for instance, by characterizing the gene expression mechanisms that cause certain disorders, it would be possible to target those genes to block the progress of the disease. Many biological processes are driven by nonlinear dynamic GRN. In this article, we propose a nonparametric differential equation (ODE) to model the nonlinear dynamic GRN. Specially, we address following questions simultaneously: (i) extract information from noisy time course gene expression data; (ii) model the nonlinear ODE through a nonparametric smoothing function; (iii) identify the important regulatory gene(s) through a group smoothly clipped absolute deviation (SCAD) approach; (iv) test the robustness of the model against possible shortening of experimental duration. We illustrate the usefulness of the model and associated statistical methods through a simulation and a real application examples.

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

    International Nuclear Information System (INIS)

    Josse, Rozenn; Dumont, Julie; Fautrel, Alain; Robin, Marie-Anne; Guillouzo, André

    2012-01-01

    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

  5. [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.

  6. 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,...

  7. Three monoclonal antibodies to the VHS virus glycoprotein: comparison of reactivity in relation to differences in immunoglobulin variable domain gene sequences

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Cupit, P.M.; Secombes, C.J.

    2000-01-01

    and their neutralising activity was evident. Binding kinetic analyses by plasmon resonance identified differences in the dissociation rate constant (kd) as a possible explanation for the different reactivity levels of the MAbs. The Ig variable heavy (VH) and light (V kappa) domain gene sequences of the three hybridomas...... were compared. The inferred amino acid sequence of the two neutralising antibody VH domains differed by three amino acid residues (97% identity) and only one residue difference was evident in the Vk. domains. In contrast, IP1H3 shared only 38 and 39% identity with the 3F1A2 and 3F1H10 VH domains...... respectively and 49 and 50% identity with the 3F1A2 and 3F1H10 VK domains respectively. The neutralising antibodies were produced by hybridomas originating from the same fusion and the high nucleotide sequence homology of the variable Ig gene regions indicated that the plasma cell partners of the hybridomas...

  8. 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.

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

    Science.gov (United States)

    Dato, Serena; De Rango, Francesco; Crocco, Paolina; Passarino, Giuseppe; Rose, Giuseppina

    2015-01-01

    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 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.

  10. Impact of strong selection for the PrP major gene on genetic variability of four French sheep breeds (Open Access publication

    Directory of Open Access Journals (Sweden)

    Pantano Thais

    2008-11-01

    Full Text Available Abstract Effective selection on the PrP gene has been implemented since October 2001 in all French sheep breeds. After four years, the ARR "resistant" allele frequency increased by about 35% in young males. The aim of this study was to evaluate the impact of this strong selection on genetic variability. It is focussed on four French sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3–4 years later. Genetic variability was assessed using genealogical and molecular data (29 microsatellite markers. The expected loss of genetic variability on the PrP gene was confirmed. Moreover, among the five markers located in the PrP region, only the three closest ones were affected. The evolution of the number of alleles, heterozygote deficiency within population, expected heterozygosity and the Reynolds distances agreed with the criteria from pedigree and pointed out that neutral genetic variability was not much affected. This trend depended on breed, i.e. on their initial states (population size, PrP frequencies and on the selection strategies for improving scrapie resistance while carrying out selection for production traits.

  11. Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene

    Energy Technology Data Exchange (ETDEWEB)

    Erichsen, Thomas J; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O; Mueller, Tordis M [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Munzel, Peter A [Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tubingen, Tubingen (Germany); Manns, Michael P [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Strassburg, Christian P. [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany)], E-mail: strassburg.christian@mh-hannover.de

    2008-07-15

    UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism.

  12. Genetic variability of aryl hydrocarbon receptor (AhR)-mediated regulation of the human UDP glucuronosyltransferase (UGT) 1A4 gene

    International Nuclear Information System (INIS)

    Erichsen, Thomas J.; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O.; Mueller, Tordis M.; Munzel, Peter A.; Manns, Michael P.; Strassburg, Christian P.

    2008-01-01

    UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism

  13. No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.

    Science.gov (United States)

    Bienertova-Vasku, Julie; Bienert, Petr; Tomandl, Josef; Forejt, Martin; Vavrina, Martin; Kudelkova, Jana; Vasku, Anna

    2008-02-01

    Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity

    Science.gov (United States)

    2014-01-01

    Background A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder. Methods Linkage in the family was searched by genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome 6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain reaction amplified and sequenced in an automated DNA sequencer. Results DNA sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G; p.Tyr26*). Conclusions Our report further confirms the recently described ELOVL4-related neuro-ichthyosis and shows that the neurological phenotype can be absent in some individuals. PMID:24571530

  19. Variability of the caprine whey protein genes and their association with milk yield, composition and renneting properties in the Sarda breed. 1. The LALBA gene.

    Science.gov (United States)

    Dettori, Maria Luisa; Pazzola, Michele; Paschino, Pietro; Pira, Maria Giovanna; Vacca, Giuseppe Massimo

    2015-11-01

    The 5' flanking region and 3' UTR of the caprine LALBA gene were analysed by SSCP and sequencing. A total of nine SNPs were detected: three in the promoter region, two were synonymous coding SNPs at exon-1, and four SNPs were in exon-4, within the 3'UTR. The nucleotide changes located in the promoter region (c.-358T>C, c.-163G>A, c.-121T>G) were genotyped by SSCP in 263 Sarda goats to evaluate their possible effect on milk yield, composition and renneting properties. We observed an effect of the three SNPs on milk yield and lactose content. Genotypes TT and CT at c.-358T>C (P A (P C and c.-121T>G were part of transcription factors binding sites, potentially involved in modulating the LALBA gene expression. The LALBA genotype affected renneting properties (P < 0.001), as heterozygotes c.-358CT and c.-163GA were characterised by delayed rennet coagulation time and curd firming time and the lowest value of curd firmness. The present investigation increases the panel of SNPs and adds new information about the effects of the caprine LALBA gene polymorphism.

  20. Performance of Glutamate Dehydrogenase and Triose Phosphate Isomerase Genes in the Analysis of Genotypic Variability of Isolates of Giardia duodenalis from Livestocks

    Science.gov (United States)

    Fava, Natália M. N.; Soares, Rodrigo M.; Scalia, Luana A. M.; Kalapothakis, Evanguedes; Pena, Isabella F.; Vieira, Carlos U.; Faria, Elaine S. M.; Cunha, Maria J.; Couto, Talles R.; Cury, Márcia Cristina

    2013-01-01

    Giardia duodenalis is a small intestinal protozoan parasite of several terrestrial vertebrates. This work aims to assess the genotypic variability of Giardia duodenalis isolates from cattle, sheep and pigs in the Southeast of Brazil, by comparing the standard characterization between glutamate dehydrogenase (gdh) and triose phosphate isomerase (tpi) primers. Fecal samples from the three groups of animals were analyzed using the zinc sulphate centrifugal flotation technique. Out of 59 positive samples, 30 were from cattle, 26 from sheep and 3 from pigs. Cyst pellets were stored and submitted to PCR and nested-PCR reactions with gdh and tpi primers. Fragment amplification of gdh and tpi genes was observed in 25 (42.4%) and 36 (61.0%) samples, respectively. Regarding the sequencing, 24 sequences were obtained with gdh and 20 with tpi. For both genes, there was a prevalence of E specific species assemblage, although some isolates have been identified as A and B, by the tpi sequencing. This has also shown a larger number of heterogeneous sequences, which have been attribute to mixed infections between assemblages B and E. The largest variability of inter-assemblage associated to the frequency of heterogeneity provided by tpi sequencing reinforces the polymorphic nature of this gene and makes it an excellent target for studies on molecular epidemiology. PMID:24308010

  1. Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene

    NARCIS (Netherlands)

    Eisenkraft, A.; Pode-Shakked, B.; Goldstein, N.; Shpirer, Z.; Bokhoven, H. van; Anikster, Y.

    2015-01-01

    Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments.

    Science.gov (United States)

    Perez, M; Pacchiarotti, A; Frontani, M; Pescarmona, E; Caprini, E; Lombardo, G A; Russo, G; Faraggiana, T

    2010-03-01

    Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1.6% to 21%, with a median rate of 9.8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series. Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.

  4. Association between the dopamine D4 receptor gene exon III variable number of tandem repeats and political attitudes in female Han Chinese.

    Science.gov (United States)

    Ebstein, Richard P; Monakhov, Mikhail V; Lu, Yunfeng; Jiang, Yushi; Lai, Poh San; Chew, Soo Hong

    2015-08-22

    Twin and family studies suggest that political attitudes are partially determined by an individual's genotype. The dopamine D4 receptor gene (DRD4) exon III repeat region that has been extensively studied in connection with human behaviour, is a plausible candidate to contribute to individual differences in political attitudes. A first United States study provisionally identified this gene with political attitude along a liberal-conservative axis albeit contingent upon number of friends. In a large sample of 1771 Han Chinese university students in Singapore, we observed a significant main effect of association between the DRD4 exon III variable number of tandem repeats and political attitude. Subjects with two copies of the 4-repeat allele (4R/4R) were significantly more conservative. Our results provided evidence for a role of the DRD4 gene variants in contributing to individual differences in political attitude particularly in females and more generally suggested that associations between individual genes, and neurochemical pathways, contributing to traits relevant to the social sciences can be provisionally identified. © 2015 The Author(s).

  5. Association between the dopamine D4 receptor gene exon III variable number of tandem repeats and political attitudes in female Han Chinese

    Science.gov (United States)

    Ebstein, Richard P.; Monakhov, Mikhail V.; Lu, Yunfeng; Jiang, Yushi; Lai, Poh San; Chew, Soo Hong

    2015-01-01

    Twin and family studies suggest that political attitudes are partially determined by an individual's genotype. The dopamine D4 receptor gene (DRD4) exon III repeat region that has been extensively studied in connection with human behaviour, is a plausible candidate to contribute to individual differences in political attitudes. A first United States study provisionally identified this gene with political attitude along a liberal–conservative axis albeit contingent upon number of friends. In a large sample of 1771 Han Chinese university students in Singapore, we observed a significant main effect of association between the DRD4 exon III variable number of tandem repeats and political attitude. Subjects with two copies of the 4-repeat allele (4R/4R) were significantly more conservative. Our results provided evidence for a role of the DRD4 gene variants in contributing to individual differences in political attitude particularly in females and more generally suggested that associations between individual genes, and neurochemical pathways, contributing to traits relevant to the social sciences can be provisionally identified. PMID:26246555

  6. 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

    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...... 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......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...

  7. 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.

  8. Same MSH2 Gene Mutation But Variable Phenotypes in 2 Families With Lynch Syndrome: Two Case Reports and Review of Genotype-Phenotype Correlation.

    Science.gov (United States)

    Liccardo, Raffaella; De Rosa, Marina; Duraturo, Francesca

    2018-01-01

    Lynch syndrome is an autosomal dominant syndrome that can be subdivided into Lynch syndrome I, or site-specific colonic cancer, and Lynch syndrome II, or extracolonic cancers, particularly carcinomas of the stomach, endometrium, biliary and pancreatic systems, and urinary tract. Lynch syndrome is associated with point mutations and large rearrangements in DNA MisMatch Repair ( MMR ) genes. This syndrome shows a variable phenotypic expression in people who carry pathogenetic mutations. So far, a correlation in genotype-phenotype has not been definitely established. In this study, we describe 2 Lynch syndrome cases presenting with the same genotype but different phenotypes and discuss possible reasons for this.

  9. Genetic alteration with variable intron/exon organization amongst five PI-homoeologous genes in Platanus acerifolia.

    Science.gov (United States)

    Zhang, Jiaqi; Guo, Cong; Liu, Guofeng; Li, Zhineng; Li, Xiaomei; Bao, Manzhu

    2011-03-01

    Flower development has been extensively characterized in the model species Arabidopsis thaliana and Antirrhinum majus. However, there have been few studies in woody species. Here, we report the isolation and characterization of five PISTILLATA (PI) homoeologous genes (PaPI1-to-5) from the London Plane tree (Platanus acerifolia Willd). PaPI1 and PaPI2 show a similar genomic structure to other known PI homoeologs, but PaPI3/4/5 lack intron sequences. In addition, PaPI5 lacks the third, fourth and fifth exons which encode the K-domain. These altered gene copies may have originated as 'processed' retrogenes. PaPI2 appears micro-regulated by alternative splicing, displaying three splice forms (PaPI2a, PaPI2b and PaPI2c). RT-PCR analysis showed different expression profiles and transcript abundance for the five PaPI genes. PaPI transcripts encoding full-length polypeptides were expressed predominantly in male/female inflorescences and PaPI2a was the most abundant transcript (59%) indicating that PaPI2 may be the major functional PI-homoeolog in London Plane. Phenotypic characterization in a heterologous expression system demonstrated that the full-length PaPI product functions as a B class gene. By contrast the PaPI5 form, which lacks the K-domain, had no apparent effect on flower development. In vitro studies also demonstrated that the K-domain is required to form PaPI/PaAP3 heterodimers. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Czech Academy of Sciences Publication Activity Database

    Sochorova, Jana; Coriton, O.; Kuderová, Alena; Lunerová Bedřichová, Jana; Chevre, A.-M.; Kovařík, Aleš

    2017-01-01

    Roč. 119, č. 1 (2017), s. 13-26 ISSN 0305-7364 R&D Projects: GA ČR(CZ) GA13-10057S Institutional support: RVO:68081707 Keywords : ribosomal-rna genes * concerted evolution * intergenic spacer Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 4.041, year: 2016

  11. Spectrum of Phenylalanine Hydroxylase Gene Mutations in Hamadan and Lorestan Provinces of Iran and Their Associations with Variable Number of Tandem Repeat Alleles

    Directory of Open Access Journals (Sweden)

    Reza Alibakhshi

    2018-05-01

    Full Text Available Phenylketonuria (PKU is one of the most common known inherited metabolic diseases. The present study aimed to investigate the status of molecular defects in phenylalanine hydroxylase (PAH gene in western Iranian PKU patients (predominantly from Kermanshah, Hamadan, and Lorestan provinces during 2014-2016. Additionally, the results were compared with similar studies in Iran. Nucleotide sequence analysis of all 13 exons and their flanking intronic regions of the PAH gene was performed in 18 western Iranian PKU patients. Moreover, a variable number of tandem repeat (VNTR located in the PAH gene was studied. The results revealed a mutational spectrum encompassing 11 distinct mutations distributed along the PAH gene sequence on 34 of the 36 mutant alleles (diagnostic efficiency of 94.4%. Also, four PAH VNTR alleles (with repeats of 3, 7, 8 and 9 were detected. The three most frequent mutations were IVS9+5G>A, IVS7-5T>C, and p.P281L with the frequency of 27.8%, 11%, and 11%, respectively. The results showed that there is not only a consanguineous relation, but also a difference in PAH characters of mutations between Kermanshah and the other two parts of western Iran (Hamadan and Lorestan. Also, it seems that the spectrum of mutations in western Iran is relatively distinct from other parts of the country, suggesting that this region might be a special PAH gene distribution region. Moreover, our findings can be useful in the identification of genotype to phenotype relationship in patients, and provide future abilities for confirmatory diagnostic testing, prognosis, and predict the severity of PKU patients.

  12. Spectrum of Phenylalanine Hydroxylase Gene Mutations in Hamadan and Lorestan Provinces of Iran and Their Associations with Variable Number of Tandem Repeat Alleles.

    Science.gov (United States)

    Alibakhshi, Reza; Moradi, Keivan; Biglari, Mostafa; Shafieenia, Samaneh

    2018-05-01

    Phenylketonuria (PKU) is one of the most common known inherited metabolic diseases. The present study aimed to investigate the status of molecular defects in phenylalanine hydroxylase ( PAH ) gene in western Iranian PKU patients (predominantly from Kermanshah, Hamadan, and Lorestan provinces) during 2014-2016. Additionally, the results were compared with similar studies in Iran. Nucleotide sequence analysis of all 13 exons and their flanking intronic regions of the PAH gene was performed in 18 western Iranian PKU patients. Moreover, a variable number of tandem repeat (VNTR) located in the PAH gene was studied. The results revealed a mutational spectrum encompassing 11 distinct mutations distributed along the PAH gene sequence on 34 of the 36 mutant alleles (diagnostic efficiency of 94.4%). Also, four PAH VNTR alleles (with repeats of 3, 7, 8 and 9) were detected. The three most frequent mutations were IVS9+5G>A, IVS7-5T>C, and p.P281L with the frequency of 27.8%, 11%, and 11%, respectively. The results showed that there is not only a consanguineous relation, but also a difference in PAH characters of mutations between Kermanshah and the other two parts of western Iran (Hamadan and Lorestan). Also, it seems that the spectrum of mutations in western Iran is relatively distinct from other parts of the country, suggesting that this region might be a special PAH gene distribution region. Moreover, our findings can be useful in the identification of genotype to phenotype relationship in patients, and provide future abilities for confirmatory diagnostic testing, prognosis, and predict the severity of PKU patients.

  13. Estimation of genetic variability and selection response for clutch length in dwarf brown-egg layers carrying or not the naked neck gene

    Directory of Open Access Journals (Sweden)

    Tixier-Boichard Michèle

    2003-03-01

    Full Text Available Abstract In order to investigate the possibility of using the dwarf gene for egg production, two dwarf brown-egg laying lines were selected for 16 generations on average clutch length; one line (L1 was normally feathered and the other (L2 was homozygous for the naked neck gene NA. A control line from the same base population, dwarf and segregating for the NA gene, was maintained during the selection experiment under random mating. The average clutch length was normalized using a Box-Cox transformation. Genetic variability and selection response were estimated either with the mixed model methodology, or with the classical methods for calculating genetic gain, as the deviation from the control line, and the realized heritability, as the ratio of the selection response on cumulative selection differentials. Heritability of average clutch length was estimated to be 0.42 ± 0.02, with a multiple trait animal model, whereas the estimates of the realized heritability were lower, being 0.28 and 0.22 in lines L1 and L2, respectively. REML estimates of heritability were found to decline with generations of selection, suggesting a departure from the infinitesimal model, either because a limited number of genes was involved, or their frequencies were changed. The yearly genetic gains in average clutch length, after normalization, were estimated to be 0.37 ± 0.02 and 0.33 ± 0.04 with the classical methods, 0.46 ± 0.02 and 0.43 ± 0.01 with animal model methodology, for lines L1 and L2 respectively, which represented about 30% of the genetic standard deviation on the transformed scale. Selection response appeared to be faster in line L2, homozygous for the NA gene, but the final cumulated selection response for clutch length was not different between the L1 and L2 lines at generation 16.

  14. Genetic variability in L1 and L2 genes of HPV-16 and HPV-58 in Southwest China.

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    Yaofei Yue

    Full Text Available HPV account for most of the incidence of cervical cancer. Approximately 90% of anal cancers and a smaller subset (<50% of other cancers (oropharyngeal, penile, vaginal, vulvar are also attributed to HPV. The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers type restricted protection. The L2 protein is a promising candidate for a broadly protective HPV vaccine. In our previous study, we found the most prevalent high-risk HPV infectious serotypes were HPV-16 and HPV-58 among women of Southwest China. To explore gene polymorphisms and intratypic variations of HPV-16 and HPV-58 L1/L2 genes originating in Southwest China, HPV-16 (L1: n = 31, L2: n = 28 and HPV-58 (L1: n = 21, L2: n = 21 L1/L2 genes were sequenced and compared to others described and submitted to GenBank. Phylogenetic trees were then constructed by Neighbor-Joining and the Kimura 2-parameters methods (MEGA software, followed by an analysis of the diversity of secondary structure. Then selection pressures acting on the L1/L2 genes were estimated by PAML software. Twenty-nine single nucleotide changes were observed in HPV-16 L1 sequences with 16/29 non-synonymous mutations and 13/29 synonymous mutations (six in alpha helix and two in beta turns. Seventeen single nucleotide changes were observed in HPV-16 L2 sequences with 8/17 non-synonymous mutations (one in beta turn and 9/17 synonymous mutations. Twenty-four single nucleotide changes were observed in HPV-58 L1 sequences with 10/24 non-synonymous mutations and 14/24 synonymous mutations (eight in alpha helix and four in beta turn. Seven single nucleotide changes were observed in HPV-58 L2 sequences with 4/7 non-synonymous mutations and 3/7 synonymous mutations. The result of selective pressure analysis showed that most of these mutations were of positive selection. This study may help understand the intrinsic geographical relatedness and biological differences of HPV-16/HPV-58 and

  15. [Variability of Cytochrome b Gene and Adjacent Section of Gene tRNA-Thr of Mitochondrial DNA in the Northern Mole Vole Ellobius talpinus (Mammalia, Rodentia)].

    Science.gov (United States)

    Bogdanov, A S; Lebedev, V S; Zykov, A E; Bakloushinskaya, I Yu

    2015-12-01

    The Northern mole vole E. talpinus, despite its wide distribution, is characterized by a stable karyotype (2n = NF = 54) and slight morphological polymorphism. We made a preliminary analysis of a mitochondrial DNA fragment to clarify the level of genetic variation and differentiation of E. talpinus. the complete cytochrome b gene (cyt b, 1143 bp) and a short part of its flanking gene tRNA-Thr (27 bp) were sequenced. We studied 16 specimens from eight localities, including Crimea, the Volga region, the Trans-Volga region, the Southern Urals, Western Siberia, and Eastern Turkmenistan. Mitotypes of E. talpinus were distributed on a ML dendrogram as four distinct clusters: the first (I) contains specimens from the Crimea, the second (II) combines individuals from the Volgograd region and the left bank of the Don River, the third (III) includes those from the Trans-Volga region, Southern Urals, the left bank of the Irtysh River, and Eastern Turkmenistan; the fourth (IV) are those from the right bank of the Irtysh River. These clusters were relatively distant from each other: the mean genetic distances (D) between them are 0.021-0.051. The Eastern mole vole E. tancrei differed from E. talpinus population groups 1.5-2 times more (D = 0.077-0.084) than the latter did among themselves. Such variations indirectly proved the unity of E. talpinus, despite its high intraspecific differentiation for the studied fragment of mitochondrial DNA. This differentiation apparently occurred because of the long isolation of E. talpinus population groups, which was due to geographic barriers, in particular, the large rivers that completely separate the species range meridionally (the Volga River, the Irtysh River). Sociality and underground lifestyle could accelerate the fixation of mutations in disjunct populations. The composition and distribution of intraspecific groups of E. talpinus, which were identified in analysis of the mitochondrial DNA fragment, do not coincide with the

  16. Intrafamilial variability of the ocular phenotype in a Polish family with a missense mutation (A63D) in the Norrie disease gene.

    Science.gov (United States)

    Zaremba, J; Feil, S; Juszko, J; Myga, W; van Duijnhoven, G; Berger, W

    1998-09-01

    To describe the phenotypic variability in a Polish Norrie disease (ND) family associated with the missense mutation A63D. A patient with spared vision from a Polish ND family underwent detailed ophthalmological examinations including slit-lamp biomicroscopy, ultrasound (USG), angiography, Goldmann kinetic visual field, and electroretinography (ERG). Mutation screening was carried out using the single-strand conformation polymorphism (SSCP) technique and subsequent DNA sequencing of the coding part of the ND gene. A mutation was detected (exon 3, A63D) in a large Polish family with 12 affected males, all but one presenting with classical ND symptoms. In one male, partially preserved vision was observed up to 40 years of age (distance acuity of the right eye 1/50 and left eye 2/50). Slit-lamp examination revealed remnants of a persistent primary vitreous and hyaloid artery. Upon angiography, the retina was vascularized within the posterior pole but not in the periphery. The ERG revealed pathological changes characteristic for chorioretinal degenerations. Within one family, individuals with identical sequence alterations in the ND gene can show remarkable phenotypic variability of the ocular symptoms. These findings indicate the involvement of additional factors (epigenetic or genetic) in ocular pathogenesis of ND.

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

    Directory of Open Access Journals (Sweden)

    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.

  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. Variable methylation of the imprinted gene, SNRPN, supports a relationship between intracranial germ cell tumours and neural stem cells.

    Science.gov (United States)

    Lee, Shih-Han; Appleby, Vanessa; Jeyapalan, Jennie N; Palmer, Roger D; Nicholson, James C; Sottile, Virginie; Gao, Erning; Coleman, Nicholas; Scotting, Paul J

    2011-02-01

    Germ cell tumours (GCTs) are a diverse group of neoplasms all of which are generally believed to arise from germ cell progenitors (PGCs). Even those that form in the nervous system are likewise believed to be PGC-derived, despite being found a great distance from the normal location of germ cells. The primary evidence in favour of this model for the origins of intracranial GCTs is that they share molecular features with other GCTs. Those features include shared gene expression and a lack of methylation of imprinted genes, including SNRPN. Contrary to this model, we have proposed that endogenous neural stem cells of the brain are a more likely origin for these tumours. We show here that the lack of methylation of SNRPN that has previously been taken to indicate an origin for GCTs from PGCs is also seen in neural stem cells of mice and humans. We believe that, in the light of these and other recent observations, endogenous neural precursors of the brain are a more plausible origin for intracranial GCTs than are misplaced PGCs.

  20. 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

  1. Low reproductive isolation and highly variable levels of gene flow reveal limited progress towards speciation between European river and brook lampreys.

    Science.gov (United States)

    Rougemont, Q; Gaigher, A; Lasne, E; Côte, J; Coke, M; Besnard, A-L; Launey, S; Evanno, G

    2015-12-01

    Ecologically based divergent selection is a factor that could drive reproductive isolation even in the presence of gene flow. Population pairs arrayed along a continuum of divergence provide a good opportunity to address this issue. Here, we used a combination of mating trials, experimental crosses and population genetic analyses to investigate the evolution of reproductive isolation between two closely related species of lampreys with distinct life histories. We used microsatellite markers to genotype over 1000 individuals of the migratory parasitic river lamprey (Lampetra fluviatilis) and freshwater-resident nonparasitic brook lamprey (Lampetra planeri) distributed in 10 sympatric and parapatric population pairs in France. Mating trials, parentage analyses and artificial fertilizations demonstrated a low level of reproductive isolation between species even though size-assortative mating may contribute to isolation. Most parapatric population pairs were strongly differentiated due to the joint effects of geographic distance and barriers to migration. In contrast, we found variable levels of gene flow between sympatric populations ranging from panmixia to moderate differentiation, which indicates a gradient of divergence with some population pairs that may correspond to alternative morphs or ecotypes of a single species and others that remain partially isolated. Ecologically based divergent selection may explain these variable levels of divergence among sympatric population pairs, but incomplete genome swamping following secondary contact could have also played a role. Overall, this study illustrates how highly differentiated phenotypes can be maintained despite high levels of gene flow that limit the progress towards speciation. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  2. Exploring Genetic Variability at PI, GSK3, HPA, and Glutamatergic Pathways in Lithium Response: Association With IMPA2, INPP1, and GSK3B Genes.

    Science.gov (United States)

    Mitjans, Marina; Arias, Bárbara; Jiménez, Esther; Goikolea, Jose M; Sáiz, Pilar A; García-Portilla, M Paz; Burón, Patricia; Bobes, Julio; Vieta, Eduard; Benabarre, Antoni

    2015-10-01

    Lithium is considered the first-line treatment in bipolar disorder, although response could range from an excellent response to a complete lack of response. Response to lithium is a complex phenotype in which different factors, part of them genetics, are involved. In this sense, the aim of this study was to investigate the potential association of genetic variability at genes related to phosphoinositide, glycogen synthetase kinase-3 (GSK3), hypothalamic-pituitary-adrenal, and glutamatergic pathways with lithium response. A sample of 131 bipolar patients (99 type I, 32 type II) were grouped and compared according to their level of response: excellent responders (ER), partial responders (PR), and nonresponders (NR). Genotype and allele distributions of the rs669838 (IMPA2), rs909270 (INNP1), rs11921360 (GSK3B), and rs28522620 (GRIK2) polymorphisms significantly differed between ER, PR, and NR. When we compared the ER versus PR+NR, the logistic regression showed significant association for rs669838-C (IMPA2; P = 0.021), rs909270-G (INPP1; P = 0.009), and rs11921360-A (GSK3B; P = 0.004) with lithium nonresponse. Haplotype analysis showed significant association for the haplotypes rs3791809-rs4853694-rs909270 (INPP1) and rs1732170-rs11921360-rs334558 (GSK3B) and lithium response. Our study is in line with previous studies reporting association between genetic variability at these genes and lithium response, pointing to an effect of IMPA2, INPP1, and GSK3B genes to lithium response in bipolar disorder patients. Further studies with larger samples are warranted to assess the strength of the reported associations.

  3. Analysis of HBV basal core promoter/precore gene variability in patients with HBV drug resistance and HIV co-infection in Northwest Ethiopia.

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    Yeshambel Belyhun

    Full Text Available We recently reported complex hepatitis B virus (HBV drug resistant and concomitant vaccine escape hepatitis B surface antigen (HBsAg variants during human immunodeficiency virus (HIV co-infection and antiretroviral therapy (ART exposure in Ethiopia. As a continuation of this report using the HBV positive sera from the same study participants, the current study further analyzed the HBV basal core promoter (BCP/precore (PC genes variability in patients with HBV drug resistance (at tyrosine-methionine-aspartate-aspartate (YMDD reverse transcriptase (RT motifs and HIV co-infection in comparison with HBV mono-infected counterparts with no HBV drug resistant gene variants.A total of 143 participants of HBV-HIV co-infected (n = 48, HBV mono-infected blood donors (n = 43 and chronic liver disease (CLD patients (n = 52 were included in the study. The BCP/PC genome regions responsible for HBeAg expression from the EcoRI site (nucleotides 1653-1959 were sequenced and analyzed for the BCP/PC mutant variants.Among the major mutant variants detected, double BCP mutations (A1762T/G1764A (25.9%, Kozak sequences mutations (nt1809-1812 (51.7% and the classical PC mutations such as A1814C/C1816T (15.4%, G1896A (25.2% and G1862T (44.8% were predominant mutant variants. The prevalence of the double BCP mutations was significantly lower in HIV co-infected patients (8.3% compared with HBV mono-infected blood donors (32.6% and CLD patients (36.5%. However, the Kozak sequences BCP mutations and the majority of PC mutations showed no significant differences among the study groups. Moreover, except for the overall BCP/PC mutant variants, co-prevalence rates of each major BCP/PC mutations and YMDDRT motif associated lamivudine (3TC/entecavir (ETV resistance mutations showed no significant differences when compared with the rates of BCP/PC mutations without YMDD RT motif drug resistance gene mutations. Unlike HIV co-infected group, no similar comparison made among HBV mono

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

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

    2016-09-01

    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. 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. 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). 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.

  5. Altered phenotypic expression of immunoglobulin heavy-chain variable-region (VH) genes in Alicia rabbits probably reflects a small deletion in the VH genes closest to the joining region.

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    Allegrucci, M; Newman, B A; Young-Cooper, G O; Alexander, C B; Meier, D; Kelus, A S; Mage, R G

    1990-07-01

    Rabbits of the Alicia strain have a mutation (ali) that segregates with the immunoglobulin heavy-chain (lgh) locus and has a cis effect upon the expression of heavy-chain variable-region (VH) genes encoding the a2 allotype. In heterozygous a1/ali or a3/ali rabbits, serum immunoglobulins are almost entirely the products of the normal a1 or a3 allele and only traces of a2 immunoglobulin are detectable. Adult homozygous ali/ali rabbits likewise have normal immunoglobulin levels resulting from increased production of a-negative immunoglobulins and some residual ability to produce the a2 allotype. By contrast, the majority of the immunoglobulins of wild-type a2 rabbits are a2-positive and only a small percentage are a-negative. Genomic DNAs from homozygous mutant and wild-type animals were indistinguishable by Southern analyses using a variety of restriction enzyme digests and lgh probes. However, when digests with infrequently cutting enzymes were analyzed by transverse alternating-field electrophoresis, the ali DNA fragments were 10-15 kilobases smaller than the wild type. These fragments hybridized to probes both for VH and for a region of DNA a few kilobases downstream of the VH genes nearest the joining region. We suggest that this relatively small deletion affects a segment containing 3' VH genes with important regulatory functions, the loss of which leads to the ali phenotype. These results, and the fact that the 3' VH genes rearrange early in B-cell development, indicate that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression.

  6. Recent habitat fragmentation caused by major roads leads to reduction of gene flow and loss of genetic variability in ground beetles.

    Science.gov (United States)

    Keller, Irene; Largiadèr, Carlo R

    2003-02-22

    Although habitat fragmentation is suspected to jeopardize the long-term survival of many species, few data are available on its impact on the genetic variability of invertebrates. We assess the genetic population structure of the flightless ground beetle Carabus violaceus L., 1758 in a Swiss forest, which is divided into several fragments by a highway and two main roads. Eight samples were collected from different forest fragments and analysed at six microsatellite loci. The largest genetic differentiation was observed between samples separated by roads and in particular by the highway. The number of roads between sites explained 44% of the variance in pairwise F(ST) estimates, whereas the age of the road and the geographical distance between locations were not significant factors. Furthermore, a comparison of allelic richness showed that the genetic variability in a small forest fragment isolated by the highway was significantly lower than in the rest of the study area. These findings strongly support the hypothesis that large roads are absolute barriers to gene flow in C. violaceus, which may lead to a loss of genetic variability in fragmented populations.

  7. Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice

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    Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W.; Rapoport, Basil

    2014-01-01

    Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

  8. Variable transcriptional responsiveness of the P2X3 receptor gene during CFA-induced inflammatory hyperalgesia.

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

    2018-05-01

    The purinergic receptor P2X3 (P2X3-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 P2X3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2X3-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 P2X3-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 P2X3-R mRNA levels, reproducible across both sides. Immunostaining assays did not reveal significant increases in the percentage of P2X3-positive neurons, indicating that increased P2X3-R at DRG somas is not critical for inducing inflammatory hyperalgesia in CFA-treated rats. Chromatin immunoprecipitation (ChIP) assays showed a correlated (R 2  = 0.671) enrichment of the transcription factor Runx1 and the epigenetic active mark histone H3 acetylation (H3Ac) at the P2X3-R gene promoter in a fraction of the CFA-treated rats. These results suggest that animal-specific increases in P2X3-R mRNA levels are likely associated with the genetic/epigenetic context of the P2X3-R locus that controls P2X3-R gene transcription by recruiting Runx1 and epigenetic co-regulators that mediate histone acetylation. © 2017 Wiley Periodicals, Inc.

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

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    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.

  10. Genetic variability among Trichuris ovis isolates from different hosts in Guangdong Province, China revealed by sequences of three mitochondrial genes.

    Science.gov (United States)

    Wang, Yan; Liu, Guo-Hua; Li, Jia-Yuan; Xu, Min-Jun; Ye, Yong-Gang; Zhou, Dong-Hui; Song, Hui-Qun; Lin, Rui-Qing; Zhu, Xing-Quan

    2013-02-01

    This study examined sequence variation in three mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunit 1 (cox1), NADH dehydrogenase subunit 5 (nad5) and cytochrome b (cytb), among Trichuris ovis isolates from different hosts in Guangdong Province, China. A portion of the cox1 (pcox1), nad5 (pnad5) and cytb (pcytb) genes was amplified separately from individual whipworms by PCR, and was subjected to sequencing from both directions. The size of the sequences of pcox1, pnad5 and pcytb was 618, 240 and 464 bp, respectively. Although the intra-specific sequence variations within T. ovis were 0-0.8% for pcox1, 0-0.8% for pnad5 and 0-1.9% for pcytb, the inter-specific sequence differences among members of the genus Trichuris were significantly higher, being 24.3-26.5% for pcox1, 33.7-56.4% for pnad5 and 24.8-26.1% for pcytb, respectively. Phylogenetic analyses using combined sequences of pcox1, pnad5 and pcytb, with three different computational algorithms (maximum likelihood, maximum parsimony and Bayesian inference), indicated that all of the T. ovis isolates grouped together with high statistical support. These findings demonstrated the existence of intra-specific variation in mtDNA sequences among T. ovis isolates from different hosts, and have implications for studying molecular epidemiology and population genetics of T. ovis.

  11. Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

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    Sobti, R C; Maithil, Nishi; Thakur, Hitender; Sharma, Yashpaul; Talwar, K K

    2010-08-01

    The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

  12. 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 (PrPC) 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 PrPC 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. PMID:23236380

  13. 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.

  14. HCV Proteins and Immunoglobulin Variable Gene (IgV Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

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    Giuseppe Sautto

    2012-01-01

    Full Text Available The association between hepatitis C virus (HCV infection and type II mixed cryoglobulinemia (MCII is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV gene subfamilies frequently endowed with rheumatoid factor (RF activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  15. HCV proteins and immunoglobulin variable gene (IgV) subfamilies in HCV-induced type II mixed cryoglobulinemia: a concurrent pathogenetic role.

    Science.gov (United States)

    Sautto, Giuseppe; Mancini, Nicasio; Solforosi, Laura; Diotti, Roberta A; Clementi, Massimo; Burioni, Roberto

    2012-01-01

    The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved.

  16. 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.

  17. Interleukin 6-174 G/C promoter and variable number of tandem repeats (VNTR) gene polymorphisms in sporadic Alzheimer's disease.

    Science.gov (United States)

    Capurso, Cristiano; Solfrizzi, Vincenzo; Colacicco, Anna Maria; D'Introno, Alessia; Frisardi, Vincenza; Imbimbo, Bruno P; Lorusso, Maria; Vendemiale, Gianluigi; Denitto, Marta; Santamato, Andrea; Seripa, Davide; Pilotto, Alberto; Fiore, Pietro; Capurso, Antonio; Panza, Francesco

    2010-02-01

    Previous studies examining the association between the interleukin 6 (IL-6)-174 C/G polymorphism and Alzheimer's disease (AD) have yielded conflicting results. Furthermore, the C allele of the IL-6 variable number of tandem repeats (VNTR) polymorphism was associated with a delayed onset and a decreased risk of AD. A total sample of 149 AD patients, and 298 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were genotyped for the apolipoprotein E (APOE) polymorphism, the VNTR polymorphism in the 3' flanking region, and the -174G/C single-nucleotide polymorphism (SNP) in the promoter region of IL-6 gene on chromosome 7. Furthermore, we performed a haplotype analysis on these two polymorphisms on IL-6 locus. IL-6 VNTR and -174G/C allele and genotype frequencies were similar between AD patients and controls, also after stratification for late-onset (> or =65 years) and early-onset (VNTR and -174G/C polymorphisms, not supporting a previous reported additive effect of both IL-6 polymorphisms on AD risk. Our findings did not support a role of IL-6-174 G/C and IL-6 VNTR polymorphisms in the risk of sporadic AD in southern Italy, suggesting that these polymorphisms of IL-6 gene were at most weak genetic determinants of AD. Copyright 2009 Elsevier Inc. All rights reserved.

  18. 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.

  19. Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.

    Directory of Open Access Journals (Sweden)

    Alireza Eshaghi

    Full Text Available Human respiratory syncytial virus (HRSV is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010-2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene.Among the 201 consecutive RSV isolates studied, RSV-A (55.7% was more commonly observed than RSV-B (42.3%. 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2% clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10% NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.

  20. 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.

  1. [Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].

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    Swarovskaya, M G; Stepanova, S K; Marussin, A V; Sukhomyasova, A L; Maximova, N R; Stepanov, V A

    2015-06-01

    The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.

  2. Polymorphisms in CYP1A1 and CYP3A5 Genes Contribute to the Variability in Granisetron Clearance and Exposure in Pregnant Women with Nausea and Vomiting.

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    Bustos, Martha L; Zhao, Yang; Chen, Huijun; Caritis, Steve N; Venkataramanan, Raman

    2016-12-01

    Nausea and vomiting affect up to 90% of pregnant women. Granisetron is a potent and highly selective serotonin receptor antagonist and is an effective antiemetic. Findings from a prior study in pregnant women demonstrated a large interindividual variability in granisetron exposure. Granisetron is primarily metabolized by the cytochrome P450 (CYP) enzymes CYP1A1 and CYP3A and is likely a substrate of the ABCB1 transporter. Single-nucleotide polymorphisms (SNPs) in CYP3A, CYP1A1, and ABCB1 can alter drug metabolism. This study evaluated the influence of polymorphisms in CYP3A4, CYP3A5, CYP1A1, and ABCB1 on the pharmacokinetic properties of granisetron in pregnant women. The study enrolled 16 pregnant women (gestational age of 12-19 wks). All patients had nausea and vomiting and were treated with granisetron 1 mg. Granisetron plasma concentrations were determined using liquid chromatography tandem-mass spectrometry. The patients' genotype was determined using TaqMan SNP Genotyping Assays. The Hardy-Weinberg equilibrium was assessed by comparing observed and expected genotype frequencies, using the exact test. Intravenous granisetron clearance was used as the dependent variable for analysis of associations. Of 16 patients, 25% were homozygous for the allele variant CYP3A5*3 and had a significantly lower granisetron clearance and increased area under the plasma concentration-versus-time curve (AUC) compared with nonhomozygous patients. Approximately one-third of patients (n=5) were carriers for the allele variant CYP1A1*2A and had a significantly higher granisetron clearance and decreased AUC. We did not find significant differences in the AUC or clearance for any SNPs in CYP3A4 and ABCB1 genes. Polymorphisms in CYP3A5 and CYP1A1 account for some of the variability in systemic clearance and exposure of granisetron in pregnant women. © 2016 Pharmacotherapy Publications, Inc.

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

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    Nisha, Kallyadan V; Veena, Shetty A; Rathika, Shenoy D; Vijaya, Shenoy M; Avinash, Shetty K

    2017-01-01

    The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become an important challenge among pediatric patients with community-acquired urinary tract infection (UTI). The aim of this study was to assess the antimicrobial susceptibility patterns, associated risk factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira (TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E. coli isolated from children with community-acquired UTI. This was a prospective study conducted from November 2012 to March 2016 in a tertiary care center. E. coli isolated in urine cultures from children aged ≤18 years was identified and confirmed for ESBL production. ESBL-positive strains were screened for ESBL encoding genes. Chi-square test and Fisher's exact test were used to compare the difference in antibiotic susceptibility with respect to ESBL positive and negative, and binary logistic regression was used to identify the risk factors associated with ESBL production. Among 523 E. coli isolates, 196 (37.5%) were ESBL positive, >90% were resistant to cephalosporins, and 56% were resistant to fluoroquinolones. Least resistance was observed for imipenem, netilmicin, and nitrofurantoin (2%, 8.6%, 15.3%). Association between ESBL production and drug resistance was significant for ceftazidime ( P antibiotics were the common risk factors. 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.

  4. Quantifying Temporal Autocorrelations for the Expression of Geobacter species mRNA Gene Transcripts at Variable Ammonium Levels during in situ U(VI) Bioremediation

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    Mouser, P. J.

    2010-12-01

    In order to develop decision-making tools for the prediction and optimization of subsurface bioremediation strategies, we must be able to link the molecular-scale activity of microorganisms involved in remediation processes with biogeochemical processes observed at the field-scale. This requires the ability to quantify changes in the in situ metabolic condition of dominant microbes and associate these changes to fluctuations in nutrient levels throughout the bioremediation process. It also necessitates a need to understand the spatiotemporal variability of the molecular-scale information to develop meaningful parameters and constraint ranges in complex bio-physio-chemical models. The expression of three Geobacter species genes (ammonium transporter (amtB), nitrogen fixation (nifD), and a housekeeping gene (recA)) were tracked at two monitoring locations that differed significantly in ammonium (NH4+) concentrations during a field-scale experiment where acetate was injected into the subsurface to simulate Geobacteraceae in a uranium-contaminated aquifer. Analysis of amtB and nifD mRNA transcript levels indicated that NH4+ was the primary form of fixed nitrogen during bioremediation. Overall expression levels of amtB were on average 8-fold higher at NH4+ concentrations of 300 μM or more than at lower NH4+ levels (average 60 μM). The degree of temporal correlation in Geobacter species mRNA expression levels was calculated at both locations using autocorrelation methods that describe the relationship between sample semi-variance and time lag. At the monitoring location with lower NH4+, a temporal correlation lag of 8 days was observed for both amtB and nifD transcript patterns. At the location where higher NH4+ levels were observed, no discernable temporal correlation lag above the sampling frequency (approximately every 2 days) was observed for amtB or nifD transcript fluctuations. Autocorrelation trends in recA expression levels at both locations indicated that

  5. Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial.

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    Parker, Maria A; Choi, Dongseok; Erker, Laura R; Pennesi, Mark E; Yang, Paul; Chegarnov, Elvira N; Steinkamp, Peter N; Schlechter, Catherine L; Dhaenens, Claire-Marie; Mohand-Said, Saddek; Audo, Isabelle; Sahel, Jose; Weleber, Richard G; Wilson, David J

    2016-10-01

    The goal of this analysis was to determine the test-retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial. Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping. Criteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg 2 , respectively), SVF full volume HOV (V TOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 μm and 0.15 mm 3 , respectively). This analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD. Determination of variability of functional and structural measures in participants with advanced stages of

  6. Test–Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial

    Science.gov (United States)

    Parker, Maria A.; Choi, Dongseok; Erker, Laura R.; Pennesi, Mark E.; Yang, Paul; Chegarnov, Elvira N.; Steinkamp, Peter N.; Schlechter, Catherine L.; Dhaenens, Claire-Marie; Mohand-Said, Saddek; Audo, Isabelle; Sahel, Jose; Weleber, Richard G.; Wilson, David J.

    2016-01-01

    Purpose The goal of this analysis was to determine the test–retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial. Methods Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping. Results Criteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg2, respectively), SVF full volume HOV (VTOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 μm and 0.15 mm3, respectively). Conclusions This analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD. Translational Relevance Determination of variability of functional and

  7. Genetic Variability of the Glucose-Dependent Insulinotropic Peptide Gene Is Involved in the Premature Coronary Artery Disease in a Chinese Population with Type 2 Diabetes

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    Xiaowei Ma

    2018-01-01

    Full Text Available Background. Glucose-dependent insulinotropic polypeptide (GIP is closely related to diabetes and obesity, both of which are confirmed to increase the risk of coronary artery disease (CAD. Our study aimed to investigate whether the polymorphisms in GIP genes could affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population. Methods. We selected and genotyped two haplotype-tagging single nucleotide polymorphisms (tag-SNPs (rs2291725 C>T, rs8078510 G>A of GIP gene based on CHB data in HapMap Phase II database (r2<0.8. The case-control study of Chinese Han population involved 390 diabetic patients with CAD as positive group and 276 diabetic patients without CAD as control group. Allele and genotype frequencies were compared between the two groups. Results. In dominant inheritance model, the carriers of T/T or T/C had a lower risk of CAD (OR = 0.635, 95% CI = 0.463–0.872, p=0.005, even after adjustment other CAD risk factors (gender, age, BMI, smoking status, dyslipidemia, hypertension history, and diabetic duration (OR′ = 0.769, 95% CI′ = 0.626–0.945, p′=0.013. The allele A at rs8078510 was associated with decreased risk of CAD (OR = 0.732, p=0.039. p=0.018 in subgroup analysis, individuals with higher BMI (≥24 kg/m2 had increased risk for CAD when carrying C/C at rs2291725 (OR′ = 1.291, 95% CI′ = 1.017–1.639, p′=0.036. In age < 55 men and age < 65 women, the carriers of allele C at rs2291725 had a higher risk of CAD than noncarriers (OR = 1.627, p=0.015. Carriers of allele G in rs8078510 had higher susceptibility to CAD (OR = 2.049, 95% = CI 1.213–3.463, p=0.007. p=0.004; in addition, allele G in rs8078510 would bring higher CAD risk to the carriers who ever smoked (OR = 1.695, 95% CI = 1.080–2.660, p=0.021. Conclusion. The genetic variability of GIP gene is associated with CAD and it may play a role in the premature CAD in the

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

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    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

    2017-11-01

    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

  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.

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    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. 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.

  11. 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

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    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

  12. Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis.

    Science.gov (United States)

    Fjeld, Karianne; Beer, Sebastian; Johnstone, Marianne; Zimmer, Constantin; Mössner, Joachim; Ruffert, Claudia; Krehan, Mario; Zapf, Christian; Njølstad, Pål Rasmus; Johansson, Stefan; Bugert, Peter; Miyajima, Fabio; Liloglou, Triantafillos; Brown, Laura J; Winn, Simon A; Davies, Kelly; Latawiec, Diane; Gunson, Bridget K; Criddle, David N; Pirmohamed, Munir; Grützmann, Robert; Michl, Patrick; Greenhalf, William; Molven, Anders; Sutton, Robert; Rosendahl, Jonas

    2016-01-01

    Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP. Overall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups. Twelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls (P = 0.03 and 0.008, respectively). However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16-16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC. We did not obtain evidence that CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts.

  13. IL1 receptor antagonist gene IL1-RN variable number of tandem repeats polymorphism and cancer risk: a literature review and meta-analysis.

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    Ying Zhang

    Full Text Available IL1 receptor antagonist (IL1RA and IL1beta (IL1β, members of the pro-inflammatory cytokine interleukin-1 (IL1 family, play a potential role against infection and in the pathogenesis of cancers. The variable number of tandem repeats (VNTR polymorphism in the second intron of the IL1 receptor antagonist gene (IL1-RN and a polymorphism in exon 5 of IL1B (IL1B+3954C>T, rs1143634 have been suggested in predisposition to cancer risk. However, studies have shown inconsistent results. To validate any association, a meta-analysis was performed with 14,854 cases and 19,337 controls from 71 published case-control studies for IL1-RN VNTR and 33 eligible studies contained 7,847 cases and 8917 controls for IL1B +3954. Odds ratios (ORs with 95% confidence intervals (CIs were calculated from comparisons to assess the strength of the association. There was significant association between the IL1-RN VNTR polymorphism and the risk of cancer for any overall comparison. Furthermore, cancer type stratification analysis revealed that there were significantly increased risks of gastric cancer, bladder cancer and other cancer groups. Infection status analysis indicated that the H. pylori or HBV/HCV infection and IL1-RN VNTR genotypes were independent factors for developing gastric or hepatocellular cancers. In addition, a borderline significant association was observed between IL1B+3954 polymorphism and the increased cancer risk. Although some modest bias could not be eliminated, this meta-analysis suggested that the IL1-RN VNTR polymorphisms may contribute to genetic susceptibility to gastric cancer. More studies are needed to further evaluate the role of the IL1B+3954 polymorphism in the etiology of cancer.

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

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    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

  15. Lack of support for a role of the insulin gene variable number of tandem repeats minisatellite (INS-VNTR) locus in fetal growth or type 2 diabetes-related intermediate traits in United Kingdom populations.

    Science.gov (United States)

    Mitchell, Simon M S; Hattersley, Andrew T; Knight, Beatrice; Turner, Tina; Metcalf, Bradley S; Voss, Linda D; Davies, David; McCarthy, Anne; Wilkin, Terence J; Smith, George Davey; Ben-Shlomo, Yoav; Frayling, Timothy M

    2004-01-01

    The insulin gene variable number of tandem repeats minisatellite (INS-VNTR) class III allele is associated with altered fetal growth, type 2 diabetes risk (especially when paternally inherited), and insulin and IGF2 gene expression. Further studies are needed to establish the role of the INS-VNTR in fetal growth and assess whether its effects depend on the parent of origin. We analyzed the INS-VNTR-linked -23 Hph1 polymorphism in 2283 subjects, comprising 1184 children and 1099 parents. There were no differences (P VNTR was nominally associated (P VNTR in fetal growth and nominal association with type 2 diabetes-related intermediate traits.

  16. 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

    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. Copyright: © 2018 SecretarÍa de Salud

  17. Effects of limited concentrate feeding on growth and blood and serum variables, and on nutrient digestibility and gene expression of hepatic gluconeogenic enzymes in dairy calves.

    Science.gov (United States)

    Lohakare, J D; van de Sand, H; Gerlach, K; Hosseini, A; Mielenz, M; Sauerwein, H; Pries, M; Südekum, K-H

    2012-02-01

    This study elucidated the effects of limited concentrate feeding on growth, nutrient digestibility, blood profile and gene expression of gluconeogenic enzymes in the liver of dairy calves. The study utilized 36 German Holstein dairy calves (5-7 days of age) divided into two groups of 18 calves each for 150 days. Control group calves received 2 kg/(calf × day) of concentrate, whereas calves in the restricted group received only 1 kg/(calf × day). Good quality forage (mixture of maize and grass silages) was available for ad libitum consumption to both groups. The intake of milk replacer before weaning, and of concentrate were recorded daily per calf; however, the consumption of forages was quantified as daily average of the group. Body weights (BW) were recorded at start and on days 35, 70, 112 and 150. Blood and serum samples and spot urinary and faecal samples were also collected at similar time points. On days 70 and 150, liver biopsies were collected from seven animals in each group. The BW was not different between the groups at all times. Total BW gain in the control group was 124 kg as opposed to 111 kg in restricted group that led to average BW gain of 827 g/day and 739 g/day in respective groups, and the differences were significant (p = 0.018). As planned, the control group had higher concentrate and lower forage intake than the restricted group. The blood haemoglobin, haematocrit and serum variables (glucose, total protein, albumin and urea) were within the normal range in both groups, but serum glucose was higher (p < 0.05) in control than in restricted group at 70 days. There was no difference between groups in organic matter (OM) digestibility which declined (p < 0.001) with increasing age in both groups. Microbial crude protein (MCP) synthesis estimated from urinary allantoin excretion increased (p < 0.001) in both groups with increasing age but was not different between groups. The mRNA expressions for the gluconeogenic enzymes, cytosolic and

  18. Intrafamiliar clinical variability of circumferential skin creases Kunze type caused by a novel heterozygous mutation of N-terminal TUBB gene.

    Science.gov (United States)

    Dentici, M L; Terracciano, A; Bellacchio, E; Capolino, R; Novelli, A; Digilio, M C; Dallapiccola, B

    2018-02-10

    Circumferential skin creases Kunze type (CSC-KT; OMIM 156610, 616734) is a rare disorder characterized by folding of excess skin, which leads to ringed creases, known as Michelin Tire Baby Syndrome (MTBS). CSC-KT patients also exhibit facial dysmorphism, growth retardation, intellectual disability (ID) and multiple congenital malformations. Recently, 2 heterozygous mutations in TUBB gene and 4 mutations (both homozygous and heterozygous) in MAPRE2 gene were identified in 3 and 4 CSC-KT patients, respectively. In the 3 TUBB gene-related CSC-KT patients, all mutations fall in the N-terminal gene domain and were de novo. Mutations in the C-terminal of TUBB gene have been associated to microcephaly and structural brain malformation, in the absence of CSC-KT features. We report a 9-year-old boy with a diagnosis of CSC-KT based on MTBS, facial dysmorphism, microcephaly, severe ID, cortical atrophy and corpus callosum hypoplasia. Sanger sequencing identified a novel heterozygous c.218T>C (p.Met73Thr) mutation in the N-terminal of TUBB gene, that was inherited from the mother affected by isolated MTBS. This is the first report of inherited TUBB gene-related CSC-KT resulting from a novel heterozygous mutation in the N-terminal domain. Present data support the role of TUBB mutations in CSC-KT and definitely includes CSC-KT syndrome within the tubulinopathies. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. 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.

  20. Preferrential rearrangement in normal rabbits of the 3' VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation/conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences.

    Science.gov (United States)

    Allegrucci, M; Young-Cooper, G O; Alexander, C B; Newman, B A; Mage, R G

    1991-02-01

    The rabbit is unique in having well-defined allotypes in the variable region of the heavy chain. Products of the VHa locus, (with alleles a1, a2, and a3), account for the majority of the serum immunoglobulins. A small percentage of the serum immunoglobulins are a-negative. In 1986, Kelus and Weiss described a mutation that depressed the expression of the Ig VH a2 genes in an a1/a2 rabbit. From this animal the Alicia rabbit strain was developed and the mutation was termed ali. We previously showed, using Southern analysis and the transverse alternating field electrophoresis technique, that the difference between the ali rabbit and normal is a relatively small deletion including some of the most 3' VH genes. The most JH proximal 3' VH1 genes in DNA from normal rabbits of a1, a2 and a3 haplotypes encode a1, a2 and a3 molecules respectively, and it has been suggested that these genes are responsible for allelic inheritance of VHa allotypes. The present study suggests that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression in rabbits because VH gene(s) in this region are the target(s) of preferential VDJ rearrangements. This raises the possibility that mechanisms such as somatic gene conversion and hypermutation are at work to generate the antibody repertoire in this species. Our data support the view that the 3' VH1 gene may be the preferred target for rearrangement in normal rabbits, and for the normal chromosome in heterozygous ali animals. However, homozygous ali rabbits with a deletion that removed the a2-encoding VH1 on both chromosomes do survive, rearrange other VH genes and produce normal levels of immunoglobulins as well as a significant percentage of B cells which bear the a2 allotype. This challenges the view that one VH gene, VH1, is solely responsible for the inheritance pattern of VHa allotypes.

  1. The role of clinical variables, neuropsychological performance and SLC6A4 and COMT gene polymorphisms on the prediction of early response to fluoxetine in major depressive disorder.

    Science.gov (United States)

    Gudayol-Ferré, Esteve; Herrera-Guzmán, Ixchel; Camarena, Beatriz; Cortés-Penagos, Carlos; Herrera-Abarca, Jorge E; Martínez-Medina, Patricia; Cruz, David; Hernández, Sandra; Genis, Alma; Carrillo-Guerrero, Mariana Y; Avilés Reyes, Rubén; Guàrdia-Olmos, Joan

    2010-12-01

    Major depressive disorder (MDD) is treated with antidepressants, but only between 50% and 70% of the patients respond to the initial treatment. Several authors suggested different factors that could predict antidepressant response, including clinical, psychophysiological, neuropsychological, neuroimaging, and genetic variables. However, these different predictors present poor prognostic sensitivity and specificity by themselves. The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms in the prediction of the response to fluoxetine after 4weeks of treatment in a sample of patient with MDD. 64 patients with MDD were genotyped according to the above-mentioned polymorphisms, and were clinically and neuropsychologically assessed before a 4-week fluoxetine treatment. Fluoxetine response was assessed by using the Hamilton Depression Rating Scale. We carried out a binary logistic regression model for the potential predictive variables. Out of the clinical variables studied, only the number of anxiety disorders comorbid with MDD have predicted a poor response to the treatment. A combination of a good performance in variables of attention and low performance in planning could predict a good response to fluoxetine in patients with MDD. None of the genetic variables studied had predictive value in our model. The possible placebo effect has not been controlled. Our study is focused on response prediction but not in remission prediction. Our work suggests that the combination of the number of comorbid anxiety disorders, an attentional variable, and two planning variables makes it possible to correctly classify 82% of the depressed patients who responded to the treatment with fluoxetine, and 74% of the patients who did not respond to that treatment. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. 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.

  3. 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.

  4. In situ analysis of the variable heavy chain gene of an IgM/IgG-expressing follicular lymphoma - Evidence for interfollicular trafficking of tumor cells

    NARCIS (Netherlands)

    Aarts, Wilhelmina M.; Bende, Richard J.; Vaandrager, Jan-Willem; Kluin, Philip M.; Langerak, Anton W.; Pals, Steven T.; van Noesel, Carel J. M.

    2002-01-01

    is generally assumed that follicular lymphomas (FL) not only morphologically resemble normal germinal centers but have retained some functional characteristics of their non-neoplastic counterparts as well. Recent IgV gene analyses on a panel of FLs however, strongly suggested that FLs do not retain

  5. Sequencing of mitochondrial genomes of nine Aspergillus and Penicillium species identifies mobile introns and accessory genes as main sources of genome size variability.

    Science.gov (United States)

    Joardar, Vinita; Abrams, Natalie F; Hostetler, Jessica; Paukstelis, Paul J; Pakala, Suchitra; Pakala, Suman B; Zafar, Nikhat; Abolude, Olukemi O; Payne, Gary; Andrianopoulos, Alex; Denning, David W; Nierman, William C

    2012-12-12

    The genera Aspergillus and Penicillium include some of the most beneficial as well as the most harmful fungal species such as the penicillin-producer Penicillium chrysogenum and the human pathogen Aspergillus fumigatus, respectively. Their mitochondrial genomic sequences may hold vital clues into the mechanisms of their evolution, population genetics, and biology, yet only a handful of these genomes have been fully sequenced and annotated. Here we report the complete sequence and annotation of the mitochondrial genomes of six Aspergillus and three Penicillium species: A. fumigatus, A. clavatus, A. oryzae, A. flavus, Neosartorya fischeri (A. fischerianus), A. terreus, P. chrysogenum, P. marneffei, and Talaromyces stipitatus (P. stipitatum). The accompanying comparative analysis of these and related publicly available mitochondrial genomes reveals wide variation in size (25-36 Kb) among these closely related fungi. The sources of genome expansion include group I introns and accessory genes encoding putative homing endonucleases, DNA and RNA polymerases (presumed to be of plasmid origin) and hypothetical proteins. The two smallest sequenced genomes (A. terreus and P. chrysogenum) do not contain introns in protein-coding genes, whereas the largest genome (T. stipitatus), contains a total of eleven introns. All of the sequenced genomes have a group I intron in the large ribosomal subunit RNA gene, suggesting that this intron is fixed in these species. Subsequent analysis of several A. fumigatus strains showed low intraspecies variation. This study also includes a phylogenetic analysis based on 14 concatenated core mitochondrial proteins. The phylogenetic tree has a different topology from published multilocus trees, highlighting the challenges still facing the Aspergillus systematics. The study expands the genomic resources available to fungal biologists by providing mitochondrial genomes with consistent annotations for future genetic, evolutionary and population

  6. Diagnostic screening identifies a wide range of mutations involving the SHOX gene, including a common 47.5 kb deletion 160 kb downstream with a variable phenotypic effect.

    Science.gov (United States)

    Bunyan, David J; Baker, Kevin R; Harvey, John F; Thomas, N Simon

    2013-06-01

    Léri-Weill dyschondrosteosis (LWD) results from heterozygous mutations of the SHOX gene, with homozygosity or compound heterozygosity resulting in the more severe form, Langer mesomelic dysplasia (LMD). These mutations typically take the form of whole or partial gene deletions, point mutations within the coding sequence, or large (>100 kb) 3' deletions of downstream regulatory elements. We have analyzed the coding sequence of the SHOX gene and its downstream regulatory regions in a cohort of 377 individuals referred with symptoms of LWD, LMD or short stature. A causative mutation was identified in 68% of the probands with LWD or LMD (91/134). In addition, a 47.5 kb deletion was found 160 kb downstream of the SHOX gene in 17 of the 377 patients (12% of the LWD referrals, 4.5% of all referrals). In 14 of these 17 patients, this was the only potentially causative abnormality detected (13 had symptoms consistent with LWD and one had short stature only), but the other three 47.5 kb deletions were found in patients with an additional causative SHOX mutation (with symptoms of LWD rather than LMD). Parental samples were available on 14/17 of these families, and analysis of these showed a more variable phenotype ranging from apparently unaffected to LWD. Breakpoint sequence analysis has shown that the 47.5 kb deletion is identical in all 17 patients, most likely due to an ancient founder mutation rather than recurrence. This deletion was not seen in 471 normal controls (P<0.0001), providing further evidence for a phenotypic effect, albeit one with variable penetration. Copyright © 2013 Wiley Periodicals, Inc.

  7. 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.

  8. 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.

  9. Phenotypic reversion in fas mutants of Arabidopsis thaliana by reintroduction of FAS genes: variable recovery of telomeres with major spatial rearrangements and transcriptional reprogramming of 45S rDNA genes

    Czech Academy of Sciences Publication Activity Database

    Pavlištová, V.; Dvořáčková, Martina; Jež, M.; Mozgová, I.; Mokroš, P.; Fajkus, Jiří

    2016-01-01

    Roč. 88, č. 3 (2016), s. 411-424 ISSN 0960-7412 Institutional support: RVO:68081707 Keywords : chromatin assembly factor-1 * ribosomal-rna genes * dosage control Subject RIV: BO - Biophysics Impact factor: 5.901, year: 2016

  10. Variability Bugs:

    DEFF Research Database (Denmark)

    Melo, Jean

    . Although many researchers suggest that preprocessor-based variability amplifies maintenance problems, there is little to no hard evidence on how actually variability affects programs and programmers. Specifically, how does variability affect programmers during maintenance tasks (bug finding in particular......)? How much harder is it to debug a program as variability increases? How do developers debug programs with variability? In what ways does variability affect bugs? In this Ph.D. thesis, I set off to address such issues through different perspectives using empirical research (based on controlled...... experiments) in order to understand quantitatively and qualitatively the impact of variability on programmers at bug finding and on buggy programs. From the program (and bug) perspective, the results show that variability is ubiquitous. There appears to be no specific nature of variability bugs that could...

  11. 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.

  12. SRSF1-3 contributes to diversification of the immunoglobulin variable region gene by promoting accumulation of AID in the nucleus

    OpenAIRE

    Kawaguchi, Yuka; Nariki, Hiroaki; Kawamoto, Naoko; Kanehiro, Yuichi; Miyazaki, Satoshi; Suzuki, Mari; Magari, Masaki; Tokumitsu, Hiroshi; Kanayama, Naoki

    2017-01-01

     Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this stu...

  13. The variability of sesquiterpenes emitted from two Zea mays cultivars is controlled by allelic variation of two terpene synthase genes encoding stereoselective multiple product enzymes.

    Science.gov (United States)

    Köllner, Tobias G; Schnee, Christiane; Gershenzon, Jonathan; Degenhardt, Jörg

    2004-05-01

    The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes.

  14. Studies of genetic variability of the hepatocyte nuclear factor-1α gene in an Indian maturity-onset diabetes of the young family.

    Science.gov (United States)

    Yang, Jing; Jiang, Feng; Guo, Hui; Soniya, Thadimacca; Yan, Chun-Xia; Tian, Zhu-Fang; Shi, Bing-Yin

    2016-01-01

    Maturity-onset diabetes of the young (MODY), one of the specific types of diabetes mellitus, is a monogenetic disorder characterized by an autosomal dominant (AD) inheritance and β-cell dysfunction. To study an Indian family with clinical diagnosis of MODY and detect the genetic mutations in the aspect of molecular mechanism, seven blood samples were obtained from the diabetic patients of this pedigree and genomic DNA was extracted from peripheral leukocytes. The exon1, exon2 and exon4 of hepatocyte nuclear factor-1α (HNF-1α) gene were amplified by polymerase chain reaction. Then the products were sequenced and compared with standard sequences on gene bank. As a result, two mutations were detected in exon1. That was CTC → CTG (Leu → Leu) in codon17 and ATC → CTC (Ile → Leu) in codon27. I27L was speculated to have a close relationship with the glycometabolism and the pathogenesis of diabetes mellitus together with the putative novel mutation existed in this Indian pedigree. Meanwhile, one mutation of GGG → GGC (Gly → Gly) in codon288 of exon4 was detected in the proband. No mutations were found in exon2 but a G → T base substitution in the intron4 region among all seven samples was detected. It may have some potential effects on the onset of diabetes in this family, but we do not have any evidence right now. Although it requires further investigation on the function of mutations found in the intron region, our research may provide some clue for this issue and it deserves more attention.

  15. 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 ...

  16. 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

  17. 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.

  18. The ITS1-5.8S rRNA gene -ITS2 sequence variability during the divergence of sweet-grass species (gen us Glyceria R. Br.

    Directory of Open Access Journals (Sweden)

    Alexander V Rodionov

    2011-12-01

    Full Text Available Comparative analysis of the sequence ITS1-5.8S rRNA gene-ITS2 of the nuclear genome of 13 species of genus Glyceria, 4 species of Melica and a species of monotypic genus Pleuropogon showed that the species of the genus Glyceria have 3 haplotypes: 1 Haplotype A was found only in species of the subgenus Glyceria section Glyceria (G. septentrionalis, G. fluitans, G. declinata, G. occidentalis, G. notata, G. borealis, G. leptostachya and in Pleuropogon sabinii; 2 Haplotype C is characteristic of the subgenus Hydropoa, section Hydropoa (G. grandis, G. х amurensis, G. triflora, G. maxima and sect. Lithuanicae (G. leptolepis; 3 Haplotype B is found in the species of the subgenus Hydropoa sections Striatae (G. elata, G. striata, G. neogaea, G. canadensis, Scolochloiformes (G. alnasteretum, G. spiculosa and G. lithuanica of sect. Lithuanicae. Species carring haplotype B are located at the base of the phylogenetic tree of the genus Glyceria and/or clustered with low bootstrap indices. On the phylogenetic trees inferred by the analysis of the sequences ITS and 5.8S rDNA both sect. Glyceria and sect. Hydropoa represented two sister monophyly branches. The species Pleuropogon sabinii belong to the branch of subgenus Glyceria as a sister monotypic branch to the branch of the sect. Glyceria.

  19. Interindividual variability in the prevalence of OPRM1 and CYP2B6 gene variations may identify drug-susceptible populations.

    Science.gov (United States)

    Bunten, H; Liang, W J; Pounder, D J; Seneviratne, C; Osselton, D

    2011-09-01

    Methadone is used worldwide for the treatment of heroin addiction; however, fatal poisonings are increasingly reported. The prevalence of CYP2B6 and μ-opioid receptor (OPRM1) gene variations were examined between a postmortem population where the deaths were associated with methadone and a live nondrug-using control population using Taqman™ SNP Genotyping assays. The CYP2B6*6 allele was higher in the postmortem population, but the difference was not significant (P = 0.92). The CYP2B6 T750C promoter variation was similar in frequency for both populations. Linkage between T750C and CYP2B6*6 was identified for both populations (P < 0.01). The prevalence of the OPRM1 A118G variation was significantly higher in the control population (P = 0.0046), which might indicate a protective mechanism against opioid toxicity. Individual susceptibility to methadone may be determined by screening for CYP2B6*6.

  20. 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.

  1. Variable effects of maternal and paternal-fetal contribution to the risk for preeclampsia combining GSTP1, eNOS, and LPL gene polymorphisms.

    Science.gov (United States)

    Pappa, Kalliopi I; Roubelakis, Maria; Vlachos, George; Marinopoulos, Spyros; Zissou, Antonia; Anagnou, Nicholas P; Antsaklis, Aris

    2011-04-01

    To evaluate the maternal, paternal, and fetal genotype contribution to preeclampsia. STUDY DESIGN, MATERIALS, AND METHODS: We combined the analysis of polymorphisms of the GSTP1, eNOS, and LPL genes - affecting biotransformation enzymes and endothelial function - in a cohort of 167 preeclamptic and normal control trios (mother, father, and child) comprising a total of 501 samples in the Greek population, never analyzed before by this approach. For the frequency of the GSTP1 Ile(105)/Val(105), the eNOS Glu298Asp and the LPL-93 polymorphisms, statistically significant differences were found between the two groups. However, the transmission rates of the parental alleles to neonates studied by the transmission disequilibrium test, disclosed no increased rate of transmission to preeclampsia children for the variant alleles of Val(105) GSTP1, 298Asp eNOS, and -93G LPL. These novel data, suggest that interaction of all three types of genotypes (mother, father and neonate), reveals no effects on the development of preeclampsia, but provide the impetus for further studies to decipher the individual contribution of each genetic parameter of preeclampsia.

  2. Pulsating variables

    International Nuclear Information System (INIS)

    1989-01-01

    The study of stellar pulsations is a major route to the understanding of stellar structure and evolution. At the South African Astronomical Observatory (SAAO) the following stellar pulsation studies were undertaken: rapidly oscillating Ap stars; solar-like oscillations in stars; 8-Scuti type variability in a classical Am star; Beta Cephei variables; a pulsating white dwarf and its companion; RR Lyrae variables and galactic Cepheids. 4 figs

  3. Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state.

    Science.gov (United States)

    Jdila, Marwa Ben; Issa, Abir Ben; Khabou, Boudour; Rhouma, Bochra Ben; Kamoun, Fatma; Ammar-Keskes, Leila; Triki, Chahnez; Fakhfakh, Faiza

    2017-10-01

    West syndrome is a rare epileptic encephalopathy of early infancy, characterized by epileptic spasms, hypsarrhythmia, and psychomotor retardation beginning in the first year of life. The present study reports the clinical, molecular and bioinformatic investigation in the three studied West patients. The results revealed a complex genotype with more than one mutation in each patient including the known mutations c.1910C>G (P2, P3); c.2372A>C in P3 and c.2395C>G in P1 and novel variants including c.616G>A, shared by the three patients P1, P2 and P3; c.1403G>C shared by P2 and P3 and c.2288A>G in patient P1. All the mutations were at somatic mosaic state and were de novo in the patients except ones (c.2372A>C). To our knowledge; the somatic mosaic state is described for the first time in patients with West syndrome. Five identified mutations were located in the C-terminal domain of the protein, while the novel mutation (c.616G>A) was in the catalytic domain. Bioinformatic tools predicted that this latter is the most pathogenic substitution affecting 3D protein structure and the secondary mRNA structure. Complex genotype composed of different combinations of mutations in each patient seems to be related to the phenotype variability. Copyright © 2017. Published by Elsevier B.V.

  4. SRSF1-3 contributes to diversification of the immunoglobulin variable region gene by promoting accumulation of AID in the nucleus.

    Science.gov (United States)

    Kawaguchi, Yuka; Nariki, Hiroaki; Kawamoto, Naoko; Kanehiro, Yuichi; Miyazaki, Satoshi; Suzuki, Mari; Magari, Masaki; Tokumitsu, Hiroshi; Kanayama, Naoki

    2017-04-01

    Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID. AID expressed alone was localized predominantly in the cytoplasm. In contrast, co-expression of AID with SRSF1-3 led to the nuclear accumulation of both AID and SRSF1-3 and the formation of a protein complex that contained them both, although SRSF1-3 was dispensable for nuclear import of AID. Expression of either SRSF1-3 or a C-terminally-truncated AID mutant increased IgV diversification in DT40 cells. However, overexpression of exogenous SRSF1-3 was unable to further enhance IgV diversification in DT40 cells expressing the truncated AID mutant, although SRSF1-3 was able to form a protein complex with the AID mutant. These results suggest that SRSF1-3 promotes nuclear localization of AID probably by forming a nuclear protein complex, which might stabilize nuclear AID and induce IgV diversification in an AID C-terminus-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Cognitive Variability

    Science.gov (United States)

    Siegler, Robert S.

    2007-01-01

    Children's thinking is highly variable at every level of analysis, from neural and associative levels to the level of strategies, theories, and other aspects of high-level cognition. This variability exists within people as well as between them; individual children often rely on different strategies or representations on closely related problems…

  6. 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

  7. 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.

  8. 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

    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.

  9. 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...

  10. 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

  11. 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

  12. Variable stars

    International Nuclear Information System (INIS)

    Feast, M.W.; Wenzel, W.; Fernie, J.D.; Percy, J.R.; Smak, J.; Gascoigne, S.C.B.; Grindley, J.E.; Lovell, B.; Sawyer Hogg, H.B.; Baker, N.; Fitch, W.S.; Rosino, L.; Gursky, H.

    1976-01-01

    A critical review of variable stars is presented. A fairly complete summary of major developments and discoveries during the period 1973-1975 is given. The broad developments and new trends are outlined. Essential problems for future research are identified. (B.R.H. )

  13. 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

  14. Variable collimator

    International Nuclear Information System (INIS)

    Richey, J.B.; McBride, T.R.; Covic, J.

    1979-01-01

    This invention describes an automatic variable collimator which controls the width and thickness of X-ray beams in X-ray diagnostic medical equipment, and which is particularly adapted for use with computerized axial tomographic scanners. A two-part collimator is provided which shapes an X-ray beam both prior to its entering an object subject to radiographic analysis and after the attenuated beam has passed through the object. Interposed between a source of radiation and the object subject to radiographic analysis is a first or source collimator. The source collimator causes the X-ray beam emitted by the source of radiation to be split into a plurality of generally rectangular shaped beams. Disposed within the source collimator is a movable aperture plate which may be used to selectively vary the thickness of the plurality of generally rectangular shaped beams transmitted through the source collimator. A second or receiver collimator is interposed between the object subject to radiographic analysis and a series of radiation detectors. The receiver collimator is disposed to receive the attenuated X-ray beams passing through the object subject to radiographic analysis. Located within the receiver collimator are a plurality of movable aperture plates adapted to be displaced relative to a plurality of fixed aperture plates for the purpose of varying the width and thickness of the attenuated X-ray beams transmitted through the object subject to radiographic analysis. The movable aperture plates of the source and receiver collimators are automatically controlled by circuitry which is provided to allow remote operation of the movable aperture plates

  15. 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 ...

  16. 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…

  17. 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

    Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether...... mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy...... comprising the DCoH gene revealed a previously described A-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects....

  18. 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. .

  19. What do we know about variability?

    Directory of Open Access Journals (Sweden)

    Sergey G Inge-Vechtomov

    2010-12-01

    Full Text Available Contemporary phenomenological classification of variability types meets lots of contradictions. There is a single group of “mutations”: gene, chromosomal, genomic ones, which originate through different mechanisms. Ontogenetic variability puts even more questions because it embraces: modifications (regulation of gene expression, genetic variations (mutations and recombination and epigenetic variations (and inheritance in addition, with no clear criterions of the latter ones definition so far. Modifications and heritable variations are appeared to be closer to each other then we suspected before. An alternative classification of variability may be proposed basing upon template principle in biology. There is no direct correspondence between mechanisms and phenomenology of variation. It is a witness of a newparadigm coming in biological variability understanding.

  20. 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

  1. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  2. Amplification factor variable 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

  3. Amplification factor variable amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2010-01-01

    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 can

  4. Simple Comparative Analyses of Differentially Expressed Gene Lists May Overestimate Gene Overlap.

    Science.gov (United States)

    Lawhorn, Chelsea M; Schomaker, Rachel; Rowell, Jonathan T; Rueppell, Olav

    2018-04-16

    Comparing the overlap between sets of differentially expressed genes (DEGs) within or between transcriptome studies is regularly used to infer similarities between biological processes. Significant overlap between two sets of DEGs is usually determined by a simple test. The number of potentially overlapping genes is compared to the number of genes that actually occur in both lists, treating every gene as equal. However, gene expression is controlled by transcription factors that bind to a variable number of transcription factor binding sites, leading to variation among genes in general variability of their expression. Neglecting this variability could therefore lead to inflated estimates of significant overlap between DEG lists. With computer simulations, we demonstrate that such biases arise from variation in the control of gene expression. Significant overlap commonly arises between two lists of DEGs that are randomly generated, assuming that the control of gene expression is variable among genes but consistent between corresponding experiments. More overlap is observed when transcription factors are specific to their binding sites and when the number of genes is considerably higher than the number of different transcription factors. In contrast, overlap between two DEG lists is always lower than expected when the genetic architecture of expression is independent between the two experiments. Thus, the current methods for determining significant overlap between DEGs are potentially confounding biologically meaningful overlap with overlap that arises due to variability in control of expression among genes, and more sophisticated approaches are needed.

  5. 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.

  6. 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...

  7. 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.

  8. Coverage analysis of lists of genes involved in heterogeneous ...

    Indian Academy of Sciences (India)

    Genes involved in myopathies: 82 genes, based on the disease groups ... 605517 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye ..... Epilepsy, X-linked, with variable learning disabilities and behavior disorders. 300491.

  9. Gene Circuit Analysis of the Terminal Gap Gene huckebein

    Science.gov (United States)

    Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes

    2009-01-01

    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. PMID:19876378

  10. Cataclysmic Variable Stars

    Science.gov (United States)

    Hellier, Coel

    2001-01-01

    Cataclysmic variable stars are the most variable stars in the night sky, fluctuating in brightness continually on timescales from seconds to hours to weeks to years. The changes can be recorded using amateur telescopes, yet are also the subject of intensive study by professional astronomers. That study has led to an understanding of cataclysmic variables as binary stars, orbiting so closely that material transfers from one star to the other. The resulting process of accretion is one of the most important in astrophysics. This book presents the first account of cataclysmic variables at an introductory level. Assuming no previous knowledge of the field, it explains the basic principles underlying the variability, while providing an extensive compilation of cataclysmic variable light curves. Aimed at amateur astronomers, undergraduates, and researchers, the main text is accessible to those with no mathematical background, while supplementary boxes present technical details and equations.

  11. Understanding Brown Dwarf Variability

    Science.gov (United States)

    Marley, Mark S.

    2013-01-01

    Surveys of brown dwarf variability continue to find that roughly half of all brown dwarfs are variable. While variability is observed amongst all types of brown dwarfs, amplitudes are typically greatest for L-T transition objects. In my talk I will discuss the possible physical mechanisms that are responsible for the observed variability. I will particularly focus on comparing and contrasting the effects of changes in atmospheric thermal profile and cloud opacity. The two different mechanisms will produce different variability signatures and I will discuss the extent to which the current datasets constrain both mechanisms. By combining constraints from studies of variability with existing spectral and photometric datasets we can begin to construct and test self-consistent models of brown dwarf atmospheres. These models not only aid in the interpretation of existing objects but also inform studies of directly imaged giant planets.

  12. Using the gene ontology to scan multilevel gene sets for associations in genome wide association studies.

    Science.gov (United States)

    Schaid, Daniel J; Sinnwell, Jason P; Jenkins, Gregory D; McDonnell, Shannon K; Ingle, James N; Kubo, Michiaki; Goss, Paul E; Costantino, Joseph P; Wickerham, D Lawrence; Weinshilboum, Richard M

    2012-01-01

    Gene-set analyses have been widely used in gene expression studies, and some of the developed methods have been extended to genome wide association studies (GWAS). Yet, complications due to linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes per gene-set, have plagued current approaches, often leading to ad hoc "fixes." To overcome some of the current limitations, we developed a general approach to scan GWAS SNP data for both gene-level and gene-set analyses, building on score statistics for generalized linear models, and taking advantage of the directed acyclic graph structure of the gene ontology when creating gene-sets. However, other types of gene-set structures can be used, such as the popular Kyoto Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes, and genes into gene-sets, but assures that positive and negative effects of genes on a trait do not cancel. To control for multiple testing of many gene-sets, we use an efficient computational strategy that accounts for LD and provides accurate step-down adjusted P-values for each gene-set. Application of our methods to two different GWAS provide guidance on the potential strengths and weaknesses of our proposed gene-set analyses. © 2011 Wiley Periodicals, Inc.

  13. Bayesian assignment of gene ontology terms to gene expression experiments.

    Science.gov (United States)

    Sykacek, P

    2012-09-15

    Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.

  14. Bayesian assignment of gene ontology terms to gene expression experiments

    Science.gov (United States)

    Sykacek, P.

    2012-01-01

    Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

  15. 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

  16. Ultrasonic variables affecting inspection

    International Nuclear Information System (INIS)

    Lautzenheiser, C.E.; Whiting, A.R.; McElroy, J.T.

    1977-01-01

    There are many variables which affect the detection of the effects and reproducibility of results when utilizing ultrasonic techniques. The most important variable is the procedure, as this document specifies, to a great extent, the controls that are exercised over the other variables. The most important variable is personnel with regards to training, qualification, integrity, data recording, and data analysis. Although the data is very limited, these data indicate that, if the procedure is carefully controlled, reliability of defect detection and reproducibility of results are both approximately 90 percent for reliability of detection, this applies to relatively small defects as reliability increases substantially as defect size increases above the recording limit. (author)

  17. 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.

  18. Collective variables and dissipation

    International Nuclear Information System (INIS)

    Balian, R.

    1984-09-01

    This is an introduction to some basic concepts of non-equilibrium statistical mechanics. We emphasize in particular the relevant entropy relative to a given set of collective variables, the meaning of the projection method in the Liouville space, its use to establish the generalized transport equations for these variables, and the interpretation of dissipation in the framework of information theory

  19. Variability: A Pernicious Hypothesis.

    Science.gov (United States)

    Noddings, Nel

    1992-01-01

    The hypothesis of greater male variability in test results is discussed in its historical context, and reasons feminists have objected to the hypothesis are considered. The hypothesis acquires political importance if it is considered that variability results from biological, rather than cultural, differences. (SLD)

  20. Reinforcing Saccadic Amplitude Variability

    Science.gov (United States)

    Paeye, Celine; Madelain, Laurent

    2011-01-01

    Saccadic endpoint variability is often viewed as the outcome of neural noise occurring during sensorimotor processing. However, part of this variability might result from operant learning. We tested this hypothesis by reinforcing dispersions of saccadic amplitude distributions, while maintaining constant their medians. In a first experiment we…

  1. POVMs and hidden variables

    International Nuclear Information System (INIS)

    Stairs, Allen

    2007-01-01

    Recent results by Paul Busch and Adan Cabello claim to show that by appealing to POVMs, non-contextual hidden variables can be ruled out in two dimensions. While the results of Busch and Cabello are mathematically correct, interpretive problems render them problematic as no hidden variable proofs

  2. Interdependence Among Organizational Variables

    Science.gov (United States)

    Knowles, M. C.

    1975-01-01

    The interrelationship between a set of organizational variables was investigated at 14 work organizations within a company. The variables were production, quality, costs, job satisfaction of operatives, job satisfaction of supervisors, work anxiety, accidents, absence, labor turnover, and industrial unrest. (Author)

  3. Ageing genes

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2018-01-01

    The idea of gerontogenes is in line with the evolutionary explanation of ageing as being an emergent phenomenon as a result of the imperfect maintenance and repair systems. Although evolutionary processes did not select for any specific ageing genes that restrict and determine the lifespan...... of an individual, the term ‘gerontogenes’ primarily refers to any genes that may seem to influence ageing and longevity, without being specifically selected for that role. Such genes can also be called ‘virtual gerontogenes’ by virtue of their indirect influence on the rate and process of ageing. More than 1000...... virtual gerontogenes have been associated with ageing and longevity in model organisms and humans. The ‘real’ genes, which do influence the essential lifespan of a species, and have been selected for in accordance with the evolutionary life history of the species, are known as the longevity assurance...

  4. Effect of demographic variables on public attitudes towards ...

    African Journals Online (AJOL)

    In conclusion, background variables do have a significant effect on some of the dimensions of Malaysians' attitudes towards modern biotechnology. The research findings will be useful for understanding the effect of background variables on public attitudes towards the application of gene technology in medicine.

  5. 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.

  6. 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

  7. 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

  8. Gene doping.

    Science.gov (United States)

    Haisma, H J; de Hon, O

    2006-04-01

    Together with the rapidly increasing knowledge on genetic therapies as a promising new branch of regular medicine, the issue has arisen whether these techniques might be abused in the field of sports. Previous experiences have shown that drugs that are still in the experimental phases of research may find their way into the athletic world. Both the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) have expressed concerns about this possibility. As a result, the method of gene doping has been included in the list of prohibited classes of substances and prohibited methods. This review addresses the possible ways in which knowledge gained in the field of genetic therapies may be misused in elite sports. Many genes are readily available which may potentially have an effect on athletic performance. The sporting world will eventually be faced with the phenomena of gene doping to improve athletic performance. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping.

  9. 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...

  10. Several complex variables

    International Nuclear Information System (INIS)

    Field, M.J.

    1976-01-01

    Topics discussed include the elementary of holomorphic functions of several complex variables; the Weierstrass preparation theorem; meromorphic functions, holomorphic line bundles and divisors; elliptic operators on compact manifolds; hermitian connections; the Hodge decomposition theorem. ( author)

  11. 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...

  12. Variable Pricing Feasibility Assessment

    National Research Council Canada - National Science Library

    2004-01-01

    ...) and Willard Bishop Consulting (Barrington, IL) to evaluate the practicality of using a variable pricing system within DeCA to maintain an average of 30 percent customer savings and lower appropriated fund costs...

  13. Evolution of variable stars

    International Nuclear Information System (INIS)

    Becker, S.A.

    1986-08-01

    Throughout the domain of the H R diagram lie groupings of stars whose luminosity varies with time. These variable stars can be classified based on their observed properties into distinct types such as β Cephei stars, δ Cephei stars, and Miras, as well as many other categories. The underlying mechanism for the variability is generally felt to be due to four different causes: geometric effects, rotation, eruptive processes, and pulsation. In this review the focus will be on pulsation variables and how the theory of stellar evolution can be used to explain how the various regions of variability on the H R diagram are populated. To this end a generalized discussion of the evolutionary behavior of a massive star, an intermediate mass star, and a low mass star will be presented. 19 refs., 1 fig., 1 tab

  14. 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.

  15. 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...... impact in software production. As is also apparent from the call for papers these perspectives focus on qualities such as reuse, adaptability, and maintainability....

  16. Suspended graphene variable capacitor

    OpenAIRE

    AbdelGhany, M.; Mahvash, F.; Mukhopadhyay, M.; Favron, A.; Martel, R.; Siaj, M.; Szkopek, T.

    2016-01-01

    The tuning of electrical circuit resonance with a variable capacitor, or varactor, finds wide application with the most important being wireless telecommunication. We demonstrate an electromechanical graphene varactor, a variable capacitor wherein the capacitance is tuned by voltage controlled deflection of a dense array of suspended graphene membranes. The low flexural rigidity of graphene monolayers is exploited to achieve low actuation voltage in an ultra-thin structure. Large arrays compr...

  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. Gene Locater

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... of flexibility in calculating genetic linkage and displaying linkage group. Among other features, this software enables user to identify linkage groups with output visualized graphically. The program calculates interference and coefficient of coincidence with elevated accuracy in sample datasets. AVAILABILITY...

  19. 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.

  20. Pulsating red variables

    International Nuclear Information System (INIS)

    Whitelock, P.A.

    1990-01-01

    The observational characteristics of pulsating red variables are reviewed with particular emphasis on the Miras. These variables represent the last stage in the evolution of stars on the Asymptotic Giant Branch (AGB). A large fraction of the IRAS sources in the Bulge are Mira variables and a subset of these are also OH/IR sources. Their periods range up to 720 days, though most are between 360 and 560 days. At a given period those stars with the highest pulsation amplitudes have the highest mass-loss rates; this is interpreted as evidence for a causal connection between mass-loss and pulsation. It is suggested that once an AGB star has become a Mira it will evolve with increasing pulsation amplitude and mass-loss, but with very little change of luminosity or logarithmic period. 26 refs

  1. Variable stator radial turbine

    Science.gov (United States)

    Rogo, C.; Hajek, T.; Chen, A. G.

    1984-01-01

    A radial turbine stage with a variable area nozzle was investigated. A high work capacity turbine design with a known high performance base was modified to accept a fixed vane stagger angle moveable sidewall nozzle. The nozzle area was varied by moving the forward and rearward sidewalls. Diffusing and accelerating rotor inlet ramps were evaluated in combinations with hub and shroud rotor exit rings. Performance of contoured sidewalls and the location of the sidewall split line with respect to the rotor inlet was compared to the baseline. Performance and rotor exit survey data are presented for 31 different geometries. Detail survey data at the nozzle exit are given in contour plot format for five configurations. A data base is provided for a variable geometry concept that is a viable alternative to the more common pivoted vane variable geometry radial turbine.

  2. 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.

  3. 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.

  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. cis sequence effects on gene expression

    Directory of Open Access Journals (Sweden)

    Jacobs Kevin

    2007-08-01

    Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

  6. Gene set analysis using variance component tests.

    Science.gov (United States)

    Huang, Yen-Tsung; Lin, Xihong

    2013-06-28

    Gene set analyses have become increasingly important in genomic research, as many complex diseases are contributed jointly by alterations of numerous genes. Genes often coordinate together as a functional repertoire, e.g., a biological pathway/network and are highly correlated. However, most of the existing gene set analysis methods do not fully account for the correlation among the genes. Here we propose to tackle this important feature of a gene set to improve statistical power in gene set analyses. We propose to model the effects of an independent variable, e.g., exposure/biological status (yes/no), on multiple gene expression values in a gene set using a multivariate linear regression model, where the correlation among the genes is explicitly modeled using a working covariance matrix. We develop TEGS (Test for the Effect of a Gene Set), a variance component test for the gene set effects by assuming a common distribution for regression coefficients in multivariate linear regression models, and calculate the p-values using permutation and a scaled chi-square approximation. We show using simulations that type I error is protected under different choices of working covariance matrices and power is improved as the working covariance approaches the true covariance. The global test is a special case of TEGS when correlation among genes in a gene set is ignored. Using both simulation data and a published diabetes dataset, we show that our test outperforms the commonly used approaches, the global test and gene set enrichment analysis (GSEA). We develop a gene set analyses method (TEGS) under the multivariate regression framework, which directly models the interdependence of the expression values in a gene set using a working covariance. TEGS outperforms two widely used methods, GSEA and global test in both simulation and a diabetes microarray data.

  7. INTER-EXAMINER VARIABILITY

    African Journals Online (AJOL)

    Objective: To establish whether inter-examiner variability is still a significant factor for the undergraduate orthopaedic clinical ... D. The scores for each student were tabulated and the range, mean, and pass rate determined for each of the examiners. ... has not the heart to reject the man”, consistently gave higher scores (1).

  8. Several real variables

    CERN Document Server

    Kantorovitz, Shmuel

    2016-01-01

    This undergraduate textbook is based on lectures given by the author on the differential and integral calculus of functions of several real variables. The book has a modern approach and includes topics such as: •The p-norms on vector space and their equivalence •The Weierstrass and Stone-Weierstrass approximation theorems •The differential as a linear functional; Jacobians, Hessians, and Taylor's theorem in several variables •The Implicit Function Theorem for a system of equations, proved via Banach’s Fixed Point Theorem •Applications to Ordinary Differential Equations •Line integrals and an introduction to surface integrals This book features numerous examples, detailed proofs, as well as exercises at the end of sections. Many of the exercises have detailed solutions, making the book suitable for self-study. Several Real Variables will be useful for undergraduate students in mathematics who have completed first courses in linear algebra and analysis of one real variable.

  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. 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…

  11. 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

  12. Surfing wave climate variability

    Science.gov (United States)

    Espejo, Antonio; Losada, Iñigo J.; Méndez, Fernando J.

    2014-10-01

    International surfing destinations are highly dependent on specific combinations of wind-wave formation, thermal conditions and local bathymetry. Surf quality depends on a vast number of geophysical variables, and analyses of surf quality require the consideration of the seasonal, interannual and long-term variability of surf conditions on a global scale. A multivariable standardized index based on expert judgment is proposed for this purpose. This index makes it possible to analyze surf conditions objectively over a global domain. A summary of global surf resources based on a new index integrating existing wave, wind, tides and sea surface temperature databases is presented. According to general atmospheric circulation and swell propagation patterns, results show that west-facing low to middle-latitude coasts are more suitable for surfing, especially those in the Southern Hemisphere. Month-to-month analysis reveals strong seasonal variations in the occurrence of surfable events, enhancing the frequency of such events in the North Atlantic and the North Pacific. Interannual variability was investigated by comparing occurrence values with global and regional modes of low-frequency climate variability such as El Niño and the North Atlantic Oscillation, revealing their strong influence at both the global and the regional scale. Results of the long-term trends demonstrate an increase in the probability of surfable events on west-facing coasts around the world in recent years. The resulting maps provide useful information for surfers, the surf tourism industry and surf-related coastal planners and stakeholders.

  13. 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.

  14. 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.

  15. Tides and Decadal Variability

    Science.gov (United States)

    Ray, Richard D.

    2003-01-01

    This paper reviews the mechanisms by which oceanic tides and decadal variability in the oceans are connected. We distinguish between variability caused by tides and variability observed in the tides themselves. Both effects have been detected at some level. The most obvious connection with decadal timescales is through the 18.6-year precession of the moon's orbit plane. This precession gives rise to a small tide of the same period and to 18.6-year modulations in the phase and amplitudes of short-period tides. The 18.6-year "node tide" is very small, no more than 2 cm anywhere, and in sea level data it is dominated by the ocean's natural Variability. Some authors have naively attributed climate variations with periods near 19 years directly to the node tide, but the amplitude of the tide is too small for this mechanism to be operative. The more likely explanation (Loder and Garrett, JGR, 83, 1967-70, 1978) is that the 18.6-y modulations in short-period tides, especially h e principal tide M2, cause variations in ocean mixing, which is then observed in temperature and other climatic indicators. Tidally forced variability has also been proposed by some authors, either in response to occasional (and highly predictable) tidal extremes or as a nonlinear low-frequency oscillation caused by interactions between short-period tides. The former mechanism can produce only short-duration events hardly more significant than normal tidal ranges, but the latter mechanism can in principle induce low-frequency oscillations. The most recent proposal of this type is by Keeling and Whorf, who highlight the 1800-year spectral peak discovered by Bond et al. (1997). But the proposal appears contrived and should be considered, in the words of Munk et al. (2002), "as the most likely among unlikely candidates."

  16. Gene doping: gene delivery for olympic victory

    OpenAIRE

    Gould, David

    2012-01-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted...

  17. Variable Permanent Magnet Quadrupole

    International Nuclear Information System (INIS)

    Mihara, T.; Iwashita, Y.; Kyoto U.; Kumada, M.; NIRS, Chiba; Spencer, C.M.; SLAC

    2007-01-01

    A permanent magnet quadrupole (PMQ) is one of the candidates for the final focus lens in a linear collider. An over 120 T/m strong variable permanent magnet quadrupole is achieved by the introduction of saturated iron and a 'double ring structure'. A fabricated PMQ achieved 24 T integrated gradient with 20 mm bore diameter, 100 mm magnet diameter and 20 cm pole length. The strength of the PMQ is adjustable in 1.4 T steps, due to its 'double ring structure': the PMQ is split into two nested rings; the outer ring is sliced along the beam line into four parts and is rotated to change the strength. This paper describes the variable PMQ from fabrication to recent adjustments

  18. On Complex Random Variables

    Directory of Open Access Journals (Sweden)

    Anwer Khurshid

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE In this paper, it is shown that a complex multivariate random variable  is a complex multivariate normal random variable of dimensionality if and only if all nondegenerate complex linear combinations of  have a complex univariate normal distribution. The characteristic function of  has been derived, and simpler forms of some theorems have been given using this characterization theorem without assuming that the variance-covariance matrix of the vector  is Hermitian positive definite. Marginal distributions of  have been given. In addition, a complex multivariate t-distribution has been defined and the density derived. A characterization of the complex multivariate t-distribution is given. A few possible uses of this distribution have been suggested.

  19. 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.

  20. Variable Kernel Density Estimation

    OpenAIRE

    Terrell, George R.; Scott, David W.

    1992-01-01

    We investigate some of the possibilities for improvement of univariate and multivariate kernel density estimates by varying the window over the domain of estimation, pointwise and globally. Two general approaches are to vary the window width by the point of estimation and by point of the sample observation. The first possibility is shown to be of little efficacy in one variable. In particular, nearest-neighbor estimators in all versions perform poorly in one and two dimensions, but begin to b...

  1. TEC variability over Havana

    International Nuclear Information System (INIS)

    Lazo, B.; Alazo, K.; Rodriguez, M.; Calzadilla, A.

    2003-01-01

    The variability of total electron content (TEC) measured over Havana using ATS-6, SMS-1 and GOES-3 geosynchronous satellite signals has been investigated for low, middle and high solar activity periods from 1974 to 1982. The obtained results show that standard deviation is smooth during nighttime hours and maximum at noon or postnoon hours. Strong solar activity dependence of standard deviation with a maximum values during HSA has been found. (author)

  2. 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%

  3. Articulatory variability in cluttering.

    Science.gov (United States)

    Hartinger, Mariam; Mooshammer, Christine

    2008-01-01

    In order to investigate the articulatory processes of the hasty and mumbled speech in cluttering, the kinematic variability was analysed by means of electromagnetic midsagittal articulography. In contrast to persons with stuttering, those with cluttering improve their intelligibility by concentrating on their speech task. Variability has always been an important criterion in comparable studies of stuttering and is discussed in terms of the stability of the speech motor system. The aim of the current study was to analyse the spatial and temporal variability in the speech of three persons with cluttering (PWC) and three control speakers. All participants were native speakers of German. The speech material consisted of repetitive CV syllables and loan words such as 'emotionalisieren', because PWC have the severest problems with long words with a complex syllable structure. The results showed a significantly higher coefficient of variation for PWC in loan word production, both in the temporal and in the spatial domain, whereas the means of displacements and durations did not differ between groups. These findings were discussed in terms of the effects of the linguistic complexity, since for the syllable repetition task, no significant differences between PWC and controls were found. Copyright 2008 S. Karger AG, Basel.

  4. Genes and Hearing Loss

    Science.gov (United States)

    ... ENTCareers Marketplace Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  5. About hidden influence of predictor variables: Suppressor and mediator variables

    Directory of Open Access Journals (Sweden)

    Milovanović Boško

    2013-01-01

    Full Text Available In this paper procedure for researching hidden influence of predictor variables in regression models and depicting suppressor variables and mediator variables is shown. It is also shown that detection of suppressor variables and mediator variables could provide refined information about the research problem. As an example for applying this procedure, relation between Atlantic atmospheric centers and air temperature and precipitation amount in Serbia is chosen. [Projekat Ministarstva nauke Republike Srbije, br. 47007

  6. Individual Movement Variability Magnitudes Are Explained by Cortical Neural Variability.

    Science.gov (United States)

    Haar, Shlomi; Donchin, Opher; Dinstein, Ilan

    2017-09-13

    Humans exhibit considerable motor variability even across trivial reaching movements. This variability can be separated into specific kinematic components such as extent and direction that are thought to be governed by distinct neural processes. Here, we report that individual subjects (males and females) exhibit different magnitudes of kinematic variability, which are consistent (within individual) across movements to different targets and regardless of which arm (right or left) was used to perform the movements. Simultaneous fMRI recordings revealed that the same subjects also exhibited different magnitudes of fMRI variability across movements in a variety of motor system areas. These fMRI variability magnitudes were also consistent across movements to different targets when performed with either arm. Cortical fMRI variability in the posterior-parietal cortex of individual subjects explained their movement-extent variability. This relationship was apparent only in posterior-parietal cortex and not in other motor system areas, thereby suggesting that individuals with more variable movement preparation exhibit larger kinematic variability. We therefore propose that neural and kinematic variability are reliable and interrelated individual characteristics that may predispose individual subjects to exhibit distinct motor capabilities. SIGNIFICANCE STATEMENT Neural activity and movement kinematics are remarkably variable. Although intertrial variability is rarely studied, here, we demonstrate that individual human subjects exhibit distinct magnitudes of neural and kinematic variability that are reproducible across movements to different targets and when performing these movements with either arm. Furthermore, when examining the relationship between cortical variability and movement variability, we find that cortical fMRI variability in parietal cortex of individual subjects explained their movement extent variability. This enabled us to explain why some subjects

  7. Gene expression and gene therapy imaging

    International Nuclear Information System (INIS)

    Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

    2007-01-01

    The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

  8. Imaging reporter gene for monitoring gene therapy

    International Nuclear Information System (INIS)

    Beco, V. de; Baillet, G.; Tamgac, F.; Tofighi, M.; Weinmann, P.; Vergote, J.; Moretti, J.L.; Tamgac, G.

    2002-01-01

    Scintigraphic images can be obtained to document gene function at cellular level. This approach is presented here and the use of a reporter gene to monitor gene therapy is described. Two main ways are presented: either the use of a reporter gene coding for an enzyme the action of which will be monitored by radiolabeled pro-drug, or a cellular receptor gene, the action of which is documented by a radio labeled cognate receptor ligand. (author)

  9. Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma. Results from a GEM/PETHEMA study.

    Science.gov (United States)

    Martinez-Lopez, Joaquin; Fernández-Redondo, Elena; García-Sánz, Ramón; Montalbán, María Angeles; Martínez-Sánchez, Pilar; Pavia, Bruno; Mateos, María Victoria; Rosiñol, Laura; Martín, Marisa; Ayala, Rosa; Martínez, Rafael; Blanchard, María Jesus; Alegre, Adrian; Besalduch, Joan; Bargay, Joan; Hernandez, Miguel T; Sarasquete, María Eugenia; Sanchez-Godoy, Pedro; Fernández, Manuela; Blade, Joan; San Miguel, Jesús F; Lahuerta, Juan Jose

    2013-12-01

    Minimal residual disease monitoring is becoming increasingly important in multiple myeloma (MM), but multiparameter flow cytometry (MFC) and allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques are not routinely available. This study investigated the prognostic influence of achieving molecular response assessed by fluorescent-PCR (F-PCR) in 130 newly diagnosed MM patients from Grupo Español Multidisciplinar de Melanoma (GEM)2000/GEM05 trials (NCT00560053, NCT00443235, NCT00464217) who achieved almost very good partial response after induction therapy. As a reference, we used the results observed with simultaneous MFC. F-PCR at diagnosis was performed on DNA using three different multiplex PCRs: IGH D-J, IGK V-J and KDE rearrangements. The applicability of F-PCR was 91·5%. After induction therapy, 64 patients achieved molecular response and 66 non-molecular response; median progression-free survival (PFS) was 61 versus 36 months, respectively (P = 0·001). Median overall survival (OS) was not reached (NR) in molecular response patients (5-year survival: 75%) versus 66 months in the non-molecular response group (P = 0·03). The corresponding PFS and OS values for patients with immunophenotypic versus non-immunophenotypic response were 67 versus 42 months (P = 0·005) and NR (5-year survival: 95%) versus 69 months (P = 0·004), respectively. F-PCR analysis is a rapid, affordable, and easily performable technique that, in some circumstances, may be a valid approach for minimal residual disease investigations in MM. © 2013 John Wiley & Sons Ltd.

  10. Understanding Solar Cycle Variability

    Energy Technology Data Exchange (ETDEWEB)

    Cameron, R. H.; Schüssler, M., E-mail: cameron@mps.mpg.de [Max-Planck-Institut für Sonnensystemforschung, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany)

    2017-07-10

    The level of solar magnetic activity, as exemplified by the number of sunspots and by energetic events in the corona, varies on a wide range of timescales. Most prominent is the 11-year solar cycle, which is significantly modulated on longer timescales. Drawing from dynamo theory, together with the empirical results of past solar activity and similar phenomena for solar-like stars, we show that the variability of the solar cycle can be essentially understood in terms of a weakly nonlinear limit cycle affected by random noise. In contrast to ad hoc “toy models” for the solar cycle, this leads to a generic normal-form model, whose parameters are all constrained by observations. The model reproduces the characteristics of the variable solar activity on timescales between decades and millennia, including the occurrence and statistics of extended periods of very low activity (grand minima). Comparison with results obtained with a Babcock–Leighton-type dynamo model confirm the validity of the normal-mode approach.

  11. 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

  12. IL26 gene inactivation in Equidae.

    Science.gov (United States)

    Shakhsi-Niaei, M; Drögemüller, M; Jagannathan, V; Gerber, V; Leeb, T

    2013-12-01

    Interleukin-26 (IL26) is a member of the IL10 cytokine family. The IL26 gene is located between two other well-known cytokines genes of this family encoding interferon-gamma (IFNG) and IL22 in an evolutionary conserved gene cluster. In contrast to humans and most other mammals, mice lack a functional Il26 gene. We analyzed the genome sequences of other vertebrates for the presence or absence of functional IL26 orthologs and found that the IL26 gene has also become inactivated in several equid species. We detected a one-base pair frameshift deletion in exon 2 of the IL26 gene in the domestic horse (Equus caballus), Przewalski horse (Equus przewalskii) and donkey (Equus asinus). The remnant IL26 gene in the horse is still transcribed and gives rise to at least five alternative transcripts. None of these transcripts share a conserved open reading frame with the human IL26 gene. A comparative analysis across diverse vertebrates revealed that the IL26 gene has also independently been inactivated in a few other mammals, including the African elephant and the European hedgehog. The IL26 gene thus appears to be highly variable, and the conserved open reading frame has been lost several times during mammalian evolution. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

  13. Climate variability and change

    International Nuclear Information System (INIS)

    Manton, M.

    2006-01-01

    When Australia's climate should not be definite barrier to the population reaching 30 million by 2050, it is recognised that our climate has limited the development of the nation over the past 200 years. Indeed in 1911, based on a comparison of the climate and development between the US and Australia. Griffith Taylor predicted that Australia's population would be 19 million at the end of the 20th century, which is a pretty good 90-year forecast. The climate constraint is not only due to much of the country being semi-arid with an annual rainfall below 400 millimetres, but also due to the large year-to-year variability of rainfall across the country

  14. 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.

  15. Statistical variability of hydro-meteorological variables as indicators ...

    African Journals Online (AJOL)

    Statistical variability of hydro-meteorological variables as indicators of climate change in north-east Sokoto-Rima basin, Nigeria. ... water resources development including water supply project, agriculture and tourism in the study area. Key word: Climate change, Climatic variability, Actual evapotranspiration, Global warming ...

  16. N-linked glycosylation of the immunoglobulin variable region

    NARCIS (Netherlands)

    van de Bovenkamp, Fleur S.; Derksen, Ninotska I. L.; Ooijevaar-de Heer, Pleuni; van Schie, Karin A.; Kruithof, Simone; Berkowska, Magdalena A.; van der Schoot, C. Ellen; Ijspeert, Hanna; van der Burg, Mirjam; Gils, Ann; Hafkenscheid, Lise; Toes, René E. M.; Rombouts, Yoann; Plomp, Rosina; Wuhrer, Manfred; van Ham, S. Marieke; Vidarsson, Gestur; Rispens, Theo

    2018-01-01

    N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we

  17. The Performance of Variable Annuities

    OpenAIRE

    Michael J. McNamara; Henry R. Oppenheimer

    1991-01-01

    Variable annuities have become increasingly important in retirement plans. This paper provides an examination of the investment performance of variable annuities for the period year-end 1973 to year-end 1988. Returns, risk, and selectivity measures are analyzed for the sample of annuities, for individual variable annuities, and for subsamples of annuities with similar portfolio size and turnover. While the investment returns of variable annuities were greater than inflation over the period, t...

  18. 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....

  19. 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…

  20. Variable angle correlation spectroscopy

    International Nuclear Information System (INIS)

    Lee, Y.K.; Lawrence Berkeley Lab., CA

    1994-05-01

    In this dissertation, a novel nuclear magnetic resonance (NMR) technique, variable angle correlation spectroscopy (VACSY) is described and demonstrated with 13 C 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

  1. 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...

  2. Common Variable Immunodeficiency Caused by FANC Mutations.

    Science.gov (United States)

    Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

    2017-07-01

    Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

  3. Climate variability and climate change

    International Nuclear Information System (INIS)

    Rind, D.

    1990-01-01

    Changes of variability with climate change are likely to have a substantial impact on vegetation and society, rivaling the importance of changes in the mean values themselves. A variety of paleoclimate and future climate simulations performed with the GISS global climate model is used to assess how the variabilities of temperature and precipitation are altered as climate warms or cools. In general, as climate warms, temperature variability decreases due to reductions in the latitudinal temperature gradient and precipitation variability increases together with the intensity of the hydrologic cycle. If future climate projections are accurate, the reduction in temperature variability will be minimized by the rapid change in mean temperatures, but the hydrologic variability will be amplified by increased evapotranspiration. Greater hydrologic variability would appear to pose a potentially severe problem for the next century

  4. Climate variability and climate change

    International Nuclear Information System (INIS)

    Rind, D.

    1991-01-01

    Changes of variability with climate change are likely to have a substantial impact on vegetation and society, rivaling the importance of changes in the mean values themselves. A variety of paleoclimate and future climate simulations performed with the GISS global climate model is used to assess how the variabilities of temperature and precipitation are altered as climate warms or cools. In general, as climate warms, temperature variability decreases due to reductions in the latitudinal temperature gradient and precipitation variability increases together with the intensity of the hydrologic cycle. If future climate projections are accurate, the reduction in temperature variability will be minimized by the rapid change in mean temperatures, but the hydrologic variability will be amplified by increased evapotranspiration. Greater hydrologic variability would appear to pose a potentially severe problem for the next century. 19 refs.; 3 figs.; 2 tabs

  5. 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.

  6. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Wiebe, Leonard I.

    1997-01-01

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

  7. Imaging gene expression in gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-12-31

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

  8. Good genes, complementary genes and human mate preferences.

    Science.gov (United States)

    Roberts, S Craig; Little, Anthony C

    2008-09-01

    The past decade has witnessed a rapidly growing interest in the biological basis of human mate choice. Here we review recent studies that demonstrate preferences for traits which might reveal genetic quality to prospective mates, with potential but still largely unknown influence on offspring fitness. These include studies assessing visual, olfactory and auditory preferences for potential good-gene indicator traits, such as dominance or bilateral symmetry. Individual differences in these robust preferences mainly arise through within and between individual variation in condition and reproductive status. Another set of studies have revealed preferences for traits indicating complementary genes, focussing on discrimination of dissimilarity at genes in the major histocompatibility complex (MHC). As in animal studies, we are only just beginning to understand how preferences for specific traits vary and inter-relate, how consideration of good and compatible genes can lead to substantial variability in individual mate choice decisions and how preferences expressed in one sensory modality may reflect those in another. Humans may be an ideal model species in which to explore these interesting complexities.

  9. 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.

  10. Gene doping: gene delivery for olympic victory.

    Science.gov (United States)

    Gould, David

    2013-08-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  11. Functional validation of candidate genes detected by genomic feature models

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Østergaard, Solveig; Kristensen, Torsten Nygaard

    2018-01-01

    Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait...... then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated...

  12. Norrie disease and MAO genes: nearest neighbors.

    Science.gov (United States)

    Chen, Z Y; Denney, R M; Breakefield, X O

    1995-01-01

    The Norrie disease and MAO genes are tandemly arranged in the p11.4-p11.3 region of the human X chromosome in the order tel-MAOA-MAOB-NDP-cent. This relationship is conserved in the mouse in the order tel-MAOB-MAOA-NDP-cent. The MAO genes appear to have arisen by tandem duplication of an ancestral MAO gene, but their positional relationship to NDP appears to be random. Distinctive X-linked syndromes have been described for mutations in the MAOA and NDP genes, and in addition, individuals have been identified with contiguous gene syndromes due to chromosomal deletions which encompass two or three of these genes. Loss of function of the NDP gene causes a syndrome of congenital blindness and progressive hearing loss, sometimes accompanied by signs of CNS dysfunction, including variable mental retardation and psychiatric symptoms. Other mutations in the NDP gene have been found to underlie another X-linked eye disease, exudative vitreo-retinopathy. An MAOA deficiency state has been described in one family to date, with features of altered amine and amine metabolite levels, low normal intelligence, apparent difficulty in impulse control and cardiovascular difficulty in affected males. A contiguous gene syndrome in which all three genes are lacking, as well as other as yet unidentified flanking genes, results in severe mental retardation, small stature, seizures and congenital blindness, as well as altered amine and amine metabolites. Issues that remain to be resolved are the function of the NDP gene product, the frequency and phenotype of the MAOA deficiency state, and the possible occurrence and phenotype of an MAOB deficiency state.

  13. Analysis of baseline gene expression levels from ...

    Science.gov (United States)

    The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in gene expression. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selectiv

  14. G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes

    Directory of Open Access Journals (Sweden)

    Lemay Danielle G

    2012-09-01

    Full Text Available Abstract Background In previous studies, gene neighborhoods—spatial clusters of co-expressed genes in the genome—have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously. Results Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods. Conclusions Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The

  15. Benchmarking Variable Selection in QSAR.

    Science.gov (United States)

    Eklund, Martin; Norinder, Ulf; Boyer, Scott; Carlsson, Lars

    2012-02-01

    Variable selection is important in QSAR modeling since it can improve model performance and transparency, as well as reduce the computational cost of model fitting and predictions. Which variable selection methods that perform well in QSAR settings is largely unknown. To address this question we, in a total of 1728 benchmarking experiments, rigorously investigated how eight variable selection methods affect the predictive performance and transparency of random forest models fitted to seven QSAR datasets covering different endpoints, descriptors sets, types of response variables, and number of chemical compounds. The results show that univariate variable selection methods are suboptimal and that the number of variables in the benchmarked datasets can be reduced with about 60 % without significant loss in model performance when using multivariate adaptive regression splines MARS and forward selection. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. A kernel regression approach to gene-gene interaction detection for case-control studies.

    Science.gov (United States)

    Larson, Nicholas B; Schaid, Daniel J

    2013-11-01

    Gene-gene interactions are increasingly being addressed as a potentially important contributor to the variability of complex traits. Consequently, attentions have moved beyond single locus analysis of association to more complex genetic models. Although several single-marker approaches toward interaction analysis have been developed, such methods suffer from very high testing dimensionality and do not take advantage of existing information, notably the definition of genes as functional units. Here, we propose a comprehensive family of gene-level score tests for identifying genetic elements of disease risk, in particular pairwise gene-gene interactions. Using kernel machine methods, we devise score-based variance component tests under a generalized linear mixed model framework. We conducted simulations based upon coalescent genetic models to evaluate the performance of our approach under a variety of disease models. These simulations indicate that our methods are generally higher powered than alternative gene-level approaches and at worst competitive with exhaustive SNP-level (where SNP is single-nucleotide polymorphism) analyses. Furthermore, we observe that simulated epistatic effects resulted in significant marginal testing results for the involved genes regardless of whether or not true main effects were present. We detail the benefits of our methods and discuss potential genome-wide analysis strategies for gene-gene interaction analysis in a case-control study design. © 2013 WILEY PERIODICALS, INC.

  17. Evolution of homeobox genes.

    Science.gov (United States)

    Holland, Peter W H

    2013-01-01

    Many homeobox genes encode transcription factors with regulatory roles in animal and plant development. Homeobox genes are found in almost all eukaryotes, and have diversified into 11 gene classes and over 100 gene families in animal evolution, and 10 to 14 gene classes in plants. The largest group in animals is the ANTP class which includes the well-known Hox genes, plus other genes implicated in development including ParaHox (Cdx, Xlox, Gsx), Evx, Dlx, En, NK4, NK3, Msx, and Nanog. Genomic data suggest that the ANTP class diversified by extensive tandem duplication to generate a large array of genes, including an NK gene cluster and a hypothetical ProtoHox gene cluster that duplicated to generate Hox and ParaHox genes. Expression and functional data suggest that NK, Hox, and ParaHox gene clusters acquired distinct roles in patterning the mesoderm, nervous system, and gut. The PRD class is also diverse and includes Pax2/5/8, Pax3/7, Pax4/6, Gsc, Hesx, Otx, Otp, and Pitx genes. PRD genes are not generally arranged in ancient genomic clusters, although the Dux, Obox, and Rhox gene clusters arose in mammalian evolution as did several non-clustered PRD genes. Tandem duplication and genome duplication expanded the number of homeobox genes, possibly contributing to the evolution of developmental complexity, but homeobox gene loss must not be ignored. Evolutionary changes to homeobox gene expression have also been documented, including Hox gene expression patterns shifting in concert with segmental diversification in vertebrates and crustaceans, and deletion of a Pitx1 gene enhancer in pelvic-reduced sticklebacks. WIREs Dev Biol 2013, 2:31-45. doi: 10.1002/wdev.78 For further resources related to this article, please visit the WIREs website. The author declares that he has no conflicts of interest. Copyright © 2012 Wiley Periodicals, Inc.

  18. Gene cluster statistics with gene families.

    Science.gov (United States)

    Raghupathy, Narayanan; Durand, Dannie

    2009-05-01

    Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such "gene clusters" is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data

  19. Carboxylesterase 1 genes

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Madsen, Majbritt Busk

    2018-01-01

    The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2...

  20. Leptin gene polymorphism in Indian Sahiwal cattle by single strand ...

    African Journals Online (AJOL)

    These leptin gene variants can be sequenced and screened in the entire population to develop single nucleotide polymorphisms (SNPs) for association studies with different productive and reproductive performances and marker assisted selection. Keywords: Leptin gene, PCR-SSCP, genetic variability, dairy cattle

  1. 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

  2. Photometric 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

    2005-01-01

    The Faint Sky Variability Survey (FSVS) is aimed at finding photometric and/or astrometric variable objects between 16th and 24th mag on time-scales between tens of minutes and years with photometric precisions ranging from 3 millimag to 0.2 mag. An area of ~23 deg2, located at mid and

  3. Noise minimization in eukaryotic gene expression.

    Directory of Open Access Journals (Sweden)

    Hunter B Fraser

    2004-06-01

    Full Text Available 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.

  4. 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.

  5. Noise minimization in eukaryotic gene expression

    International Nuclear Information System (INIS)

    Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

    2004-01-01

    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

  6. Plant domestication and gene banks

    International Nuclear Information System (INIS)

    Perrino, P.

    1989-01-01

    At the time of the dawn of agriculture, plant domestication was very slow. As agriculture progressed, however, domestication began to evolve faster and reached its highest point with the advent of plant breeders who played a very important role in solving the world food problem. One of the fastest moving strategies was a better exploitation of genetic diversity, both natural and induced. However, intensive plant breeding activity caused a heavy fall in genetic variability. Gene banks then provided a further tool for modern agriculture, specifically to preserve genetic resources and to help breeders to further domesticate important crops and to introduce and domesticate new species. (author). 3 refs

  7. 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.

  8. 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.

  9. Inferring gene dependency network specific to phenotypic alteration based on gene expression data and clinical information of breast cancer.

    Science.gov (United States)

    Zhou, Xionghui; Liu, Juan

    2014-01-01

    Although many methods have been proposed to reconstruct gene regulatory network, most of them, when applied in the sample-based data, can not reveal the gene regulatory relations underlying the phenotypic change (e.g. normal versus cancer). In this paper, we adopt phenotype as a variable when constructing the gene regulatory network, while former researches either neglected it or only used it to select the differentially expressed genes as the inputs to construct the gene regulatory network. To be specific, we integrate phenotype information with gene expression data to identify the gene dependency pairs by using the method of conditional mutual information. A gene dependency pair (A,B) means that the influence of gene A on the phenotype depends on gene B. All identified gene dependency pairs constitute a directed network underlying the phenotype, namely gene dependency network. By this way, we have constructed gene dependency network of breast cancer from gene expression data along with two different phenotype states (metastasis and non-metastasis). Moreover, we have found the network scale free, indicating that its hub genes with high out-degrees may play critical roles in the network. After functional investigation, these hub genes are found to be biologically significant and specially related to breast cancer, which suggests that our gene dependency network is meaningful. The validity has also been justified by literature investigation. From the network, we have selected 43 discriminative hubs as signature to build the classification model for distinguishing the distant metastasis risks of breast cancer patients, and the result outperforms those classification models with published signatures. In conclusion, we have proposed a promising way to construct the gene regulatory network by using sample-based data, which has been shown to be effective and accurate in uncovering the hidden mechanism of the biological process and identifying the gene signature for

  10. Soil variability in mountain areas

    OpenAIRE

    Zanini, E.; Freppaz, M.; Stanchi, S.; Bonifacio, E.; Egli, M.

    2015-01-01

    The high spatial variability of soils is a relevant issue at local and global scales, and determines the complexity of soil ecosystem functions and services. This variability derives from strong dependencies of soil ecosystems on parent materials, climate, relief and biosphere, including human impact. Although present in all environments, the interactions of soils with these forming factors are particularly striking in mountain areas.

  11. 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...

  12. Delta Scuti variables. Lecture 6

    International Nuclear Information System (INIS)

    Cox, A.N.

    1983-01-01

    The class of variables near or on the upper main sequence, the delta Scuti variables, are not only the usual ones about the masses, radii, and luminosities, but also the age, rotation, element diffusion to change the surface layer composition, the occurance of convection and the presence of radial and nonradial pulsation modes

  13. 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.

  14. THE VARIABILITY OF INTERLANGUAGE USE

    African Journals Online (AJOL)

    www

    Variability is evident in the interlanguage grammars of all L2 learners, irrespective of their levels of proficiency; their interlanguage use is characterised by the variable occurrence of target L2 forms, and the .... instruction and negative feedback to discover that their hypotheses about the L2 are incorrect. 4.1. Krashen's view.

  15. Independent SU(2)-loop variables

    International Nuclear Information System (INIS)

    Loll, R.

    1991-04-01

    We give a reduction procedure for SU(2)-trace variables and introduce a complete set of indepentent, gauge-invariant and almost local loop variables for the configuration space of SU(2)-lattice gauge theory in 2+1 dimensions. (orig.)

  16. Operant Variability: Procedures and Processes

    Science.gov (United States)

    Machado, Armando; Tonneau, Francois

    2012-01-01

    Barba's (2012) article deftly weaves three main themes in one argument about operant variability. From general theoretical considerations on operant behavior (Catania, 1973), Barba derives methodological guidelines about response differentiation and applies them to the study of operant variability. In the process, he uncovers unnoticed features of…

  17. Gene doping in sports.

    Science.gov (United States)

    Unal, Mehmet; Ozer Unal, Durisehvar

    2004-01-01

    Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement. Copyright 2004 Adis Data Information BV

  18. 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…

  19. Imaging Variable Stars with HST

    Science.gov (United States)

    Karovska, M.

    2012-06-01

    (Abstract only) The Hubble Space Telescope (HST) observations of astronomical sources, ranging from objects in our solar system to objects in the early Universe, have revolutionized our knowledge of the Universe its origins and contents. I highlight results from HST observations of variable stars obtained during the past twenty or so years. Multiwavelength observations of numerous variable stars and stellar systems were obtained using the superb HST imaging capabilities and its unprecedented angular resolution, especially in the UV and optical. The HST provided the first detailed images probing the structure of variable stars including their atmospheres and circumstellar environments. AAVSO observations and light curves have been critical for scheduling of many of these observations and provided important information and context for understanding of the imaging results of many variable sources. I describe the scientific results from the imaging observations of variable stars including AGBs, Miras, Cepheids, semiregular variables (including supergiants and giants), YSOs and interacting stellar systems with a variable stellar components. These results have led to an unprecedented understanding of the spatial and temporal characteristics of these objects and their place in the stellar evolutionary chains, and in the larger context of the dynamic evolving Universe.

  20. 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

  1. 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.

  2. Low-Frequency Temporal Variability in Mira and Semiregular Variables

    Science.gov (United States)

    Templeton, Matthew R.; Karovska, M.; Waagen, E. O.

    2012-01-01

    We investigate low-frequency variability in a large sample of Mira and semiregular variables with long-term visual light curves from the AAVSO International Database. Our aim is to determine whether we can detect and measure long-timescale variable phenomena in these stars, for example photometric variations that might be associated with supergranular convection. We analyzed the long-term light curves of 522 variable stars of the Mira and SRa, b, c, and d classes. We calculated their low-frequency time-series spectra to characterize rednoise with the power density spectrum index, and then correlate this index with other observable characteristics such as spectral type and primary pulsation period. In our initial analysis of the sample, we see that the semiregular variables have a much broader range of spectral index than the Mira types, with the SRb subtype having the broadest range. Among Mira variables we see that the M- and S-type Miras have similarly wide ranges of index, while the C-types have the narrowest with generally shallower slopes. There is also a trend of steeper slope with larger amplitude, but at a given amplitude, a wide range of slopes are seen. The ultimate goal of the project is to identify stars with strong intrinsic red noise components as possible targets for resolved surface imaging with interferometry.

  3. Longitudinal Research with Latent Variables

    CERN Document Server

    van Montfort, Kees; Satorra, Albert

    2010-01-01

    This book combines longitudinal research and latent variable research, i.e. it explains how longitudinal studies with objectives formulated in terms of latent variables should be carried out, with an emphasis on detailing how the methods are applied. Because longitudinal research with latent variables currently utilizes different approaches with different histories, different types of research questions, and different computer programs to perform the analysis, the book is divided into nine chapters. Starting from some background information about the specific approach, short history and the ma

  4. Structure and chromosomal localization of the human renal kallikrein gene

    International Nuclear Information System (INIS)

    Evans, B.A.; Yun, Z.X.; Close, J.A.

    1988-01-01

    Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. The authors have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. They find four sequence elements conserved between renal kallikrein genes from the two species. They have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7

  5. Functional validation of candidate genes detected by genomic feature models

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Østergaard, Solveig; Kristensen, Torsten Nygaard

    2018-01-01

    to investigate locomotor activity, and applied genomic feature prediction models to identify gene ontology (GO) cate- gories predictive of this phenotype. Next, we applied the covariance association test to partition the genomic variance of the predictive GO terms to the genes within these terms. We...... then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated......Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait...

  6. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  7. 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...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

  8. Manipulating continuous variable photonic entanglement

    International Nuclear Information System (INIS)

    Plenio, M.B.

    2005-01-01

    I will review our work on photonic entanglement in the continuous variable regime including both Gaussian and non-Gaussian states. The feasibility and efficiency of various entanglement purification protocols are discussed this context. (author)

  9. Intensive variable and its application

    CERN Document Server

    Zheng, Xinqi; Yuan, Zhiyuan

    2014-01-01

    Opening with intensive variables theory, using a combination of static and dynamic GIS and integrating numerical calculation and spatial optimization, this book creates a framework and methodology for evaluating land use effect, among other concepts.

  10. Variability of nitrate and phosphate

    Digital Repository Service at National Institute of Oceanography (India)

    Sardessai, S.; Sundar, D.

    Nitrate and phosphate are important elements of the biogeochemical system of an estuary. Observations carried out during the dry season April-May 2002, and March 2003 and wet season September 2002, show temporal and spatial variability of these two...

  11. 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...

  12. Systematic identification of human housekeeping genes possibly useful as references in gene expression studies.

    Science.gov (United States)

    Caracausi, Maria; Piovesan, Allison; Antonaros, Francesca; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara

    2017-09-01

    The ideal reference, or control, gene for the study of gene expression in a given organism should be expressed at a medium‑high level for easy detection, should be expressed at a constant/stable level throughout different cell types and within the same cell type undergoing different treatments, and should maintain these features through as many different tissues of the organism. From a biological point of view, these theoretical requirements of an ideal reference gene appear to be best suited to housekeeping (HK) genes. Recent advancements in the quality and completeness of human expression microarray data and in their statistical analysis may provide new clues toward the quantitative standardization of human gene expression studies in biology and medicine, both cross‑ and within‑tissue. The systematic approach used by the present study is based on the Transcriptome Mapper tool and exploits the automated reassignment of probes to corresponding genes, intra‑ and inter‑sample normalization, elaboration and representation of gene expression values in linear form within an indexed and searchable database with a graphical interface recording quantitative levels of expression, expression variability and cross‑tissue width of expression for more than 31,000 transcripts. The present study conducted a meta‑analysis of a pool of 646 expression profile data sets from 54 different human tissues and identified actin γ 1 as the HK gene that best fits the combination of all the traditional criteria to be used as a reference gene for general use; two ribosomal protein genes, RPS18 and RPS27, and one aquaporin gene, POM121 transmembrane nucleporin C, were also identified. The present study provided a list of tissue‑ and organ‑specific genes that may be most suited for the following individual tissues/organs: Adipose tissue, bone marrow, brain, heart, kidney, liver, lung, ovary, skeletal muscle and testis; and also provides in these cases a representative

  13. Genome-wide gene expression regulation as a function of genotype and age in C. elegans

    NARCIS (Netherlands)

    Viñuela Rodriguez, A.; Snoek, L.B.; Riksen, J.A.G.; Kammenga, J.E.

    2010-01-01

    Gene expression becomes more variable with age, and it is widely assumed that this is due to a decrease in expression regulation. But currently there is no understanding how gene expression regulatory patterns progress with age. Here we explored genome-wide gene expression variation and regulatory

  14. 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

  15. Flow variability and hillslope hydrology

    Energy Technology Data Exchange (ETDEWEB)

    Huff, D D; O' Neill, R V; Emanuel, W R; Elwood, J W; Newbold, J D

    1982-01-01

    Examination of spatial variability of streamflow in headwater areas can provide important insight about factors that influence hillslope hydrology. Detailed observations of variations in stream channel input, based on a tracer experiment, indicate that topography alone cannot explain flow variability. However, determination of changes in channel input on a small spatial scale can provide valuable clues to factors, such as structural geology that control subsurface flows.

  16. 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.

  17. 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.

  18. Variable stars in the classroom

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Bajo, F [Departamento de Electronica e IngenierIa Electromecanica, Escuela de IngenierIas Industriales, Universidad de Extremadura, Avda de Elvas s/n, 06071 Badajoz (Spain); Vaquero, J M [Departamento de Fisica, Escuela Politecnica, Universidad de Extremadura, Avda de la Universidad s/n, 10071 Caceres (Spain)

    2006-05-01

    Variable stars offer interesting possibilities from the point of view of educational applications, from the experimental collection of data to analysis to obtain physical information. In this paper, brightness measurements of two periodic variable stars easily accessible with small telescopes are presented and analysed. This practical experiment is highly appropriate for educational use in undergraduate physics and astrophysics laboratories and allows students to approximate scientific research.

  19. Variable stars in the classroom

    International Nuclear Information System (INIS)

    Sanchez-Bajo, F; Vaquero, J M

    2006-01-01

    Variable stars offer interesting possibilities from the point of view of educational applications, from the experimental collection of data to analysis to obtain physical information. In this paper, brightness measurements of two periodic variable stars easily accessible with small telescopes are presented and analysed. This practical experiment is highly appropriate for educational use in undergraduate physics and astrophysics laboratories and allows students to approximate scientific research

  20. Ordering variable for parton showers

    International Nuclear Information System (INIS)

    Nagy, Zoltan; Soper, Davison E.

    2014-01-01

    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.

  1. 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.

  2. [Gene method for inconsistent hydrological frequency calculation. 2: Diagnosis system of hydrological genes and method of hydrological moment genes with inconsistent characters].

    Science.gov (United States)

    Xie, Ping; Zhao, Jiang Yan; Wu, Zi Yi; Sang, Yan Fang; Chen, Jie; Li, Bin Bin; Gu, Hai Ting

    2018-04-01

    The analysis of inconsistent hydrological series is one of the major problems that should be solved for engineering hydrological calculation in changing environment. In this study, the diffe-rences of non-consistency and non-stationarity were analyzed from the perspective of composition of hydrological series. The inconsistent hydrological phenomena were generalized into hydrological processes with inheritance, variability and evolution characteristics or regulations. Furthermore, the hydrological genes were identified following the theory of biological genes, while their inheritance bases and variability bases were determined based on composition of hydrological series under diffe-rent time scales. To identify and test the components of hydrological genes, we constructed a diagnosis system of hydrological genes. With the P-3 distribution as an example, we described the process of construction and expression of the moment genes to illustrate the inheritance, variability and evolution principles of hydrological genes. With the annual minimum 1-month runoff series of Yunjinghong station in Lancangjiang River basin as an example, we verified the feasibility and practicability of hydrological gene theory for the calculation of inconsistent hydrological frequency. The results showed that the method could be used to reveal the evolution of inconsistent hydrological series. Therefore, it provided a new research pathway for engineering hydrological calculation in changing environment and an essential reference for the assessment of water security.

  3. 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.

  4. Radiotechnologies and gene therapy

    International Nuclear Information System (INIS)

    Xia Jinsong

    2001-01-01

    Gene therapy is an exciting frontier in medicine today. Radiologist will make an uniquely contribution to these exciting new technologies at every level by choosing sites for targeting therapy, perfecting and establishing routes of delivery, developing imaging strategies to monitor therapy and assess gene expression, developing radiotherapeutic used of gene therapy

  5. 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)

  6. Identification of reference genes and validation for gene expression studies in diverse axolotl (Ambystoma mexicanum) tissues.

    Science.gov (United States)

    Guelke, Eileen; Bucan, Vesna; Liebsch, Christina; Lazaridis, Andrea; Radtke, Christine; Vogt, Peter M; Reimers, Kerstin

    2015-04-10

    For the precise quantitative RT-PCR normalization a set of valid reference genes is obligatory. Moreover have to be taken into concern the experimental conditions as they bias the regulation of reference genes. Up till now, no reference targets have been described for the axolotl (Ambystoma mexicanum). In a search in the public database SalSite for genetic information of the axolotl we identified fourteen presumptive reference genes, eleven of which were further tested for their gene expression stability. This study characterizes the expressional patterns of 11 putative endogenous control genes during axolotl limb regeneration and in an axolotl tissue panel. All 11 reference genes showed variable expression. Strikingly, ACTB was to be found most stable expressed in all comparative tissue groups, so we reason it to be suitable for all different kinds of axolotl tissue-type investigations. Moreover do we suggest GAPDH and RPLP0 as suitable for certain axolotl tissue analysis. When it comes to axolotl limb regeneration, a validated pair of reference genes is ODC and RPLP0. With these findings, new insights into axolotl gene expression profiling might be gained. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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

  8. 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.

  9. Gene therapy in periodontics.

    Science.gov (United States)

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-03-01

    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.

  10. Sequences of the joining region genes for immunoglobulin heavy chains and their role in generation of antibody diversity.

    OpenAIRE

    Gough, N M; Bernard, O

    1981-01-01

    To assess the contribution to immunoglobulin heavy chain diversity made by recombination between variable region (VH) genes and joining region (JH) genes, we have determined the sequence of about 2000 nucleotides spanning the rearranged JH gene cluster associated with the VH gene expressed in plasmacytoma HPC76. The active VH76 gene has recombined with the second germ-line JH gene. The region we have studied contains two other JH genes, designated JH3 and JH4. No other JH gene was found withi...

  11. 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.

  12. Variable sensory perception in autism.

    Science.gov (United States)

    Haigh, Sarah M

    2018-03-01

    Autism is associated with sensory and cognitive abnormalities. Individuals with autism generally show normal or superior early sensory processing abilities compared to healthy controls, but deficits in complex sensory processing. In the current opinion paper, it will be argued that sensory abnormalities impact cognition by limiting the amount of signal that can be used to interpret and interact with environment. There is a growing body of literature showing that individuals with autism exhibit greater trial-to-trial variability in behavioural and cortical sensory responses. If multiple sensory signals that are highly variable are added together to process more complex sensory stimuli, then this might destabilise later perception and impair cognition. Methods to improve sensory processing have shown improvements in more general cognition. Studies that specifically investigate differences in sensory trial-to-trial variability in autism, and the potential changes in variability before and after treatment, could ascertain if trial-to-trial variability is a good mechanism to target for treatment in autism. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Cataclysmic variables, Hubble-Sandage variables and eta Carinae

    International Nuclear Information System (INIS)

    Bath, G.T.

    1980-01-01

    The Hubble-Sandage variables are the most luminous stars in external galaxies. They were first investigated by Hubble and Sandage (1953) for use as distance indicators. Their main characteristics are high luminosity, blue colour indices, and irregular variability. Spectroscopically they show hydrogen and helium in emission with occasionally weaker FeII and [FeII], and no Balmer jump (Humphreys 1975, 1978). In this respect they closely resemble cataclysmic variables, particularly dwarf novae. In the quiescent state dwarf novae show broad H and HeI, together with a strong UV continuum. In contrast to the spectroscopic similarities, the luminosities could hardly differ more. Rather than being the brightest stars known, quiescent dwarf novae are as faint or fainter than the sun. It is suggested that the close correspondence between the spectral appearance of the two classes combined with the difference in luminosity is well accounted for by a model of Hubble-Sandage variables in which the same physical processes are occurring, but on a larger scale. (Auth.)

  14. Observations of fast variable objects

    International Nuclear Information System (INIS)

    Alekseev, G.N.

    1978-01-01

    A problem on studying fast variable astronomic objects is considered. The basis of the method used in the experiment is a detailed photoelectric study of a fast variableness along with spectroscopy of a high time resolution. Power spectrum of the SS Cyg brightness oscillations and autocorrelation function of the AX Mon brightness are analyzed as an example. To provide a reliable identification of parameters of star active regions responsible for the fast variableness, an experiment is proposed, the ''synchronous spectroscopy'' method being used. The method is based on the supposition about temporary stationarity of occasional processes within the limits of the time scale of several hours. The block diagram of the experiment is described

  15. 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.

  16. Progress with variable cycle engines

    Science.gov (United States)

    Westmoreland, J. S.

    1980-01-01

    The evaluation of components of an advanced propulsion system for a future supersonic cruise vehicle is discussed. These components, a high performance duct burner for thrust augmentation and a low jet noise coannular exhaust nozzle, are part of the variable stream control engine. An experimental test program involving both isolated component and complete engine tests was conducted for the high performance, low emissions duct burner with excellent results. Nozzle model tests were completed which substantiate the inherent jet noise benefit associated with the unique velocity profile possible of a coannular exhaust nozzle system on a variable stream control engine. Additional nozzle model performance tests have established high thrust efficiency levels at takeoff and supersonic cruise for this nozzle system. Large scale testing of these two critical components is conducted using an F100 engine as the testbed for simulating the variable stream control engine.

  17. The enrichment of TATA box and the scarcity of depleted proximal nucleosome in the promoters of duplicated yeast genes.

    Science.gov (United States)

    Kim, Yuseob; Lee, Jang H; Babbitt, Gregory A

    2010-01-01

    Population genetic theory of gene duplication suggests that the preservation of duplicate copies requires functional divergence upon duplication. Genes that can be readily modified to produce new gene expression patterns may thus be duplicated often. In yeast, genes exhibit dichotomous expression patterns based on their promoter architectures. The expression of genes that contain TATA box or occupied proximal nucleosome (OPN) tends to be variable and respond to external signals. On the other hand, genes without TATA box or with depleted proximal nucleosome (DPN) are expressed constitutively. We find that recent duplicates in the yeast genome are heavily biased to be TATA box containing genes and not to be DPN genes. This suggests that variably expressed genes, due to the functional organization in their promoters, have higher duplicability than constitutively expressed genes.

  18. Strategies in Gene Therapy for Glioblastoma

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. Primetime for Learning Genes.

    Science.gov (United States)

    Keifer, Joyce

    2017-02-11

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene ( BDNF ), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  1. Gallbladder microbiota variability in Colombian gallstones patients.

    Science.gov (United States)

    Arteta, Ariel Antonio; Carvajal-Restrepo, Hernan; Sánchez-Jiménez, Miryan Margot; Diaz-Rodriguez, Sergio; Cardona-Castro, Nora

    2017-03-31

    Gallbladder stones are a very frequently occurring condition. Despite bile bactericidal activity, many bacteria have been detected inside the gallbladder, and gallstones facilitate their presence. Between 3% and 5% of the patients with Salmonella spp. infection develop the carrier stage, with the bacteria persisting inside the gallbladder, shedding bacteria in their feces without signs of infection. The aim of this study was to isolate bacteria from Colombian patients with gallstones, using standard culturing methods, and to identify Salmonella spp. carriers by molecular techniques. A total of 149 patients (120 female and 29 male) diagnosed with gallstones who underwent cholecystectomy and who did not have symptoms of acute inflammation were included. Gallbladder tissue and bile were cultured and used for DNA extraction and Salmonella spp. hilA gene detection. Of the 149 patients 28 (19%) had positive cultures. Twenty-one (75%) patients with positive cultures were from Medellin's metropolitan area. In this geographical location, the most frequent isolations were Pseudomonas spp. (38%), Klebsiella spp. (23%), and Proteus spp. (9%) in addition to unique cases of other bacteria. In Apartado, the isolates found were Enterobacter cloacae (50%), Raoultella terrigena (32%), and both Enterobacter cloacae and Raoultella terrigena were isolated in one (18%) male patient. Five (3.3%) of the 149 patients had positive polymerase chain reaction (PCR) results for the hilA gene of Salmonella spp., all of whom were female and residents of the Medellín metropolitan area. The gallbladder microbiota variability found could be related to geographical, ethnic, and environmental conditions.

  2. Preferential transcription of conserved rif genes in two phenotypically distinct Plasmodium falciparum parasite lines

    DEFF Research Database (Denmark)

    Wang, Christian W; Magistrado, Pamela A; Nielsen, Morten A

    2009-01-01

    transcribed in the VAR2CSA-expressing parasite line. In addition, two rif genes were found transcribed at early and late intra-erythrocyte stages independently of var gene transcription. Rif genes are organised in groups and inter-genomic conserved gene families, suggesting that RIFIN sub-groups may have......Plasmodium falciparum variant surface antigens (VSA) are targets of protective immunity to malaria. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and repetitive interspersed family (RIFIN) proteins are encoded by the two variable multigene families, var and rif genes, respectively...... novel rif gene groups, rifA1 and rifA2, containing inter-genomic conserved rif genes, were identified. All rifA1 genes were orientated head-to-head with a neighbouring Group A var gene whereas rifA2 was present in all parasite genomes as a single copy gene with a unique 5' untranslated region. Rif...

  3. 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…

  4. Visualization of Variation and Variability

    NARCIS (Netherlands)

    Busking, S.

    2014-01-01

    As datasets grow in size and complexity, the importance of comparison as a tool for analysis is growing. We define comparison as the act of analyzing variation or variability based on two or more specific instances of the data. This thesis explores a number of cases spread across the range of

  5. 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...

  6. Variable & Recode Definitions - SEER Documentation

    Science.gov (United States)

    Resources that define variables and provide documentation for reporting using SEER and related datasets. Choose from SEER coding and staging manuals plus instructions for recoding behavior, site, stage, cause of death, insurance, and several additional topics. Also guidance on months survived, calculating Hispanic mortality, and site-specific surgery.

  7. Unsupervised classification of variable stars

    Science.gov (United States)

    Valenzuela, Lucas; Pichara, Karim

    2018-03-01

    During the past 10 years, a considerable amount of effort has been made to develop algorithms for automatic classification of variable stars. That has been primarily achieved by applying machine learning methods to photometric data sets where objects are represented as light curves. Classifiers require training sets to learn the underlying patterns that allow the separation among classes. Unfortunately, building training sets is an expensive process that demands a lot of human efforts. Every time data come from new surveys; the only available training instances are the ones that have a cross-match with previously labelled objects, consequently generating insufficient training sets compared with the large amounts of unlabelled sources. In this work, we present an algorithm that performs unsupervised classification of variable stars, relying only on the similarity among light curves. We tackle the unsupervised classification problem by proposing an untraditional approach. Instead of trying to match classes of stars with clusters found by a clustering algorithm, we propose a query-based method where astronomers can find groups of variable stars ranked by similarity. We also develop a fast similarity function specific for light curves, based on a novel data structure that allows scaling the search over the entire data set of unlabelled objects. Experiments show that our unsupervised model achieves high accuracy in the classification of different types of variable stars and that the proposed algorithm scales up to massive amounts of light curves.

  8. Cataclysmic variables observed with INTEGRAL

    Czech Academy of Sciences Publication Activity Database

    Šimon, Vojtěch; Hudec, René; Münz, Filip; Štrobl, Jan

    2006-01-01

    Roč. 6, č. 1 (2006), s. 149-154 ISSN 1009-9271 R&D Projects: GA ČR GA205/05/2167 Institutional research plan: CEZ:AV0Z10030501 Keywords : cataclysmic variables * intermediate polars * X-rays Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 0.746, year: 2006

  9. Choice of the thermodynamic variables

    International Nuclear Information System (INIS)

    Balian, R.

    1985-09-01

    Some basic ideas of thermodynamics and statistical mechanics, both at equilibrium and off equilibrium, are recalled. In particular, the selection of relevant variables which underlies any macroscopic description is discussed, together with the meaning of the various thermodynamic quantities, in order to set the thermodynamic approaches used in nuclear physics in a general prospect [fr

  10. 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…

  11. Contextual Variability in Free Recall

    Science.gov (United States)

    Lohnas, Lynn J.; Polyn, Sean M.; Kahana, Michael J.

    2011-01-01

    According to contextual-variability theory, experiences encoded at different times tend to be associated with different contextual states. The gradual evolution of context implies that spaced items will be associated with more distinct contextual states, and thus have more unique retrieval cues, than items presented in proximity. Ross and Landauer…

  12. Solar-cosmic-ray variability

    International Nuclear Information System (INIS)

    Reedy, R.C.

    1976-01-01

    The maximum flux of particles from solar events that should be considered in designing the shielding for a space habitation is discussed. The activities of various radionuclides measured in the top few centimeters of lunar rocks are used to examine the variability of solar cosmic ray fluxes over the last five million years. 10 references

  13. Operant Variability: A Conceptual Analysis

    Science.gov (United States)

    Barba, Lourenco de Souza

    2012-01-01

    Some researchers claim that variability is an operant dimension of behavior. The present paper reviews the concept of operant behavior and emphasizes that differentiation is the behavioral process that demonstrates an operant relation. Differentiation is conceived as change in the overlap between two probability distributions: the distribution of…

  14. 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

  15. Identification of suitable reference genes for gene expression studies of shoulder instability.

    Directory of Open Access Journals (Sweden)

    Mariana Ferreira Leal

    Full Text Available Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results. In the present study, we evaluated the suitability of a set of reference genes using samples from the glenohumeral capsules of individuals with and without shoulder instability. We analyzed the expression of six commonly used reference genes (ACTB, B2M, GAPDH, HPRT1, TBP and TFRC in the antero-inferior, antero-superior and posterior portions of the glenohumeral capsules of cases and controls. The stability of the candidate reference gene expression was determined using four software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1 was the best single reference gene, and HPRT1 and B2M composed the best pair of reference genes from different analysis groups, including simultaneous analysis of all tissue samples. GenEx software was used to identify the optimal number of reference genes to be used for normalization and demonstrated that the accumulated standard deviation resulting from the use of 2 reference genes was similar to that resulting from the use of 3 or more reference genes. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1. Although the use of different reference gene combinations yielded variable normalized quantities, the relative quantities within sample groups were similar and confirmed that no obvious differences were observed when using 2, 3 or 4 reference genes. Consequently, the use of 2 stable reference genes for normalization, especially

  16. Genes and Social Behavior

    OpenAIRE

    Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

    2008-01-01

    What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence beh...

  17. Beat to beat variability in cardiovascular variables: noise or music?

    Science.gov (United States)

    Appel, M. L.; Berger, R. D.; Saul, J. P.; Smith, J. M.; Cohen, R. J.

    1989-01-01

    Cardiovascular variables such as heart rate, arterial blood pressure, stroke volume and the shape of electrocardiographic complexes all fluctuate on a beat to beat basis. These fluctuations have traditionally been ignored or, at best, treated as noise to be averaged out. The variability in cardiovascular signals reflects the homeodynamic interplay between perturbations to cardiovascular function and the dynamic response of the cardiovascular regulatory systems. Modern signal processing techniques provide a means of analyzing beat to beat fluctuations in cardiovascular signals, so as to permit a quantitative, noninvasive or minimally invasive method of assessing closed loop hemodynamic regulation and cardiac electrical stability. This method promises to provide a new approach to the clinical diagnosis and management of alterations in cardiovascular regulation and stability.

  18. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

    DEFF Research Database (Denmark)

    Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

    2014-01-01

    to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

  19. Screening for the Most Suitable Reference Genes for Gene Expression Studies in Equine Milk Somatic Cells.

    Directory of Open Access Journals (Sweden)

    Jakub Cieslak

    Full Text Available Apart from the well-known role of somatic cell count as a parameter reflecting the inflammatory status of the mammary gland, the composition of cells isolated from milk is considered as a valuable material for gene expression studies in mammals. Due to its unique composition, in recent years an increasing interest in mare's milk consumption has been observed. Thus, investigating the genetic background of horse's milk variability presents and interesting study model. Relying on 39 milk samples collected from mares representing three breeds (Polish Primitive Horse, Polish Cold-blooded Horse, Polish Warmblood Horse we aimed to investigate the utility of equine milk somatic cells as a source of mRNA and to screen the best reference genes for RT-qPCR using geNorm and NormFinder algorithms. The results showed that despite relatively low somatic cell counts in mare's milk, the amount and the quality of the extracted RNA are sufficient for gene expression studies. The analysis of the utility of 7 potential reference genes for RT-qPCR experiments for the normalization of equine milk somatic cells revealed some differences between the outcomes of the applied algorithms, although in both cases the KRT8 and TOP2B genes were pointed as the most stable. Analysis by geNorm showed that the combination of 4 reference genes (ACTB, GAPDH, TOP2B and KRT8 is required for apropriate RT-qPCR experiments normalization, whereas NormFinder algorithm pointed the combination of KRT8 and RPS9 genes as the most suitable. The trial study of the relative transcript abundance of the beta-casein gene with the use of various types and numbers of internal control genes confirmed once again that the selection of proper reference gene combinations is crucial for the final results of each real-time PCR experiment.

  20. History of gene therapy.

    Science.gov (United States)

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Refining discordant gene trees.

    Science.gov (United States)

    Górecki, Pawel; Eulenstein, Oliver

    2014-01-01

    Evolutionary studies are complicated by discordance between gene trees and the species tree in which they evolved. Dealing with discordant trees often relies on comparison costs between gene and species trees, including the well-established Robinson-Foulds, gene duplication, and deep coalescence costs. While these costs have provided credible results for binary rooted gene trees, corresponding cost definitions for non-binary unrooted gene trees, which are frequently occurring in practice, are challenged by biological realism. We propose a natural extension of the well-established costs for comparing unrooted and non-binary gene trees with rooted binary species trees using a binary refinement model. For the duplication cost we describe an efficient algorithm that is based on a linear time reduction and also computes an optimal rooted binary refinement of the given gene tree. Finally, we show that similar reductions lead to solutions for computing the deep coalescence and the Robinson-Foulds costs. Our binary refinement of Robinson-Foulds, gene duplication, and deep coalescence costs for unrooted and non-binary gene trees together with the linear time reductions provided here for computing these costs significantly extends the range of trees that can be incorporated into approaches dealing with discordance.

  2. Genetic Influence on Slope Variability in a Childhood Reflexive Attention Task.

    Directory of Open Access Journals (Sweden)

    Rebecca A Lundwall

    Full Text Available Individuals are not perfectly consistent, and interindividual variability is a common feature in all varieties of human behavior. Some individuals respond more variably than others, however, and this difference may be important to understanding how the brain works. In this paper, we explore genetic contributions to response time (RT slope variability on a reflexive attention task. We are interested in such variability because we believe it is an important part of the overall picture of attention that, if understood, has the potential to improve intervention for those with attentional deficits. Genetic association studies are valuable in discovering biological pathways of variability and several studies have found such associations with a sustained attention task. Here, we expand our knowledge to include a reflexive attention task. We ask whether specific candidate genes are associated with interindividual variability on a childhood reflexive attention task in 9-16 year olds. The genetic makers considered are on 11 genes: APOE, BDNF, CHRNA4, COMT, DRD4, HTR4, IGF2, MAOA, SLC5A7, SLC6A3, and SNAP25. We find significant associations with variability with markers on nine and we discuss the results in terms of neurotransmitters associated with each gene and the characteristics of the associated measures from the reflexive attention task.

  3. Risk assessment of groundwater level variability using variable Kriging methods

    Science.gov (United States)

    Spanoudaki, Katerina; Kampanis, Nikolaos A.

    2015-04-01

    Assessment of the water table level spatial variability in aquifers provides useful information regarding optimal groundwater management. This information becomes more important in basins where the water table level has fallen significantly. The spatial variability of the water table level in this work is estimated based on hydraulic head measured during the wet period of the hydrological year 2007-2008, in a sparsely monitored basin in Crete, Greece, which is of high socioeconomic and agricultural interest. Three Kriging-based methodologies are elaborated in Matlab environment to estimate the spatial variability of the water table level in the basin. The first methodology is based on the Ordinary Kriging approach, the second involves auxiliary information from a Digital Elevation Model in terms of Residual Kriging and the third methodology calculates the probability of the groundwater level to fall below a predefined minimum value that could cause significant problems in groundwater resources availability, by means of Indicator Kriging. The Box-Cox methodology is applied to normalize both the data and the residuals for improved prediction results. In addition, various classical variogram models are applied to determine the spatial dependence of the measurements. The Matérn model proves to be the optimal, which in combination with Kriging methodologies provides the most accurate cross validation estimations. Groundwater level and probability maps are constructed to examine the spatial variability of the groundwater level in the basin and the associated risk that certain locations exhibit regarding a predefined minimum value that has been set for the sustainability of the basin's groundwater resources. Acknowledgement The work presented in this paper has been funded by the Greek State Scholarships Foundation (IKY), Fellowships of Excellence for Postdoctoral Studies (Siemens Program), 'A simulation-optimization model for assessing the best practices for the

  4. Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence.

    Science.gov (United States)

    Wiley, Christopher D; Flynn, James M; Morrissey, Christapher; Lebofsky, Ronald; Shuga, Joe; Dong, Xiao; Unger, Marc A; Vijg, Jan; Melov, Simon; Campisi, Judith

    2017-10-01

    Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single-cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall gene expression profile of senescent human fibroblast populations. Individual senescent cells were surprisingly heterogeneous in their gene expression signatures. This cell-to-cell variability resulted in a loss of correlation among the expression of several senescence-associated genes. Many genes encoding senescence-associated secretory phenotype (SASP) factors, a major contributor to the effects of senescent cells in vivo, showed marked variability with a subset of highly induced genes accounting for the increases observed at the population level. Inflammatory genes in clustered genomic loci showed a greater correlation with senescence compared to nonclustered loci, suggesting that these genes are coregulated by genomic location. Together, these data offer new insights into how genes are regulated in senescent cells and suggest that single markers are inadequate to identify senescent cells in vivo. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  5. 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.

  6. Genetic variability of genital mycoplasmas and its clinical value

    Directory of Open Access Journals (Sweden)

    K. I. Plakhova

    2015-01-01

    Full Text Available The article presents data on genetic variability of genital mycoplasmas. The author presents the results of genetic variability studies for M. hominis, gene vaa, U. parvum, gene mba, and M. genitalium, gene mg192, sampled from women with different clinical manifestations of inflammatory diseases of the urogenital system. Based on the molecular typing results for 138 samples of genital mycoplasmas, the author revealed a relationship between clinical manifestations of inflammatory diseases of the urogenital system caused by U. parvum and different U. parvum serovars as well as different genetic variations of M. hominis.Infection with 6 U. parvum serovar results in the development of inflammatory diseases of the urogenital tract accompanied by subjective manifestations (р < 0.05. Genetic variant II of М. hominis was revealed more often in patients with clinical manifestations of inflammatory diseases while variant I was revealed more often in patients infected with М. hominis without any signs of inflammation (р < 0.05. Genetic variants of M. genitalium were determined; no significant differences in terms of their prevalence in the examined patients were revealed.

  7. 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

  8. Phasevarion mediated epigenetic gene regulation in Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Yogitha N Srikhanta

    Full Text Available Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression. In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M system, controls expression of a phase-variable regulon of genes (a "phasevarion", via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16% of isolates. Microarray analysis comparing the wild-type P12modH5 ON strain to a P12ΔmodH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis.

  9. Polarimetry of magnetic catalysmic variables

    Energy Technology Data Exchange (ETDEWEB)

    Cropper, M

    1985-01-01

    The design and construction of an astronomical polarimeter is described and an evaluation made of its performance. Extensive observations of cataclysmic variables with emphasis on the AM Her and DQ Her classes are then presented. The polarimeter permitted simultaneous linear and circular polarisation measurements, or, by rearranging the order of the retarders in the beam, linear polarisation measurements alone, or circular polarisation measurements alone, with enhanced efficiency. Extensive sets of observations using the polarimeter were obtained for six of the ten AM Her variables. A comparison was made between the competing models for the cyclotron emission, showing that those which take into account the temperature structure of the accretion region provide the best results.

  10. Photometric variability in earthshine observations.

    Science.gov (United States)

    Langford, Sally V; Wyithe, J Stuart B; Turner, Edwin L

    2009-04-01

    The identification of an extrasolar planet as Earth-like will depend on the detection of atmospheric signatures or surface non-uniformities. In this paper we present spatially unresolved flux light curves of Earth for the purpose of studying a prototype extrasolar terrestrial planet. Our monitoring of the photometric variability of earthshine revealed changes of up to 23% per hour in the brightness of Earth's scattered light at around 600 nm, due to the removal of specular reflection from the view of the Moon. This variability is accompanied by reddening of the spectrum and results from a change in surface properties across the continental boundary between the Indian Ocean and Africa's east coast. Our results based on earthshine monitoring indicate that specular reflection should provide a useful tool in determining the presence of liquid water on extrasolar planets via photometric observations.

  11. 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.

  12. Variable frequency microwave heating apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Bible, D.W.; Lauf, R.J.; Johnson, A.C.; Thigpen, L.T.

    1999-10-05

    A variable frequency microwave heating apparatus (10) designed to allow modulation of the frequency of the microwaves introduced into a multi-mode microwave cavity (34) for testing or other selected applications. The variable frequency microwave heating apparatus (10) includes a microwave signal generator (12) and a high-power microwave amplifier (20) or a high-power microwave oscillator (14). A power supply (22) is provided for operation of the high-power microwave oscillator (14) or microwave amplifier (20). A directional coupler (24) is provided for detecting the direction and amplitude of signals incident upon and reflected from the microwave cavity (34). A first power meter (30) is provided for measuring the power delivered to the microwave furnace (32). A second power meter (26) detects the magnitude of reflected power. Reflected power is dissipated in the reflected power load (28).

  13. Biological variability of glycated hemoglobin.

    Science.gov (United States)

    Braga, Federica; Dolci, Alberto; Mosca, Andrea; Panteghini, Mauro

    2010-11-11

    The measurement of glycated hemoglobin (HbA(1c)) has a pivotal role in monitoring glycemic state in diabetic patients. Furthermore, the American Diabetes Association has recently recommended the use of HbA(1c) for diabetes diagnosis, but a clear definition of the clinically allowable measurement error is still lacking. Information on biological variability of the analyte can be used to achieve this goal. We systematically reviewed the published studies on the biological variation of HbA(1c) to check consistency of available data in order to accurately define analytical goals. The nine recruited studies were limited by choice of analytic methodology, population selection, protocol application and statistical analyses. There is an urgent need to determine biological variability of HbA(1c) using a specific and traceable assay, appropriate protocol and appropriate statistical evaluation of data. 2010 Elsevier B.V. All rights reserved.

  14. RADIO VARIABILITY IN SEYFERT NUCLEI

    International Nuclear Information System (INIS)

    Mundell, C. G.; Ferruit, P.; Nagar, N.; Wilson, A. S.

    2009-01-01

    Comparison of 8.4 GHz radio images of a sample of eleven, early-type Seyfert galaxies with previous observations reveals possible variation in the nuclear radio flux density in five of them over a seven year period. Four Seyferts (NGC 2110, NGC 3081, MCG -6-30-15, and NGC 5273) show a decline in their 8.4 GHz nuclear flux density between 1992 and 1999, while one (NGC 4117) shows an increase; the flux densities of the remaining six Seyferts (Mrk 607, NGC 1386, Mrk 620, NGC 3516, NGC 4968, and NGC 7465) have remained constant over this period. New images of MCG -5-23-16 are also presented. We find no correlation between radio variability and nuclear radio luminosity or Seyfert nuclear type, although the sample is small and dominated by type 2 Seyferts. Instead, a possible correlation between the presence of nuclear radio variability and the absence of hundred parsec-scale radio emission is seen, with four out of five marginally resolved or unresolved nuclei showing a change in nuclear flux density, while five out of six extended sources show no nuclear variability despite having unresolved nuclear sources. NGC 2110 is the only source in our sample with significant extended radio structure and strong nuclear variability (∼38% decline in nuclear flux density over seven years). The observed nuclear flux variability indicates significant changes are likely to have occurred in the structure of the nucleus on scales smaller than the VLA beam size (i.e., within the central ∼0.''1 (15 pc)), between the two epochs, possibly due to the appearance and fading of new components or shocks in the jet, consistent with previous detection of subparsec-scale nuclear structure in this Seyfert. Our results suggest that all Seyferts may exhibit variation in their nuclear radio flux density at 8.4 GHz, but that variability is more easily recognized in compact sources in which emission from the variable nucleus is not diluted by unresolved, constant flux density radio jet emission

  15. Variables associated with active spondylolysis.

    Science.gov (United States)

    Gregg, Chris D; Dean, Sarah; Schneiders, Anthony G

    2009-11-01

    Retrospective non-experimental study. To investigate variables associated with active spondylolysis. A retrospective study audited clinical data over a two year period from patients with suspected spondylolysis that were referred for a SPECT bone scan. Six exploratory variables were identified and analysed using uni- and multi-variate regression from 82 patient records to determine the association between symptomatic, physical and demographic characteristics, and the presence of an active spondylolysis. Tertiary level multidisciplinary private practice sports medicine clinic. All patients with low back pain that required a SPECT bone scan to confirm suspected spondylolysis. 82 subjects were included in the final sample group. The six exploratory variables included Age, Gender, Injury duration, Injury onset, Sports participation and the result of the Single Leg Hyperextension Test. The dependent outcome variable was the result of the SPECT bone scan (scan-positive or scan-negative). Adolescent males had a higher incidence of spondylolysis detected by SPECT bone scan compared to other patients and a statistically significant association was demonstrated for both age (p=0.01) and gender (p=0.01). Subjects with an active spondylolysis were nearly five times more likely to be male and aged less than 20 years. Furthermore, the likelihood ratio indicated that adolescent males with suspected spondylolysis were three and a half times more likely to have a positive bone scan result. The Single Leg Hyperextension Test did not demonstrate a statistically significant association with spondylolysis (p=0.47). Clinicians assessing for a predisposition to the development of spondylolysis should consider the gender and age of the patient and not rely on the predictive ability of the Single Leg Hyperextension Test.

  16. Ashtekar formalism with real variables

    International Nuclear Information System (INIS)

    Kalau, W.; Nationaal Inst. voor Kernfysica en Hoge-Energiefysica

    1990-12-01

    A new approach to canonical gravity is presented which is based on the Ashtekar formalism. But, in contrast to Ashtekar's variables, this formulation does not need complex quantities nor does it lead to second class constraints. This is achieved using SO(3,1) as a gauge group instead of complexified SO(3). Because of the larger group additional first class constraints are needed which turn out to be cubic and quartic in the momenta. (author). 13 refs

  17. Chromatin loops, gene positioning, and gene expression

    NARCIS (Netherlands)

    Holwerda, S.; de Laat, W.

    2012-01-01

    Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the alpha- and beta-globin

  18. Distinguishing the rates of gene activation from phenotypic variations

    OpenAIRE

    Chen, Ye; Lv, Cheng; Li, Fangting; Li, Tiejun

    2015-01-01

    Background Stochastic genetic switching driven by intrinsic noise is an important process in gene expression. When the rates of gene activation/inactivation are relatively slow, fast, or medium compared with the synthesis/degradation rates of mRNAs and proteins, the variability of protein and mRNA levels may exhibit very different dynamical patterns. It is desirable to provide a systematic approach to identify their key dynamical features in different regimes, aiming at distinguishing which r...

  19. Dynamics of Variable Mass Systems

    Science.gov (United States)

    Eke, Fidelis O.

    1998-01-01

    This report presents the results of an investigation of the effects of mass loss on the attitude behavior of spinning bodies in flight. The principal goal is to determine whether there are circumstances under which the motion of variable mass systems can become unstable in the sense that their transverse angular velocities become unbounded. Obviously, results from a study of this kind would find immediate application in the aerospace field. The first part of this study features a complete and mathematically rigorous derivation of a set of equations that govern both the translational and rotational motions of general variable mass systems. The remainder of the study is then devoted to the application of the equations obtained to a systematic investigation of the effect of various mass loss scenarios on the dynamics of increasingly complex models of variable mass systems. It is found that mass loss can have a major impact on the dynamics of mechanical systems, including a possible change in the systems stability picture. Factors such as nozzle geometry, combustion chamber geometry, propellant's initial shape, size and relative mass, and propellant location can all have important influences on the system's dynamic behavior. The relative importance of these parameters on-system motion are quantified in a way that is useful for design purposes.

  20. 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.

  1. Hardness variability in commercial technologies

    International Nuclear Information System (INIS)

    Shaneyfelt, M.R.; Winokur, P.S.; Meisenheimer, T.L.; Sexton, F.W.; Roeske, S.B.; Knoll, M.G.

    1994-01-01

    The radiation hardness of commercial Floating Gate 256K E 2 PROMs from a single diffusion lot was observed to vary between 5 to 25 krad(Si) when irradiated at a low dose rate of 64 mrad(Si)/s. Additional variations in E 2 PROM hardness were found to depend on bias condition and failure mode (i.e., inability to read or write the memory), as well as the foundry at which the part was manufactured. This variability is related to system requirements, and it is shown that hardness level and variability affect the allowable mode of operation for E 2 PROMs in space applications. The radiation hardness of commercial 1-Mbit CMOS SRAMs from Micron, Hitachi, and Sony irradiated at 147 rad(Si)/s was approximately 12, 13, and 19 krad(Si), respectively. These failure levels appear to be related to increases in leakage current during irradiation. Hardness of SRAMs from each manufacturer varied by less than 20%, but differences between manufacturers are significant. The Qualified Manufacturer's List approach to radiation hardness assurance is suggested as a way to reduce variability and to improve the hardness level of commercial technologies

  2. Clinical variables in radiotracer biodistributions

    International Nuclear Information System (INIS)

    Lentle, B.C.; Scott, J.R.; Schmidt, R.P.; Noujaim, A.A.

    1981-01-01

    Radionuclide dosimetry must, by its nature, define tissue irradiation in terms of mean exposure in a population of a statistically acceptable size. In the daily practice of clinical nuclear medicine there are, however, quite large variations in the biodistribution of tracers and thus in resulting radiation doses. Age is a variable, particularly in respect of bone-seeking tracers. Sex imposes variations in radiation dose on account of the differing anatomical configurations of the gonads. Breast uptake and excretion of certain tracers in women are additional variables. Activity and occupation are occasional variables. Numerous iatrogenic causes of altered radiotracer biodistributions have been described. Cancer chemotherapy is a particularly potent cause of changed biodistributions while even a trivial matter such as preparing the skin with an iodine containing antiseptic may cause displacement of technetium from its compounds. In the blocking of thyroid uptake of radioiodines, there is good precedent for the manipulation of regional tissue dosimetry. It is possible to go beyond the mere cataloguing of these effects to look creatively at the subject of comparative tissue biodistributions and hence comparative dosimetry. Effects such as the clinical observation of the interference by cis-platinum with the usual biodistribution of radio-gallium suggest that such compounds can be used as probes each to lead to a better understanding of the mechanism of action of the other

  3. Your Genes, Your Choices

    Science.gov (United States)

    Table of Contents Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social issues that are ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

  4. DNA repair genes

    International Nuclear Information System (INIS)

    Morimyo, Mitsuoki

    1995-01-01

    Fission yeast S. pombe is assumed to be a good model for cloning of human DNA repair genes, because human gene is normally expressed in S. pombe and has a very similar protein sequence to yeast protein. We have tried to elucidate the DNA repair mechanisms of S. pombe as a model system for those of mammals. (J.P.N.)

  5. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...

  6. Radionuclide reporter gene imaging

    International Nuclear Information System (INIS)

    Min, Jung Joon

    2004-01-01

    Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate model validation as well as allow for clinical monitoring of human diseases

  7. Radionuclide reporter gene imaging

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon [School of Medicine, Chonnam National Univ., Gwangju (Korea, Republic of)

    2004-04-01

    Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate model validation as well as allow for clinical monitoring of human diseases.

  8. Gene selection heuristic algorithm for nutrigenomics studies.

    Science.gov (United States)

    Valour, D; Hue, I; Grimard, B; Valour, B

    2013-07-15

    Large datasets from -omics studies need to be deeply investigated. The aim of this paper is to provide a new method (LEM method) for the search of transcriptome and metabolome connections. The heuristic algorithm here described extends the classical canonical correlation analysis (CCA) to a high number of variables (without regularization) and combines well-conditioning and fast-computing in "R." Reduced CCA models are summarized in PageRank matrices, the product of which gives a stochastic matrix that resumes the self-avoiding walk covered by the algorithm. Then, a homogeneous Markov process applied to this stochastic matrix converges the probabilities of interconnection between genes, providing a selection of disjointed subsets of genes. This is an alternative to regularized generalized CCA for the determination of blocks within the structure matrix. Each gene subset is thus linked to the whole metabolic or clinical dataset that represents the biological phenotype of interest. Moreover, this selection process reaches the aim of biologists who often need small sets of genes for further validation or extended phenotyping. The algorithm is shown to work efficiently on three published datasets, resulting in meaningfully broadened gene networks.

  9. 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.

  10. 5S rRNA gene arrangements in protists: a case of nonadaptive evolution.

    Science.gov (United States)

    Drouin, Guy; Tsang, Corey

    2012-06-01

    Given their high copy number and high level of expression, one might expect that both the sequence and organization of eukaryotic ribosomal RNA genes would be conserved during evolution. Although the organization of 18S, 5.8S and 28S ribosomal RNA genes is indeed relatively well conserved, that of 5S rRNA genes is much more variable. Here, we review the different types of 5S rRNA gene arrangements which have been observed in protists. This includes linkages to the other ribosomal RNA genes as well as linkages to ubiquitin, splice-leader, snRNA and tRNA genes. Mapping these linkages to independently derived phylogenies shows that these diverse linkages have repeatedly been gained and lost during evolution. This argues against such linkages being the primitive condition not only in protists but also in other eukaryote species. Because the only characteristic the diverse genes with which 5S rRNA genes are found linked with is that they are tandemly repeated, these arrangements are unlikely to provide any selective advantage. Rather, the observed high variability in 5S rRNA genes arrangements is likely the result of the fact that 5S rRNA genes contain internal promoters, that these genes are often transposed by diverse recombination mechanisms and that these new gene arrangements are rapidly homogenized by unequal crossingovers and/or by gene conversions events in species with short generation times and frequent founder events.

  11. 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,...

  12. 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

  13. 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.

  14. Utilization technique on variable speed device

    International Nuclear Information System (INIS)

    1989-12-01

    This reports of workshop on power technology describes using technique on variable speed device, which deals with alternating current situation and prospect of current variable speed device, technical trend and prospect of electronics, reduce expenses by variable speed device, control technique, measurement technology, high voltage variable speed device, recent trend of inverter technology, low voltage and high voltage variable speed device control device, operating variable speed device in cooling fan, FDF application and defect case of variable speed device, cooling pump application of water variable transformer, inverter application and energy effect of ventilation equipment, application of variable speed device and analysis of the result of operation and study for application of variable speed technology.

  15. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  16. Heart rate variability in newborns.

    Science.gov (United States)

    Javorka, K; Lehotska, Z; Kozar, M; Uhrikova, Z; Kolarovszki, B; Javorka, M; Zibolen, M

    2017-09-22

    Heart rate (HR) and heart rate variability (HRV) in newborns is influenced by genetic determinants, gestational and postnatal age, and other variables. Premature infants have a reduced HRV. In neonatal HRV evaluated by spectral analysis, a dominant activity can be found in low frequency (LF) band (combined parasympathetic and sympathetic component). During the first postnatal days the activity in the high frequency (HF) band (parasympathetic component) rises, together with an increase in LF band and total HRV. Hypotrophy in newborn can cause less mature autonomic cardiac control with a higher contribution of sympathetic activity to HRV as demonstrated by sequence plot analysis. During quiet sleep (QS) in newborns HF oscillations increase - a phenomenon less expressed or missing in premature infants. In active sleep (AS), HRV is enhanced in contrast to reduced activity in HF band due to the rise of spectral activity in LF band. Comparison of the HR and HRV in newborns born by physiological vaginal delivery, without (VD) and with epidural anesthesia (EDA) and via sectio cesarea (SC) showed no significant differences in HR and in HRV time domain parameters. Analysis in the frequency domain revealed, that the lowest sympathetic activity in chronotropic cardiac chronotropic regulation is in the VD group. Different neonatal pathological states can be associated with a reduction of HRV and an improvement in the health conditions is followed by changes in HRV what can be use as a possible prognostic marker. Examination of heart rate variability in neonatology can provide information on the maturity of the cardiac chronotropic regulation in early postnatal life, on postnatal adaptation and in pathological conditions about the potential dysregulation of cardiac function in newborns, especially in preterm infants.

  17. Pleistocene Indian Monsoon Rainfall Variability

    Science.gov (United States)

    Yirgaw, D. G.; Hathorne, E. C.; Giosan, L.; Collett, T. S.; Sijingeo, A. V.; Nath, B. N.; Frank, M.

    2014-12-01

    The past variability of the Indian Monsoon is mostly known from records of wind strength over the Arabian Sea. Here we investigate proxies for fresh water input and runoff in a region of strong monsoon precipitation that is a major moisture source for the east Asian Monsoon. A sediment core obtained by the IODP vessel JOIDES Resolution and a gravity core from the Alcock Seamount complex in the Andaman Sea are used to examine the past monsoon variability on the Indian sub-continent and directly over the ocean. The current dataset covers the last glacial and deglacial but will eventually provide a Pleistocene record. We utilise the ecological habitats of G. sacculifer and N. dutertrei to investigate the freshwater-induced stratification with paired Mg/Ca and δ18O analyses to estimate seawater δ18O (δ18Osw). During the last 60 kyrs, Ba/Ca ratios and δ18Osw values generally agree well between the two cores and suggest the weakest surface runoff and monsoon during the LGM and strongest monsoon during the Holocene. The difference in δ18O between the species, interpreted as a proxy for upper ocean stratification, implies stratification developed around 37 ka and remained relatively constant during the LGM, deglacial and Holocene. To investigate monsoon variability for intervals in the past, single shell Mg/Ca and δ18O analyses have been conducted. Mg/Ca ratios from individual shells of N. dutertrei suggest relatively small changes in temperature. However, individual N. dutertrei δ18O differ greatly between the mid-Holocene and samples from the LGM and a nearby core top. The mid-Holocene individuals have a greater range and large skew towards negative values indicating greater fresh water influence.

  18. The masses of cataclysmic variables

    International Nuclear Information System (INIS)

    Robinson, E.L.

    1976-01-01

    Masses are derived for the individual components of six cataclysmic variables. There is a considerable spread in the masses of the white dwarf components, which range from 0.73 M/sub sun/ in EM Cyg to 1.26 M/sub sun/ in Z Cam. All of the white dwarfs have masses greater than 0.70 M/sub sun/, but there is no evidence that there is any preferred mass. It is found that the morphology of the eruptions (i.e., nova versus dwarf nova) is independent of the mass of both the white dwarf and the late-type star

  19. Variable retinal presentations in nanophthalmos

    International Nuclear Information System (INIS)

    Khan, A.; Zafar, S.N.

    2009-01-01

    Nanophthalmos is an uncommon developmental ocular disorder characterized by a small eye with short axial length, high hyperopia and high lens/eye volume ratio due to arrested development of the globe in all directions. Different types of fundus changes can rarely occur with nanophthalmos. We describe five cases of nanophthalmos, each of them presenting with a different fundus appearance. Our case series highlights variability of pigmentary changes from retinal flecks to bone spicules and bull's eye maculopathy, which are rare in the combinations described here. (author)

  20. Continuous-variable quantum games

    International Nuclear Information System (INIS)

    Li Hui; Du Jiangfeng; Massar, Serge

    2002-01-01

    We investigate the quantization of games in which the players can access to a continuous set of classical strategies, making use of continuous-variable quantum systems. For the particular case of the Cournot's duopoly, we find that, even though the two players both act as 'selfishly' in the quantum game as they do in the classical game, they are found to virtually cooperate due to the quantum entanglement between them. We also find that the original Einstein-Podolksy-Rosen state contributes to the best profits that the two firms could ever attain. Moreover, we propose a practical experimental setup for the implementation of such quantum games

  1. Variability of ethane on Jupiter

    Science.gov (United States)

    Kostiuk, Theodor; Espenak, Fred; Mumma, Michael J.; Deming, Drake; Zipoy, David

    1987-01-01

    Varying stratospheric temperature profiles and C2H6 altitude distributions furnish contexts for the evaluation of ethane abundances and distributions in the Jupiter stratosphere. Substantial ethane line emission and retrieved mole fraction variability is noted near the footprint of Io's flux tube, as well as within the auroral regions. It is suggested that this and other observed phenomena are due to the modification of local stratospheric chemistry by higher-order effects, which are in turn speculated to be due to the precipitation of charged particles along magnetic field lines.

  2. Climatic variability of east Malaysia

    International Nuclear Information System (INIS)

    Camerlengo, A.L.; Saadon, M.N.; Awang, M.; Somchit, H.; Rang, L.Y.

    2001-01-01

    The objective of this paper is to learn the variability of atmospheric pressure, relative humidity and insolation in East Malaysia. The main results of our study are: (1) a gentle pressure gradient is observed at the east coast in the boreal winter, (2) smaller atmospheric pressure values are noted during the first inter-monsoon period all across East Malaysia, (3) lesser insolation values are observed in Sarawak and at the east coast during the boreal winter as compared to the boreal summer, and (4) a poleward increase of insolation is registered. (author)

  3. Pulse timing for cataclysmic variables

    International Nuclear Information System (INIS)

    Chester, T.J.

    1979-01-01

    It is shown that present pulse timing measurements of cataclysmic variables can be explained by models of accretion disks in these systems, and thus such measurements can constrain disk models. The model for DQ Her correctly predicts the amplitude variation of the continuum pulsation and can also perhaps explain the asymmetric amplitude of the pulsed lambda4686 emission line. Several other predictions can be made from the model. In particular, if pulse timing measurements that resolve emission lines both in wavelength and in binary phase can be made, the projected orbital radius of the white dwarf could be deduced

  4. Reflecting variable opening insulating panel

    International Nuclear Information System (INIS)

    Nungesser, W.T.

    1976-01-01

    A description is given of a reflecting variable opening insulating panel assembly, comprising a static panel assembly of reflecting insulation sheets forming a cavity along one side of the panel and a movable panel opening out by sliding from the cavity of the static panel, and a locking device for holding the movable panel in a position extending from the cavity of the static panel. This can apply to a nuclear reactor of which the base might require maintenance and periodical checking and for which it is desirable to have available certain processes for the partial dismantling of the insulation [fr

  5. Identification of valid endogenous control genes for determining gene expression in C6 glioma cell line treated with conditioned medium from adipose-derived stem cell.

    Science.gov (United States)

    Iser, I C; de Campos, R P; Bertoni, A P S; Wink, M R

    2015-10-01

    There is growing evidence that mesenchymal stem cells (MSCs) can be important players in the tumor microenvironment. They can affect the glioma progression through the modulation of different genes. This modulation can be evaluated through a very useful model, treating the tumor cells with MSC-conditioned medium. However, for an accurate and reliable gene expression analysis, normalization of gene expression data against reference genes is a prerequisite. We performed a systematic review in an attempt to find a reference gene to use when analyzing gene expression in C6 glioma cells lines. Considering that we were not able to find a reference gene originated by an appropriate validation, in this study we evaluated candidate genes to be used as reference gene in C6 cells under different treatments with adipose-derived stem cells conditioned medium (CM-ADSCs). β-actin (ACTB); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); hypoxanthine-guanine phosphoribosyltransferase I (HPRT-1); TATA box binding protein (TBP) and beta-2-microglobulin (B2M) were evaluated by real-time reverse transcription PCR (RT-qPCR). The mean Cq, the maximum fold change (MFC) and NormFinder software were used for reference gene evaluation and selection. The GAPDH and ACTB genes have been the most widely used reference genes to normalize among the different investigated genes in our review, however, controversially these genes underwent a substantial variability among the genes evaluated in the present work. Individually, TBP gene was more stable when compared with other genes analyzed and the combination of TBP and HPRT-1 was even more stable. These results evidence the importance of appropriate validation of reference genes before performing qPCR experiments. Besides, our data will contribute with researchers that work analyzing the role of ADSCs in glioma microenvironment through gene expression. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. The significance of IL-1β +3953C>T, IL-6 -174G>C and -596G>A, TNF-α -308G>A gene polymorphisms and 86 bp variable number tandem repeat polymorphism of IL-1RN in bronchopulmonary dysplasia in infants born before 32 weeks of gestation

    Directory of Open Access Journals (Sweden)

    Dawid Szpecht

    2017-06-01

    Full Text Available Introduction : Bronchopulmonary dysplasia (BPD is a chronic lung disease that affects primarily preterm infants. Genetic factors are also taken into consideration in the pathogenesis of BPD. Genetic predispositions to higher production of inflammation mediators seem to be crucial. Material and methods: The aim of this study was to evaluate the possible relationship between polymorphisms: interleukin-1β +3953 C>T, interleukin-6 -174 G>C and -596 G>A, tumour necrosis factor -308 G>A and interleukin-1RN VNTR 86bp and the occurrence of BPD in a population of 100 preterm infants born from singleton pregnancy, before 32+0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities.  Results : In the study population BPD was diagnosed in 36 (36% newborns. Among the studied polymorphisms we found the higher prevalence for BPD developing of the following genotypes: 1/2 (OR 1.842 [0.673-5.025] and 2/2 IL-1RN (OR 1.75 [0.418-6.908] 86bpVNTR; GC (2.222 [0.658-8.706] and CC IL-6 -174G>C (1.6 [0.315-8.314] and GA (2.753 [0.828-10.64] and AA (1.5 [0.275-8.067] IL-6 -596G>A, GA 1.509 (0.515-4.301 TNF-α -308G>A. However, these finding were not statistically significant.  Conclusions : Genetic factors are undeniably involved in the pathogenesis of BPD. In the times of individualised therapy finding genes responsible for BPD might allow the development of new treatment strategies. A new way of specific therapy could ensure the reduction of complications connected with BPD and treatment costs.

  7. Joubert syndrome: large clinical variability and a unique neuroimaging aspect

    International Nuclear Information System (INIS)

    Leao, Emilia Katiane Embirucu; Lima, Marcilia Martyn; Kok, Fernando; Parizotto, Juliana; Maia Junior, Otacilio de Oliveira

    2010-01-01

    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)

  8. 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)

  9. Methanogenesis and methane genes

    International Nuclear Information System (INIS)

    Reeve, J.N.; Shref, B.A.

    1991-01-01

    An overview of the pathways leading to methane biosynthesis is presented. The steps investigated to date by gene cloning and DNA sequencing procedures are identified and discussed. The primary structures of component C of methyl coenzyme M reductase encoded by mcr operons in different methanogens are compared. Experiments to detect the primary structure of the genes encoding F420 reducing hydrogenase (frhABG) and methyl hydrogen reducing hydrogenase (mvhDGA) in methanobacterium thermoautotrophicum strain H are compared with each other and with eubacterial hydrogenase encoding genes. A biotechnological use for hydrogenases from hypermorphillic archaebacteria is suggested. (author)

  10. 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.

  11. Gene Expression Commons: an open platform for absolute gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Jun Seita

    Full Text Available Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000 of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/ which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.

  12. Interobserver variability in the evaluation of mismatch repair protein immunostaining

    DEFF Research Database (Denmark)

    Klarskov, Louise Laurberg; Ladelund, Steen; Holck, Susanne

    2010-01-01

    Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data on reliabi......Immunohistochemical staining for mismatch repair proteins has during recent years been established as a routine analysis in many pathology laboratories with the aim to identify tumors linked to the hereditary nonpolyposis colorectal cancer syndrome. Despite widespread application, data...... on reliability are lacking. We therefore evaluated interobserver variability among 6 pathologists, 3 experienced gastrointestinal pathologists and 3 residents. In total, 225 immunohistochemically stained colorectal cancers were evaluated as having normal, weak, loss of, or nonevaluable mismatch repair protein...... variability was considerable, though experienced pathologists and residents reached the same level of consensus. Because results from immunohistochemical mismatch repair protein stainings are used for decisions on mutation analysis and as an aid in the interpretation of gene variants of unknown significance...

  13. Plant gene bank and vegetable varieties biodiversity in Smederevska Palanka

    Directory of Open Access Journals (Sweden)

    Pavlović Nenad

    2011-01-01

    Full Text Available Biodiversity protection and preservation of genetic variability is based on the fact that plant varieties are irreplaceable in production process and that they are more and more jeopardized by urban and industrial development. The most common way of preserving and at the same time the safest way is a storage in a gene bank. Prior to storage comes collecting, studying and replanting for Institute Gene Bank, Central State Gene Bank and for Regional Gene Banks. Institute for Vegetable Crops in Smederevska Palanka preserves a wide variety of vegetable germplasm. This is, so called, work collection, used as a gene resource for breeding purposes. Seed samples are stored at 4±2°C and 50% relative humidity. At the moment, the collection has 2265 samples. Almost all samples have the passport data, but only 10% of samples have been further characterized and evaluated.

  14. 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)

  15. Variable speed electrical driving systems; Entrainements electriques a vitesse variable

    Energy Technology Data Exchange (ETDEWEB)

    Bonal, J. [ESE, Promethee, Groupe Schneider (France)

    1997-12-31

    This book is the first of a series of 3 volumes which synthesize the most recent knowledge on variable speed electrical driving systems. It is devoted to electronic and electromechanical engineers and technicians and to manufacturers of electrical equipments involving such systems. after a recall of basic electrotechnical and mechanical notions, this book focusses on the functionalities and criteria of definition of driving systems, and shows the interactions between the different parts of these equipments. It develops a methodological approach of the choice for the most suitable technology with respect to the application under consideration. Various industrial sectors are concerned and a particular attention is paid to the driving of receptive turbo-machineries which play a major role in the energy balance sheet of the industrial electrical power force. (J.S.) 28 refs.

  16. Progress on Variable Cycle Engines

    Science.gov (United States)

    Westmoreland, J. S.; Howlett, R. A.; Lohmann, R. P.

    1979-01-01

    Progress in the development and future requirements of the Variable Stream Control Engine (VSCE) are presented. The two most critical components of this advanced system for future supersonic transports, the high performance duct burner for thrust augmentation, and the low jet coannular nozzle were studied. Nozzle model tests substantiated the jet noise benefit associated with the unique velocity profile possible with a coannular nozzle system on a VSCE. Additional nozzle model performance tests have established high thrust efficiency levels only at takeoff and supersonic cruise for this nozzle system. An experimental program involving both isolated component and complete engine tests has been conducted for the high performance, low emissions duct burner with good results and large scale testing of these two components is being conducted using a F100 engine as the testbed for simulating the VSCE. Future work includes application of computer programs for supersonic flow fields to coannular nozzle geometries, further experimental testing with the duct burner segment rig, and the use of the Variable Cycle Engine (VCE) Testbed Program for evaluating the VSCE duct burner and coannular nozzle technologies.

  17. The variable finesse locking technique

    International Nuclear Information System (INIS)

    Acernese, F; Al-Shourbagy, M

    2006-01-01

    Virgo is a power recycled Michelson interferometer, with 3 km long Fabry-Perot cavities in the arms. The locking of the interferometer has been obtained with an original lock acquisition technique. The main idea is to lock the instrument away from its working point. Lock is obtained by misaligning the power recycling mirror and detuning the Michelson from the dark fringe. In this way, a good fraction of light escapes through the antisymmetric port and the power build-up inside the recycling cavity is extremely low. The benefit is that all the degrees of freedom are controlled when they are almost decoupled, and the linewidth of the recycling cavity is large. The interferometer is then adiabatically brought on to the dark fringe. This technique is referred to as variable finesse, since the recycling cavity is considered as a variable finesse Fabry-Perot. This technique has been widely tested and allows us to reach the dark fringe in few minutes, in an essentially deterministic way

  18. Variability of femoral muscle attachments.

    Science.gov (United States)

    Duda, G N; Brand, D; Freitag, S; Lierse, W; Schneider, E

    1996-09-01

    Analytical and experimental models of the musculoskeletal system often assume single values rather than ranges for anatomical input parameters. The hypothesis of the present study was that anatomical variability significantly influences the results of biomechanical analyses, specifically regarding the moment arms of the various thigh muscles. Insertions and origins of muscles crossing or attaching to the femur were digitized in six specimens. Muscle volumes were measured; muscle attachment area and centroid location were computed. To demonstrate the influence of inter-individual anatomic variability on a mechanical modeling parameter, the corresponding range of muscle moment arms were calculated. Standard deviations, as a percentage of the mean, were about 70% for attachment area and 80% for muscle volume and attachment centroid location. The resulting moment arms of the m. gluteus maximus and m. rectus femoris were especially sensitive to anatomical variations (SD 65%). The results indicate that sensitivity to anatomical variations should be analyzed in any investigation simulating musculoskeletal interactions. To avoid misinterpretations, investigators should consider using several anatomical configurations rather than relying on a mean data set.

  19. Pneumatic Variable Series Elastic Actuator.

    Science.gov (United States)

    Zheng, Hao; Wu, Molei; Shen, Xiangrong

    2016-08-01

    Inspired by human motor control theory, stiffness control is highly effective in manipulation and human-interactive tasks. The implementation of stiffness control in robotic systems, however, has largely been limited to closed-loop control, and suffers from multiple issues such as limited frequency range, potential instability, and lack of contribution to energy efficiency. Variable-stiffness actuator represents a better solution, but the current designs are complex, heavy, and bulky. The approach in this paper seeks to address these issues by using pneumatic actuator as a variable series elastic actuator (VSEA), leveraging the compressibility of the working fluid. In this work, a pneumatic actuator is modeled as an elastic element with controllable stiffness and equilibrium point, both of which are functions of air masses in the two chambers. As such, for the implementation of stiffness control in a robotic system, the desired stiffness/equilibrium point can be converted to the desired chamber air masses, and a predictive pressure control approach is developed to control the timing of valve switching to obtain the desired air mass while minimizing control action. Experimental results showed that the new approach in this paper requires less expensive hardware (on-off valve instead of proportional valve), causes less control action in implementation, and provides good control performance by leveraging the inherent dynamics of the actuator.

  20. 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.

  1. Correlated Temporal and Spectral Variability

    Science.gov (United States)

    Swank, Jean H.

    2007-01-01

    The variability of neutron star and black hole X-ray sources has several dimensions, because of the roles played by different important time-scales. The variations on time scales of hours, weeks, and months, ranging from 50% to orders of magnitude, arise out of changes in the flow in the disk. The most important driving forces for those changes are probably various possible instabilities in the disk, though there may be effects with other dominant causes. The changes in the rate of flow appear to be associated with changes in the flow's configuration, as the accreting material approaches the compact object, for there are generally correlated changes in both the Xray spectra and the character of the faster temporal variability. There has been a lot of progress in tracking these correlations, both for Z and Atoll neutron star low-mass X-ray binaries, and for black hole binaries. I will discuss these correlations and review briefly what they tell us about the physical states of the systems.

  2. A survey of Type III restriction-modification systems reveals numerous, novel epigenetic regulators controlling phase-variable regulons; phasevarions

    Science.gov (United States)

    Atack, John M; Yang, Yuedong; Jennings, Michael P

    2018-01-01

    Abstract Many bacteria utilize simple DNA sequence repeats as a mechanism to randomly switch genes on and off. This process is called phase variation. Several phase-variable N6-adenine DNA-methyltransferases from Type III restriction-modification systems have been reported in bacterial pathogens. Random switching of DNA methyltransferases changes the global DNA methylation pattern, leading to changes in gene expression. These epigenetic regulatory systems are called phasevarions — phase-variable regulons. The extent of these phase-variable genes in the bacterial kingdom is unknown. Here, we interrogated a database of restriction-modification systems, REBASE, by searching for all simple DNA sequence repeats in mod genes that encode Type III N6-adenine DNA-methyltransferases. We report that 17.4% of Type III mod genes (662/3805) contain simple sequence repeats. Of these, only one-fifth have been previously identified. The newly discovered examples are widely distributed and include many examples in opportunistic pathogens as well as in environmental species. In many cases, multiple phasevarions exist in one genome, with examples of up to 4 independent phasevarions in some species. We found several new types of phase-variable mod genes, including the first example of a phase-variable methyltransferase in pathogenic Escherichia coli. Phasevarions are a common epigenetic regulation contingency strategy used by both pathogenic and non-pathogenic bacteria. PMID:29554328

  3. Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo

    International Nuclear Information System (INIS)

    Vaiphei, S. Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Sharan, R.N.; Chaubey, R.C.; Kma, L.

    2015-01-01

    In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving 60 Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of 60 Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min -1 at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. (author)

  4. Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo.

    Science.gov (United States)

    Vaiphei, S Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Chaubey, R C; Kma, L; Sharan, R N

    2015-01-01

    In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving (60)Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of (60)Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min(-1) at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  5. Expression profiling of interindividual variability following xenobiotic exposures in primary human hepatocyte cultures

    International Nuclear Information System (INIS)

    Goyak, Katy M.O.; Johnson, Mary C.; Strom, Stephen C.; Omiecinski, Curtis J.

    2008-01-01

    To examine the magnitude of human variability across the entire transcriptome after chemical challenge, we profiled gene expression responses to three different prototypic chemical inducers in primary human hepatocyte cultures from ten independent donors. Correlation between basal expression in any two hepatocyte donors ranged from r 2 values of 0.967 to 0.857, and chemical treatment tended to negatively impact correlation between donors. Including anticipated target genes, 10,812, 8373, and 7847 genes were changed in at least one donor by Aroclor 1254 (A1254), di(2-ethylhexyl) phthalate (DEHP), and phenobarbital (PB), respectively. A subset of these gene targets (n = 41) were altered with a high level of reproducibility in at least 9 donors, gene responses that correlated well with literature-reported mechanism of action. Filtering responses to the level of gene subsets clarified the biological impact associated with the respective chemical effectors, in lieu of substantial interindividual variation among donor responses. In these respects, the use of hierarchical clustering methods successfully grouped seven of the ten donors into chemical-specific rather than donor-specific clusters. However, at the whole-genome level, the magnitude of conserved gene expression changes among donors was surprisingly small, with fewer than 50% of the gene responses altered by a single chemical conserved in more than one donor. The use of higher level descriptors, such as those defined by the PANTHER classification system, may enable more consistent categorization of gene expression changes across individuals, as increased reproducibility was identified using this method

  6. Partial Granger causality--eliminating exogenous inputs and latent variables.

    Science.gov (United States)

    Guo, Shuixia; Seth, Anil K; Kendrick, Keith M; Zhou, Cong; Feng, Jianfeng

    2008-07-15

    Attempts to identify causal interactions in multivariable biological time series (e.g., gene data, protein data, physiological data) can be undermined by the confounding influence of environmental (exogenous) inputs. Compounding this problem, we are commonly only able to record a subset of all related variables in a system. These recorded variables are likely to be influenced by unrecorded (latent) variables. To address this problem, we introduce a novel variant of a widely used statistical measure of causality--Granger causality--that is inspired by the definition of partial correlation. Our 'partial Granger causality' measure is extensively tested with toy models, both linear and nonlinear, and is applied to experimental data: in vivo multielectrode array (MEA) local field potentials (LFPs) recorded from the inferotemporal cortex of sheep. Our results demonstrate that partial Granger causality can reveal the underlying interactions among elements in a network in the presence of exogenous inputs and latent variables in many cases where the existing conditional Granger causality fails.

  7. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  8. Lack of association of PTPN1 gene polymorphisms with type 2 ...

    Indian Academy of Sciences (India)

    2011-08-19

    Aug 19, 2011 ... Details of methods used for estimating fasting plasma glu- cose, serum insulin, serum ... Data for continuous variables were expressed as mean±SD. ..... bility gene for type 2 diabetes mellitus or obesity among Pima. Indians.

  9. The evolution of Dscam genes across the arthropods.

    Science.gov (United States)

    Armitage, Sophie A O; Freiburg, Rebecca Y; Kurtz, Joachim; Bravo, Ignacio G

    2012-04-13

    One way of creating phenotypic diversity is through alternative splicing of precursor mRNAs. A gene that has evolved a hypervariable form is Down syndrome cell adhesion molecule (Dscam-hv), which in Drosophila melanogaster can produce thousands of isoforms via mutually exclusive alternative splicing. The extracellular region of this protein is encoded by three variable exon clusters, each containing multiple exon variants. The protein is vital for neuronal wiring where the extreme variability at the somatic level is required for axonal guidance, and it plays a role in immunity where the variability has been hypothesised to relate to recognition of different antigens. Dscam-hv has been found across the Pancrustacea. Additionally, three paralogous non-hypervariable Dscam-like genes have also been described for D. melanogaster. Here we took a bioinformatics approach, building profile Hidden Markov Models to search across species for putative orthologs to the Dscam genes and for hypervariable alternatively spliced exons, and inferring the phylogenetic relationships among them. Our aims were to examine whether Dscam orthologs exist outside the Bilateria, whether the origin of Dscam-hv could lie outside the Pancrustacea, when the Dscam-like orthologs arose, how many alternatively spliced exons of each exon cluster were present in the most common recent ancestor, and how these clusters evolved. Our results suggest that the origin of Dscam genes may lie after the split between the Cnidaria and the Bilateria and supports the hypothesis that Dscam-hv originated in the common ancestor of the Pancrustacea. Our phylogeny of Dscam gene family members shows six well-supported clades: five containing Dscam-like genes and one containing all the Dscam-hv genes, a seventh clade contains arachnid putative Dscam genes. Furthermore, the exon clusters appear to have experienced different evolutionary histories. Dscam genes have undergone independent duplication events in the insects and

  10. The evolution of Dscam genes across the arthropods

    Directory of Open Access Journals (Sweden)

    Armitage Sophie AO

    2012-04-01

    Full Text Available Abstract Background One way of creating phenotypic diversity is through alternative splicing of precursor mRNAs. A gene that has evolved a hypervariable form is Down syndrome cell adhesion molecule (Dscam-hv, which in Drosophila melanogaster can produce thousands of isoforms via mutually exclusive alternative splicing. The extracellular region of this protein is encoded by three variable exon clusters, each containing multiple exon variants. The protein is vital for neuronal wiring where the extreme variability at the somatic level is required for axonal guidance, and it plays a role in immunity where the variability has been hypothesised to relate to recognition of different antigens. Dscam-hv has been found across the Pancrustacea. Additionally, three paralogous non-hypervariable Dscam-like genes have also been described for D. melanogaster. Here we took a bioinformatics approach, building profile Hidden Markov Models to search across species for putative orthologs to the Dscam genes and for hypervariable alternatively spliced exons, and inferring the phylogenetic relationships among them. Our aims were to examine whether Dscam orthologs exist outside the Bilateria, whether the origin of Dscam-hv could lie outside the Pancrustacea, when the Dscam-like orthologs arose, how many alternatively spliced exons of each exon cluster were present in the most common recent ancestor, and how these clusters evolved. Results Our results suggest that the origin of Dscam genes may lie after the split between the Cnidaria and the Bilateria and supports the hypothesis that Dscam-hv originated in the common ancestor of the Pancrustacea. Our phylogeny of Dscam gene family members shows six well-supported clades: five containing Dscam-like genes and one containing all the Dscam-hv genes, a seventh clade contains arachnid putative Dscam genes. Furthermore, the exon clusters appear to have experienced different evolutionary histories. Conclusions Dscam genes have

  11. Finding Genes for Schizophrenia

    OpenAIRE

    Åberg, Karolina

    2005-01-01

    Schizophrenia is one of our most common psychiatric diseases. It severely affects all aspects of psychological functions and results in loss of contact with reality. No cure exists and the treatments available today produce only partial relief for disease symptoms. The aim of this work is to better understand the etiology of schizophrenia by identification of candidate genes and gene pathways involved in the development of the disease. In a preliminarily study, the effects of medication and g...

  12. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A

    2009-06-01

    Full Text Available in forestry breeding. Keywords Gene regulation; chromatin; histone code hyporthesis; RNA silencing; post transcriptional gene silencing; forestry. Introduction to epigenetic phenomena Most living organisms share a vast amount of genetic information... (Rapp and Wendel, 2005). Epigenetic phenomena pervade all aspects of cell proliferation and plant development and are often in conflict with Mendelian models of genetics (Grant-Downton and Dickinson, 2005). A key element in many epigenetic effects...

  13. A longitudinal study of gene expression in healthy individuals

    Directory of Open Access Journals (Sweden)

    Tessier Michel

    2009-06-01

    Full Text Available Abstract Background The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22–55 years and > 55 years and gender. Methods Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR, as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays. Results Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with ~2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF, 95% of all samples profiled fell within 1.5–2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers. Conclusion This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated

  14. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    National Research Council Canada - National Science Library

    Adegoke, Olufemi

    2003-01-01

    The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

  15. Radiosensitivity and genes

    Energy Technology Data Exchange (ETDEWEB)

    Qiyue, Hu; Mingyue, Lun [Suzhou Medical Coll., JS (China)

    1995-07-01

    Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G{sub 1} phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM{sub 9} cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation.

  16. Radiosensitivity and genes

    International Nuclear Information System (INIS)

    Hu Qiyue; Lun Mingyue

    1995-07-01

    Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G 1 phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM 9 cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation

  17. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  18. Culture–gene coevolution of individualism–collectivism and the serotonin transporter gene

    Science.gov (United States)

    Chiao, Joan Y.; Blizinsky, Katherine D.

    2010-01-01

    Culture–gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism–collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture–gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism–collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture–gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism–collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture–gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed. PMID:19864286

  19. Culture-gene coevolution of individualism-collectivism and the serotonin transporter gene.

    Science.gov (United States)

    Chiao, Joan Y; Blizinsky, Katherine D

    2010-02-22

    Culture-gene coevolutionary theory posits that cultural values have evolved, are adaptive and influence the social and physical environments under which genetic selection operates. Here, we examined the association between cultural values of individualism-collectivism and allelic frequency of the serotonin transporter functional polymorphism (5-HTTLPR) as well as the role this culture-gene association may play in explaining global variability in prevalence of pathogens and affective disorders. We found evidence that collectivistic cultures were significantly more likely to comprise individuals carrying the short (S) allele of the 5-HTTLPR across 29 nations. Results further show that historical pathogen prevalence predicts cultural variability in individualism-collectivism owing to genetic selection of the S allele. Additionally, cultural values and frequency of S allele carriers negatively predict global prevalence of anxiety and mood disorder. Finally, mediation analyses further indicate that increased frequency of S allele carriers predicted decreased anxiety and mood disorder prevalence owing to increased collectivistic cultural values. Taken together, our findings suggest culture-gene coevolution between allelic frequency of 5-HTTLPR and cultural values of individualism-collectivism and support the notion that cultural values buffer genetically susceptible populations from increased prevalence of affective disorders. Implications of the current findings for understanding culture-gene coevolution of human brain and behaviour as well as how this coevolutionary process may contribute to global variation in pathogen prevalence and epidemiology of affective disorders, such as anxiety and depression, are discussed.

  20. 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.

  1. Variable-bias coin tossing

    International Nuclear Information System (INIS)

    Colbeck, Roger; Kent, Adrian

    2006-01-01

    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

  2. Winds in cataclysmic variable stars

    International Nuclear Information System (INIS)

    Cordova, F.A.; Ladd, E.F.; Mason, K.O.

    1984-01-01

    Ultraviolet spectrophotometry of two dwarf novae, CN Ori and RX And, at various phases of their outburst cycles confirms that the far uv flux increases dramatically about 1-2 days after the optical outburst begins. At this time the uv spectral line profiles indicate the presence of a high velocity wind. The detectability of the wind depends more on the steepness of the spectrum, and thus on the flux in the extreme ultraviolet, than on the absolute value of the far uv luminosity. The uv continuum during outburst consists of (at least) two components, the most luminous of which is located behind the wind and is completely absorbed by the wind at the line frequencies. Several pieces of evidence suggest that the uv emission lines that are observed in many cataclysmic variables during quiescence have a different location in the binary than the wind, and are affected very little by the outburst

  3. 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.

  4. Variable flexure-based fluid filter

    Science.gov (United States)

    Brown, Steve B.; Colston, Jr., Billy W.; Marshall, Graham; Wolcott, Duane

    2007-03-13

    An apparatus and method for filtering particles from a fluid comprises a fluid inlet, a fluid outlet, a variable size passage between the fluid inlet and the fluid outlet, and means for adjusting the size of the variable size passage for filtering the particles from the fluid. An inlet fluid flow stream is introduced to a fixture with a variable size passage. The size of the variable size passage is set so that the fluid passes through the variable size passage but the particles do not pass through the variable size passage.

  5. Solar Variability Magnitudes and Timescales

    Science.gov (United States)

    Kopp, Greg

    2015-08-01

    The Sun’s net radiative output varies on timescales of minutes to many millennia. The former are directly observed as part of the on-going 37-year long total solar irradiance climate data record, while the latter are inferred from solar proxy and stellar evolution models. Since the Sun provides nearly all the energy driving the Earth’s climate system, changes in the sunlight reaching our planet can have - and have had - significant impacts on life and civilizations.Total solar irradiance has been measured from space since 1978 by a series of overlapping instruments. These have shown changes in the spatially- and spectrally-integrated radiant energy at the top of the Earth’s atmosphere from timescales as short as minutes to as long as a solar cycle. The Sun’s ~0.01% variations over a few minutes are caused by the superposition of convection and oscillations, and even occasionally by a large flare. Over days to weeks, changing surface activity affects solar brightness at the ~0.1% level. The 11-year solar cycle has comparable irradiance variations with peaks near solar maxima.Secular variations are harder to discern, being limited by instrument stability and the relatively short duration of the space-borne record. Proxy models of the Sun based on cosmogenic isotope records and inferred from Earth climate signatures indicate solar brightness changes over decades to millennia, although the magnitude of these variations depends on many assumptions. Stellar evolution affects yet longer timescales and is responsible for the greatest solar variabilities.In this talk I will summarize the Sun’s variability magnitudes over different temporal ranges, showing examples relevant for climate studies as well as detections of exo-solar planets transiting Sun-like stars.

  6. Alteration of gene expression by alcohol exposure at early neurulation.

    Science.gov (United States)

    Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

    2011-02-21

    We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube

  7. Identification of Phosphoglycerate Kinase 1 (PGK1 as a reference gene for quantitative gene expression measurements in human blood RNA

    Directory of Open Access Journals (Sweden)

    Unger Elizabeth R

    2011-09-01

    Full Text Available Abstract Background Blood is a convenient sample and increasingly used for quantitative gene expression measurements with a variety of diseases including chronic fatigue syndrome (CFS. Quantitative gene expression measurements require normalization of target genes to reference genes that are stable and independent from variables being tested in the experiment. Because there are no genes that are useful for all situations, reference gene selection is an essential step to any quantitative reverse transcription-PCR protocol. Many publications have described appropriate genes for a wide variety of tissues and experimental conditions, however, reference genes that may be suitable for the analysis of CFS, or human blood RNA derived from whole blood as well as isolated peripheral blood mononuclear cells (PBMCs, have not been described. Findings Literature review and analyses of our unpublished microarray data were used to narrow down the pool of candidate reference genes to six. We assayed whole blood RNA from Tempus tubes and cell preparation tube (CPT-collected PBMC RNA from 46 subjects, and used the geNorm and NormFinder algorithms to select the most stable reference genes. Phosphoglycerate kinase 1 (PGK1 was one of the optimal normalization genes for both whole blood and PBMC RNA, however, additional genes differed for the two sample types; Ribosomal protein large, P0 (RPLP0 for PBMC RNA and Peptidylprolyl isomerase B (PPIB for whole blood RNA. We also show that the use of a single reference gene is sufficient for normalization when the most stable candidates are used. Conclusions We have identified PGK1 as a stable reference gene for use with whole blood RNA and RNA derived from PBMC. When stable genes are selected it is possible to use a single gene for normalization rather than two or three. Optimal normalization will improve the ability of results from PBMC RNA to be compared with those from whole blood RNA and potentially allows comparison of

  8. Clinical Trials With Large Numbers of Variables: Important Advantages of Canonical Analysis.

    Science.gov (United States)

    Cleophas, Ton J

    2016-01-01

    Canonical analysis assesses the combined effects of a set of predictor variables on a set of outcome variables, but it is little used in clinical trials despite the omnipresence of multiple variables. The aim of this study was to assess the performance of canonical analysis as compared with traditional multivariate methods using multivariate analysis of covariance (MANCOVA). As an example, a simulated data file with 12 gene expression levels and 4 drug efficacy scores was used. The correlation coefficient between the 12 predictor and 4 outcome variables was 0.87 (P = 0.0001) meaning that 76% of the variability in the outcome variables was explained by the 12 covariates. Repeated testing after the removal of 5 unimportant predictor and 1 outcome variable produced virtually the same overall result. The MANCOVA identified identical unimportant variables, but it was unable to provide overall statistics. (1) Canonical analysis is remarkable, because it can handle many more variables than traditional multivariate methods such as MANCOVA can. (2) At the same time, it accounts for the relative importance of the separate variables, their interactions and differences in units. (3) Canonical analysis provides overall statistics of the effects of sets of variables, whereas traditional multivariate methods only provide the statistics of the separate variables. (4) Unlike other methods for combining the effects of multiple variables such as factor analysis/partial least squares, canonical analysis is scientifically entirely rigorous. (5) Limitations include that it is less flexible than factor analysis/partial least squares, because only 2 sets of variables are used and because multiple solutions instead of one is offered. We do hope that this article will stimulate clinical investigators to start using this remarkable method.

  9. Variabilidad anatómica de los sistemas de conducción y estomático de genotipos de Prunus spp. de diferentes orígenes Anatomical variability of water conduction and stomatal systems in genotypes of Prunus spp. of different origins

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Núñez-Colín

    2006-02-01

    Full Text Available El propósito de esta investigación fue estudiar las relaciones ambientales de disponibilidad de humedad, con las características anatómicas del sistema de conducción de agua y estomático, en cinco genotipos de duraznos mexicanos con diferentes orígenes (Jalatzingo y Misantla, Veracruz; Temascaltepec, México; Tulancingo, Oaxaca; Sombrerete, Zacatecas, un almendro y el portainjerto Nemaguard. Fueron caracterizados anatómicamente brotes, hojas y estomas de plántulas de seis meses de edad, mediante 25 caracteres. El almendro y el portainjerto Nemaguard presentaron diferencias con respecto a los duraznos, los cuales tuvieron mayor similitud, aunque mantuvieron una separación acorde con su origen. Los caracteres que diferenciaron los grupos fueron: densidad estomática, grosor de la epidermis superior, número, frecuencia y perímetro de vasos, el índice de vulnerabilidad de la nervadura central, y el porcentaje de médula, xilema y floema del brote. Las condiciones de disponibilidad de humedad del origen presentaron fuerte asociación con las características anatómicas estudiadas, debido a que los ambientes con mayor déficit de humedad (Tulancingo y Sombrerete presentaron mayor tamaño y menor frecuencia de vasos de xilema, así como bajo porcentaje de xilema y floema en brote, lo que puede interpretarse como adaptaciones de resistencia a sequía. La zona donde es rara la ocurrencia de sequía (Jalatzingo presentó características opuestas.The aim of this research was to study the relationships between environmental humidity availability and the anatomical characteristics of water conduction and stomatal systems, in five Mexican peach genotypes with different origins (Jalatzingo and Misantla, Veracruz; Temascaltepec, México; Tulancingo, Oaxaca; Sombrerete, Zacatecas, one almond and Nemaguard rootstock. Shoots, leaves and stomata of six months old plants were anatomically characterized by means of 25 characters. The almond tree and

  10. Mononucleotide repeats are asymmetrically distributed in fungal genes

    NARCIS (Netherlands)

    Passel, van M.W.J.; Graaff, de L.H.

    2008-01-01

    ABSTRACT: BACKGROUND: Systematic analyses of sequence features have resulted in a better characterisation of the organisation of the genome. A previous study in prokaryotes on the distribution of sequence repeats, which are notoriously variable and can disrupt the reading frame in genes, showed that

  11. Human cytomegalovirus UL145 gene is highly conserved among ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    capable of causing infections that persist lifelong, and normally ... 1 Virus Laboratory, Affiliated ShengJing Hospital, China Medical University, Shenyang 110004, P. R. China. 2Department of .... Elmer, USA), and negative controls were included in each round of .... variability of the UL145 gene in field isolates. To answer this.

  12. Regulation of the cytochrome P450 2A genes

    International Nuclear Information System (INIS)

    Su Ting; Ding Xinxin

    2004-01-01

    Cytochrome P450 monooxygenases of the CYP2A subfamily play important roles in xenobiotic disposition in the liver and in metabolic activation in extrahepatic tissues. Many of the CYP2A transcripts and enzymes are inducible by xenobiotic compounds, and the expression of at least some of the CYP2A genes is influenced by physiological status, such as circadian rhythm, and pathological conditions, such as inflammation, microbial infection, and tumorigenesis. Variability in the expression of the CYP2A genes, which differs by species, animal strain, gender, and organ, may alter the risks of chemical toxicity for numerous compounds that are CYP2A substrates. The mechanistic bases of these variabilities are generally not well understood. However, recent studies have yielded interesting findings in several areas, such as the role of nuclear factor 1 in the tissue-selective expression of CYP2A genes in the olfactory mucosa (OM); the roles of constitutive androstane receptor, pregnane X receptor (PXR), and possibly, peroxisome proliferator-activated receptors in transcriptional regulation of the Cyp2a5 gene; and the involvement of heterogeneous nuclear ribonucleoprotein A1 in pyrazole-induced stabilization of CYP2A5 mRNA. The aims of this minireview are to summarize current knowledge of the regulation of the CYP2A genes in rodents and humans, and to stimulate further mechanistic studies that will ultimately improve our ability to determine, and to understand, these variabilities in humans

  13. Expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori

    NARCIS (Netherlands)

    Joosten, V.; Gouka, R.J.; Hondel, C.A.M.J.J. van den; Verrips, C.T.; Lokman, B.C.

    2005-01-01

    We report the expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori. Fragments encoding VHHs were cloned in a suitable Aspergillus expression vector and transformants secreting VHH fragments were analysed for integrated gene copy-numbers, mRNA

  14. A Bayesian Hierarchical Model for Relating Multiple SNPs within Multiple Genes to Disease Risk

    Directory of Open Access Journals (Sweden)

    Lewei Duan

    2013-01-01

    Full Text Available A variety of methods have been proposed for studying the association of multiple genes thought to be involved in a common pathway for a particular disease. Here, we present an extension of a Bayesian hierarchical modeling strategy that allows for multiple SNPs within each gene, with external prior information at either the SNP or gene level. The model involves variable selection at the SNP level through latent indicator variables and Bayesian shrinkage at the gene level towards a prior mean vector and covariance matrix that depend on external information. The entire model is fitted using Markov chain Monte Carlo methods. Simulation studies show that the approach is capable of recovering many of the truly causal SNPs and genes, depending upon their frequency and size of their effects. The method is applied to data on 504 SNPs in 38 candidate genes involved in DNA damage response in the WECARE study of second breast cancers in relation to radiotherapy exposure.

  15. The role of IL-4 gene 70 bp VNTR and ACE gene I/D variants in Familial Mediterranean fever.

    Science.gov (United States)

    Yigit, Serbülent; Tural, Sengul; Tekcan, Akın; Tasliyurt, Turker; Inanir, Ahmet; Uzunkaya, Süheyla; Kismali, Gorkem

    2014-05-01

    Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (pACE gene DD genotype was associated with an increased risk in FMF [pACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (pACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Unstable Expression of Commonly Used Reference Genes in Rat Pancreatic Islets Early after Isolation Affects Results of Gene Expression Studies.

    Directory of Open Access Journals (Sweden)

    Lucie Kosinová

    Full Text Available The use of RT-qPCR provides a powerful tool for gene expression studies; however, the proper interpretation of the obtained data is crucially dependent on accurate normalization based on stable reference genes. Recently, strong evidence has been shown indicating that the expression of many commonly used reference genes may vary significantly due to diverse experimental conditions. The isolation of pancreatic islets is a complicated procedure which creates severe mechanical and metabolic stress leading possibly to cellular damage and alteration of gene expression. Despite of this, freshly isolated islets frequently serve as a control in various gene expression and intervention studies. The aim of our study was to determine expression of 16 candidate reference genes and one gene of interest (F3 in isolated rat pancreatic islets during short-term cultivation in order to find a suitable endogenous control for gene expression studies. We compared the expression stability of the most commonly used reference genes and evaluated the reliability of relative and absolute quantification using RT-qPCR during 0-120 hrs after isolation. In freshly isolated islets, the expression of all tested genes was markedly depressed and it increased several times throughout the first 48 hrs of cultivation. We observed significant variability among samples at 0 and 24 hrs but substantial stabilization from 48 hrs onwards. During the first 48 hrs, relative quantification failed to reflect the real changes in respective mRNA concentrations while in the interval 48-120 hrs, the relative expression generally paralleled the results determined by absolute quantification. Thus, our data call into question the suitability of relative quantification for gene expression analysis in pancreatic islets during the first 48 hrs of cultivation, as the results may be significantly affected by unstable expression of reference genes. However, this method could provide reliable information

  17. Amino acid metabolic signaling influences Aedes aegypti midgut microbiome variability.

    Directory of Open Access Journals (Sweden)

    Sarah M Short

    2017-07-01

    Full Text Available The mosquito midgut microbiota has been shown to influence vector competence for multiple human pathogens. The microbiota is highly variable in the field, and the sources of this variability are not well understood, which limits our ability to understand or predict its effects on pathogen transmission. In this work, we report significant variation in female adult midgut bacterial load between strains of A. aegypti which vary in their susceptibility to dengue virus. Composition of the midgut microbiome was similar overall between the strains, with 81-92% of reads coming from the same five bacterial families, though we did detect differences in the presence of some bacterial families including Flavobacteriaceae and Entobacteriaceae. We conducted transcriptomic analysis on the two mosquito strains that showed the greatest difference in bacterial load, and found that they differ in transcript abundance of many genes implicated in amino acid metabolism, in particular the branched chain amino acid degradation pathway. We then silenced this pathway by targeting multiple genes using RNA interference, which resulted in strain-specific bacterial proliferation, thereby eliminating the difference in midgut bacterial load between the strains. This suggests that the branched chain amino acid (BCAA degradation pathway controls midgut bacterial load, though the mechanism underlying this remains unclear. Overall, our results indicate that amino acid metabolism can act to influence the midgut microbiota. Moreover, they suggest that genetic or physiological variation in BCAA degradation pathway activity may in part explain midgut microbiota variation in the field.

  18. Complex single gene disorders and epilepsy.

    LENUS (Irish Health Repository)

    Merwick, Aine

    2012-09-01

    Epilepsy is a heterogeneous group of disorders, often associated with significant comorbidity, such as intellectual disability and skin disorder. The genetic underpinnings of many epilepsies are still being elucidated, and we expect further advances over the coming 5 years, as genetic technology improves and prices fall for whole exome and whole genome sequencing. At present, there are several well-characterized complex epilepsies associated with single gene disorders; we review some of these here. They include well-recognized syndromes such as tuberous sclerosis complex, epilepsy associated with Rett syndrome, some of the progressive myoclonic epilepsies, and novel disorders such as epilepsy associated with mutations in the PCDH 19 gene. These disorders are important in informing genetic testing to confirm a diagnosis and to permit better understanding of the variability in phenotype-genotype correlation.

  19. Compact Spectrometers Based on Linear Variable Filters

    Data.gov (United States)

    National Aeronautics and Space Administration — Demonstrate a linear-variable spectrometer with an H2RG array. Linear Variable Filter (LVF) spectrometers provide attractive resource benefits – high optical...

  20. Eternity Variables to Prove Simulation of Specifications

    NARCIS (Netherlands)

    Hesselink, Wim H.

    2005-01-01

    Simulations of specifications are introduced as a unification and generalization of refinement mappings, history variables, forward simulations, prophecy variables, and backward simulations. A specification implements another specification if and only if there is a simulation from the first one to