WorldWideScience

Sample records for alleles determine responsiveness

  1. Determination of allele frequencies in nine short tandem repeat loci ...

    African Journals Online (AJOL)

    Determination of allele frequencies in nine short tandem repeat loci of five human sub-populations in Botswana. ... use in individual identification. ... Targeted regions of DNA (vWA, FGA, D3S1358, D5S818, D7S820, D8S1179, D13S317, D18S51, D21S11 and the sex determining locus Amelogenin) were amplified using ...

  2. Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.

    LENUS (Irish Health Repository)

    Fang, Fang

    2009-09-01

    Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.

  3. Allelic polymorphism of GIGANTEA is responsible for naturally occurring variation in circadian period in Brassica rapa.

    Science.gov (United States)

    Xie, Qiguang; Lou, Ping; Hermand, Victor; Aman, Rashid; Park, Hee Jin; Yun, Dae-Jin; Kim, Woe Yeon; Salmela, Matti Juhani; Ewers, Brent E; Weinig, Cynthia; Khan, Sarah L; Schaible, D Loring P; McClung, C Robertson

    2015-03-24

    GIGANTEA (GI) was originally identified by a late-flowering mutant in Arabidopsis, but subsequently has been shown to act in circadian period determination, light inhibition of hypocotyl elongation, and responses to multiple abiotic stresses, including tolerance to high salt and cold (freezing) temperature. Genetic mapping and analysis of families of heterogeneous inbred lines showed that natural variation in GI is responsible for a major quantitative trait locus in circadian period in Brassica rapa. We confirmed this conclusion by transgenic rescue of an Arabidopsis gi-201 loss of function mutant. The two B. rapa GI alleles each fully rescued the delayed flowering of Arabidopsis gi-201 but showed differential rescue of perturbations in red light inhibition of hypocotyl elongation and altered cold and salt tolerance. The B. rapa R500 GI allele, which failed to rescue the hypocotyl and abiotic stress phenotypes, disrupted circadian period determination in Arabidopsis. Analysis of chimeric B. rapa GI alleles identified the causal nucleotide polymorphism, which results in an amino acid substitution (S264A) between the two GI proteins. This polymorphism underlies variation in circadian period, cold and salt tolerance, and red light inhibition of hypocotyl elongation. Loss-of-function mutations of B. rapa GI confer delayed flowering, perturbed circadian rhythms in leaf movement, and increased freezing and increased salt tolerance, consistent with effects of similar mutations in Arabidopsis. Collectively, these data suggest that allelic variation of GI-and possibly of clock genes in general-offers an attractive target for molecular breeding for enhanced stress tolerance and potentially for improved crop yield.

  4. Immunization with different PfAMA1 alleles in sequence induces clonal imprint humoral responses that are similar to responses induced by the same alleles as a vaccine cocktail in rabbits

    Directory of Open Access Journals (Sweden)

    Thomas Alan W

    2011-02-01

    Full Text Available Abstract Background Antibodies to key Plasmodium falciparum surface antigens have been shown to be important effectors that mediate clinical immunity to malaria. The cross-strain fraction of anti-malarial antibodies may however be required to achieve strain-transcending immunity. Such antibody responses against Plasmodium falciparum apical membrane antigen 1 (PfAMA1, a vaccine target molecule that is expressed in both liver and blood stages of the parasite, can be elicited through immunization with a mixture of allelic variants of the parasite molecule. Cross-strain antibodies are most likely elicited against epitopes that are shared by the allelic antigens in the vaccine cocktail. Methods A standard competition ELISA was used to address whether the antibody response can be further focused on shared epitopes by exclusively boosting these common determinants through immunization of rabbits with different PfAMA1 alleles in sequence. The in vitro parasite growth inhibition assay was used to further evaluate the functional effects of the broadened antibody response that is characteristic of multi-allele vaccine strategies. Results A mixed antigen immunization protocol elicited humoral responses that were functionally similar to those elicited by a sequential immunization protocol (p > 0.05. Sequential exposure to the different PfAMA1 allelic variants induced immunological recall of responses to previous alleles and yielded functional cross-strain antibodies that would be capable of optimal growth inhibition of variant parasites at high enough concentrations. Conclusions These findings may have implications for the current understanding of the natural acquisition of clinical immunity to malaria as well as for rational vaccine design.

  5. SIMPLIFYING CELIAC DISEASE PREDISPOSING HLA-DQ ALLELES DETERMINATION BY THE REAL TIME PCR METHOD

    Directory of Open Access Journals (Sweden)

    Nicole SELLESKI

    2015-06-01

    Full Text Available Background Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Genetic susceptibility is associated with two sets of alleles, DQA1*05 - DQB1*02 and DQA1*03 - DQB1*03:02, which code for class II MHC DQ2 and DQ8 molecules, respectively. Approximately 90%-95% of celiac patients are HLA-DQ2 positive, and half of the remaining patients are HLA-DQ8 positive. In fact, during a celiac disease diagnostic workup, the absence of these specific DQA and DQB alleles has a near perfect negative predictive value. Objective Improve the detection of celiac disease predisposing alleles by combining the simplicity and sensitivity of real-time PCR (qPCR and melting curve analysis with the specificity of sequence-specific primers (SSP. Methods Amplifications of sequence-specific primers for DQA1*05 (DQ2, DQB1*02 (DQ2, and DQA1*03 (DQ8 were performed by the real time PCR method to determine the presence of each allele in independent reactions. Primers for Human Growth Hormone were used as an internal control. A parallel PCR-SSP protocol was used as a reference method to validate our results. Results Both techniques yielded equal results. From a total of 329 samples the presence of HLA predisposing alleles was determined in 187 (56.8%. One hundred fourteen samples (61% were positive for a single allele, 68 (36.3% for two alleles, and only 5 (2.7% for three alleles. Conclusion Results obtained by qPCR technique were highly reliable with no discordant results when compared with those obtained using PCR-SSP.

  6. Determining the frequencies of B1, B2, B3 and E alleles of the ...

    African Journals Online (AJOL)

    Ada

    2016-06-04

    Jun 4, 2016 ... AN, and AF) in Alpine, Saanen and Toggenburg goats (Vázquez-Flores et al., 2012). Despite the number of studies that determined the frequency of CSN1S1 alleles, investigations into the effects of the CSN1S1 gene on milk yield and composition are limited. Furthermore, there is no published information ...

  7. Allelic determinants of vitamin d insufficiency, bone mineral density, and bone fractures.

    Science.gov (United States)

    Trummer, Olivia; Schwetz, Verena; Walter-Finell, Daniela; Lerchbaum, Elisabeth; Renner, Wilfried; Gugatschka, Markus; Dobnig, Harald; Pieber, Thomas R; Obermayer-Pietsch, Barbara

    2012-07-01

    Low 25-hydroxycholecalciferol [25(OH) vitamin D] status is known to play an important role in many diseases with focus on bone health. Based on recently reported genetic determinants of vitamin D insufficiency, we aimed to analyze genetic variants of group-specific component (GC), 7-dehydrocholesterol reductase (DHCR7), and cytochrome P450IIR-1 (CYP2R1) for association with vitamin D levels, bone mineral density (BMD), and bone fractures. We conducted a cross-sectional BMD and fracture study and a prospective cohort study. The cross-sectional study comprised participants of a BMD screening study, and the prospective cohort study comprised nursing home subjects. The cross-sectional study included 342 subjects (mean age, 55.3 ± 12.0 yr), and the prospective study included 1093 subjects (mean age, 84.0 ± 6.0 yr). Patients were stratified by GC, DHCR7, and CYP2R1 genotypes. For each gene, the allele associated with lower 25(OH) vitamin D levels was designated as "risk allele." The potential role of these risk alleles in fracture risk was analyzed by logistic regression analysis including age and sex as confounders. We measured BMD and fractures. GC genotypes were significantly associated with lower mean 25(OH) vitamin D levels in both cohorts (P = 0.001 and P = 0.048, respectively). There was no significant association of BMD with any of the genotypes. None of the alleles was associated with past fractures, whereas the DHCR7 G-allele was significantly associated with prospective fractures (odds ratio, 0.68; 95% confidence interval, 0.51-0.92; P = 0.011). The DHCR7 gene polymorphism may be a predictor for fracture risk.

  8. Reward Region Responsivity Predicts Future Weight Gain and Moderating Effects of the TaqIA Allele.

    Science.gov (United States)

    Stice, Eric; Burger, Kyle S; Yokum, Sonja

    2015-07-15

    Because no large prospective study has investigated neural vulnerability factors that predict future weight gain, we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over a 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. A total of 153 adolescents completed fMRI paradigms assessing response to these events; body fat was assessed annually over follow-up. Elevated orbitofrontal cortex response to cues signaling impending milkshake receipt predicted future body fat gain (r = 0.32), which is a novel finding that provides support for the incentive sensitization theory of obesity. Neural response to receipt and anticipated receipt of monetary reward did not predict body fat gain, which has not been tested previously. Replicating an earlier finding (Stice et al., 2008a), elevated caudate response to milkshake receipt predicted body fat gain for adolescents with a genetic propensity for greater dopamine signaling by virtue of possessing the TaqIA A2/A2 allele, but lower caudate response predicted body fat gain for adolescents with a genetic propensity for less dopamine signaling by virtue of possessing a TaqIA A1 allele, though this interaction was only marginal [p-value monetary reward predicted body fat gain over 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. Elevated reward activation in response to food cues predicted future body fat gain. Elevated reward response to food receipt predicted body fat gain for adolescents with a TaqIA A2/A2 allele and lower reward response predicted body fat gain for those with a TaqIA A1 allele. Results imply that too much or too little dopamine signaling and reward region responsivity increases risk for overeating. Copyright © 2015 the authors 0270-6474/15/3510316-09$15.00/0.

  9. An improved assay for the determination of Huntington`s disease allele size

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, C.; Klinger, K.; Miller, G. [Intergrated Genetics, Framingham, MA (United States)

    1994-09-01

    The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra- or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.

  10. Determining the frequencies of B1, B2, B3 and E alleles of the ...

    African Journals Online (AJOL)

    The allelic frequencies of the B1, B2, B3 and E alleles were 0.927, 0.073, 0.390, and 0.272, respectively. B1 and B2 alleles did not affect milk yield and composition. B3 allele had significant effects on protein, fat, total solid (TS), solid not fat (SNF), casein and lactose percentages, but not on lactose yield. E allele significantly ...

  11. Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Mary Anna Carbone

    Full Text Available The statistical power of genome-wide association (GWA studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG. Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR upon overexpression of transgenic human glaucoma-associated myocilin (MYOC. We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

  12. Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

    Science.gov (United States)

    Carbone, Mary Anna; Chen, Yuhong; Hughes, Guy A; Weinreb, Robert N; Zabriskie, Norman A; Zhang, Kang; Anholt, Robert R H

    2011-01-01

    The statistical power of genome-wide association (GWA) studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG). Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG) remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR) upon overexpression of transgenic human glaucoma-associated myocilin (MYOC). We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

  13. Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine.

    Science.gov (United States)

    Olkhovych, N V; Gorovenko, N G

    2016-01-01

    The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W) and c.745C>T (R249W) in the HEXA gene, c.1726G>A (G576S) and c.2065G>A (E689K) in the GAA gene, c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease). The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes) was 10.3%. The frequency of c.739C>T (R247W) allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes) was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of pseudodeficiency may

  14. Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine

    Directory of Open Access Journals (Sweden)

    N. V. Olkhovych

    2016-10-01

    Full Text Available The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W and c.745C>T (R249W in the HEXA gene, c.1726G>A (G576S and c.2065G>A (E689K in the GAA gene, c.937G>T (D313Y in the GLA1 gene and c.898G>A (A300T in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease. The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes was 10.3%. The frequency of c.739C>T (R247W allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y in the GLA1 gene and c.898G>A (A300T in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of

  15. Effects of antibiotic resistance alleles on bacterial evolutionary responses to viral parasites.

    Science.gov (United States)

    Arias-Sánchez, Flor I; Hall, Alex R

    2016-05-01

    Antibiotic resistance has wide-ranging effects on bacterial phenotypes and evolution. However, the influence of antibiotic resistance on bacterial responses to parasitic viruses remains unclear, despite the ubiquity of such viruses in nature and current interest in therapeutic applications. We experimentally investigated this by exposing various Escherichia coli genotypes, including eight antibiotic-resistant genotypes and a mutator, to different viruses (lytic bacteriophages). Across 960 populations, we measured changes in population density and sensitivity to viruses, and tested whether variation among bacterial genotypes was explained by their relative growth in the absence of parasites, or mutation rate towards phage resistance measured by fluctuation tests for each phage. We found that antibiotic resistance had relatively weak effects on adaptation to phages, although some antibiotic-resistance alleles impeded the evolution of resistance to phages via growth costs. By contrast, a mutator allele, often found in antibiotic-resistant lineages in pathogenic populations, had a relatively large positive effect on phage-resistance evolution and population density under parasitism. This suggests costs of antibiotic resistance may modify the outcome of phage therapy against pathogenic populations previously exposed to antibiotics, but the effects of any co-occurring mutator alleles are likely to be stronger. © 2016 The Authors.

  16. Root biomass response to foliar application of imazapyr for two imidazolinone tolerant alleles of sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Sala, Carlos A; Bulos, Mariano; Altieri, Emiliano; Ramos, María Laura

    2012-09-01

    Imisun and CLPlus are two imidazolinone tolerance traits in sunflower (Helianthus annuus L.) determined by the expression of two alleles at the locus Ahasl1. Both traits differed in their tolerance level to imazapyr -a type of imidazolinone herbicide- when aboveground biomass is considered, but the concomitant herbicide effect over the root system has not been reported. The objective of this work was to quantify the root biomass response to increased doses of imazapyr in susceptible (ahasl1/ahasl1), Imisun (Ahasl1-1/Ahasl1-1) and CLPlus (Ahasl1-3/Ahasl1-3) homozygous sunflower genotypes. These materials were sprayed at the V2-V4 stage with increased doses of imazapyr (from 0 to 480 g active ingredient ha(-1)) and 14 days after treatment root biomass of each plant was assessed. Genotype at the Ahasl1 locus, dose of imazapyr and their interaction significantly contributed (P < 0.001) to explain the reduction in root biomass accumulation after herbicide application. Estimated dose of imazapyr required to reduce root biomass accumulation by fifty percent (GR(50)) differed statistically for the three genotypes under study (P < 0.001). CLPlus genotypes showed the highest values of GR(50), 300 times higher on average than the susceptible genotypes, and almost 8 times higher than Imisun materials, demonstrating that both alleles differ in their root biomass response to foliar application of increased doses of imazapyr.

  17. SNPs and real-time quantitative PCR method for constitutional allelic copy number determination, the VPREB1 marker case

    Directory of Open Access Journals (Sweden)

    Costa Elena

    2011-05-01

    Full Text Available Abstract Background 22q11.2 microdeletion is responsible for the DiGeorge Syndrome, characterized by heart defects, psychiatric disorders, endocrine and immune alterations and a 1 in 4000 live birth prevalence. Real-time quantitative PCR (qPCR approaches for allelic copy number determination have recently been investigated in 22q11.2 microdeletions detection. The qPCR method was performed for 22q11.2 microdeletions detection as a first-level screening approach in a genetically unknown series of patients with congenital heart defects. A technical issue related to the VPREB1 qPCR marker was pointed out. Methods A set of 100 unrelated Italian patients with congenital heart defects were tested for 22q11.2 microdeletions by a qPCR method using six different markers. Fluorescence In Situ Hybridization technique (FISH was used for confirmation. Results qPCR identified six patients harbouring the 22q11.2 microdeletion, confirmed by FISH. The VPREB1 gene marker presented with a pattern consistent with hemideletion in one 3 Mb deleted patient, suggestive for a long distal deletion, and in additional five non-deleted patients. The long distal 22q11.2 deletion was not confirmed by Comparative Genomic Hybridization. Indeed, the VPREB1 gene marker generated false positive results in association with the rs1320 G/A SNP, a polymorphism localized within the VPREB1 marker reverse primer sequence. Patients heterozygous for rs1320 SNP, showed a qPCR profile consistent with the presence of a hemideletion. Conclusions Though the qPCR technique showed advantages as a screening approach in terms of cost and time, the VPREB1 marker case revealed that single nucleotide polymorphisms can interfere with qPCR data generating erroneous allelic copy number interpretations.

  18. Performance of Molecular Inversion Probes (MIP) in Allele CopyNumber Determination

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuker; Moorhead, Martin; Karlin-Neumann, George; Wang,Nicolas J.; Ireland, James; Lin, Steven; Chen, Chunnuan; Heiser, LauraM.; Chin, Koei; Esserman, Laura; Gray, Joe W.; Spellman, Paul T.; Faham,Malek

    2007-05-14

    We have developed a new protocol for using MolecularInversion Probes (MIP) to accurately and specifically measure allele copynumber (ACN). The new protocol provides for significant improvementsincluding the reduction of input DNA (from 2?g) by more than 25 fold (to75ng total genomic DNA), higher overall precision resulting in one orderof magnitude lower false positive rate, and greater dynamic range withaccurate absolute copy number up to 60 copies.

  19. Killer Immunoglobulin-Like Receptor Allele Determination Using Next-Generation Sequencing Technology

    Directory of Open Access Journals (Sweden)

    Bercelin Maniangou

    2017-05-01

    Full Text Available The impact of natural killer (NK cell alloreactivity on hematopoietic stem cell transplantation (HSCT outcome is still debated due to the complexity of graft parameters, HLA class I environment, the nature of killer cell immunoglobulin-like receptor (KIR/KIR ligand genetic combinations studied, and KIR+ NK cell repertoire size. KIR genes are known to be polymorphic in terms of gene content, copy number variation, and number of alleles. These allelic polymorphisms may impact both the phenotype and function of KIR+ NK cells. We, therefore, speculate that polymorphisms may alter donor KIR+ NK cell phenotype/function thus modulating post-HSCT KIR+ NK cell alloreactivity. To investigate KIR allele polymorphisms of all KIR genes, we developed a next-generation sequencing (NGS technology on a MiSeq platform. To ensure the reliability and specificity of our method, genomic DNA from well-characterized cell lines were used; high-resolution KIR typing results obtained were then compared to those previously reported. Two different bioinformatic pipelines were used allowing the attribution of sequencing reads to specific KIR genes and the assignment of KIR alleles for each KIR gene. Our results demonstrated successful long-range KIR gene amplifications of all reference samples using intergenic KIR primers. The alignment of reads to the human genome reference (hg19 using BiRD pipeline or visualization of data using Profiler software demonstrated that all KIR genes were completely sequenced with a sufficient read depth (mean 317× for all loci and a high percentage of mapping (mean 93% for all loci. Comparison of high-resolution KIR typing obtained to those published data using exome capture resulted in a reported concordance rate of 95% for centromeric and telomeric KIR genes. Overall, our results suggest that NGS can be used to investigate the broad KIR allelic polymorphism. Hence, these data improve our knowledge, not only on KIR+ NK cell alloreactivity in

  20. Response to imazapyr and dominance relationships of two imidazolinone-tolerant alleles at the Ahasl1 locus of sunflower.

    Science.gov (United States)

    Sala, Carlos A; Bulos, Mariano; Altieri, Emiliano; Weston, Brigitte

    2012-02-01

    Imisun and CLPlus are two imidazolinone (IMI) tolerance traits in sunflower (Helianthus annuus L.) determined by the expression of different alleles at the same locus, Ahasl1-1 and Ahasl1-3, respectively. This paper reports the level of tolerance expressed by plants containing both alleles in a homozygous, heterozygous and in a heterozygous stacked state to increasing doses of IMI at the enzyme and whole plant levels. Six genotypes of the Ahasl1 gene were compared with each other in three different genetic backgrounds. These materials were treated at the V2-V4 stage with increasing doses of imazapyr (from 0 to 480 g a.i. ha(-1)) followed by an assessment of the aboveground biomass and herbicide phytotoxicity. The estimated dose of imazapyr required to reduce biomass accumulation by 50% (GR(50)) differed statistically for the six genotypes of the Ahasl1 gene. Homozygous CLPlus (Ahasl1-3/Ahasl1-3) genotypes and materials containing a combination of both tolerant alleles (Imisun/CLPlus heterozygous stack, Ahasl1-1/Ahasl1-3) showed the highest values of GR(50), 300 times higher than the susceptible genotypes and more than 2.5 times higher than homozygous Imisun materials (Ahasl1-1/Ahasl1-1). In vitro AHAS enzyme activity assays using increasing doses of herbicide (from 0 to 100 μM) showed similar trends, where homozygous CLPlus materials and those containing heterozygous stacks of Imisun/CLPlus were statistically similar and showed the least level of inhibition of enzyme activity to increasing doses of herbicide. The degree of dominance for the accumulation of biomass after herbicide application calculated for the Ahasl1-1 allele indicated that it is co-dominant to recessive depending on the imazapyr dose used. By the contrary, the Ahasl1-3 allele showed dominance to semi dominance according to the applied dose. This last allele is dominant over Ahasl1-1 over the entire range of herbicide rates tested. At the level of enzymatic activity, however, both alleles showed

  1. Generation time and the stability of sex-determining alleles in oyster populations as deduced using a gene-based population dynamics model.

    Science.gov (United States)

    Powell, Eric N; Klinck, John M; Hofmann, Eileen E

    2011-02-21

    Crassostrea oysters are protandrous hermaphrodites. Sex is thought to be determined by a single gene with a dominant male allele M and a recessive protandrous allele F, such that FF animals are protandrous and MF animals are permanent males. We investigate the possibility that a reduction in generation time, brought about for example by disease, might jeopardize retention of the M allele. Simulations show that MF males have a significantly lessened lifetime fecundity when generation time declines. The allele frequency of the M allele declines and eventually the M allele is lost. The probability of loss is modulated by population abundance. As abundance increases, the probability of M allele loss declines. Simulations suggest that stabilization of the female-to-male ratio when generation time is long is the dominant function of the M allele. As generation time shortens, the raison d'être for the M allele also fades as mortality usurps the stabilizing role. Disease and exploitation have shortened oyster generation time: one consequence may be to jeopardize retention of the M allele. Two alternative genetic bases for protandry also provide stable sex ratios when generation time is long; an F-dominant protandric allele and protandry restricted to the MF heterozygote. In both cases, simulations show that FF individuals become rare in the population at high abundance and/or long generation time. Protandry restricted to the MF heterozygote maintains sex ratio stability over a wider range of generation times and abundances than the alternatives, suggesting that sex determination based on a male-dominant allele (MM/MF) may not be the optimal solution to the genetic basis for protandry in Crassostrea. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Frequency of Class I and II HLA alleles in patients with lung cancer according to chemotherapy response and 5-year survival.

    Science.gov (United States)

    Araz, Omer; Ucar, Elif Yilmazel; Meral, Mehmet; Yalcin, Aslıhan; Acemoglu, Hamit; Dogan, Hasan; Karaman, Adem; Aydin, Yener; Gorguner, Metin; Akgun, Metin

    2015-07-01

    Lung cancer is the most common cause of cancer death in the world, and the most common type is non-small-cell lung cancer (NSCLC). At present, surgical resection, chemotherapy, and radiation therapy are the main treatments for patients with NSCLC, but unfortunately outcome remains unsatisfactory. This study aimed to determine whether Class I and II histocompatibility leukocyte antigen (HLA) alleles are related with response to chemotherapy and survival of lung cancer. A total of 65 NSCLC patients (56 men and 9 women, mean age 58.4 ± 11 years) were included in the study. Patient groups were compared with a control group of 88 unrelated healthy kidney or bone marrow donors in order to clearly identify susceptible and protective HLA alleles in lung cancer. Target lesions and tumor response were assessed using the Response Evaluation Criteria for Solid Tumors (RECIST) guidelines. Results were classified into two groups: complete-partial response and stable-progressive disease. We found that expression of HLA-A32, HLA-B41, HLA-B57, HLA-DRB1*13, and HLA-DQ5 were more frequent in the complete and partial response groups to chemotherapy than in the control group. The frequency of HLA-A11, HLA-A29, HLA-BW6, HLA-CW3, HLA-DR1*1, and HLA-DRB1*3 were determined to be higher in the stable and progressive disease groups taking chemotherapy than in the control group. Additionally, expressions of HLA-A2 and HLA-B49 were statistically related with 5-year survival. Our results suggested that expressions of HLA-BW6 and HLA-DRB1*13 alleles may be predictable markers for response to chemotherapy in lung cancer patients. © 2014 John Wiley & Sons Ltd.

  3. Toward fully automated genotyping: Allele assignment, pedigree construction, phase determination, and recombination detection in Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Perlin, M.W.; Burks, M.B. [Carnegie Mellon Univ., Pittsburgh, PA (United States); Hoop, R.C.; Hoffman, E.P. [Univ. of Pittsburgh School of Medicine, PA (United States)

    1994-10-01

    Human genetic maps have made quantum leaps in the past few years, because of the characterization of >2,000 CA dinucleotide repeat loci: these PCR-based markers offer extraordinarily high PIC, and within the next year their density is expected to reach intervals of a few centimorgans per marker. These new genetic maps open new avenues for disease gene research, including large-scale genotyping for both simple and complex disease loci. However, the allele patterns of many dinucleotide repeat loci can be complex and difficult to interpret, with genotyping errors a recognized problem. Furthermore, the possibility of genotyping individuals at hundreds or thousands of polymorphic loci requires improvements in data handling and analysis. The automation of genotyping and analysis of computer-derived haplotypes would remove many of the barriers preventing optimal use of dense and informative dinucleotide genetic maps. Toward this end, we have automated the allele identification, genotyping, phase determinations, and inheritance consistency checks generated by four CA repeats within the 2.5-Mbp, 10-cM X-linked dystrophin gene, using fluorescein-labeled multiplexed PCR products analyzed on automated sequencers. The described algorithms can deconvolute and resolve closely spaced alleles, despite interfering stutter noise; set phase in females; propagate the phase through the family; and identify recombination events. We show the implementation of these algorithms for the completely automated interpretation of allele data and risk assessment for five Duchenne/Becker muscular dystrophy families. The described approach can be scaled up to perform genome-based analyses with hundreds or thousands of CA-repeat loci, using multiple fluorophors on automated sequencers. 16 refs., 5 figs., 1 tab.

  4. Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations.

    Science.gov (United States)

    Hofer, D; Paul, K; Fantur, K; Beck, M; Roubergue, A; Vellodi, A; Poorthuis, B J; Michelakakis, H; Plecko, B; Paschke, E

    2010-09-01

    GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid beta-galactosidase (GLB1). In addition, allelic variants of this gene can result in Morquio B disease (MBD), a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1 gene have been identified so far, but only few could be proven to be predictive for one of the GM1 gangliosidosis subtypes or MBD. We performed genotype analyses in 16 GM1 gangliosidosis patients of all phenotypes and detected 28 different genetic lesions. Among these, p.I55FfsX16, p.W65X, p.F107L, p.H112P, p.C127Y, p.W161X, p.I181K, p.C230R, p.W273X, p.R299VfsX5, p.A301V, p.F357L, p.K359KfsX23, p.L389P, p.D448V, p.D448GfsX8, and the intronic mutation IVS6-8A>G have not been published so far. Due to their occurrence in homozygous patients, four mutations could be correlated to a distinct GM1 gangliosidosis phenotype. Furthermore, the missense mutations from heteroallelic patients and three artificial nonsense mutations were characterized by overexpression in COS-1 cells, and the subcellular localization of the mutant proteins in fibroblasts was assessed. The phenotype specificity of 10 alleles can be proposed on the basis of our results and previous data.

  5. Allelic variation in two distinct Pseudomonas syringae flagellin epitopes modulates the strength of plant immune responses but not bacterial motility

    Science.gov (United States)

    Clarke, Christopher R.; Chinchilla, Delphine; Hind, Sarah R.; Taguchi, Fumiko; Miki, Ryuji; Ichinose, Yuki; Martin, Gregory B.; Leman, Scotland; Felix, Georg; Vinatzer, Boris A.

    2013-01-01

    Summary The bacterial flagellin (FliC) epitopes flg22 and flgII-28 are microbe-associated molecular patterns (MAMPs). While flg22 is recognized by many plant species via the pattern recognition receptor FLS2, neither the flgII-28 receptor nor the extent of flgII-28 recognition by different plant families is known.Here we tested the significance of flgII-28 as a MAMP and the importance of allelic diversity in flg22 and flgII-28 in plant–pathogen interactions using purified peptides and a Pseudomonas syringae ΔfliC mutant complemented with different fliC alleles.Plant genotype and allelic diversity in flg22 and flgII-28 were found to significantly affect the plant immune response but not bacterial motility. Recognition of flgII-28 is restricted to a number of Solanaceous species. While the flgII-28 peptide does not trigger any immune response in Arabidopsis, mutations in both flg22 and flgII-28 have FLS2-dependent effects on virulence. However, expression of a tomato allele of FLS2 does not confer to Nicotiana benthamiana the ability to detect flgII-28 and tomato plants silenced for FLS2 are not altered in flgII-28 recognition.Therefore, MAMP diversification is an effective pathogen virulence strategy and flgII-28 appears to be perceived by a yet unidentified receptor in the Solanaceae although it has an FLS2-dependent virulence effect in Arabidopsis. PMID:23865782

  6. Natural allelic variation defines a role for ATMYC1: trichome cell fate determination.

    Directory of Open Access Journals (Sweden)

    V Vaughan Symonds

    2011-06-01

    Full Text Available The molecular nature of biological variation is not well understood. Indeed, many questions persist regarding the types of molecular changes and the classes of genes that underlie morphological variation within and among species. Here we have taken a candidate gene approach based on previous mapping results to identify the gene and ultimately a polymorphism that underlies a trichome density QTL in Arabidopsis thaliana. Our results show that natural allelic variation in the transcription factor ATMYC1 alters trichome density in A. thaliana; this is the first reported function for ATMYC1. Using site-directed mutagenesis and yeast two-hybrid experiments, we demonstrate that a single amino acid replacement in ATMYC1, discovered in four ecotypes, eliminates known protein-protein interactions in the trichome initiation pathway. Additionally, in a broad screen for molecular variation at ATMYC1, including 72 A. thaliana ecotypes, a high-frequency block of variation was detected that results in >10% amino acid replacement within one of the eight exons of the gene. This sequence variation harbors a strong signal of divergent selection but has no measurable effect on trichome density. Homologs of ATMYC1 are pleiotropic, however, so this block of variation may be the result of natural selection having acted on another trait, while maintaining the trichome density role of the gene. These results show that ATMYC1 is an important source of variation for epidermal traits in A. thaliana and indicate that the transcription factors that make up the TTG1 genetic pathway generally may be important sources of epidermal variation in plants.

  7. A microsatellite study for determination of allelic variation of Kurdish population-Kurdistan region-Iraq

    Science.gov (United States)

    Murad, Media J.; Amin, Bushra K.

    2017-09-01

    The purpose of this study was detecting genetic variations for the Kurdish population in Kurdistan region-Iraq, using fifteen autosomal STR loci. Buccal swabs were collected and depositing on Nucleic Card (Copan, Italia Spa) from 302 healthy unrelated Iraqi Kurds in five provinces of Kurdistan region-Iraq. Fifteen autosomal STR loci are D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, FGA and Amelogenin included in the AmpFlSTR Identifiler® Direct PCR Amplification Kit (Applied Biosystems, Foster City, CA, USA). No significant departure from Hardy Weinberg Equilibrium (HWE) expectations were observed in 10 from 15 STR loci analyzed (a 5% significance level was taken). The exceptions were the CSF1PO, D3S1358, D13S317, D16S539 and D2S1338 loci. Statistical parameters of forensic efficiencies were estimated for the loci, based on allelic frequencies. The mean of observed heterozygosity, expected heterozygosity and PIC values across the 15 loci were 0.762, 0.797 and 0.768 respectively, indicating high gene diversity. The combined probability of exclusion, power of discrimination, probability of matching value for all the 15 STR loci were 0.9999968; 0.9999999 and 4.966×10-17, respectively. These parameters indicated the importance of the loci for forensic genetic purposes and paternity testing.

  8. Allelic heterogeneity and trade-off shape natural variation for response to soil micronutrient.

    Directory of Open Access Journals (Sweden)

    Seifollah Poormohammad Kiani

    Full Text Available As sessile organisms, plants have to cope with diverse environmental constraints that may vary through time and space, eventually leading to changes in the phenotype of populations through fixation of adaptive genetic variation. To fully comprehend the mechanisms of evolution and make sense of the extensive genotypic diversity currently revealed by new sequencing technologies, we are challenged with identifying the molecular basis of such adaptive variation. Here, we have identified a new variant of a molybdenum (Mo transporter, MOT1, which is causal for fitness changes under artificial conditions of both Mo-deficiency and Mo-toxicity and in which allelic variation among West-Asian populations is strictly correlated with the concentration of available Mo in native soils. In addition, this association is accompanied at different scales with patterns of polymorphisms that are not consistent with neutral evolution and show signs of diversifying selection. Resolving such a case of allelic heterogeneity helps explain species-wide phenotypic variation for Mo homeostasis and potentially reveals trade-off effects, a finding still rarely linked to fitness.

  9. Allelic heterogeneity and trade-off shape natural variation for response to soil micronutrient.

    Science.gov (United States)

    Poormohammad Kiani, Seifollah; Trontin, Charlotte; Andreatta, Matthew; Simon, Matthieu; Robert, Thierry; Salt, David E; Loudet, Olivier

    2012-01-01

    As sessile organisms, plants have to cope with diverse environmental constraints that may vary through time and space, eventually leading to changes in the phenotype of populations through fixation of adaptive genetic variation. To fully comprehend the mechanisms of evolution and make sense of the extensive genotypic diversity currently revealed by new sequencing technologies, we are challenged with identifying the molecular basis of such adaptive variation. Here, we have identified a new variant of a molybdenum (Mo) transporter, MOT1, which is causal for fitness changes under artificial conditions of both Mo-deficiency and Mo-toxicity and in which allelic variation among West-Asian populations is strictly correlated with the concentration of available Mo in native soils. In addition, this association is accompanied at different scales with patterns of polymorphisms that are not consistent with neutral evolution and show signs of diversifying selection. Resolving such a case of allelic heterogeneity helps explain species-wide phenotypic variation for Mo homeostasis and potentially reveals trade-off effects, a finding still rarely linked to fitness.

  10. Rare allelic variants determine folate status in an unsupplemented European population

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, Markéta; Sokolová, J.; Janošíková, B.; Melenovská, P.; Krupková, L.; Zvárová, Jana; Kožich, V.

    2012-01-01

    Roč. 142, č. 8 (2012), s. 1403-1409 ISSN 0022-3166 R&D Projects: GA MZd(CZ) NS10036 Institutional research plan: CEZ:AV0Z10300504 Keywords : glutamate-carboxypeptidase-ii * coronary-artery-disease * one-carbon metabolism * methylenetetrahydrofolate reductase * homocysteine concentrations * genetic-determinants * common mutation * serum folate * polymorphisms * prevalence Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.196, year: 2012

  11. Human class I major histocompatibility complex alleles determine central nervous system injury versus repair.

    Science.gov (United States)

    Wootla, Bharath; Denic, Aleksandar; Watzlawik, Jens O; Warrington, Arthur E; Zoecklein, Laurie J; Papke-Norton, Louisa M; David, Chella; Rodriguez, Moses

    2016-11-17

    We investigated the role of human HLA class I molecules in persistent central nervous system (CNS) injury versus repair following virus infection of the CNS. Human class I A11 + and B27 + transgenic human beta-2 microglobulin positive (Hβ2m + ) mice of the H-2 b background were generated on a combined class I-deficient (mouse beta-2 microglobulin deficient, β2m 0 ) and class II-deficient (mouse Aβ 0 ) phenotype. Intracranial infection with Theiler's murine encephalomyelitis virus (TMEV) in susceptible SJL mice results in acute encephalitis with prominent injury in the hippocampus, striatum, and cortex. Following infection with TMEV, a picornavirus, the Aβ 0 .β2m 0 mice lacking active immune responses died within 18 to 21 days post-infection. These mice showed severe encephalomyelitis due to rapid replication of the viral genome. In contrast, transgenic Hβ2m mice with insertion of a single human class I MHC gene in the absence of human or mouse class II survived the acute infection. Both A11 + and B27 + mice significantly controlled virus RNA expression by 45 days and did not develop late-onset spinal cord demyelination. By 45 days post-infection (DPI), B27 + transgenic mice showed almost complete repair of the virus-induced brain injury, but A11 + mice conversely showed persistent severe hippocampal and cortical injury. The findings support the hypothesis that the expression of a single human class I MHC molecule, independent of persistent virus infection, influences the extent of sub frequent chronic neuronal injury or repair in the absence of a class II MHC immune response.

  12. QTL analysis of the photoperiodic response and clinal distribution of period alleles in Nasonia vitripennis.

    Science.gov (United States)

    Paolucci, Silvia; Salis, Lucia; Vermeulen, Cornelis J; Beukeboom, Leo W; van de Zande, Louis

    2016-10-01

    In seasonal environments, organisms synchronize their life cycle with the annual cycle of environmental factors. In many insect species, this includes a diapause response: a timed dormant stage that allows to survive harsh winter conditions. Previously, we have shown that larval diapause in the parasitic wasp Nasonia vitripennis is induced by the mother upon exposure to a threshold number of short photoperiods (named switch point) and diapause response follows a latitudinal cline in natural populations. Here, we present a QTL analysis using two lines derived from the extremes of this clinal distribution: a northern line from Oulu, Finland and a southern line from Corsica, France. A genomic region on chromosome 1 and one on chromosome 5 were found to be associated with photoperiodic diapause induction. Interestingly, these regions contain the putative clock genes period, cycle (chromosome 1) and cryptochrome (chromosome 5). An analysis of period polymorphisms in seven European populations showed a clinal distribution of two main haplotypes that correlate with the latitudinal cline for diapause induction. © 2016 John Wiley & Sons Ltd.

  13. The dominant allele Aft induces a shift from flavonol to anthocyanin production in response to UV-B radiation in tomato fruit.

    Science.gov (United States)

    Catola, Stefano; Castagna, Antonella; Santin, Marco; Calvenzani, Valentina; Petroni, Katia; Mazzucato, Andrea; Ranieri, Annamaria

    2017-08-01

    The introgression of the A ft allele into domesticated tomato induced a shift from flavonol to anthocyanin production in response to UV-B radiation, while the hp - 1 allele negatively influenced the response of flavonoid biosynthesis to UV-B. Introgression of the dominant allele Anthocyanin fruit (Aft) from Solanum chilense induces anthocyanin accumulation in the peel of tomato (Solanum lycopersicum L.) fruit. UV-B radiation can influence plant secondary metabolism regulating the expression of several genes, among which those involved in flavonoid biosynthesis. Here, we investigated whether post-harvest UV-B treatment could up-regulate flavonoid production in tomato fruits and whether the Aft allele could affect flavonoid biosynthesis under UV-B radiation. Mature green fruits of an anthocyanin-rich tomato mutant line (SA206) and of its wild-type reference, cv. Roma, were daily subjected to post-harvest UV-B treatment until full ripening. Up-regulation of CHS and CHI transcription by UV-B treatment induced flavonoid accumulation in the peel of cv. Roma. Conversely, UV-B decreased the total flavonoid content and CHS transcript levels in the SA206 peel. SA206 being a double mutant containing also hp-1 allele, we investigated also the behavior of hp-1 fruit. The decreased peel flavonoid accumulation and gene transcription in response to UV-B suggest that hp-1 allele is involved in the marked down-regulation of the flavonoid biosynthesis observed in SA206 fruit. Interestingly, in SA206, UV-B radiation promoted the synthesis of delphinidin, petunidin, and malvidin by increasing F3'5'H and DFR transcription, but it decreased rutin production, suggesting a switch from flavonols to anthocyanins. Finally, although UV-B radiation does not reach the inner fruit tissues, it down-regulated flavonoid biosynthesis in the flesh of both genotypes. This study provides, for the first time, evidence that the presence of the functional Aft allele, under UV-B radiation, redirects

  14. Novel SLC19A3 Promoter Deletion and Allelic Silencing in Biotin-Thiamine-Responsive Basal Ganglia Encephalopathy.

    Directory of Open Access Journals (Sweden)

    Irene Flønes

    Full Text Available Biotin-thiamine responsive basal ganglia disease is a severe, but potentially treatable disorder caused by mutations in the SLC19A3 gene. Although the disease is inherited in an autosomal recessive manner, patients with typical phenotypes carrying single heterozygous mutations have been reported. This makes the diagnosis uncertain and may delay treatment.In two siblings with early-onset encephalopathy dystonia and epilepsy, whole-exome sequencing revealed a novel single heterozygous SLC19A3 mutation (c.337T>C. Although Sanger-sequencing and copy-number analysis revealed no other aberrations, RNA-sequencing in brain tissue suggested the second allele was silenced. Whole-genome sequencing resolved the genetic defect by revealing a novel 45,049 bp deletion in the 5'-UTR region of the gene abolishing the promoter. High dose thiamine and biotin therapy was started in the surviving sibling who remains stable. In another patient two novel compound heterozygous SLC19A3 mutations were found. He improved substantially on thiamine and biotin therapy.We show that large genomic deletions occur in the regulatory region of SLC19A3 and should be considered in genetic testing. Moreover, our study highlights the power of whole-genome sequencing as a diagnostic tool for rare genetic disorders across a wide spectrum of mutations including non-coding large genomic rearrangements.

  15. Negative BOLD response and serotonin concentration within rostral subgenual portion of the anterior cingulate cortex for long-allele carriers during perceptual processing of emotional tasks

    Science.gov (United States)

    Hadi, Shamil M.; Siadat, Mohamad R.; Babajani-Feremi, Abbas

    2012-03-01

    We investigated the effect of synaptic serotonin concentration on hemodynamic responses. The stimuli paradigm involved the presentation of fearful and threatening facial expressions to a set of 24 subjects who were either5HTTLPR long- or short-allele carriers (12 of each type in each group). The BOLD signals of the rACC from subjects of each group were averaged to increase the signal-to-noise ratio. We used a Bayesian approach to estimate the parameters of the underlying hemodynamic model. Our results, during this perceptual processing of emotional task, showed a negative BOLD signal in the rACC in the subjects with long-alleles. In contrast, the subjects with short-alleles showed positive BOLD signals in the rACC. These results suggest that high synaptic serotonin concentration in the rACC inhibits neuronal activity in a fashion similar to GABA, and a consequent negative BOLD signal ensues.

  16. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

    Swanton, C.; Nicke, B.; Schuett, M.

    2009-01-01

    Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting...... chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival'' genes is associated with poor outcome in estrogen receptor......-positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane...

  17. Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?

    Directory of Open Access Journals (Sweden)

    Faure Eric

    2008-10-01

    Full Text Available Abstract Background In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32 raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. Results Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. Conclusion We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding

  18. Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?

    Science.gov (United States)

    Faure, Eric

    2008-01-01

    Background In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. Results Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. Conclusion We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of

  19. Human Platelet Antigen Alleles in 998 Taiwanese Blood Donors Determined by Sequence-Specific Primer Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    Shun-Chung Pai

    2013-01-01

    Full Text Available Polymorphism of human platelet antigens (HPAs leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT, posttransfusion purpura (PTP, and platelet transfusion refractoriness (PTR. HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on their immunogenicity. A larger-scale study will now be conducted to confirm these hypotheses and to establish an apheresis donor database for the procurement of HPA-matched apheresis platelets for patients with PTR.

  20. Human platelet antigen alleles in 998 Taiwanese blood donors determined by sequence-specific primer polymerase chain reaction.

    Science.gov (United States)

    Pai, Shun-Chung; Burnouf, Thierry; Chen, Jen-Wei; Lin, Liang-In

    2013-01-01

    Polymorphism of human platelet antigens (HPAs) leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP), and platelet transfusion refractoriness (PTR). HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on their immunogenicity. A larger-scale study will now be conducted to confirm these hypotheses and to establish an apheresis donor database for the procurement of HPA-matched apheresis platelets for patients with PTR.

  1. Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses

    Science.gov (United States)

    Maddox, Dennis M; Vessey, Kirstan A; Yarbrough, Gary L; Invergo, Brandon M; Cantrell, Donald R; Inayat, Samsoon; Balannik, Victoria; Hicks, Wanda L; Hawes, Norman L; Byers, Shannon; Smith, Richard S; Hurd, Ron; Howell, Douglas; Gregg, Ronald G.; Chang, Bo; Naggert, Jürgen K; Troy, John B; Pinto, Lawrence H; Nishina, Patsy M; McCall, Maureen A

    2008-01-01

    An electroretinogram (ERG) screen identified a mouse with a normal a-wave but lacking a b-wave, and as such it was designated no b-wave3 (nob3). The nob3 phenotype mapped to chromosome 11 in a region containing the metabotropic glutamate receptor 6 gene (Grm6). Sequence analyses of cDNA identified a splicing error in Grm6, introducing an insertion and an early stop codon into the mRNA of affected mice (designated Grm6nob3). Immunohistochemistry of the Grm6nob3 retina showed that GRM6 was absent. The ERG and visual behaviour abnormalities of Grm6nob3 mice are similar to Grm6nob4 animals, and similar deficits were seen in compound heterozygotes (Grm6nob4/nob3), indicating that Grm6nob3 is allelic to Grm6nob4. Visual responses of Grm6nob3 retinal ganglion cells (RGCs) to light onset were abnormal. Grm6nob3 ON RGCs were rarely recorded, but when they were, had ill-defined receptive field (RF) centres and delayed onset latencies. When Grm6nob3 OFF-centre RGC responses were evoked by full-field stimulation, significantly fewer converted that response to OFF/ON compared to Grm6nob4 RGCs. Grm6nob4/nob3 RGC responses verified the conclusion that the two mutants are allelic. We propose that Grm6nob3 is a new model of human autosomal recessive congenital stationary night blindness. However, an allelic difference between Grm6nob3 and Grm6nob4 creates a disparity in inner retinal processing. Because the localization of GRM6 is limited to bipolar cells in the On pathway, the observed difference between RGCs in these mutants is likely to arise from differences in their inputs. PMID:18687716

  2. Association of H2A{sup b} with resistance to collagen-induced arthritis in H2-recombinant mouse strains: An allele associated with reduction of several apparently unrelated responses

    Energy Technology Data Exchange (ETDEWEB)

    Mitchison, N.A.; Brunner, M.C. [Deutsches Rheuma-Forschungszentrum, Berlin (Germany)

    1995-02-01

    HLA class II alleles can protect against immunological diseases. Seeking an animal model for a naturally occurring protective allele, we screened a panel of H2-congenic and recombinant mouse strains for ability to protect against collagen-induced arthritis. The strains were crossed with the susceptible strain DBA/1, and the F{sub 1} hybrids immunized with cattle and chicken type II collagen. Hybrids having the H2A{sup b} allele displayed a reduced incidence and duration of the disease. They also had a reduced level of pre-disease inflammation, but not of anti-collagen antibodies. The allele is already known to be associated with reduction of other apparently unrelated immune responses, suggesting that some form of functional differentiation may operate that is not exclusively related to epitope-binding. It is suggested that this may reflect allelic variation in the class II major histocompatibility complex promoter region. 42 refs., 7 figs., 1 tab.

  3. Molecular and structural determinants of adamantyl susceptibility to HLA-DRs allelic variants: an in silico approach to understand the mechanism of MLEs

    Science.gov (United States)

    Zaheer-ul-Haq; Khan, Waqasuddin

    2011-01-01

    Class II major histocompatibility complex (MHC II) molecules as expressed by antigen-presenting cells are heterodimeric cell-surface glycoprotein receptors that are fundamental in initiating and propagating an immune response by presenting tumor-associated antigenic peptides to CD4+/TH cells. The loading efficiency of such peptides can be improved by small organic compounds (MHC Loading Enhancers—MLEs), that convert the non-receptive peptide conformation of MHC II to a peptide-receptive conformation. In a reversible reaction, these compounds open up the binding site of MHC II molecules by specific interactions with a yet undefined pocket. Here, we performed molecular docking and molecular dynamics simulation studies of adamantyl compounds on the predicted cavity around the P1 pocket of 2 allelic variants of HLA-DRs. The purpose was to investigate the suitability of adamantyl compounds as MLEs at the dimorphic β86 position. Docking studies revealed that besides numerous molecular interactions formed by the adamantyl compounds, Asnβ82, Tyrβ83, and Thrβ90 are the crucial amino acid residues that are characterized as the "sensors" of peptide loading. Molecular dynamics simulation studies exposed the dynamical structural changes that HLA-DRs adopted as a response to binding of 3-(1-adamantyl)-5-hydrazidocarbonyl-1H-pyrazole (AdCaPy). The conformations of AdCaPy complexed with the Glyβ86 HLA-DR allelic variant are well correlated with the stabilized form of peptide-loaded HLA-DRs, further confirming the role of AdCaPy as a MLE. Hydrogen bonding interaction analysis clearly demonstrated that after making suitable contacts with AdCaPy, HLA-DR changes its local conformation. However, AdCaPy complexed with HLA-DR having Valβ86 at the dimorphic position did not accommodate AdCaPy as MLE due to steric hindrance caused by the valine.

  4. A new allele of flower color gene W1 encoding flavonoid 3'5'-hydroxylase is responsible for light purple flowers in wild soybean Glycine soja.

    Science.gov (United States)

    Takahashi, Ryoji; Dubouzet, Joseph G; Matsumura, Hisakazu; Yasuda, Kentaro; Iwashina, Tsukasa

    2010-07-28

    Glycine soja is a wild relative of soybean that has purple flowers. No flower color variant of Glycine soja has been found in the natural habitat. B09121, an accession with light purple flowers, was discovered in southern Japan. Genetic analysis revealed that the gene responsible for the light purple flowers was allelic to the W1 locus encoding flavonoid 3'5'-hydroxylase (F3'5'H). The new allele was designated as w1-lp. The dominance relationship of the locus was W1 >w1-lp >w1. One F2 plant and four F3 plants with purple flowers were generated in the cross between B09121 and a Clark near-isogenic line with w1 allele. Flower petals of B09121 contained lower amounts of four major anthocyanins (malvidin 3,5-di-O-glucoside, petunidin 3,5-di-O-glucoside, delphinidin 3,5-di-O-glucoside and delphinidin 3-O-glucoside) common in purple flowers and contained small amounts of the 5'-unsubstituted versions of the above anthocyanins, peonidin 3,5-di-O-glucoside, cyanidin 3,5-di-O-glucoside and cyanidin 3-O-glucoside, suggesting that F3'5'H activity was reduced and flavonoid 3'-hydroxylase activity was increased. F3'5'H cDNAs were cloned from Clark and B09121 by RT-PCR. The cDNA of B09121 had a unique base substitution resulting in the substitution of valine with methionine at amino acid position 210. The base substitution was ascertained by dCAPS analysis. The polymorphism associated with the dCAPS markers co-segregated with flower color in the F2 population. F3 progeny test, and dCAPS and indel analyses suggested that the plants with purple flowers might be due to intragenic recombination and that the 65 bp insertion responsible for gene dysfunction might have been eliminated in such plants. B09121 may be the first example of a flower color variant found in nature. The light purple flower was controlled by a new allele of the W1 locus encoding F3'5'H. The flower petals contained unique anthocyanins not found in soybean and G. soja. B09121 may be a useful tool for studies of

  5. Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

    Science.gov (United States)

    Crux, Nicole B.; Elahi, Shokrollah

    2017-01-01

    The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV) and hepatitis C virus (HCV), is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA)-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C), class Ib (HLA-E, -F, -G, -H), and class II (HLA-DR, -DQ, -DM, and -DP) in immune regulation and viral pathogenesis (e.g., HIV and HCV). To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections. PMID:28769934

  6. Human Leukocyte Antigen (HLA and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

    Directory of Open Access Journals (Sweden)

    Nicole B. Crux

    2017-07-01

    Full Text Available The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV and hepatitis C virus (HCV, is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C, class Ib (HLA-E, -F, -G, -H, and class II (HLA-DR, -DQ, -DM, and -DP in immune regulation and viral pathogenesis (e.g., HIV and HCV. To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections.

  7. Multiple phosphoglucomutase alleles in Toxorhynchites splendens (Diptera: Culcidae).

    Science.gov (United States)

    Yong, H S; Chan, K L; Dhaliwal, S S; Burton, J J; Cheong, W H; Mak, J W

    1980-09-15

    Multiple phosphoglucomutase (E.C. 2.7.5.1) alleles are found in the mosquito Toxorhynchites splendens. The sample studied reveals 3 Pgm alleles whose frequencies are in good accord with Hardy-Weinberg expectations. The most frequent allele is that controlling a phenotype with an intermediate electrophoretic mobility. Each Pgm allele determines a two-band electrophoretic pattern.

  8. Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion.

    Directory of Open Access Journals (Sweden)

    Sanjay Sarkar

    2016-12-01

    Full Text Available Equine arteritis virus (EAV is the causative agent of equine viral arteritis (EVA, a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10-70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16 that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1 having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001 and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence in the male reproductive tract. EqCXCL16Sa and

  9. Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

    Science.gov (United States)

    Cook, R. Frank; Eberth, John; Chelvarajan, R. Lakshman; Artiushin, Sergey; Timoney, Peter J.

    2016-01-01

    Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and Eq

  10. The probability to initiate X chromosome inactivation is determined by the X to autosomal ratio and X chromosome specific allelic properties.

    Directory of Open Access Journals (Sweden)

    Kim Monkhorst

    Full Text Available In female mammalian cells, random X chromosome inactivation (XCI equalizes the dosage of X-encoded gene products to that in male cells. XCI is a stochastic process, in which each X chromosome has a probability to be inactivated. To obtain more insight in the factors setting up this probability, we studied the role of the X to autosome (X ratio A ratio in initiation of XCI, and have used the experimental data in a computer simulation model to study the cellular population dynamics of XCI.To obtain more insight in the role of the XratioA ratio in initiation of XCI, we generated triploid mouse ES cells by fusion of haploid round spermatids with diploid female and male ES cells. These fusion experiments resulted in only XXY triploid ES cells. XYY and XXX ES lines were absent, suggesting cell death related either to insufficient X-chromosomal gene dosage (XYY or to inheritance of an epigenetically modified X chromosome (XXX. Analysis of active (Xa and inactive (Xi X chromosomes in the obtained triploid XXY lines indicated that the initiation frequency of XCI is low, resulting in a mixed population of XaXiY and XaXaY cells, in which the XaXiY cells have a small proliferative advantage. This result, and findings on XCI in diploid and tetraploid ES cell lines with different X ratio A ratios, provides evidence that the X ratio A ratio determines the probability for a given X chromosome to be inactivated. Furthermore, we found that the kinetics of the XCI process can be simulated using a probability for an X chromosome to be inactivated that is proportional to the X ratio A ratio. These simulation studies re-emphasize our hypothesis that the probability is a function of the concentration of an X-encoded activator of XCI, and of X chromosome specific allelic properties determining the threshold for this activator.The present findings reveal that the probability for an X chromosome to be inactivated is proportional to the X ratio A ratio. This finding

  11. Membrane Transition Temperature Determines Cisplatin Response

    Science.gov (United States)

    Raghunathan, Krishnan; Ahsan, Aarif; Ray, Dipankar; Nyati, Mukesh K.; Veatch, Sarah L.

    2015-01-01

    Cisplatin is a classical chemotherapeutic agent used in treating several forms of cancer including head and neck. However, cells develop resistance to the drug in some patients through a range of mechanisms, some of which are poorly understood. Using isolated plasma membrane vesicles as a model system, we present evidence suggesting that cisplatin induced resistance may be due to certain changes in the bio-physical properties of plasma membranes. Giant plasma membrane vesicles (GPMVs) isolated from cortical cytoskeleton exhibit a miscibility transition between a single liquid phase at high temperature and two distinct coexisting liquid phases at low temperature. The temperature at which this transition occurs is hypothesized to reflect the magnitude of membrane heterogeneity at physiological temperature. We find that addition of cisplatin to vesicles isolated from cisplatin-sensitive cells result in a lowering of this miscibility transition temperature, whereas in cisplatin-resistant cells such treatment does not affect the transition temperature. To explore if this is a cause or consequence of cisplatin resistance, we tested if addition of cisplatin in combination with agents that modulate GPMV transition temperatures can affect cisplatin sensitivity. We found that cells become more sensitive to cisplatin when isopropanol, an agent that lowers GPMV transition temperature, was combined with cisplatin. Conversely, cells became resistant to cisplatin when added in combination with menthol that raises GPMV transition temperatures. These data suggest that changes in plasma membrane heterogeneity augments or suppresses signaling events initiated in the plasma membranes that can determine response to cisplatin. We postulate that desired perturbations of membrane heterogeneity could provide an effective therapeutic strategy to overcome cisplatin resistance for certain patients. PMID:26484687

  12. Molecular Basis of Allele-Specific Efficacy of a Blood-Stage Malaria Vaccine: Vaccine Development Implications

    Science.gov (United States)

    Ouattara, Amed; Takala-Harrison, Shannon; Thera, Mahamadou A.; Coulibaly, Drissa; Niangaly, Amadou; Saye, Renion; Tolo, Youssouf; Dutta, Sheetij; Heppner, D. Gray; Soisson, Lorraine; Diggs, Carter L.; Vekemans, Johan; Cohen, Joe; Blackwelder, William C.; Dube, Tina; Laurens, Matthew B.; Doumbo, Ogobara K.; Plowe, Christopher V.

    2013-01-01

    The disappointing efficacy of blood-stage malaria vaccines may be explained in part by allele-specific immune responses that are directed against polymorphic epitopes on blood-stage antigens. FMP2.1/AS02A, a blood-stage candidate vaccine based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, had allele-specific efficacy against clinical malaria in a phase II trial in Malian children. We assessed the cross-protective efficacy of the malaria vaccine and inferred which polymorphic amino acid positions in AMA1 were the targets of protective allele-specific immune responses. FMP2.1/AS02A had the highest efficacy against AMA1 alleles that were identical to the 3D7 vaccine-type allele at 8 highly polymorphic amino acid positions in the cluster 1 loop (c1L) but differed from 3D7 elsewhere in the molecule. Comparison of the incidence of vaccine-type alleles before and after vaccination in the malaria vaccine and control groups and examination of the patterns of allele change at polymorphic positions in consecutive malaria episodes suggest that the highly polymorphic amino acid position 197 in c1L was the most critical determinant of allele-specific efficacy. These results indicate that a multivalent AMA1 vaccine with broad efficacy could include only a limited set of key alleles of this extremely polymorphic antigen. PMID:23204168

  13. Allele identification using immobilized mismatch binding protein: detection and identification of antibiotic-resistant bacteria and determination of sheep susceptibility to scrapie.

    OpenAIRE

    Debbie, P; Young, K; Pooler, L; Lamp, C; Marietta, P; Wagner, R

    1997-01-01

    A novel method for detection and identification of specific alleles has been developed utilizing immobilized mismatch binding protein (IMBP). The assay involves the use of biotin-labeled probes, which are prepared by PCR amplification of cloned fragments with known sequence. The use of probes avoids many of the problems associated with the extreme sensitivity of IMBP assays to errors in PCR amplification. The method can be used to monitor PCR fidelity and to genotype both diploid and haploid ...

  14. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    Directory of Open Access Journals (Sweden)

    Carol A Soderlund

    Full Text Available Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor, where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense, and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available

  15. Determination of physiological responses on hyacinth ( Hyacinthus ...

    African Journals Online (AJOL)

    In this study, the physiological responses of hyacinth (Hyacinthus orientalis) exposed to different salt concentrations (0, 50, 100, 200 and 400 mM) were investigated. The stomata status, osmotic potential, proline content, chlorophyll and caretonoid contents and protein variances were examined in the plants exposed to salt.

  16. Soybean Yield Determinants and Response to Rhizobial

    African Journals Online (AJOL)

    komla

    Abstract. The response of two soybean varieties (Samsoy—2 and improved variety TGx 1448-2E) to Bradyrhizobium inoculation in the northern Guinea savanna of Nigeria was tested in a researcher-managed on-farm trial. There were variations in soybean yields between and within farmers' fields. Data obtained from 24.

  17. Procedure for determining the SSE response from the OBE response

    International Nuclear Information System (INIS)

    Curreri, J.

    1985-01-01

    Regulatory Guide 1.61 specifies the damping that should be used for all modes that are considered in an elastic spectral or time history dynamic seismic analysis of Seismic Category I components. Table 1 of R.G 1.61 specifies damping values for dynamic analysis for two different earthquakes, the Safe Shutdown Earthquake and the Operating Basis Earthquake. The guide specifies that ''...if the maximum stresses due to static, seismic and other dynamic loading are significantly lower than the yield stresses and 1/2 yield stress for SSE and 1/2 SSE respectively, in any structure a component damping values lower than those specified in Table 1 ....should be used .... to avoid underestimating the amplitude of vibration of dynamic stress.'' The guide requires that the appropiate damping values be used which reflect the state of stress that will be experienced by the equipment. In applying these values to the response of equipment, to an OBE and to an SSE, the selected damping should result in a dynamic response for the SSE that is greater than the response due to the OBE, all other factors being equal. The purpose of the statement in the guide is to note that at higher stress levels, the higher damping values could be used, but at lower stress levels, the lower values of damping should be used. Current procedures that are used in implementing R.G. 1.61 frequently result in an OBE response that is greater than the SSE response. This is because the higher damping under the SSE is used at all stress levels, low as well as high. This is obviously not the intent of the Regulatory Guide. A procedure has been developed which derives an expression relating the SSE response to the OBE response. Two factors are involved in the equation. The first involves the damping ratios for the SSE and OBE events and the second is the ratio between the levels of the OBE and SSE

  18. Allelic diversity of S-RNase alleles in diploid potato species.

    Science.gov (United States)

    Dzidzienyo, Daniel K; Bryan, Glenn J; Wilde, Gail; Robbins, Timothy P

    2016-10-01

    The S-ribonuclease sequences of 16 S-alleles derived from diploid types of Solanum are presented. A phylogenetic analysis and partial phenotypic analysis support the conclusion that these are functional S-alleles. S-Ribonucleases (S-RNases) control the pistil specificity of the self-incompatibility (SI) response in the genus Solanum and several other members of the Solanaceae. The nucleotide sequences of S-RNases corresponding to a large number of S-alleles or S-haplotypes have been characterised. However, surprisingly, few S-RNase sequences are available for potato species. The identification of new S-alleles in diploid potato species is desirable as these stocks are important sources of traits such as biotic and abiotic resistance. S-RNase sequences are reported here from three distinct diploid types of potato: cultivated Solanum tuberosum Group Phureja, S. tuberosum Group Stenotomum, and the wild species Solanum okadae. Partial S-RNase sequences were obtained from pistil RNA by RT-PCR or 3'RACE (Rapid Amplification of cDNA Ends) using a degenerate primer. Full-length sequences were obtained for two alleles by 5'RACE. Database searches with these sequences identified 16 S-RNases in total, all of which are novel. The sequence analysis revealed all the expected features of functional S-RNases. Phylogenetic analysis with selected published S-RNase and S-like-RNase sequences from the Solanaceae revealed extensive trans-generic evolution of the S-RNases and a clear distinction from S-like-RNases. Pollination tests were used to confirm the self-incompatibility status and cross-compatibility relationships of the S. okadae accessions. All the S. okadae accessions were found to be self-incompatible as expected with crosses amongst them exhibiting both cross-compatibility and semi-compatibility consistent with the S-genotypes determined from the S-RNase sequence data. The progeny analysis of four semi-compatible crosses examined by allele-specific PCR provided further

  19. Frequent Unanticipated Alleles of lethal giant larvae in Drosophila Second Chromosome Stocks

    Science.gov (United States)

    Roegiers, Fabrice; Kavaler, Joshua; Tolwinski, Nicholas; Chou, Yu-Ting; Duan, Hong; Bejarano, Fernando; Zitserman, Diana; Lai, Eric C.

    2009-01-01

    Forty years ago, a high frequency of lethal giant larvae (lgl) alleles in wild populations of Drosophila melanogaster was reported. This locus has been intensively studied for its roles in epithelial polarity, asymmetric neural divisions, and restriction of tissue proliferation. Here, we identify a high frequency of lgl alleles in the Bloomington second chromosome deficiency kit and the University of California at Los Angeles Bruinfly FRT40A-lethal P collection. These unrecognized aberrations confound the use of these workhorse collections for phenotypic screening or genetic mapping. In addition, we determined that independent alleles of insensitive, reported to affect asymmetric cell divisions during sensory organ development, carry lgl deletions that are responsible for the observed phenotypes. Taken together, these results encourage the routine testing of second chromosome stocks for second-site alleles of lgl. PMID:19279324

  20. Allelic genealogies in sporophytic self-incompatibility systems in plants

    DEFF Research Database (Denmark)

    Schierup, M H; Vekemans, X; Christiansen, F B

    1998-01-01

    Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model...... action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles...

  1. Allele-specific KRT1 expression is a complex trait.

    Directory of Open Access Journals (Sweden)

    Heng Tao

    2006-06-01

    Full Text Available The differential expression of alleles occurs commonly in humans and is likely an important genetic factor underlying heritable differences in phenotypic traits. Understanding the molecular basis of allelic expression differences is thus an important challenge. Although many genes have been shown to display differential allelic expression, this is the first study to examine in detail the cumulative effects of multiple cis-regulatory polymorphisms responsible for allele-specific expression differences. We have used a variety of experimental approaches to identify and characterize cis-regulatory polymorphisms responsible for the extreme allele-specific expression differences of keratin-1 (KRT1 in human white blood cells. The combined data from our analyses provide strong evidence that the KRT1 allelic expression differences result from the haplotypic combinations and interactions of five cis-regulatory single nucleotide polymorphisms (SNPs whose alleles differ in their affinity to bind transcription factors and modulate KRT1 promoter activity. Two of these cis-regulatory SNPs bind transcriptional activators with the alleles on the high-expressing KRT1 haplotype pattern having a higher affinity than the alleles on the low-expressing haplotype pattern. In contrast, the other three cis-regulatory SNPs bind transcriptional inhibitors with the alleles on the low-expressing haplotype pattern having a higher affinity than the alleles on the high-expressing haplotype pattern. Our study provides important new insights into the degree of complexity that the cis-regulatory sequences responsible for allele-specific transcriptional regulation have. These data suggest that allelic expression differences result from the cumulative contribution of multiple DNA sequence polymorphisms, with each having a small effect, and that allele-specific expression can thus be viewed as a complex trait.

  2. Observations Suggesting Allelism of the Achondroplasia and Hypochondroplasia Genes

    Science.gov (United States)

    McKusick, Victor A.; Kelly, Thaddeus E.; Dorst, John P.

    1973-01-01

    It is argued that there are at least two alleles at the achondroplasia locus: one responsible for classic achondroplasia and one responsible for hypochondroplasia. Homozygosity for the achondroplasia gene produces a lethal skeletal dysplasia; homozygosity for hypochondroplasia has not been described. We report here a child considered to be a genetic compound for the achondroplasia and hypochondroplasia alleles. Images PMID:4697848

  3. Update on allele nomenclature for human cytochromes P450 and the Human Cytochrome P450 Allele (CYP-allele) Nomenclature Database.

    Science.gov (United States)

    Sim, Sarah C; Ingelman-Sundberg, Magnus

    2013-01-01

    Interindividual variability in xenobiotic metabolism and drug response is extensive and genetic factors play an important role in this variation. A majority of clinically used drugs are substrates for the cytochrome P450 (CYP) enzyme system and interindividual variability in expression and function of these enzymes is a major factor for explaining individual susceptibility for adverse drug reactions and drug response. Because of the existence of many polymorphic CYP genes, for many of which the number of allelic variants is continually increasing, a universal and official nomenclature system is important. Since 1999, all functionally relevant polymorphic CYP alleles are named and published on the Human Cytochrome P450 Allele (CYP-allele) Nomenclature Web site (http://www.cypalleles.ki.se). Currently, the database covers nomenclature of more than 660 alleles in a total of 30 genes that includes 29 CYPs as well as the cytochrome P450 oxidoreductase (POR) gene. On the CYP-allele Web site, each gene has its own Webpage, which lists the alleles with their nucleotide changes, their functional consequences, and links to publications identifying or characterizing the alleles. CYP2D6, CYP2C9, CYP2C19, and CYP3A4 are the most important CYPs in terms of drug metabolism, which is also reflected in their corresponding highest number of Webpage hits at the CYP-allele Web site.The main advantage of the CYP-allele database is that it offers a rapid online publication of CYP-alleles and their effects and provides an overview of peer-reviewed data to the scientific community. Here, we provide an update of the CYP-allele database and the associated nomenclature.

  4. Comparative frequency and allelic distribution of ABO and Rh (D ...

    African Journals Online (AJOL)

    Background: Allelic distribution of major blood groups (ABO and rhesus) has not been defined in Bangladeshi population. Determinants of blood group frequency in this region have not been studied properly. Aim: To determine ABO and rhesus blood group frequency and allelic distribution in a multiethnic area of ...

  5. Comparative frequency and allelic distribution of ABO and Rh (D ...

    African Journals Online (AJOL)

    Gourab Dewan

    2015-02-18

    Feb 18, 2015 ... Abstract Background: Allelic distribution of major blood groups (ABO and rhesus) has not been defined in Bangladeshi population. Determinants of blood group frequency in this region have not been studied properly. Aim: To determine ABO and rhesus blood group frequency and allelic distribution in a.

  6. HLA-DQ B1*0201 and A1*0102 alleles are not responsible of antituberculosis drugs induced hepatotoxicity risk in Spanish population

    Directory of Open Access Journals (Sweden)

    VIRGINIA LEIRO-FERNÁNDEZ

    2016-08-01

    Full Text Available Aims: To evaluate the role of HLA class II DQB1*0201 and DQA1*0102 in the risk of antituberculosis drug-induced hepatotoxicity in a cohort of tuberculosis patients of Caucasian origin from Spain.Methods: Matched case-control study including active tuberculosis (TB patients from Spain (Caucasian treated with first line antituberculosis drugs (ATD (Isoniazid, Rifampin and Pyrazinamide. Presence or absence HLA class II DQB1*0201 and DQA1*0102 alleles were compared between cases and controls.Results: We included 110 TB patients, 55 antituberculosis drug-induced hepatotoxicity (ATDH cases and 55 sex-matched controls. The analysis of the presence of HLADQB1*0201 and HLADQA*0102, did not show significative differences between both groups [presence of HLADQB1*0201 53.6% of cases vs 45.4% of controls, OR: 1.63 95% CI (0.62-4.52 p= 0.38; presence of HLADQA*0102 7.5% of cases vs 20% of controls OR: 0.36 95%CI (0.08-1.23, p=0.12]. After multivariate logistic regression analysis including in the model other potential risk factors of hepatotoxicity HLA class II DQB1*0201 and DQA1*0102 alleles were not found significantly associated with the risk of development ATD-induced hepatotoxicty.Results: We could not demonstrate an association between HLADQA1*0102 and HLADQB1*0201 with the risk of ATDH in this Caucasian population of Spanish origin.

  7. Characterization of a new full length TMPRSS3 isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan

    Directory of Open Access Journals (Sweden)

    Shotland Lawrence I

    2004-09-01

    Full Text Available Abstract Background Mutant alleles of TMPRSS3 are associated with nonsyndromic recessive deafness (DFNB8/B10. TMPRSS3 encodes a predicted secreted serine protease, although the deduced amino acid sequence has no signal peptide. In this study, we searched for mutant alleles of TMPRSS3 in families from Pakistan and Newfoundland with recessive deafness co-segregating with DFNB8/B10 linked haplotypes and also more thoroughly characterized the genomic structure of TMPRSS3. Methods We enrolled families segregating recessive hearing loss from Pakistan and Newfoundland. Microsatellite markers flanking the TMPRSS3 locus were used for linkage analysis. DNA samples from participating individuals were sequenced for TMPRSS3. The structure of TMPRSS3 was characterized bioinformatically and experimentally by sequencing novel cDNA clones of TMPRSS3. Results We identified mutations in TMPRSS3 in four Pakistani families with recessive, nonsyndromic congenital deafness. We also identified two recessive mutations, one of which is novel, of TMPRSS3 segregating in a six-generation extended family from Newfoundland. The spectrum of TMPRSS3 mutations is reviewed in the context of a genotype-phenotype correlation. Our study also revealed a longer isoform of TMPRSS3 with a hitherto unidentified exon encoding a signal peptide, which is expressed in several tissues. Conclusion Mutations of TMPRSS3 contribute to hearing loss in many communities worldwide and account for 1.8% (8 of 449 of Pakistani families segregating congenital deafness as an autosomal recessive trait. The newly identified TMPRSS3 isoform e will be helpful in the functional characterization of the full length protein.

  8. Corporate environmental responsibility – a key determinant of corporate reputation

    OpenAIRE

    Cristina Ganescu; Laura Dindire

    2014-01-01

    This paper aims to determine the trend of the relationship between corporate environmental responsibility and corporate reputation by focusing on a study of the European automotive sector. The starting point of our research is content analysis of the sustainability or social responsibility reports published in 2010, 2011, and 2012 by 13 businesses operating in the European automotive industry. Content analysis was carried out in order to identify the indicators used to assess corporate enviro...

  9. Multiple alleles for resistance and susceptibility modulate the defense response in the interaction of tetraploid potato (Solanum tuberosum) with Synchytrium endobioticum pathotypes 1, 2, 6 and 18.

    Science.gov (United States)

    Ballvora, Agim; Flath, Kerstin; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhard; Gebhardt, Christiane

    2011-12-01

    localization of the Sen loci. Thirty-three SNP markers linked to the Sen loci permitted the dissection of Sen alleles that increased or decreased resistance to wart. The alleles were inherited from both the resistant and susceptible parents.

  10. Apolipoprotein E4 allele does not influence serum triglyceride ...

    African Journals Online (AJOL)

    This study investigated how the APOε4 allele affects the serum triglyceride response after a fatmeal in apparently healthy black South African young adults. Sixty students were successfully screened for APOE genotype using Restriction Fragment Length Polymorphism (RFLP) and were divided into four groups; the ε2 allele ...

  11. Determination of eddy current response with magnetic measurements

    Science.gov (United States)

    Jiang, Y. Z.; Tan, Y.; Gao, Z.; Nakamura, K.; Liu, W. B.; Wang, S. Z.; Zhong, H.; Wang, B. B.

    2017-09-01

    Accurate mutual inductances between magnetic diagnostics and poloidal field coils are an essential requirement for determining the poloidal flux for plasma equilibrium reconstruction. The mutual inductance calibration of the flux loops and magnetic probes requires time-varying coil currents, which also simultaneously drive eddy currents in electrically conducting structures. The eddy current-induced field appearing in the magnetic measurements can substantially increase the calibration error in the model if the eddy currents are neglected. In this paper, an expression of the magnetic diagnostic response to the coil currents is used to calibrate the mutual inductances, estimate the conductor time constant, and predict the eddy currents response. It is found that the eddy current effects in magnetic signals can be well-explained by the eddy current response determination. A set of experiments using a specially shaped saddle coil diagnostic are conducted to measure the SUNIST-like eddy current response and to examine the accuracy of this method. In shots that include plasmas, this approach can more accurately determine the plasma-related response in the magnetic signals by eliminating the field due to the eddy currents produced by the external field.

  12. Information About Alcohol Consumption as a Determinant of Responsibility Attributions.

    Science.gov (United States)

    Kreutzer, Jeffrey S.; And Others

    For many years researchers have investigated the relationship between alcohol consumption and human aggression. A "policy-capturing" methodology was used to determine how judgments of responsibility for aggressive behavior are influenced by information about a person's alcohol consumption, sex, and degree of injury to a victim. Male subjects (N=8)…

  13. Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch in allelic gene expression.

    Science.gov (United States)

    Stratigi, Kalliopi; Kapsetaki, Manouela; Aivaliotis, Michalis; Town, Terrence; Flavell, Richard A; Spilianakis, Charalampos G

    2015-03-31

    Physiological processes rely on the regulation of total mRNA levels in a cell. In diploid organisms, the transcriptional activation of one or both alleles of a gene may involve trans-allelic interactions that provide a tight spatial and temporal level of gene expression regulation. The mechanisms underlying such interactions still remain poorly understood. Here, we demonstrate that lipopolysaccharide stimulation of murine macrophages rapidly resulted in the actin-mediated and transient homologous spatial proximity of Tnfα alleles, which was necessary for the mono- to biallelic switch in gene expression. We identified two new complementary long noncoding RNAs transcribed from the TNFα locus and showed that their knockdown had opposite effects in Tnfα spatial proximity and allelic expression. Moreover, the observed spatial proximity of Tnfα alleles depended on pyruvate kinase muscle isoform 2 (PKM2) and T-helper-inducing POZ-Krüppel-like factor (ThPOK). This study suggests a role for lncRNAs in the regulation of somatic homologous spatial proximity and allelic expression control necessary for fine-tuning mammalian immune responses.

  14. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  15. Allelic genealogies in sporophytic self-incompatibility systems in plants

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1998-01-01

    Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model...

  16. Novel method for analysis of allele specific expression in triploid Oryzias latipes reveals consistent pattern of allele exclusion.

    Directory of Open Access Journals (Sweden)

    Tzintzuni I Garcia

    Full Text Available Assessing allele-specific gene expression (ASE on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types and diseased tissues (trisomies, non-disjunction events, cancerous tissues. In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82% shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18% displayed a wide range of ASE levels. Interestingly the majority of genes (78% displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.

  17. Corporate environmental responsibility – a key determinant of corporate reputation

    Directory of Open Access Journals (Sweden)

    Cristina GĂNESCU

    2014-06-01

    Full Text Available This paper aims to determine the trend of the relationship between corporate environmental responsibility and corporate reputation by focusing on a study of the European automotive sector. The starting point of our research is content analysis of the sustainability or social responsibility reports published in 2010, 2011, and 2012 by 13 businesses operating in the European automotive industry. Content analysis was carried out in order to identify the indicators used to assess corporate environmental responsibility. The methodology aimed to produce an evaluation model for corporate environmental responsibility based on the following variables reported by companies: carbon dioxide emissions, water consumption, energy consumption, and amount of waste. Corporate reputation of sampled organizations was assessed based on content analysis of the 2010, 2011, and 2012 reports of the Reputation Institute. We applied the correlation of panel data and emphasised the fact that high levels of corporate environmental responsibility sustain high levels of corporate reputation. The study highlights the theoretical considerations that support this relationship. As companies become increasingly accountable, the methodology described in our study can be developed in further research by using other variables to measure corporate environmental responsibility.

  18. Determination Method of Bridge Rotation Angle Response Using MEMS IMU.

    Science.gov (United States)

    Sekiya, Hidehiko; Kinomoto, Takeshi; Miki, Chitoshi

    2016-11-09

    To implement steel bridge maintenance, especially that related to fatigue damage, it is important to monitor bridge deformations under traffic conditions. Bridges deform and rotate differently under traffic load conditions because their structures differ in terms of length and flexibility. Such monitoring enables the identification of the cause of stress concentrations that cause fatigue damage and the proposal of appropriate countermeasures. However, although bridge deformation monitoring requires observations of bridge angle response as well as the bridge displacement response, measuring the rotation angle response of a bridge subject to traffic loads is difficult. Theoretically, the rotation angle response can be calculated by integrating the angular velocity, but for field measurements of actual in-service bridges, estimating the necessary boundary conditions would be difficult due to traffic-induced vibration. To solve the problem, this paper proposes a method for determining the rotation angle response of an in-service bridge from its angular velocity, as measured by a inertial measurement unit (IMU). To verify our proposed method, field measurements were conducted using nine micro-electrical mechanical systems (MEMS) IMUs and two contact displacement gauges. The results showed that our proposed method provided high accuracy when compared to the reference responses calculated by the contact displacement gauges.

  19. Determination of response level for imported meat and poultry

    International Nuclear Information System (INIS)

    Houston, Donald L.; Engel, Ronald E.

    1986-01-01

    The response level of 75,000 picocuries per kilogram (pci/kg) for imported meat and poultry was determined in accordance with the Food and Drug Administration's (FDA's) Accidental Radioactive Contamination of Human Food and Animal Feeds, Recommendations for State and Local Agencies which was published in the Federal Register of October 22, 1982, and in consultation with FDA. The response level takes into account the total intake of activity from a radionuclide and the average daily consumption of food in the United States. This response level value is based, in part, upon the expectation that the major contributors of radiation to imported meat and poultry will be cesium-134 (half-life 2.1 years) and cesium-137 (half-life 30 years)

  20. A simple PCR-RFLP test for direct identification of Melanocortin Receptor 1 (MC1R alleles causing red coat colour in Holstein cattle

    Directory of Open Access Journals (Sweden)

    Alessio Valentini

    2010-01-01

    Full Text Available A direct test to determine the presence of the recessive alleles causing red colour in Holstein cattle at DNA level is proposed.Digestions with two restriction enzymes were used to detect individuals carrying recessive alleles of MelanocortinReceptor 1 (MC1R gene, responsible for coat coloration. Direct sequencing of the PCR products confirmed the identifiedgenotypes. Compared to previously described methods this is an effective, relatively economic and quick method. Thistest could be employed not only to facilitate the detection of polymorphisms in populations but also to exclude animalscarrying alleles resulting in an undesired coat colour from breeding schemes.

  1. Marker-assisted selection of high molecular weight glutenin alleles ...

    Indian Academy of Sciences (India)

    2012-08-08

    Triticum aestivum L.), while their allelic variation explains ... Glutamine-rich repetitive sequences that comprise the central part of the. HMW subunits are actually responsible for the elastic prop- erties due to extensive arrays of ...

  2. Response diversity determines the resilience of ecosystems to environmental change.

    Science.gov (United States)

    Mori, Akira S; Furukawa, Takuya; Sasaki, Takehiro

    2013-05-01

    A growing body of evidence highlights the importance of biodiversity for ecosystem stability and the maintenance of optimal ecosystem functionality. Conservation measures are thus essential to safeguard the ecosystem services that biodiversity provides and human society needs. Current anthropogenic threats may lead to detrimental (and perhaps irreversible) ecosystem degradation, providing strong motivation to evaluate the response of ecological communities to various anthropogenic pressures. In particular, ecosystem functions that sustain key ecosystem services should be identified and prioritized for conservation action. Traditional diversity measures (e.g. 'species richness') may not adequately capture the aspects of biodiversity most relevant to ecosystem stability and functionality, but several new concepts may be more appropriate. These include 'response diversity', describing the variation of responses to environmental change among species of a particular community. Response diversity may also be a key determinant of ecosystem resilience in the face of anthropogenic pressures and environmental uncertainty. However, current understanding of response diversity is poor, and we see an urgent need to disentangle the conceptual strands that pervade studies of the relationship between biodiversity and ecosystem functioning. Our review clarifies the links between response diversity and the maintenance of ecosystem functionality by focusing on the insurance hypothesis of biodiversity and the concept of functional redundancy. We provide a conceptual model to describe how loss of response diversity may cause ecosystem degradation through decreased ecosystem resilience. We explicitly explain how response diversity contributes to functional compensation and to spatio-temporal complementarity among species, leading to long-term maintenance of ecosystem multifunctionality. Recent quantitative studies suggest that traditional diversity measures may often be uncoupled from

  3. Augmenting Plant Immune Responses and Biological Control by Microbial Determinants

    Directory of Open Access Journals (Sweden)

    Sang Moo Lee

    2015-09-01

    Full Text Available Plant have developed sophisticated defence mechanisms against microbial pathogens. The recent accumulated information allow us to understand the nature of plant immune responses followed by recognition of microbial factors/determinants through cutting-edge genomics and multi-omics techniques. However, the practical approaches to sustain plant health using enhancement of plant immunity is yet to be fully appreciated. Here, we overviewed the general concept and representative examples on the plant immunity. The fungal, bacterial, and viral determinants that was previously reported as the triggers of plant immune responses are introduced and described as the potential protocol of biological control. Specifically, the role of chitin, glucan, lipopolysaccharides/extracellular polysaccharides, microbe/pathogen-associated molecular pattern, antibiotics, mimic-phytohormones, N-acyl homoserine lactone, harpin, vitamins, and volatile organic compounds are considered. We hope that this review stimulates scientific community and farmers to broaden their knowledge on the microbial determinant-based biological control and to apply the technology on the integrated pest management program.

  4. Biogastronomy: Factors that determine the biological response to meal ingestion.

    Science.gov (United States)

    Pribic, T; Azpiroz, F

    2018-02-02

    The biological response to a meal includes physiological changes, primarily related to the digestive process, and a sensory experience, involving sensations related to the homeostatic control of food consumption, eg, satiety and fullness, with a hedonic dimension, ie associated with changes in digestive well-being and mood. The responses to a meal include a series of events before, during and after ingestion. While much attention has been paid to the events before and during ingestion, relatively little is known about the postprandial sensations, which are key to the gastronomical experience. The aim of this narrative review is to provide a comprehensive overview and to define the framework to investigate the factors that determine the postprandial experience. Based on a series of proof-of-concept studies and related information, we propose that the biological responses to a meal depend on the characteristics of the meal, primarily its palatability and composition, and the responsiveness of the guest, which may be influenced by multiple previous and concurrent conditioning factors. This information provides the scientific backbone to the development of personalized gastronomy. © 2018 John Wiley & Sons Ltd.

  5. The internal structure of magnetic nanoparticles determines the magnetic response.

    Science.gov (United States)

    Pacakova, B; Kubickova, S; Salas, G; Mantlikova, A R; Marciello, M; Morales, M P; Niznansky, D; Vejpravova, J

    2017-04-20

    This work aims to emphasize that the magnetic response of single-domain magnetic nanoparticles (NPs) is driven by the NPs' internal structure, and the NP size dependencies of magnetic properties are overestimated. The relationship between the degree of the NPs' crystallinity and magnetic response is unambiguously demonstrated in eight samples of uniform maghemite/magnetite NPs and corroborated with the results obtained for about 20 samples of spinel ferrite NPs with different degrees of crystallinity. The NP samples were prepared by the thermal decomposition of an organic iron precursor subjected to varying reaction conditions, yielding variations in the NP size, shape and relative crystallinity. We characterized the samples by using several complementary methods, such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM), high resolution TEM (HR-TEM) and Mössbauer spectroscopy (MS). We evaluated the NPs' relative crystallinity by comparing the NP sizes determined from TEM and PXRD and further inspecting the NPs' internal structure and relative crystallinity by using HR-TEM. The results of the structural characterization were put in the context of the NPs' magnetic response. In this work, the highest saturation magnetization (M s ) was measured for the smallest but well-crystalline NPs, while the larger NPs exhibiting worse crystallinity revealed a lower M s . Our results clearly demonstrate that the NP crystallinity level that is mirrored in the internal spin order drives the specific magnetic response of the single-domain NPs.

  6. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. \\paragraph*{Results:} Theoretical derivations showed that parameter...

  7. Induction of CD8 T-cell responses restricted to multiple HLA class I alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide.

    Science.gov (United States)

    Eikawa, Shingo; Kakimi, Kazuhiro; Isobe, Midori; Kuzushima, Kiyotaka; Luescher, Immanuel; Ohue, Yoshihiro; Ikeuchi, Kazuhiro; Uenaka, Akiko; Nishikawa, Hiroyoshi; Udono, Heiichiro; Oka, Mikio; Nakayama, Eiichi

    2013-01-15

    Immunogenicity of a long 20-mer NY-ESO-1f peptide vaccine was evaluated in a lung cancer patient TK-f01, immunized with the peptide with Picibanil OK-432 and Montanide ISA-51. We showed that internalization of the peptide was necessary to present CD8 T-cell epitopes on APC, contrasting with the direct presentation of the short epitope. CD8 T-cell responses restricted to all five HLA class I alleles were induced in the patient after the peptide vaccination. Clonal analysis showed that B*35:01 and B*52:01-restricted CD8 T-cell responses were the two dominant responses. The minimal epitopes recognized by A*24:02, B*35:01, B*52:01 and C*12:02-restricted CD8 T-cell clones were defined and peptide/HLA tetramers were produced. NY-ESO-1 91-101 on A*24:02, NY-ESO-1 92-102 on B*35:01, NY-ESO-1 96-104 on B*52:01 and NY-ESO-1 96-104 on C*12:02 were new epitopes first defined in this study. Identification of the A*24:02 epitope is highly relevant for studying the Japanese population because of its high expression frequency (60%). High affinity CD8 T-cells recognizing tumor cells naturally expressing the epitopes and matched HLA were induced at a significant level. The findings suggest the usefulness of a long 20-mer NY-ESO-1f peptide harboring multiple CD8 T-cell epitopes as an NY-ESO-1 vaccine. Characterization of CD8 T-cell responses in immunomonitoring using peptide/HLA tetramers revealed that multiple CD8 T-cell responses comprised the dominant response. Copyright © 2012 UICC.

  8. Determination of the NPP Cernavoda reactor building seismic response

    International Nuclear Information System (INIS)

    Krutzik, N.J.; Rotaru, I.; Bobei, M.; Mingiuc, C.; Serban, V.

    1997-01-01

    Seismic input for systems and equipment installed in buildings depends on: - the seismic movement in free field on site; - the building movement in the soil; - the building deflection. The percentage of the 3 movements for the system and equipment input, depends on the position of the systems and equipment inside the building as well on the type of the foundation soil. The type of the foundation soil is important because if it is stiff it transfers a lot of energy to the building, energy which amplify the movement of the building on the top. If the foundation soil is soft, it accommodates the overall movement of the building in the soil, amplifying the movement to lower levels and the building response is attenuated if a resonance phenomenon between the whole building movement and the seismic excitation does not exist. This input is given with the design floor response spectra (FRS), in the logarithmic scale and seismic anchor movement (SAM). The design floor response spectra for NPP Cernavoda U1 Nuclear Building were determined in several stages starting with simple models (STICK type) without twisting movement and ending with detailed 3-dimensional models. From the point of view of dynamic behavior, the Reactor Building can be considered to be made up of 4 sub-structures: the containment building, internal structures containing separate elements such as the reactor vault, the fuel transfer structure and itself. Each sub-structure has its own movement (some of the structures present also some local effects) which combines with the overall movement of the building in the soil and the seismic excitation produce the total movement so that the response spectrum for each point of the sub-structure is specific. One should note that for structures which also show the twisting effect, the selection of the points on the floor, for the determination on the response spectra, is an engineering decision so that the response should be relevant for the equipment installed on the

  9. Transcriptome analysis of Brassica rapa near-isogenic lines carrying clubroot-resistant and –susceptible alleles in response to Plasmodiophora brassicae during early infection

    Directory of Open Access Journals (Sweden)

    Jingjing eChen

    2016-01-01

    Full Text Available Although Plasmodiophora brassicae is one of the most common pathogens worldwide, the causal agent of clubroot disease in Brassica crops, resistance mechanisms to it are still only poorly understood. To study the early defense response induced by P. brassicae infection, a global transcriptome profiling of the roots of two near-isogenic lines (NILs of clubroot-resistant (CR BJN3-2 and clubroot-susceptible (BJN3-2 Chinese cabbage (Brassica rapa was performed by RNA-seq. Among the 42,730 unique genes mapped to the reference genome of B. rapa, 1,875 and 2,103 genes were found to be up- and down-regulated between CR BJN3-2 and BJN3-2, respectively, at 0, 12, 72, and 96 hours after inoculation (hai. Functional annotation showed that most of the differently expressed genes are involved in metabolism, transport, signal transduction, and defense. Of the genes assigned to plant-pathogen interactions, 151 showed different expression patterns between two NILs, including genes associated with pathogen-associated molecular patterns (PAMPs and effectors recognition, calcium ion influx, hormone signaling, pathogenesis-related (PR genes, transcription factors, and cell wall modification. In particular, the expression level of effector receptors (resistance proteins, PR genes involved in salicylic acid (SA signaling pathway, were higher in clubroot-resistant NIL, while half of the PAMP receptors were suppressed in CR BJN3-2. This suggests that there was a more robust effector-triggered immunity (ETI response in CR BJN3-2 and that SA signaling was important to clubroot resistance. The dataset generated by our transcriptome profiling may prove invaluable for further exploration of the different responses to P. brassicae between clubroot-resistant and clubroot-susceptible genotypes, and it will strongly contribute to a better understanding of the molecular mechanisms of resistance genes of B. rapa against P. brassicae infection.

  10. Two key polymorphisms in a newly discovered allele of the Vitis vinifera TPS24 gene are responsible for the production of the rotundone precursor α-guaiene

    DEFF Research Database (Denmark)

    Drew, Damian Paul; Andersen, Trine Bundgaard; Sweetman, Crystal

    2016-01-01

    Rotundone was initially identified as a grape-derived compound responsible for the peppery aroma of Shiraz wine varieties. It has subsequently been found in black and white pepper and several other spices. Because of its potent aroma, the molecular basis for rotundone formation is of particular...... relevance to grape and wine scientists and industry. We have identified and functionally characterized in planta a sesquiterpene synthase, VvGuaS, from developing grape berries, and have demonstrated that it produces the precursor of rotundone, α-guaiene, as its main product. The VvGuaS enzyme is a novel...

  11. Homozygous carriers of the TCF7L2 rs7903146 T-allele show altered postprandial response in triglycerides and triglyceride-rich lipoproteins

    DEFF Research Database (Denmark)

    Engelbrechtsen, L; Hansen, T H; Mahendran, Y

    2017-01-01

    to CC carriers. Additionally, TT carriers had lower postprandial levels of total triglycerides (TG) (q = 0.03), VLDL-TG (q = 0.05, including medium, small and extra small, q = 0.048, q = 0.0009, q = 0.04, respectively), HDL-TG (triglycerides in high density lipoproteins q = 0.037) and S-HDL-TG (q = 0.......00003). In conclusion, TT carriers show altered postprandial triglyceride response, mainly influencing VLDL and HDL subclasses suggesting a genotype-mediated effect on hepatic lipid regulation....

  12. Self-incompatibility of Prunus tenella and evidence that reproductively isolated species of Prunus have different SFB alleles coupled with an identical S-RNase allele.

    Science.gov (United States)

    Surbanovski, Nada; Tobutt, Kenneth R; Konstantinović, Miroslav; Maksimović, Vesna; Sargent, Daniel J; Stevanović, Vladimir; Bosković, Radovan I

    2007-05-01

    Many species of Prunus display an S-RNase-based gametophytic self-incompatibility (SI), controlled by a single highly polymorphic multigene complex termed the S-locus. This comprises tightly linked stylar- and pollen-expressed genes that determine the specificity of the SI response. We investigated SI of Prunus tenella, a wild species found in small, isolated populations on the Balkan peninsula, initially by pollination experiments and identifying stylar-expressed RNase alleles. Nine P. tenella S-RNase alleles (S(1)-S(9)) were cloned; their sequence analysis showed a very high ratio of non-synonymous to synonymous nucleotide substitutions (K(a)/K(s)) and revealed that S-RNase alleles of P. tenella, unlike those of Prunus dulcis, show positive selection in all regions except the conserved regions and that between C2 and RHV. Remarkably, S(8)-RNase, was found to be identical to S(1)-RNase from Prunus avium, a species that does not interbreed with P. tenella and, except for just one amino acid, to S(11) of P. dulcis. However, the corresponding introns and S-RNase-SFB intergenic regions showed considerable differences. Moreover, protein sequences of the pollen-expressed SFB alleles were not identical, harbouring 12 amino-acid replacements between those of P. tenella SFB(8) and P. avium SFB(1). Implications of this finding for hypotheses about the evolution of new S-specificities are discussed.

  13. Diversity of MHC class I alleles in Spheniscus humboldti.

    Science.gov (United States)

    Kikkawa, Eri; Tanaka, Masafumi; Naruse, Taeko K; Tsuda, Tomi T; Tsuda, Michio; Murata, Koichi; Kimura, Akinori

    2017-02-01

    The major histocompatibility complex locus (MHC) is a gene region related to immune response and exhibits a remarkably great diversity. We deduced that polymorphisms in MHC genes would help to solve several issues on penguins, including classification, phylogenetic relationship, and conservation. This study aimed to elucidate the structure and diversity of the so far unknown MHC class I gene in a penguin species. The structure of an MHC class I gene from the Humboldt penguin (Spheniscus humboldti) was determined by using an inverse PCR method. We designed PCR primers to directly determine nucleotide sequences of PCR products from the MHC class I gene and to obtain recombinant clones for investigating the diversity of the MHC class I gene in Humboldt penguins. A total of 24 MHC class I allele sequences were obtained from 40 individuals. Polymorphisms were mainly found in exons 2 and 3, as expected from the nature of MHC class I genes in vertebrate species including birds and mammals. Phylogenetic analyses of MHC class I alleles have revealed that the Humboldt penguin is closely related to the Red Knot (Calidris canutus) belonging to Charadriiformes.

  14. Characterization of ROP18 alleles in human toxoplasmosis.

    Science.gov (United States)

    Sánchez, Víctor; de-la-Torre, Alejandra; Gómez-Marín, Jorge Enrique

    2014-04-01

    The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis. © 2013.

  15. Assigning breed origin to alleles in crossbred animals.

    Science.gov (United States)

    Vandenplas, Jérémie; Calus, Mario P L; Sevillano, Claudia A; Windig, Jack J; Bastiaansen, John W M

    2016-08-22

    For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed-specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed-specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. The BOA approach accurately assigns

  16. Determination of photoperiod response characteristics using a greenhouse

    Science.gov (United States)

    Major, D. J.

    1983-06-01

    The photoperiod response characteristics of two cultivars of seven long-day species of crop plants were determined by seeding at 33 biweekly intervals in a greenhouse at 49‡ 43' N Latitude. Parameters of a segmented linear regression were estimated using a non-linear computer program. This gave good estimates of the length of the basic vegetative and reproductive phases, the photoperiod sensitivity and minimum optimal photoperiods. It was apparent that the photoperiod of importance was that of the day of floral initiation. If the plant is old enough and the photoperiod of the day is not inhibitory, initiation will occur. At certain times of the year, the photoperiod changes so rapidly that flower initiation is prevented. Using this method of analysis, comparisons of large numbers of genotypes can be made.

  17. Determinants of ambulance response time: A study in Sabah, Malaysia

    Science.gov (United States)

    Chin, Su Na; Cheah, Phee Kheng; Arifin, Muhamad Yaakub; Wong, Boh Leng; Omar, Zaturrawiah; Yassin, Fouziah Md; Gabda, Darmesah

    2017-04-01

    Ambulance response time (ART) is one of the standard key performance indicators (KPI) in measuring the emergency medical services (EMS) delivery performances. When the mean time of ART of EMS system reaches the KPI target, it shows that the EMS system performs well. This paper considers the determinants of ART, using data sampled from 967 ambulance runs in a government hospital in Sabah. Multiple regression analysis with backward elimination was proposed for the identification of significant factors. Amongst the underlying factors, travel distance, age of patients, type of treatment and peak hours were identified to be significantly affecting ART. Identifying factors that influence ART helps the development of strategic improvement planning for reducing the ART.

  18. Burn size determines the inflammatory and hypermetabolic response.

    Science.gov (United States)

    Jeschke, Marc G; Mlcak, Ronald P; Finnerty, Celeste C; Norbury, William B; Gauglitz, Gerd G; Kulp, Gabriela A; Herndon, David N

    2007-01-01

    Increased burn size leads to increased mortality of burned patients. Whether mortality is due to inflammation, hypermetabolism or other pathophysiologic contributing factors is not entirely determined. The purpose of the present study was to determine in a large prospective clinical trial whether different burn sizes are associated with differences in inflammation, body composition, protein synthesis, or organ function. Pediatric burned patients were divided into four burn size groups: 80% TBSA burn. Demographic and clinical data, hypermetabolism, the inflammatory response, body composition, the muscle protein net balance, serum and urine hormones and proteins, and cardiac function and changes in liver size were determined. One hundred and eighty-nine pediatric patients of similar age and gender distribution were included in the study (80% TBSA burn, n = 21). Patients with larger burns had more operations, a greater incidence of infections and sepsis, and higher mortality rates compared with the other groups (P 80% TBSA group, followed by the 60-79% TBSA burn group (P 80% burns lost the most body weight, lean body mass, muscle protein and bone mineral content (P < 0.05). The urine cortisol concentration was highest in the 80-99% and 60-79% TBSA burn groups, associated with significant myocardial depression and increased change in liver size (P < 0.05). The cytokine profile showed distinct differences in expression of IL-8, TNF, IL-6, IL-12p70, monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor (P < 0.05). Morbidity and mortality in burned patients is burn size dependent, starts at a 60% TBSA burn and is due to an increased hypermetabolic and inflammatory reaction, along with impaired cardiac function.

  19. TNF-α-308 polymorphism determines clinical manifestations and therapeutic response of ankylosing spondylitis in Han Chinese.

    Science.gov (United States)

    Ma, Hai-Jun; Yin, Qing-Feng; Wu, Yin; Guo, Ming-Hao

    2017-12-20

    There is ongoing debate as to whether tumor necrosis factor alpha (TNF-α)-308 is associated with ankylosing spondylitis (AS). The aim of the present study was to determine whether TNF-α-308 is involved into genetic susceptibility, clinical features and therapeutic response of AS in Han Chinese. Two hundred and sixty AS patients with 260 ethnically matched healthy blood donors were enrolled into the present study. TNF-α-308 promoter polymorphism was identified using polymerase chain reaction amplification with restriction fragment length polymorphism assay. Population genetic analysis showed that the prevalence of allele A and G/A genotype was equally infrequent in both AS patients (3.85% and 7.69%) and healthy subjects (4.23% and 8.46%). Compared with the carriers of G/G genotype, remarkably elevated erythrocyte sedimentation rate and serum C-reactive protein were observed in AS patients with G/A variant (87.06±49.40 vs. 55.53±42.99mm/h, P=.0126; 54.95±27.77 vs. 34.36±36.13mg/dl, P=.0116, respectively), and they always presented with inflammatory spinal pain (70.00% vs. 43.33%, P=0.0214) and suffered relatively mild sacroiliitis (65.00% vs. 41.67%, P=0.0431). The allele G and G/G genotype were more frequent in good responders to anti-TNF-α treatment (96.55% vs. 73.53%, P=.0032; 93.10% vs. 47.06%, P=.0015), whereas there was no obvious superiority of them in predicting therapeutic response of conventional medications for AS. Our data suggest that TNF-α-308 polymorphism may influence the clinical features rather than susceptibility to AS in our Han Chinese. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  20. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans O.

    2002-01-01

    /GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease......OBJECTIVE: To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical...... phenotypes of PMR/GCA. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 102 Danish patients with PMR (n = 37) or GCA (n = 65). Two hundred fifty and 193 healthy individuals served as controls for MBL and HLA genotyping, respectively. RESULTS: The prevalence of MBL variant...

  1. Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles

    DEFF Research Database (Denmark)

    Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.

    2017-01-01

    specificities and binding pocket structure. We demonstrate that primary predisposition to cutaneous NVP HSR, seen across ancestral groups, can be attributed to a cluster of HLA-C alleles sharing a common binding groove F pocket with HLA-C*04:01. An independent association with a group of class II alleles which......Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP......), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding...

  2. HLA Dr beta 1 alleles in Pakistani patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Naqi, N.; Ahmed, T.A.; Bashir, M.M.

    2011-01-01

    Objective: To determine frequencies of HLA DR beta 1 alleles in rheumatoid arthritis in Pakistani patients. Study Design: Cross sectional / analytical study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Rheumatology departments of Military Hospital, Rawalpindi and Fauji Foundation Hospital, Rawalpindi, from January 2009 to January 2010. Methodology: HLA DR beta 1 genotyping of one hundred Pakistani patients, diagnosed as having RA as per American College of Rheumatology revised criteria 1987, was done. HLA DR beta 1 genotyping was carried out at allele group level (DR beta 1*01-DR beta 1*16) by sequence specific primers in RA patients. Comparison of HLA DR beta 1 allele frequencies between patients and control groups was made using Pearson's chi-square test to find possible association of HLA DR?1 alleles with RA in Pakistani rheumatoid patients. Results: HLA DR beta 1*04 was expressed with significantly increased frequency in patients with rheumatoid arthritis (p <0.05). HLA DR?1*11 was expressed statistically significantly more in control group as compared to rheumatoid patients indicating a possible protective effect. There was no statistically significant difference observed in frequencies of HLA DR beta 1 allele *01, DR beta 1 allele *03, DR beta 1 allele *07, DR beta 1 allele *08, DR beta 1 allele *09, DR beta 1 allele *10, DR beta 1 allele *12, DR beta 1 allele *13, DR beta 1 allele *14, DR?1 allele *15 and DR beta 1 allele *16 between patients and control groups. Conclusion: The identification of susceptible HLA DR beta 1 alleles in Pakistani RA patients may help physicians to make early decisions regarding initiation of early intensive therapy with disease modifying anti rheumatic medicines and biological agents decreasing disability in RA patients. (author)

  3. Cognitive and Ocular Factors Jointly Determine Pupil Responses under Equiluminance.

    Directory of Open Access Journals (Sweden)

    Tomas Knapen

    Full Text Available Changes in pupil diameter can reflect high-level cognitive signals that depend on central neuromodulatory mechanisms. However, brain mechanisms that adjust pupil size are also exquisitely sensitive to changes in luminance and other events that would be considered a nuisance in cognitive experiments recording pupil size. We implemented a simple auditory experiment involving no changes in visual stimulation. Using finite impulse-response fitting we found pupil responses triggered by different types of events. Among these are pupil responses to auditory events and associated surprise: cognitive effects. However, these cognitive responses were overshadowed by pupil responses associated with blinks and eye movements, both inevitable nuisance factors that lead to changes in effective luminance. Of note, these latter pupil responses were not recording artifacts caused by blinks and eye movements, but endogenous pupil responses that occurred in the wake of these events. Furthermore, we identified slow (tonic changes in pupil size that differentially influenced faster (phasic pupil responses. Fitting all pupil responses using gamma functions, we provide accurate characterisations of cognitive and non-cognitive response shapes, and quantify each response's dependence on tonic pupil size. These results allow us to create a set of recommendations for pupil size analysis in cognitive neuroscience, which we have implemented in freely available software.

  4. DRD4 dopamine receptor allelic diversity in various primate species

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, M.; Higley, D. [NIAAA, Rockville, MD (United States); O`Brien, S. [NCI, Frederick, MD (United States)] [and others

    1994-09-01

    The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypes in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.

  5. Origin of allelic diversity in antirrhinum S locus RNases.

    Science.gov (United States)

    Xue, Y; Carpenter, R; Dickinson, H G; Coen, E S

    1996-01-01

    In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate. PMID:8672882

  6. A WIDE DISTRIBUTION OF A NEW VRN-B1c ALLELE OF WHEAT TRITICUM AESTIVUM L. IN RUSSIA, UKRAINE AND ADJACENT REGIONS: A LINK WITH THE HEADING TIME AND ADAPTIVE POTENTIAL

    Directory of Open Access Journals (Sweden)

    Shcherban A.

    2012-08-01

    Full Text Available The adaptation of common wheat (T. aestivum L. to diverse environmental conditions is greatly under the control of genes involved in determination of vernalization response (Vrn-1 genes. It was found that the variation in common wheat heading time is affected not only by combination of Vrn-1 homoeoalleles but also by multiple alleles at a separate Vrn-1 locus. Previously, we described the Vrn-B1c allele from T.aestivum cv. 'Saratovskaya 29' and found significant differences in the structure of the first (1st intron of this allele when compared to another highly abundant Vrn-B1a allele, specifically, the deletion of 0.8 kb coupled with the duplication of 0.4 kb. We suggested that the changes in the intron 1 of Vrn-B1c allele caused earlier ear emergence in the near-isogenic line and cultivars, carrying this allele. In this study we investigate the distribution of the Vrn-B1c allele in a wide set of spring wheat cultivars from Russia, Ukraine and adjacent regions. The analysis revealed that 40% of Russian and 53% of Ukranian spring wheat cultivars contain the Vrn-B1c allele. The high distribution of the Vrn-B1c allele can be explained by a frequent using of 'Saratovskaya 29' in the breeding process inside the studied area. From the other hand, the predominance of the Vrn-B1c allele among cultivars cultivated in West Siberia and Kazakhstan may be due to the selective advantage of this allele for the region where there is a high risk of early fall frosts.

  7. Mediterranean river buffalo oxytocin-neurophysin I (OXT gene: structure, promoter analysis and allele detection

    Directory of Open Access Journals (Sweden)

    L. Ramunno

    2010-02-01

    Full Text Available Oxytocin (OXT is a very abundant nonapeptide neurohypophysial hormone implicated in several aspects of reproduction, including social, sexual and maternal behaviour, induction of labour and milk ejection. The nucleotide sequence of the whole OXTneurophysin I encoding gene (OXT in Mediterranean river buffalo was determined, plus 993 nucleotides at the 5’ flanking region. Buffalo oxytocin gene sequence analysis showed two transitions in the promoter region (C→T in position – 966 and G→A in position – 790 and one transversion G→T at the 170th nucleotide of the second exon, responsible for the Arg97→Leu aa substitution which identifies an allele named OXT B. A PCR-RFLP based method for a rapid identification of carriers of these alleles has been developed.

  8. Demography can favour female-advantageous alleles

    Science.gov (United States)

    Harts, Anna M. F.; Schwanz, Lisa E.; Kokko, Hanna

    2014-01-01

    When female fecundity is relatively independent of male abundance, while male reproduction is proportional to female abundance, females have a larger effect on population dynamics than males (i.e. female demographic dominance). This population dynamic phenomenon might not appear to influence evolution, because male and female genomes still contribute equally much to the next generation. However, here we examine two evolutionary scenarios to provide a proof of principle that spatial structure can make female demographic dominance matter. Our two simulation models combine dispersal evolution with local adaptation subjected to intralocus sexual conflict and environmentally driven sex ratio biases, respectively. Both models have equilibria where one environment (without being intrinsically poorer) has so few reproductive females that trait evolution becomes disproportionately determined by those environments where females survive better (intralocus sexual conflict model), or where daughters are overproduced (environmental sex determination model). Surprisingly, however, the two facts that selection favours alleles that benefit females, and population growth is improved when female fitness is high, together do not imply that all measures of population performance are improved. The sex-specificity of the source–sink dynamics predicts that populations can evolve to fail to persist in habitats where alleles do poorly when expressed in females. PMID:25056617

  9. Genetic and pharmacokinetic determinants of response to transdermal nicotine in white, black, and Asian nonsmokers.

    Science.gov (United States)

    Dempsey, D A; St Helen, G; Jacob, P; Tyndale, R F; Benowitz, N L

    2013-12-01

    The aim of the study was to examine genetic, pharmacokinetic, and demographic factors that influence sensitivity to nicotine in never-smokers. Sixty never-smokers, balanced for gender and race (white, black, and Asian), wore 7-mg nicotine skin patches for up to 8 h. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, encoding the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in nine subjects and was strongly associated with rate of increase and peak concentrations of plasma nicotine. Toxicity and subjective and cardiovascular effects of nicotine were associated with the presence of reduced-function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when they are used for treating medical conditions in nonsmokers, and possibly in vulnerability to developing nicotine dependence.

  10. The SLC6A4 VNTR genotype determines transcription factor binding and epigenetic variation of this gene in response to cocaine in vitro.

    Science.gov (United States)

    Vasiliou, Sylvia A; Ali, Fahad R; Haddley, Kate; Cardoso, M Cristina; Bubb, Vivien J; Quinn, John P

    2012-01-01

    We demonstrated that the genotype of the variable number tandem repeats (VNTRs) in the linked polymorphic region (LPR) of the 5' promoter and in the intron 2 (Stin2) transcriptional regulatory domains of the serotonin transporter SLC6A4 gene determined its promoter interactions with transcription factors and co-activators in response to cocaine in the JAr cell line. The LPR variants contain 14 (short, s) or 16 (long, l) copies of a 22-23 bp repeat element, whereas the Stin2 VNTR exists as three variants containing 9, 10 or 12 copies of a 16-17 bp repeat. We observed a differential effect of cocaine on the association of the promoter with the transcription factor CTCF, which bound to both LPR alleles prior to cocaine exposure but only to the l-allele following exposure. Significantly, this differential effect of cocaine was correlated with the binding of the transcriptional regulator MeCP2 specifically to the s-allele and recruiting the histone deacetylase complex (HDAC). Concurrently, cocaine increased the association of positive histone marks over the SLC6A4 gene locus. At the Stin2 domain, we lost binding of the transcription factor YB-1, while CTCF remained bound. Our biochemical data are consistent with differential reporter gene activity directed by the individual or dual domains in response to cocaine in an Epstein-Barr virus-based episome model of stable transfections. These observations suggest that exposure of JAr cells to cocaine may result in differential binding of transcription factors and activators based on a specific genotype that might alter epigenetic parameters affecting gene expression after the initial challenge. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  11. A Genetic Polymorphism of the Human Dopamine Transporter Determines the Impact of Sleep Deprivation on Brain Responses to Rewards and Punishments.

    Science.gov (United States)

    Greer, Stephanie M; Goldstein, Andrea N; Knutson, Brian; Walker, Matthew P

    2016-06-01

    Despite an emerging link between alterations in motivated behavior and a lack of sleep, the impact of sleep deprivation on human brain mechanisms of reward and punishment remain largely unknown, as does the role of trait dopamine activity in modulating such effects in the mesolimbic system. Combining fMRI with an established incentive paradigm and individual genotyping, here, we test the hypothesis that trait differences in the human dopamine transporter (DAT) gene-associated with altered synaptic dopamine signalling-govern the impact of sleep deprivation on neural sensitivity to impending monetary gains and losses. Consistent with this framework, markedly different striatal reward responses were observed following sleep loss depending on the DAT functional polymorphisms. Only participants carrying a copy of the nine-repeat DAT allele-linked to higher phasic dopamine activity-expressed amplified striatal response during anticipation of monetary gain following sleep deprivation. Moreover, participants homozygous for the ten-repeat DAT allele-linked to lower phasic dopamine activity-selectively demonstrated an increase in sensitivity to monetary loss within anterior insula following sleep loss. Together, these data reveal a mechanistic dependency on human of trait dopaminergic function in determining the interaction between sleep deprivation and neural processing of rewards and punishments. Such findings have clinical implications in disorders where the DAT genetic polymorphism presents a known risk factor with comorbid sleep disruption, including attention hyperactive deficit disorder and substance abuse.

  12. Effects of an MHC-DRB genotype and allele number on the load of gut parasites in the bank vole Myodes glareolus.

    Science.gov (United States)

    Kloch, Agnieszka; Babik, Wiesław; Bajer, Anna; Siński, Edward; Radwan, Jacek

    2010-03-01

    The major histocompatibility complex (MHC) genes code for the proteins responsible for pathogen recognition. The MHC class II DRB gene is multiplicated in the bank vole, Myodes glareolus, with different numbers of loci found in different individuals. Possessing large numbers of loci should increase the probability of pathogen recognition, but according to the optimality hypothesis, there is a cost of possessing too many MHC alleles. Using 454 technology, we determined the individual DRB allelic diversity and related it to the load of intestinal parasites in voles collected from three sites separated by a distance of 12 to 27 km. The analysis of six microsatellite loci revealed significant population structure (F(ST) = 0.07). The sites differed significantly in the prevalence and abundance of nematode species as well. We found two significant associations between MHC alleles and the intensity of the infection with the most prevalent nematode, Aspiculuris tetraptera. One of these associations was population-specific. This result suggests that the directions of selection can differ between populations connected by a low level of gene flow, which may contribute to the maintenance of high DRB allele diversity. In accordance with the optimality hypothesis, individuals with an intermediate number of alleles carried the lowest number of nematode species and had the lowest prevalence of A. tetraptera. However, the intensity of infection with A. tetraptera was linearly and negatively associated with the number of alleles.

  13. Determinants of Coping Responses among Mexican American Adolescents.

    Science.gov (United States)

    Guinn, Bobby; Vincent, Vern

    2002-01-01

    Examined the relationship of perceived stress, self-esteem, acculturation, and gender to the coping response of Mexican American adolescents. Data from self-report surveys indicated that adolescents had relatively high perceived stress levels, low acculturation, and a moderate self-esteem, with no significant gender differences. Self-esteem was…

  14. Application of response surface methodology for determining cutting ...

    Indian Academy of Sciences (India)

    by software Minitab (multiple linear regression and response surface methodology) in order to express the influence degree of the main cutting variables such as cutting speed, feed rate and depth of cut on cutting force components. These models would be helpful in selecting cutting variables for optimization of hard cutting ...

  15. MHC class II DR allelic diversity in bighorn sheep

    Science.gov (United States)

    We hypothesized that decreased diversity and/or unique polymorphisms in MHC class II alleles of bighorn sheep (BHS, Ovis canadensis) are responsible for lower titer of antibodies against Mannheimia haemolytica leukotoxin, in comparison to domestic sheep (DS, Ovis aries). To test this hypothesis, DRA...

  16. Comparison of bovine lymphocyte antigen DRB3.2 allele ...

    African Journals Online (AJOL)

    The bovine lymphocyte antigen (BoLA-DRB3) gene encodes cell surface glycoproteins that initiate immune responses by presenting processed antigenic peptides to CD4 T helper cells. DRB3 is the most polymorphic bovine MHC class II gene which encodes the peptide-binding groove. Since different alleles favor the ...

  17. A Unique ISR Program Determines Cellular Responses to Chronic Stress

    Czech Academy of Sciences Publication Activity Database

    Guan, B.J.; van Hoef, V.; Jobava, R.; Elroy-Stein, O.; Valášek, Leoš Shivaya; Cargnello, M.; Gao, X.H.; Krokowski, D.; Merrick, W.C.; Kimball, S.R.; Komar, A.A.; Koromilas, A.E.; Wynshaw-Boris, A.; Topisirovic, I.; Larsson, O.; Hatzoglou, M.

    2017-01-01

    Roč. 68, č. 5 (2017), s. 885-900 ISSN 1097-2765 R&D Projects: GA ČR(CZ) GA17-06238S EU Projects: Wellcome Trust(GB) 090812/B/09/A Institutional support: RVO:61388971 Keywords : UNFOLDED PROTEIN RESPONSE * EUKARYOTIC TRANSLATION INITIATION * ENDOPLASMIC-RETICULUM STRESS Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 14.714, year: 2016

  18. Calcium influx determines the muscular response to electrotransfer

    DEFF Research Database (Denmark)

    Møller, Pernille Højman; Brolin, Camilla; Gissel, Hanne

    2012-01-01

    Cell membrane permeabilization by electric pulses (electropermeabilization), results in free exchange of ions across the cell membrane. The role of electrotransfer-mediated Ca(2+)-influx on muscle signaling pathways involved in degeneration (β-actin and MurF), inflammation (IL-6 and TNF-α), and r......Cell membrane permeabilization by electric pulses (electropermeabilization), results in free exchange of ions across the cell membrane. The role of electrotransfer-mediated Ca(2+)-influx on muscle signaling pathways involved in degeneration (β-actin and MurF), inflammation (IL-6 and TNF...... low-voltage pulse (HVLV), either alone or in combination with injection of DNA. Mice and rats were anesthetized before pulsing. At the times given, animals were killed, and intact tibialis cranialis muscles were excised for analysis. Uptake of Ca(2+) was assessed using (45)Ca as a tracer. Using gene...... expression analyses and histology, we showed a clear association between Ca(2+) influx and muscular response. Moderate Ca(2+) influx induced by HVLV pulses results in activation of pathways involved in immediate repair and hypertrophy. This response could be attenuated by intramuscular injection of EGTA...

  19. Topologically determined optimal stochastic resonance responses of spatially embedded networks

    International Nuclear Information System (INIS)

    Gosak, Marko; Marhl, Marko; Korosak, Dean

    2011-01-01

    We have analyzed the stochastic resonance phenomenon on spatial networks of bistable and excitable oscillators, which are connected according to their location and the amplitude of external forcing. By smoothly altering the network topology from a scale-free (SF) network with dominating long-range connections to a network where principally only adjacent oscillators are connected, we reveal that besides an optimal noise intensity, there is also a most favorable interaction topology at which the best correlation between the response of the network and the imposed weak external forcing is achieved. For various distributions of the amplitudes of external forcing, the optimal topology is always found in the intermediate regime between the highly heterogeneous SF network and the strong geometric regime. Our findings thus indicate that a suitable number of hubs and with that an optimal ratio between short- and long-range connections is necessary in order to obtain the best global response of a spatial network. Furthermore, we link the existence of the optimal interaction topology to a critical point indicating the transition from a long-range interactions-dominated network to a more lattice-like network structure.

  20. Calcineurin determines toxic versus beneficial responses to α-synuclein.

    Science.gov (United States)

    Caraveo, Gabriela; Auluck, Pavan K; Whitesell, Luke; Chung, Chee Yeun; Baru, Valeriya; Mosharov, Eugene V; Yan, Xiaohui; Ben-Johny, Manu; Soste, Martin; Picotti, Paola; Kim, Hanna; Caldwell, Kim A; Caldwell, Guy A; Sulzer, David; Yue, David T; Lindquist, Susan

    2014-08-26

    Calcineurin (CN) is a highly conserved Ca(2+)-calmodulin (CaM)-dependent phosphatase that senses Ca(2+) concentrations and transduces that information into cellular responses. Ca(2+) homeostasis is disrupted by α-synuclein (α-syn), a small lipid binding protein whose misfolding and accumulation is a pathological hallmark of several neurodegenerative diseases. We report that α-syn, from yeast to neurons, leads to sustained highly elevated levels of cytoplasmic Ca(2+), thereby activating a CaM-CN cascade that engages substrates that result in toxicity. Surprisingly, complete inhibition of CN also results in toxicity. Limiting the availability of CaM shifts CN's spectrum of substrates toward protective pathways. Modulating CN or CN's substrates with highly selective genetic and pharmacological tools (FK506) does the same. FK506 crosses the blood brain barrier, is well tolerated in humans, and is active in neurons and glia. Thus, a tunable response to CN, which has been conserved for a billion years, can be targeted to rebalance the phosphatase's activities from toxic toward beneficial substrates. These findings have immediate therapeutic implications for synucleinopathies.

  1. Ethnic differences in allelic distribution of IFN-g in South African women but no link with cervical cancer

    Directory of Open Access Journals (Sweden)

    Govan Vandana A

    2003-05-01

    Full Text Available Abstract Background The failure of specific types of human papillomaviruses (HPV to raise effective immune responses may be important in the pathogenesis of cervical cancer, the second most common cancer in South African women. Polymorphisms of a number of cytokine genes have been implicated in inducing susceptibility or resistance to cancers caused by infectious agents owing to their role in determining host immune response. Polymorphisms of IL-10 and IFN-γ genes are believed to influence the expression and/or secretion levels of their respective cytokines. Methods and Results In this study, women with histologically proven cancer of the cervix (n = 458 and hospital-based controls (n = 587 were investigated for bi-allelic -1082 (A/G polymorphisms of IL-10 and the bi-allelic +874(A/T polymorphisms of IFN-γ. In addition, the distributions of the allelic frequencies were stratified in both the African and mixed race population groups of South Africa. We found striking differences in the allele distribution of IFN-γ (X2 = 0.02 among the two ethnic groups. A significant increase in the allele distribution of the IFN-γ AA genotype was found in the African group compared to the mixed population group (OR, 0.5; 95% CI, 0.2–1.0. For IL-10 there were no significant allelic differences between the two South African ethnic groups. Furthermore, when the ethnic groups were combined the IL-10 allelic frequencies in the combined South African data were similar to those observed in an Oriental population from Southern China and in an Italian population. However, the allele frequencies of the IFN-γ genotype among the two South African ethnic groups were different when compared to an Italian Caucasoid group. While crude analysis of these data showed both statistically significantly increased and diminished risks of cervical cancer among high producers of INF-γ and low producers of IL-10 respectively, these associations were no longer significant when the

  2. Status epilepticus: Role for etiology in determining response to benzodiazepines.

    Science.gov (United States)

    Joshi, Suchitra; Rajasekaran, Karthik; Hawk, Kyle M; Chester, Stephen J; Goodkin, Howard P

    2018-04-01

    Clinical factors contributing to benzodiazepine failure in treating status epilepticus (SE) include suboptimal dosing and seizure duration. As many benzodiazepine-refractory episodes of SE arise from acute etiologies, we sought to determine whether etiology impacts SE treatment. The potency of diazepam to terminate SE induced by lithium-pilocarpine (LiPilo-SE) or kainic acid (KA-SE) in 3-week-old rats was studied by video-electroencephalography. Synaptic γ-aminobutyric acid type A receptor (GABAR)-mediated currents were recorded from dentate granule cells using voltage-clamp electrophysiology. Surface expression of γ2 subunit-containing GABARs and Kv4.2 potassium channels in hippocampal slices was determined using a biotinylation assay. Expression of phosphorylated forms of β2/3 and γ2 subunits was determined using phosphospecific antibodies and Western blotting. Diazepam failed to terminate late SE in LiPilo-SE animals but was successful in terminating KA-SE of 1- and 3-hour duration. One hour after SE onset, GABAR-mediated synaptic inhibition and γ2 subunit-containing GABAR surface expression were reduced in LiPilo-SE animals. These were unchanged in KA-SE animals at 1 and 3 hours. Phosphorylation of γ2 subunit residue S327 was unchanged in both models, although GABAR β3 subunit S408/409 residues were dephosphorylated in the LiPilo-SE animals. Kv4.2 potassium channel surface expression was increased in LiPilo-SE animals but reduced in KA-SE animals. SE-model-dependent differences support a novel hypothesis that the development of benzodiazepine pharmacoresistance may be etiologically predetermined. Further studies are required to investigate the mechanisms that underlie such etiological differences during SE and whether etiology-dependent protocols for the treatment of SE need to be developed. Ann Neurol 2018;83:830-841. © 2018 American Neurological Association.

  3. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans O.

    2002-01-01

    phenotypes of PMR/GCA. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 102 Danish patients with PMR (n = 37) or GCA (n = 65). Two hundred fifty and 193 healthy individuals served as controls for MBL and HLA genotyping, respectively. RESULTS: The prevalence of MBL variant...

  4. Genetically determined differences in brain response to a primary food reward.

    Science.gov (United States)

    Felsted, Jennifer A; Ren, Xueying; Chouinard-Decorte, Francois; Small, Dana M

    2010-02-17

    Combining genetic and neuroimaging techniques may elucidate the biological underpinnings of individual differences in neurophysiology and potential vulnerabilities to disease. The TaqIA A1 variant is associated with diminished dopamine D(2) receptor density, higher body mass, and food reinforcement. It also moderates the relationship between brain response to food and future weight gain. This suggests that the polymorphism is associated with a fundamental difference in the neurophysiology of food that may predispose toward overeating. An alternative possibility is that factors, such as impulsivity, eating style, reward drive, and perception, which may covary with the polymorphism, influence reward coding and eating behavior. To distinguish between these alternatives, we used functional magnetic resonance imaging to measure neural response to the ingestion of palatable and caloric milkshakes in healthy subjects with (A1+; n = 13) and without (A1-; n = 13) the TaqIA A1 allele. The groups were selected from a larger group to be matched for linked individual factors such as age, gender, education, body mass index, impulsivity, eating style, and perceptual responses to the milkshake. We demonstrate an interaction between genotype (A1+ vs A1-) and stimulus (milkshake vs a tasteless/odorless baseline) in the midbrain, thalamus, and orbital frontal cortex; whereas A1- shows increased responses to milkshake, A1+ shows decreased responses to milkshake relative to baseline. This interaction occurs despite similar ratings of milkshake pleasantness, intensity, and familiarity. We therefore conclude that there is a specific association between the TaqIA A1 polymorphism and brain response during ingestion of a palatable food.

  5. Distribution of a pseudodeficiency allele among Tay-Sachs carriers

    Energy Technology Data Exchange (ETDEWEB)

    Tomczak, J.; Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Boogen, C. (Univ. of Essen Medical School (Germany))

    1993-08-01

    Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

  6. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

    Science.gov (United States)

    Cross, Deanna S; Ivacic, Lynn C; Stefanski, Elisha L; McCarty, Catherine A

    2010-06-17

    There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and

  7. BGMUT: NCBI dbRBC database of allelic variations of genes encoding antigens of blood group systems.

    Science.gov (United States)

    Patnaik, Santosh Kumar; Helmberg, Wolfgang; Blumenfeld, Olga O

    2012-01-01

    Analogous to human leukocyte antigens, blood group antigens are surface markers on the erythrocyte cell membrane whose structures differ among individuals and which can be serologically identified. The Blood Group Antigen Gene Mutation Database (BGMUT) is an online repository of allelic variations in genes that determine the antigens of various human blood group systems. The database is manually curated with allelic information collated from scientific literature and from direct submissions from research laboratories. Currently, the database documents sequence variations of a total of 1251 alleles of all 40 gene loci that together are known to affect antigens of 30 human blood group systems. When available, information on the geographic or ethnic prevalence of an allele is also provided. The BGMUT website also has general information on the human blood group systems and the genes responsible for them. BGMUT is a part of the dbRBC resource of the National Center for Biotechnology Information, USA, and is available online at http://www.ncbi.nlm.nih.gov/projects/gv/rbc/xslcgi.fcgi?cmd=bgmut. The database should be of use to members of the transfusion medicine community, those interested in studies of genetic variation and related topics such as human migrations, and students as well as members of the general public.

  8. Allelic structure and distribution of 103 STR loci in a Southern ...

    Indian Academy of Sciences (India)

    Unknown

    In particular, the use of DNA typing systems in forensic identification has been criticized, in part, on the grounds that the calculations used for asses- sing likelihood of matches were allele frequency depen- dent, which raised the question of what constituted a proper reference population for determining allele frequencies.

  9. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Øhlenschlaeger, Tommy; Garred, Peter; Madsen, Hans O

    2004-01-01

    Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated ...

  10. Allelic analysis of low molecular weight glutenin subunits using 2-DGE in Korean wheat cultivars

    Science.gov (United States)

    Two-dimensional gel electrophoresis (2-DGE) was used to determine the allelic compositions of LMW-GS in 32 Korean wheat cultivars. Protein patterns generated by 2-DGE from each cultivar were compared to patterns from standard wheat cultivars for each allele. At the Glu-A3 locus, thirteen c, twelve ...

  11. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Øhlenschlaeger, Tommy; Garred, Peter; Madsen, Hans O

    2004-01-01

    Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated...... with an increased risk of arterial thrombosis among patients with SLE....

  12. Chinese white Rongchang pig does not have the dominant white allele of KIT but has the dominant black allele of MC1R.

    Science.gov (United States)

    Lai, Fenju; Ren, Jun; Ai, Huashui; Ding, Nengshui; Ma, Junwu; Zeng, Daiqin; Chen, Congyin; Guo, Yuanmei; Huang, Lusheng

    2007-01-01

    The mast/stem cell growth factor receptor (KIT) and melanocortin receptor 1 (MC1R) mutations are responsible for coat color phenotypes in domestic pigs. Rongchang is a Chinese indigenous pig breed with a white coat color phenotype. To investigate the genetic variability of the KIT and MC1R genes and their possible association with the coat color phenotype in this breed, a gene duplication and splice mutation of KIT were diagnosed in a sample of 93 unrelated Rongchang animals. The results show that Rongchang pigs have a single copy of KIT without the splice mutation at the first nucleotide of intron 17, indicating that the dominant white I allele of KIT is not responsible for their white phenotype. The KIT mRNA and MC1R coding sequences were also determined in this breed. Three putative amino acid substitutions were found in the KIT gene between Rongchang and Western white pigs, their association with the Rongchang white phenotype remains unknown. For the MC1R gene, Rongchang pigs were demonstrated to have the same dominant black allele (E(D1)) as other Chinese breeds, supporting the previous conclusion that Chinese and Western pigs have independent domestication origin. We also clarified that the Rongchang white phenotype was recessive to nonwhite color phenotypes. Our results provide a good starting point for the identification of the mutations underlying the white coat color in Rongchang pigs.

  13. Impact of pre-existing MSP142-allele specific immunity on potency of an erythrocytic Plasmodium falciparum vaccine

    Directory of Open Access Journals (Sweden)

    Bergmann-Leitner Elke S

    2012-09-01

    hindered by clonally imprinted p33 responses mainly restricted at the T cell level. In this study, the homology of the p33 sequence between the clonally imprinted response and the vaccine allele determines the magnitude of vaccine induced responses.

  14. Hypermethylated SUPERMAN epigenetic alleles in arabidopsis.

    Science.gov (United States)

    Jacobsen, S E; Meyerowitz, E M

    1997-08-22

    Mutations in the SUPERMAN gene affect flower development in Arabidopsis. Seven heritable but unstable sup epi-alleles (the clark kent alleles) are associated with nearly identical patterns of excess cytosine methylation within the SUP gene and a decreased level of SUP RNA. Revertants of these alleles are largely demethylated at the SUP locus and have restored levels of SUP RNA. A transgenic Arabidopsis line carrying an antisense methyltransferase gene, which shows an overall decrease in genomic cytosine methylation, also contains a hypermethylated sup allele. Thus, disruption of methylation systems may yield more complex outcomes than expected and can result in methylation defects at known genes. The clark kent alleles differ from the antisense line because they do not show a general decrease in genomic methylation.

  15. Allele-specific enzymatic amplification of. beta. -globin genomic DNA for diagnosis of sickle cell anemia

    Energy Technology Data Exchange (ETDEWEB)

    Wu, D.Y.; Ugozzoli, L.; Pal, B.K.; Wallace, B. (Beckman Research Institute of the City of Hope, Duarte, CA (USA))

    1989-04-01

    A rapid nonradioactive approach to the diagnosis of sickle cell anemia is described based on an allele-specific polymerase chain reaction (ASPCR). This method allows direct detection of the normal or the sickle cell {beta}-globin allele in genomic DNA without additional steps of probe hybridization, ligation, or restriction enzyme cleavage. Two allele-specific oligonucleotide primers, one specific for the sickle cell allele and one specific for the normal allele, together with another primer complementary to both alleles were used in the polymerase chain reaction with genomic DNA templates. The allele-specific primers differed from each other in their terminal 3{prime} nucleotide. Under the proper annealing temperature and polymerase chain reaction conditions, these primers only directed amplification on their complementary allele. In a single blind study of DNA samples from 12 individuals, this method correctly and unambiguously allowed for the determination of the genotypes with no false negatives or positives. If ASPCR is able to discriminate all allelic variation (both transition and transversion mutations), this method has the potential to be a powerful approach for genetic disease diagnosis, carrier screening, HLA typing, human gene mapping, forensics, and paternity testing.

  16. Multifragment alleles in DNA fingerprints of the parrot, Amazona ventralis

    Science.gov (United States)

    Brock, M.K.; White, B.N.

    1991-01-01

    Human DNA probes that identify variable numbers of tandem repeat loci are being used to generate DNA fingerprints in many animal and plant species. In most species the majority of the sc rable autoradiographic bands of the DNA fingerprint represent alleles from numerous unlinked loci. This study was initiated to use DNA fingerprints to determine the amount of band-sharing among captive Hispaniolan parrots (Amazona ventralis) with known genetic relationships. This would form the data base to examine DNA fingerprints of the closely related and endangered Puerto Rican parrot (A. vittata) and to estimate the degree of inbreeding in the relic population. We found by segregation analysis of the bands scored in the DNA fingerprints of the Hispaniolan parrots that there may be as few as two to five loci identified by the human 33.15 probe. Furthermore, at one locus we identified seven alleles, one of which is represented by as many as 19 cosegregating bands. It is unknown how common multiband alleles might be in natural populations, and their existence will cause problems in the assessment of relatedness by band-sharing analysis. We believe, therefore, that a pedigree analysis should be included in all DNA fingerprinting studies, where possible, in order to estimate the number of loci identified by a minisatellite DNA probe and to examine the nature of their alleles.

  17. Novel alleles of 31-bp VNTR polymorphism in the human ...

    Indian Academy of Sciences (India)

    We report here for the first time, the detection of allele 20, which was absent in Caucasian and Indo–Caucasoid populations, as a common allele present in Singaporean Chinese (6.25%), Indians (11.7%), and Malays (11.5%). Hence, allele 20 might be a specific allele for Asian populations. A relatively common allele 19 ...

  18. Victim's Response and Alcohol-Related Factors as Determinants of Women's Responses to Violent Pornography

    Science.gov (United States)

    Norris, Jeanette; Davis, Kelly Cue; George, William H.; Martell, Joel; Heiman, Julia R.

    2004-01-01

    Women suffer a variety of detrimental effects from exposure to violent pornography. This study examined the role of specific situational cues embedded within a violent pornographic story, as well as alcohol consumption and alcohol expectancies, to determine potential mechanisms through which these effects occur. Female social drinkers (N=123),…

  19. Influence determination of social responsibility to the productivity enterprise activity level

    OpenAIRE

    Kavun, Sergii; Zhosan, Ganna

    2016-01-01

    The purpose of this paper is to develop a scientific and methodical approach for determination of the comprehensive social responsibility indicator in this paper based on estimation of influence degree for the economical, ecological, social and labour, standard and legal components. There is allowance for determining of some level of enterprise social responsibility. In addition, there is a basis for development some ways of their increasing. The essence of the used approach is clotting of th...

  20. A Study on the Determinants of Earnings Response Coefficient in an Emerging Market

    OpenAIRE

    Bita Mashayekhi; Zeynab Lotfi Aghel

    2016-01-01

    The determinants of Earnings Response Coefficient (ERC), including firm size, earnings growth, and earnings persistence are studied in this research. These determinants are supposed to be moderator variables that affect ERC and Return Response Coefficient. The research sample contains 82 Iranian listed companies in Tehran Stock Exchange (TSE) from 2001 to 2012. Gathered data have been processed by EVIEWS Software. Results show a significant positive relation between firm size and ERC, and als...

  1. A rapid challenge protocol for determination of non-specific bronchial responsiveness

    DEFF Research Database (Denmark)

    Madsen, F; Nielsen, N H; Holstein-Rathlou, N H

    1986-01-01

    A rapid method for determination of non-specific bronchial hyperreactivity was developed. Resistance to breathing was determined by a modified expiratory airway interrupter technique and combined with a dosimeter-controlled nebulizer which made continuous determination of response possible during...... hyperreactivity since individual dose titration is easily performed, and the method could be valuable in epidemiological and occupational surveys as well.......A rapid method for determination of non-specific bronchial hyperreactivity was developed. Resistance to breathing was determined by a modified expiratory airway interrupter technique and combined with a dosimeter-controlled nebulizer which made continuous determination of response possible during...... challenge. The patients inhaled histamine chloride 8 mg/ml at every eighth breath until resistance to breathing (Rt) was increased by 60%. The number of inhalations (NI) or the provocative concentration (PC60-Rt) of histamine increasing Rt by 60% were determined in 68 patients. The new method correlated...

  2. Transcriptional profiling identifies physicochemical properties of nanomaterials that are determinants of the in vivo pulmonary response

    DEFF Research Database (Denmark)

    Halappanavar, Sabina; Saber, Anne Thoustrup; Decan, Nathalie

    2015-01-01

    We applied transcriptional profiling to elucidate the mechanisms associated with pulmonary responses to titanium dioxide (TiO2) nanoparticles (NPs) of different sizes and surface coatings, and to determine if these responses are modified by NP size, surface area, surface modification, and embeddi...

  3. Nucleotide variation and identification of novel blast resistance alleles of Pib by allele mining strategy.

    Science.gov (United States)

    Ramkumar, G; Madhav, M S; Devi, S J S Rama; Prasad, M S; Babu, V Ravindra

    2015-04-01

    Pib is one of significant rice blast resistant genes, which provides resistance to wide range of isolates of rice blast pathogen, Magnaporthe oryzae. Identification and isolation of novel and beneficial alleles help in crop enhancement. Allele mining is one of the best strategies for dissecting the allelic variations at candidate gene and identification of novel alleles. Hence, in the present study, Pib was analyzed by allele mining strategy, and coding and non-coding (upstream and intron) regions were examined to identify novel Pib alleles. Allelic sequences comparison revealed that nucleotide polymorphisms at coding regions affected the amino acid sequences, while the polymorphism at upstream (non-coding) region affected the motifs arrangements. Pib alleles from resistant landraces, Sercher and Krengosa showed better resistance than Pib donor variety, might be due to acquired mutations, especially at LRR region. The evolutionary distance, Ka/Ks and phylogenetic analyzes also supported these results. Transcription factor binding motif analysis revealed that Pib (Sr) had a unique motif (DPBFCOREDCDC3), while five different motifs differentiated the resistance and susceptible Pib alleles. As the Pib is an inducible gene, the identified differential motifs helps to understand the Pib expression mechanism. The identified novel Pib resistant alleles, which showed high resistance to the rice blast, can be used directly in blast resistance breeding program as alternative Pib resistant sources.

  4. KIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles

    Science.gov (United States)

    Bari, Rafijul; Thapa, Rajoo; Bao, Ju; Li, Ying; Zheng, Jie; Leung, Wing

    2016-03-01

    KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E35 could kill more target cells lacking their ligands than NK cells with the weaker -Q35 alleles, indicating better licensing of KIR2DL2/L3+ NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.

  5. Response to rocuronium and its determinants in patients with myasthenia gravis: A case-control study.

    Science.gov (United States)

    Fujimoto, Masafumi; Terasaki, Shuhei; Nishi, Masaaki; Yamamoto, Tatsuo

    2015-10-01

    Several previous studies using univariate analysis have suggested that the pre-anaesthetic train-of-four (TOF) ratio, concentration of anti-acetylcholine receptor (AChR) antibodies and the presence of preoperative generalised muscular involvement are determinants of an increased response to neuromuscular blocking agents (NMBAs) in patients with myasthenia gravis. However, the determinants of the response of patients with myasthenia gravis to rocuronium, which is expected to be used more frequently since the advent of sugammadex, have not been studied. To clarify whether previously suggested determinants of the response to other intermediate-acting NMBAs would also affect the response to rocuronium and to reveal the determinants of the increased response to rocuronium in individual patients with myasthenia gravis using multivariate analysis. Case control study. Kumamoto University Hospital, November 2010 to September 2013. Thirty-eight patients with myasthenia gravis having surgery using a total intravenous anaesthetic technique were investigated. After induction of general anaesthesia, the 95% effective dose (ED95) of rocuronium was calculated using cumulative dose-finding methods. Neuromuscular function was monitored by acceleromyographic assessment of TOF responses of the adductor pollicis muscle to ulnar nerve stimulation. Patients were then divided into the increased response (ED95 gravis in the two groups were compared. Stepwise logistic regression identified baseline TOF ratio and age of onset of myasthenia gravis as determinants of the increased response to rocuronium in patients with myasthenia gravis [odds ratios (95% confidence interval) of 0.87 (0.77 to 0.98; P = 0.02) and 0.92 (0.86 to 0.99; P = 0.03), respectively]. Multivariate analysis identified baseline TOF ratio and age of disease onset as determinants of the increased response to rocuronium in patients with myasthenia gravis. Registered with UMIN Clinical Trials Registry, identifier: UMIN

  6. Comparison of HLA allelic imputation programs.

    Directory of Open Access Journals (Sweden)

    Jason H Karnes

    Full Text Available Imputation of human leukocyte antigen (HLA alleles from SNP-level data is attractive due to importance of HLA alleles in human disease, widespread availability of genome-wide association study (GWAS data, and expertise required for HLA sequencing. However, comprehensive evaluations of HLA imputations programs are limited. We compared HLA imputation results of HIBAG, SNP2HLA, and HLA*IMP:02 to sequenced HLA alleles in 3,265 samples from BioVU, a de-identified electronic health record database coupled to a DNA biorepository. We performed four-digit HLA sequencing for HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1 using long-read 454 FLX sequencing. All samples were genotyped using both the Illumina HumanExome BeadChip platform and a GWAS platform. Call rates and concordance rates were compared by platform, frequency of allele, and race/ethnicity. Overall concordance rates were similar between programs in European Americans (EA (0.975 [SNP2HLA]; 0.939 [HLA*IMP:02]; 0.976 [HIBAG]. SNP2HLA provided a significant advantage in terms of call rate and the number of alleles imputed. Concordance rates were lower overall for African Americans (AAs. These observations were consistent when accuracy was compared across HLA loci. All imputation programs performed similarly for low frequency HLA alleles. Higher concordance rates were observed when HLA alleles were imputed from GWAS platforms versus the HumanExome BeadChip, suggesting that high genomic coverage is preferred as input for HLA allelic imputation. These findings provide guidance on the best use of HLA imputation methods and elucidate their limitations.

  7. SORT1 protective allele is associated with attenuated postprandial: lipaemia in young adults.

    Science.gov (United States)

    Connors, Kimberly E; Karlos, Angela E; Gnatiuk, Elizabeth A; Shearer, Jane; Reimer, Raylene A; Hittel, Dustin S

    2014-10-01

    Elevated levels of lipids and lipoproteins have strong genetic determinants and are recognized as key risk factors for atherogenesis and cardiovascular disease, particularly in the postprandial state. The aim of the study to determine whether young adults, when stratified by genotype at the rs646776 variant of the 1p13 locus, displayed differential postprandial responses to an oral fat tolerance test. Participants (n=30) received a high-fat mixed meal (91 g; 55% kcal from fat) after an overnight fast and a fat-exclusion meal (3.9 g; 6% kcal from fat) at 8 hours postprandially. Blood samples were obtained at t=0, 2, 4, 6, 8, and 24 hours for lipoprotein analyses via nuclear magnetic resonance profiling. Carriers of the minor, protective allele (TC/CC) displayed lower fasting (TC/CC, 30.1±3.0 nmol/L versus TT, 48.8±5.1 nmol/L; Ppostprandial (TC/CC, 44.2±3.1 nmol/L versus TT, 57.0±4.5 nmol/L; P=0.03) very low-density lipoprotein and chylomicron particle number in addition to triglyceride content when compared with individuals homozygous for the major, risk allele (TT). We report a novel association between the SORT1 1p13 locus and extent of postprandial lipaemia. These results provide evidence of decreased exposure to atherogenic particles in carriers of the minor SORT1 allele, suggesting relative protection against cardiovascular disease when compared with TT homozygotes. © 2014 American Heart Association, Inc.

  8. Local Adaptation by Alleles of Small Effect.

    Science.gov (United States)

    Yeaman, Sam

    2015-10-01

    Population genetic models predict that alleles with small selection coefficients may be swamped by migration and will not contribute to local adaptation. But if most alleles contributing to standing variation are of small effect, how does local adaptation proceed? Here I review predictions of population and quantitative genetic models and use individual-based simulations to illustrate how the architecture of local adaptation depends on the genetic redundancy of the trait, the maintenance of standing genetic variation (V(G)), and the susceptibility of alleles to swamping. Even when population genetic models predict swamping for individual alleles, considerable local adaptation can evolve at the phenotypic level if there is sufficient V(G). However, in such cases the underlying architecture of divergence is transient: F(ST) is low across all loci, and no locus makes an important contribution for very long. Because this kind of local adaptation is mainly due to transient frequency changes and allelic covariances, these architectures will be difficult--if not impossible--to detect using current approaches to studying the genomic basis of adaptation. Even when alleles are large and resistant to swamping, architectures can be highly transient if genetic redundancy and mutation rates are high. These results suggest that drift can play a critical role in shaping the architecture of local adaptation, both through eroding V(G) and affecting the rate of turnover of polymorphisms with redundant phenotypic effects.

  9. HLA- DR Alleles in Pakistani Patients of Pemphigus Vulgaris.

    Science.gov (United States)

    Khan, Sara Waqar; Iftikhar, Nadia; Ahmed, Tahir Aziz; Bashir, Mukarram

    2015-04-01

    To determine frequency of HLA-DR alleles in Pakistani patients of pemphigus vulgaris in comparison with local healthy controls. Cross-sectional, comparative study. Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January 2011 to January 2014. Twenty eight patients with biopsy proven diagnosis of pemphigus vulgaris referred from Department of Dermatology, Military Hospital, Rawalpindi were included. Patients were compared with a group of 150 unrelated local healthy subjects. DNA was extracted from peripheral blood collected in Tri-potassium EDTA. HLA-DRB1 typing was carried out on allele level (DRB1*01--DRB1*16) using SSP (sequence specific primers). HLA type was determined by agarose gel electrophoresis and results recorded. Phenotype frequency of various alleles among patient group and control group was calculated by direct counting and significance of their association was determined by Fisher's exact test/ Chi square test. A total of 12 male and 16 female patients, with age ranging from 21 to 34 (mean 23.4 years) were genotyped for HLA-DRB1 loci. A statistically significant association of the disease with HLA-DRB1*04 was observed (50% versus 20.7% in controls, p pemphigus vulgaris in Pakistani population.

  10. HLA- DR Alleles in Pakistani Patients of Pemphigus Vulgaris

    International Nuclear Information System (INIS)

    Khan, S. W.; Ahmad, T. A.; Bashir, M.; Iftikhar, N.

    2015-01-01

    Objective: To determine frequency of HLA-DR alleles in Pakistani patients of pemphigus vulgaris in comparison with local healthy controls. Study Design: Cross-sectional, comparative study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January 2011 to January 2014. Methodology: Twenty eight patients with biopsy proven diagnosis of pemphigus vulgaris referred from Department of Dermatology, Military Hospital, Rawalpindi were included. Patients were compared with a group of 150 unrelated local healthy subjects. DNA was extracted from peripheral blood collected in Tri-potassium EDTA. HLA-DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using SSP (sequence specific primers). HLA type was determined by agarose gel electrophoresis and results recorded. Phenotype frequency of various alleles among patient group and control group was calculated by direct counting and significance of their association was determined by Fisher's exact test/ Chi square test. Results: A total of 12 male and 16 female patients, with age ranging from 21 to 34 (mean 23.4 years) were genotype for HLA-DRB1 loci. A statistically significant association of the disease with HLA-DRB1*04 was observed (50% versus 20.7% in controls, p < 0.05). Conclusion: There is a strong association of HLA-DRB1*04 with pemphigus vulgaris in Pakistani population. (author)

  11. The effect of wild card designations and rare alleles in forensic DNA database searches.

    Science.gov (United States)

    Tvedebrink, Torben; Bright, Jo-Anne; Buckleton, John S; Curran, James M; Morling, Niels

    2015-05-01

    Forensic DNA databases are powerful tools used for the identification of persons of interest in criminal investigations. Typically, they consist of two parts: (1) a database containing DNA profiles of known individuals and (2) a database of DNA profiles associated with crime scenes. The risk of adventitious or chance matches between crimes and innocent people increases as the number of profiles within a database grows and more data is shared between various forensic DNA databases, e.g. from different jurisdictions. The DNA profiles obtained from crime scenes are often partial because crime samples may be compromised in quantity or quality. When an individual's profile cannot be resolved from a DNA mixture, ambiguity is introduced. A wild card, F, may be used in place of an allele that has dropped out or when an ambiguous profile is resolved from a DNA mixture. Variant alleles that do not correspond to any marker in the allelic ladder or appear above or below the extent of the allelic ladder range are assigned the allele designation R for rare allele. R alleles are position specific with respect to the observed/unambiguous allele. The F and R designations are made when the exact genotype has not been determined. The F and R designation are treated as wild cards for searching, which results in increased chance of adventitious matches. We investigated the probability of adventitious matches given these two types of wild cards. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest

    DEFF Research Database (Denmark)

    Alibegovic, Amra C; Sonne, Mette P; Højbjerre, Lise

    2010-01-01

    , the TCF7L2 rs7903146 did not influence peripheral insulin action or the rate of lipolysis before or after bed rest. CONCLUSIONS: Healthy carriers of the T-allele of TCF7L2 rs7903146 exhibit a diminished increase of insulin secretion in response to intravenous glucose to compensate for insulin resistance......OBJECTIVE: The aim of this study was to determine whether the type 2 diabetes-associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. RESEARCH DESIGN AND METHODS: A total of 38....... The genetic analyses were done assuming a dominant model of inheritance. RESULTS: The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise...

  13. The miR9863 family regulates distinct Mla alleles in barley to attenuate NLR receptor-triggered disease resistance and cell-death signaling.

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2014-12-01

    Full Text Available Barley (Hordeum vulgare L. Mla alleles encode coiled-coil (CC, nucleotide binding, leucine-rich repeat (NB-LRR receptors that trigger isolate-specific immune responses against the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh. How Mla or NB-LRR genes in grass species are regulated at post-transcriptional level is not clear. The microRNA family, miR9863, comprises four members that differentially regulate distinct Mla alleles in barley. We show that miR9863 members guide the cleavage of Mla1 transcripts in barley, and block or reduce the accumulation of MLA1 protein in the heterologous Nicotiana benthamiana expression system. Regulation specificity is determined by variation in a unique single-nucleotide-polymorphism (SNP in mature miR9863 family members and two SNPs in the Mla miR9863-binding site that separates these alleles into three groups. Further, we demonstrate that 22-nt miR9863s trigger the biogenesis of 21-nt phased siRNAs (phasiRNAs and together these sRNAs form a feed-forward regulation network for repressing the expression of group I Mla alleles. Overexpression of miR9863 members specifically attenuates MLA1, but not MLA10-triggered disease resistance and cell-death signaling. We propose a key role of the miR9863 family in dampening immune response signaling triggered by a group of MLA immune receptors in barley.

  14. Altering the sex determination pathway in Drosophila fat body modifies sex-specific stress responses

    Science.gov (United States)

    Neckameyer, Wendi S.

    2014-01-01

    The stress response in Drosophila melanogaster reveals sex differences in behavior, similar to what has been observed in mammals. However, unlike mammals, the sex determination pathway in Drosophila is well established, making this an ideal system to identify factors involved in the modulation of sex-specific responses to stress. In this study, we show that the Drosophila fat body, which has been shown to be important for energy homeostasis and sex determination, is a dynamic tissue that is altered in response to stress in a sex and time-dependent manner. We manipulated the sex determination pathway in the fat body via targeted expression of transformer and transformer-2 and analyzed these animals for changes in their response to stress. In the majority of cases, manipulation of transformer or transformer-2 was able to change the physiological output in response to starvation and oxidative stress to that of the opposite sex. Our data also uncover the possibility of additional downstream targets for transformer and transformer-2 that are separate from the sex determination pathway and can influence behavioral and physiological responses. PMID:24789992

  15. Host microsatellite alleles in malaria predisposition?

    Directory of Open Access Journals (Sweden)

    Trivedi Rajni

    2005-10-01

    Full Text Available Abstract Background Malaria is a serious, sometimes fatal, disease caused by Plasmodium infection of human red blood cells. The host-parasite co-evolutionary processes are well understood by the association of coding variations such as G6PD, Duffy blood group receptor, HLA, and beta-globin gene variants with malaria resistance. The profound genetic diversity in host is attributed to polymorphic microsatellites loci. The microsatellite alleles in bacterial species are known to have aided their survival in fatal environmental conditions. The fascinating question is whether microsatellites are genomic cushion in the human genome to combat disease stress and has cause-effect relationships with infections. Presentation of the hypothesis It is hypothesized that repeat units or alleles of microsatellites TH01 and D5S818, located in close proximity to beta-globin gene and immune regulatory region in human play a role in malaria predisposition. Association of alleles at aforesaid microsatellites with malaria infection was analysed. To overrule the false association in unrecognized population stratification, structure analysis and AMOVA were performed among the sampled groups. Testing of hypothesis Associations of microsatellite alleles with malaria infection were verified using recombination rate, Chi-square, and powerful likelihood tests. Further investigation of population genetic structure, and AMOVA was done to rule out the confounding effects of population stratification in interpretation of association studies. Implication of the hypothesis Lower recombination rate (θ between microsatellites and genes implicated in host fitness; positive association between alleles -13 (D5S818, 9 (TH01 and strong susceptibility to Plasmodium falciparum; and alleles-12 (D5S818 and 6 (TH01 rendering resistance to human host were evident. The interesting fact emerging from the study was that while predisposition to malaria was a prehistoric attribute, among TH01

  16. Determining the Response Behaviors of Middle School Students for Open-Ended Questions

    Directory of Open Access Journals (Sweden)

    Neslihan Tuğçe ŞİMŞEK

    2017-04-01

    Full Text Available When the literature for measurement and evaluation in education is reviewed, research related to student achievement are mainly outcome-oriented rather than process-oriented. Researchers pay attention to the responses that a student constructs or chooses, and ignore the cognitive processes that forces students to construct or choose that specific response. Recognizing the cognitive processes a student uses in responding to a question affects the item construction process and psychometric audit on items. Response behavior is a result of a cognitive process used to respond to a question and is accepted as an indicator of student cognitive competence. This study aims to determine the students’ response behaviors for open-ended questions. The study group consisted of 70 students from the 5th grade studying during the 2015-2016 education year spring term in the Cankaya and Mamak districts of Ankara province, Turkey. An authentic achievement test which consisted of eight open-ended questions is used as the data collection tool. Students are asked to write in detail how they construct their response in their mind in the blank space set aside after each question. Data is analyzed via grouping students’ response behaviors and expert opinions. Research findings revealed that students perform 14 different response behaviors for open-ended questions. These behaviors are themed as responses constructed directly from the text, responses constructed by interpreting the text, and responses constructed by linking real life and the text.

  17. Allele frequencies of 15 autosomal STR loci in the Caymanian population.

    Science.gov (United States)

    Faris, Jonathan S; Tanzillo-Swarts, Angela

    2015-05-01

    Allele frequency distributions in the Caymanian population were determined using the AmpFlSTR® Identifiler® PCR amplification kit. Little evidence of departure from Hardy-Weinberg equilibrium or the association of alleles of different loci was detected. Comparison with relevant population groups supports the Caymanian population having a distinct allelic distribution. The 15 Identifiler® loci provide combined power of discrimination and exclusion values of 0.999999999999999995 and 0.9999992, respectively, proving suitable for the forensic and paternity testing requirements of the Cayman Islands.

  18. Baroreflex sensitivity as a determinant of responses to hydralazine in dogs.

    Science.gov (United States)

    Vidrio, H

    1983-01-01

    In order to evaluate the relation between hypotension induced by hydralazine and the resultant reflex tachycardia, as well as the role of baroreflex sensitivity in determining the magnitude of these responses, the drug was administered orally at a dose of 1 mg/kg to a group of trained conscious normotensive and renal hypertensive dogs. Responses were assessed by measuring blood pressure and heart rate for 8 hr after dosing and integrating the changes observed over time in order to obtain a mean value. Baroreflex gain was calculated as the ratio of heart rate to blood pressure responses. Hypotension was greater in hypertensives, whereas tachycardia was not different between groups. Gain was therefore smaller in hypertensives, but not uniformly so, a portion of these animals having values within the normotensive range. This high gain group responded with less hypotension and more tachycardia than did the low gain group. Differences in pressure and rate responses to repeated administration of hydralazine between the two groups were minimal. It is suggested that baroreflex gain, an innate individual characteristic, is an important determinant of acute pressure responses to hydralazine in dogs, hypertensive animals having less gain than normotensives and showing increased hypotensive responses. Gain appears not to be as important in determining the chronic effects of the drug.

  19. The protease inhibitor PI*S allele and COPD

    DEFF Research Database (Denmark)

    Hersh, C P; Ly, N P; Berkey, C S

    2005-01-01

    In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current...... authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared...... with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting...

  20. Comparative study for methods to determine the seismic response of NPP structures

    International Nuclear Information System (INIS)

    Varpasuo, P.

    1995-01-01

    There are many different important problem areas in evaluating the seismic response of structures. In this study the effort is concentrated on three of these areas. The first task is the mathematical formulation of earthquake excitation. The random vibration theory is taken as the tool in this task. The second area of interest in this study is the soil-structure interaction analysis. The approach of impedance functions is chosen and the focal point of interest is the significance of frequency dependent impedance functions. The third area of interest is the methods to determine the structural response. The following three methods were tested: the mode superposition time history method; the complex frequency response method; the response spectrum method. The comparison was made with the aid of MSC/NASTRAN code. The three methods gave for outer containment building response results which were in good agreement with each other. (author). 4 refs., 5 figs

  1. AB0 blood subgroup allele frequencies in the Turkish population.

    Science.gov (United States)

    Akbas, Fahri; Aydin, Müge; Cenani, Asim

    2003-09-01

    We determined the AB0 blood group system with a PCR based technique termed APLP (Amplified Product Length Polymorphism) in the Turkish population. The method includes ten different allele specific primers and permits identification of the major AB0 genotypes and its suballeles (A1-A2-B-0A-02-0G-AG). The suballeles were amplified in a single tube reaction. We have determined AB0 phenotypes in 129 Turkish individuals. No significant deviation from the Hardy-Weinberg equilibrium was observed.

  2. Expression of human PTPN22 alleles

    DEFF Research Database (Denmark)

    Nielsen, C; Barington, T; Husby, S

    2007-01-01

    Considering the female predominance in most of the autoimmune disorders that associate with the PTPN22 Trp620 variant and the complexity by which this variant influences immunologic tolerance, the objective of this study was to ascertain if the allele-specific expression of the disease...... and 72 h of activation, respectively, the expression of PTPN22 1858C- and T-alleles increased to the same extent (P=0.64). The present result essentially excludes such phenomena as a partial explanation for the female predominance in most of the autoimmune disorders that associate with the PTPN22 Trp620...

  3. Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar

    Science.gov (United States)

    Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F. Javier

    2010-12-01

    Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar ( Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

  4. Use of inelastic analysis to determine the response of packages to puncture accidents

    International Nuclear Information System (INIS)

    Ammerman, D.J.; Ludwigsen, J.S.

    1996-01-01

    The accurate analytical determination of the response of radioactive material transportation packages to the hypothetical puncture accident requires inelastic analysis techniques. Use of this improved analysis method recudes the reliance on empirical and approximate methods to determine the safety for puncture accidents. This paper will discuss how inelastic analysis techniques can be used to determine the stresses, strains and deformations resulting from puncture accidents for thin skin materials with different backing materials. A method will be discussed to assure safety for all of these types of packages

  5. 21 CFR 111.73 - What is your responsibility for determining whether established specifications are met?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What is your responsibility for determining whether established specifications are met? 111.73 Section 111.73 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD...

  6. Determination of the parameters of a microscopic object from a complex response of a differential microscope

    International Nuclear Information System (INIS)

    Baranov, D V; Egorov, Alexander A; Zolotov, Evgenii M; Svidzinsky, K K

    1998-01-01

    An analysis of the amplitude and phase of a complex response of a heterodyne differential microscope was used to demonstrate experimentally the feasibility of determination of the parameters of a composite microscopic object representing a combination of a step with a groove. (laser applications and other topics in quantum electronics)

  7. DETERMINING THE RESPONSE IN CASE OF VIBRATIONS OF STRAIGHT BARS WITH RANDOM EXCITATIONS

    Directory of Open Access Journals (Sweden)

    Monica BALDEA

    2012-05-01

    Full Text Available By applying the finite element calculus to the study of bar vibrations, one obtains a system of linear diferential equations. One carries out the determination of the response to random stimulations by calculating the statistical terms as a function of the statistical terms of the stimulation

  8. Determining generator parameters of Camargos hydroelectric power plant through frequency response measurement

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Sebastiao E.M. de; Padua Guarini, Antonio de [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Souza, Joao A. de; Valgas, Helio M.; Pinto, Roberto del Giudice R. [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil)

    1994-12-31

    This work describes the results of the set frequency response tests performed in the generator number 2, 6.9 kV, 25 MVA, of Camargos hydroelectric power plant, CEMIG, and the parameters relatives to determined structures of model. This tests are unpublished in Brazil. (author) 7 refs., 16 figs., 7 tabs.

  9. Acceptance criteria for determining armed response force size at nuclear power plants

    International Nuclear Information System (INIS)

    1983-02-01

    This guidance document contains acceptance criteria to be used in the NRC license review process. It consists of a scored worksheet and guidelines for interpreting the worksheet score that can be used in determining the adequacy of the armed response force size at a nuclear power reactor facility

  10. 12 CFR 652.75 - Your responsibility for determining the risk-based capital level.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Your responsibility for determining the risk-based capital level. 652.75 Section 652.75 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM FEDERAL AGRICULTURAL MORTGAGE CORPORATION FUNDING AND FISCAL AFFAIRS Risk-Based Capital...

  11. On Values, Determinants of Spending, and Civil Rights: Response to Commentaries on Braddock et al.

    Science.gov (United States)

    Braddock, David

    1987-01-01

    In response to comments on his nationwide study of public mental retardation/developmental disabilities spending in the states, the author considers classification of funds (income maintenance, large private facilities and prisons, nursing homes, and education/vocational rehabilitation), values, determinants, civil rights, and reform. (DB)

  12. Standardized SSR allele naming and binning among projects.

    Science.gov (United States)

    Deemer, Dennis L; Nelson, C Dana

    2010-11-01

    Simple sequence repeats (SSRs) have proven to be extremely valuable DNA markers for genetic mapping and population genetic analyses. However, data collected across laboratories or even within laboratories are difficult to combine due to challenges in standardizing allele names, especially for nonmodel systems. Here we provide a new approach for standardizing SSR allele names that combines several previously recognized components for standardization, including reference samples/alleles, cumulative binsets, static between-allele spacing, and interval allele naming.

  13. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility.

    Science.gov (United States)

    Clark, Taane G; Fry, Andrew E; Auburn, Sarah; Campino, Susana; Diakite, Mahamadou; Green, Angela; Richardson, Anna; Teo, Yik Y; Small, Kerrin; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Sabeti, Pardis; Kwiatkowski, Dominic P; Rockett, Kirk A

    2009-08-01

    Several lines of evidence link glucose-6-phosphate dehydrogenase (G6PD) deficiency to protection from severe malaria. Early reports suggested most G6PD deficiency in sub-Saharan Africa was because of the 202A/376G G6PD A- allele, and recent association studies of G6PD deficiency have employed genotyping as a convenient way to determine enzyme status. However, further work has suggested that other G6PD deficiency alleles are relatively common in some regions of West Africa. To investigate the consequences of unrecognized allelic heterogeneity on association studies, in particular studies of G6PD deficiency and malaria, we carried out a case-control analysis of 2488 Gambian children with severe malaria and 3875 controls. No significant association was found between severe malaria and the 202A/376G G6PD A- allele when analyzed alone, but pooling 202A/376G with other deficiency alleles revealed the signal of protection (male odds ratio (OR) 0.77, 95% CI 0.62-0.95, P=0.016; female OR 0.71, 95% CI 0.56-0.89, P=0.004). We have identified the 968C mutation as the most common G6PD A- allele in The Gambia. Our results highlight some of the consequences of allelic heterogeneity, particularly the increased type I error. They also suggest that G6PD-deficient male hemizygotes and female heterozygotes are protected from severe malaria.

  14. Molecular and Genomic Determinants of Response to Immune Checkpoint Inhibition in Cancer.

    Science.gov (United States)

    Jenkins, Russell W; Thummalapalli, Rohit; Carter, Jacob; Cañadas, Israel; Barbie, David A

    2018-01-29

    Molecularly targeted therapy and immunotherapy have dramatically changed the landscape of available treatment options for patients with advanced cancer. Improved understanding of the molecular and genomic features of cancers over the last decade has led to the development of successful targeted therapies and the field of precision cancer medicine. As a result of these advances, patients whose tumors harbor select molecular alterations are eligible for treatment with targeted therapies active against the unique molecular aberration. Concurrently, advances in tumor immunology have led to the development of immunomodulatory antibodies targeting T cell coinhibitory receptors CTLA-4 and PD-1 (programmed death-1) that have shown activity in several cancer histologies, reinvigorating antitumor immune responses in a subset of patients. These immunomodulatory antibodies offer the promise of durable disease control. However, discrete genomic determinants of response to cancer immunotherapy, unlike molecularly targeted therapies, have remained elusive, and robust biomarkers are lacking. Recent advances in tumor profiling have begun to identify novel genomic features that may influence response and resistance to cancer immunotherapy, including tumor mutational burden (e.g., microsatellite instability), copy-number alterations, and specific somatic alterations that influence immune recognition and response. Further investigation into the molecular and genomic features of response and resistance to cancer immunotherapy will be needed. We review the recent advances in understanding the molecular and genomic determinants of response to cancer immunotherapy, with an emphasis on immune checkpoint inhibitors.

  15. Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients

    International Nuclear Information System (INIS)

    Tipu, H.N.; Ahmed, T.A.; Bashir, M.M.

    2010-01-01

    To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. Cross-sectional comparative study. Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p 0.005). HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus. (author)

  16. RHD alleles in the Tunisian population

    Science.gov (United States)

    Ouchari, Mouna; Jemni-Yaacoub, Saloua; Chakroun, Taher; Abdelkefi, Saida; Houissa, Batoul; Hmida, Slama

    2013-01-01

    Background: A comprehensive survey of RHD alleles in Tunisia population was lacking. The aim of this study was to use a multiplex RHD typing assay for simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic acid (DNA) sequence exchange mechanism and some weak D alleles. Materials and Methods: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D-) from several regions was selected for RHD genotyping using a PCR multiplex assay. Further molecular investigations were done to characterize the RHD variants that were identified by the PCR multiplex assay. Results: In the 1777 D+ samples, only 10 individuals showed the absence of amplification of exons 4 and 5 that were subsequently identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected. In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4 individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5. These samples were then screened by PCR-SSPs on d(C) ces and weak D type 4, respectively. Conclusion: The weak D type 4 appears to be the most common D variant allele. We have not found any partial D variant. Findings also indicated that RHD gene deletion is the most prevalent cause of the D- phenotype in the Tunisian population. PMID:24014941

  17. RHD alleles in the Tunisian population

    Directory of Open Access Journals (Sweden)

    Mouna Ouchari

    2013-01-01

    Full Text Available Background: A comprehensive survey of RHD alleles in Tunisia population was lacking. The aim of this study was to use a multiplex RHD typing assay for simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic acid (DNA sequence exchange mechanism and some weak D alleles. Materials and Methods: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D- from several regions was selected for RHD genotyping using a PCR multiplex assay. Further molecular investigations were done to characterize the RHD variants that were identified by the PCR multiplex assay. Results: In the 1777 D+ samples, only 10 individuals showed the absence of amplification of exons 4 and 5 that were subsequently identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected. In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4 individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5. These samples were then screened by PCR-SSPs on d(C ce s and weak D type 4, respectively. Conclusion: The weak D type 4 appears to be the most common D variant allele. We have not found any partial D variant. Findings also indicated that RHD gene deletion is the most prevalent cause of the D- phenotype in the Tunisian population.

  18. Diversity of Lactase Persistence Alleles in Ethiopia

    DEFF Research Database (Denmark)

    Jones, BL; Raga, TO; Liebert, Anke

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene ...

  19. Microangiopathic complications related to different alleles of ...

    African Journals Online (AJOL)

    Microangiopathic complications related to different alleles of manganese superoxide dismutase gene in diabetes mellitus type 1. TM EL Masry, MA Abou Zahra, Kh. A Soliman, M El-Taweel. Abstract. No Abstract. The Egyptian Journal of Biochemistry and Molecular Biology Vol. 23(2) 2005: 155-167. Full Text: EMAIL FULL ...

  20. Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

    Science.gov (United States)

    Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

    2015-01-01

    The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Identification and characterization of two CD4 alleles in Microminipigs

    OpenAIRE

    Matsubara, Tatsuya; Nishii, Naohito; Takashima, Satoshi; Takasu, Masaki; Imaeda, Noriaki; Aiki-Oshimo, Kayo; Yamazoe, Kazuaki; Kakisaka, Michinori; Takeshima, Shin-nosuke; Aida, Yoko; Kametani, Yoshie; Kulski, Jerzy K.; Ando, Asako; Kitagawa, Hitoshi

    2016-01-01

    Background We previously identified two phenotypes of CD4+ cells with and without reactions to anti-pig CD4 monoclonal antibodies by flow cytometry in a herd of Microminipigs. In this study, we analyzed the coding sequences of CD4 and certified the expression of CD4 molecules in order to identify the genetic sequence variants responsible for the positive and negative PBMCs reactivity to anti-pig CD4 monoclonal antibodies. Results We identified two CD4 alleles, CD4.A and CD4.B, corresponding t...

  2. Determination of Flaw Size and Depth From Temporal Evolution of Thermal Response

    Science.gov (United States)

    Winfree, William P.; Zalameda, Joseph N.; Cramer, Elliott; Howell, Patricia A.

    2015-01-01

    Simple methods for reducing the pulsed thermographic responses of flaws have tended to be based on either the spatial or temporal response. This independent assessment limits the accuracy of characterization. A variational approach is presented for reducing the thermographic data to produce an estimated size for a flaw that incorporates both the temporal and spatial response to improve the characterization. The size and depth are determined from both the temporal and spatial thermal response of the exterior surface above a flaw and constraints on the length of the contour surrounding the delamination. Examples of the application of the technique to simulation and experimental data acquired are presented to investigate the limitations of the technique.

  3. Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents

    DEFF Research Database (Denmark)

    Birkbak, Nicolai J.; Wang, Zhigang C.; Kim, Ji-Young

    2012-01-01

    also benefit from these agents. NtAI, a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair. Cancer Discov; 2(4); 366–75. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 288......DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact DNA repair can avoid the accumulation of genome damage during growth and also can repair platinum-induced DNA damage. We sought genomic signatures indicative...... of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (NtAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients...

  4. Estimating the probability of allelic drop-out of STR alleles in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt

    2009-01-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

  5. The ACE deletion allele is associated with Israeli elite endurance athletes.

    Science.gov (United States)

    Amir, Offer; Amir, Ruthie; Yamin, Chen; Attias, Eric; Eynon, Nir; Sagiv, Moran; Sagiv, Michael; Meckel, Yoav

    2007-09-01

    An Alu insertion (I)/deletion (D) polymorphism in the angiotensin I converting enzyme (ACE) gene has been associated with ACE activity. Opposing effects on elite athletic performance have been proposed for the I and D alleles; while the D allele favours improved endurance ability, the I allele promotes more power-orientated events. We tested this hypothesis by determining the frequency of ACE ID alleles amongst 121 Israeli top-level athletes classified by their sporting discipline (marathon runners or sprinters). Genotyping for ACE ID was performed using polymerase chain reaction on DNA from leucocytes. The ACE genotype and allele frequencies were compared with those of 247 healthy individuals. Allele and genotype frequencies differed significantly between the groups. The frequency of the D allele was 0.77 in the marathon runners, 0.66 in the control subjects (P = 0.01) and 0.57 in the sprinters (P = 0.002). The ACE DD genotype was more prevalent among the endurance athletes (0.62) than among the control subjects (0.43, P = 0.004) and the power athletes (0.34, P = 0.004). In the group of elite athletes, the odds ratio of ACE DD genotype being an endurance athlete was 3.26 (95% confidence interval 1.49-7.11), and of ACE II genotype was 0.41 (95% confidence interval 0.14-1.19). We conclude that in Israeli elite marathon runners the frequency of the ACE D allele and ACE DD genotype seems to be higher than in sprinters, suggesting a positive association between the D allele and the likelihood of being an elite endurance athlete in some ethnic groups.

  6. Personal and Social Responsibility Among Athletes: the Role of Self-Determination, Achievement Goals and Engagement

    Directory of Open Access Journals (Sweden)

    Martins Paulo

    2017-06-01

    Full Text Available The purpose of this study was to assess the relationship between motivation, engagement and personal and social responsibility among athletes. Based on the literature, a survey was conducted including measures of motivation, considering task orientation and ego orientation, intrinsic and extrinsic motivation, and amotivation. We also measured the components of engagement (dedication, confidence, vigor and enthusiasm and the components of personal and social responsibility. A total of 517 athletes from different types of sports participated in the study. The results gathered through a structural equation model revealed that task orientation had the strongest relationship with personal responsibility and social responsibility, followed by engagement. Self-determination levels were not associated with personal and social responsibility. These results suggest that monitoring of task orientation and engagement levels should be performed by coaches as a strategy to develop personal and social responsibility among their athletes. Moreover, findings from this study provide scholars with a tool to aid them in managing athletes’ levels of personal and social responsibility.

  7. Personal and Social Responsibility among Athletes: the Role of Self-Determination, Achievement Goals and Engagement.

    Science.gov (United States)

    Martins, Paulo; Rosado, António; Ferreira, Vítor; Biscaia, Rui

    2017-06-01

    The purpose of this study was to assess the relationship between motivation, engagement and personal and social responsibility among athletes. Based on the literature, a survey was conducted including measures of motivation, considering task orientation and ego orientation, intrinsic and extrinsic motivation, and amotivation. We also measured the components of engagement (dedication, confidence, vigor and enthusiasm) and the components of personal and social responsibility. A total of 517 athletes from different types of sports participated in the study. The results gathered through a structural equation model revealed that task orientation had the strongest relationship with personal responsibility and social responsibility, followed by engagement. Self-determination levels were not associated with personal and social responsibility. These results suggest that monitoring of task orientation and engagement levels should be performed by coaches as a strategy to develop personal and social responsibility among their athletes. Moreover, findings from this study provide scholars with a tool to aid them in managing athletes' levels of personal and social responsibility.

  8. The Gly16 allele of the G16R single nucleotide polymorphism in the β2-adrenergic receptor gene augments the glycemic response to adrenaline in humans

    DEFF Research Database (Denmark)

    Rokamp, Kim Z.; Staalsø, Jonatan M.; Zaar, Morten

    2017-01-01

    Cerebral non-oxidative carbohydrate consumption may be driven by a ß2-adrenergic mechanism. This study tested whether the 46G > A (G16R) single nucleotide polymorphism of the ß2-adrenergic receptor gene (ADRB2) influences the metabolic and cerebrovascular responses to administration of adrenaline...

  9. HLA-B*57 Micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control

    DEFF Research Database (Denmark)

    Kløverpris, Henrik Nyhus; Buus, Anette Stryhn; van der Stok, Mary

    2012-01-01

    of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both...... by unique CD8(+) T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8(+) T-cell responses and immune selection pressures for which these protective alleles are responsible....... These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8(+) T-cell responses generated that can drive significant selection pressure on the virus....

  10. Effect of Diffusion Limitations on Multianalyte Determination from Biased Biosensor Response

    Science.gov (United States)

    Baronas, Romas; Kulys, Juozas; Lančinskas, Algirdas; Žilinskas, Antanas

    2014-01-01

    The optimization-based quantitative determination of multianalyte concentrations from biased biosensor responses is investigated under internal and external diffusion-limited conditions. A computational model of a biocatalytic amperometric biosensor utilizing a mono-enzyme-catalyzed (nonspecific) competitive conversion of two substrates was used to generate pseudo-experimental responses to mixtures of compounds. The influence of possible perturbations of the biosensor signal, due to a white noise- and temperature-induced trend, on the precision of the concentration determination has been investigated for different configurations of the biosensor operation. The optimization method was found to be suitable and accurate enough for the quantitative determination of the concentrations of the compounds from a given biosensor transient response. The computational experiments showed a complex dependence of the precision of the concentration estimation on the relative thickness of the outer diffusion layer, as well as on whether the biosensor operates under diffusion- or kinetics-limited conditions. When the biosensor response is affected by the induced exponential trend, the duration of the biosensor action can be optimized for increasing the accuracy of the quantitative analysis. PMID:24608006

  11. Non-steady response of BOD biosensor for the determination of biochemical oxygen demand in wastewater.

    Science.gov (United States)

    Velling, Siiri; Mashirin, Alexey; Hellat, Karin; Tenno, Toomas

    2011-01-01

    A biochemical oxygen demand (BOD) biosensor for effective and expeditious BOD(7) estimations was constructed and the non-steady phase of the output signal was extensively studied. The modelling approach introduced allows response curve reconstruction and a curve fitting procedure of good quality, resulting in parameters indicating the relationship between response and organic substrate concentration and stability properties of the BOD biosensor. Also, the immobilization matrixes of different thicknesses were characterized to determine their suitability for bio-sensing measurements in non-stationary conditions, as well as for the determination of the mechanical durability of the BOD biosensor in time. The non-steady response of the experimental output of the BOD biosensor was fitted according to the developed model that enables to determine the stability of the biosensor output and dependency on biodegradable organic substrate concentration. The calibration range of the studied BOD biosensor in OECD synthetic wastewater was 15-110 mg O(2) L(-1). Repeatability tests showed relative standard deviation (RSD) values of 2.8% and 5.8% for the parameter τ(d), characterizing the transient output of the amperometric oxygen sensor in time, and τ(s), describing the dependency of the transient response of the BOD biosensor on organic substrate concentration, respectively. BOD biosensor experiments for the evaluation of the biochemical oxygen demand of easily degradable and refractory municipal wastewater showed good concurrence with traditional BOD(7) analysis.

  12. Determinants of abnormal blood pressure response to exercise in coronary artery disease

    International Nuclear Information System (INIS)

    Hakki, A.H.; Munley, B.M.; Hadjimiltiades, S.; Meissner, M.D.; Iskandrian, A.S.

    1986-01-01

    This study assessed the determinants of exercise-induced abnormal systolic blood pressure (BP) response in 127 patients with documented coronary artery disease (CAD) who underwent exercise thallium-201 scintigraphy. Three types of systolic BP response to exercise were identified: an increase by more than 20 mm Hg (group I, n = 74); an increase by 20 mm Hg or less (group II, n = 36); and a decrease of at least 10 mm Hg (group III, n = 17). The 3 groups were not significantly different in age, gender or medications. The number of segments with perfusion defects was significantly higher in groups II and III than group I (group III, 2.9 +/- 1.5; group II, 2.9 +/- 2.1; and group I, 1.8 +/- 1.4, p = 0.009). Prior myocardial infarction, abnormal left ventricular ejection fraction, and multivessel CAD were more common in group III than in groups I and II. Stepwise discriminant analysis of 15 relevant clinical, angiographic and exercise scintigraphic descriptors showed that the number of thallium perfusion defects, abnormal LV ejection fraction at rest and multivessel CAD to be important predictors of hypotensive BP response. Multivariate analysis, however, showed that the number of thallium perfusion defects was the only important predictor of the hypotensive response. Thus, it is the functional significance of CAD assessed by the extent of thallium perfusion abnormalities rather than the extent of CAD or left ventricular dysfunction at rest that determines the systolic BP response to exercise

  13. Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Aurore Curie

    Full Text Available Genetically determined Intellectual Disability (ID is an intractable condition that involves severe impairment of mental abilities such as learning, reasoning and predicting the future. As of today, little is known about the placebo response in patients with ID.To determine if placebo response exists in patients with genetically determined ID.We searched Medline/PubMed, EMBASE, CENTRAL and PsycINFO to find all placebo-controlled double-blind randomized clinical trials (RCTs in patients with genetically determined ID, published up to April 2013, focusing on core ID symptoms.Two investigators extracted outcome data independently.Bias-corrected standardized mean difference (Hedge's g was computed for each outcome measure, using the Comprehensive Meta-Analysis software. A priori defined patient sub-groups were analyzed using a mixed-effect model. The relationship between pre-defined continuous variable moderators (age, IQ, year of publication and trial duration and effect size was analyzed using meta-regression.Twenty-two placebo-controlled double-blind RCTs met the inclusion criteria (n = 721, mean age = 17.1 years, 62% men, mean trial duration = 35 weeks. There was a significant overall placebo response from pre- to post-treatment in patients with ID (g = 0.468, p = 0.002, both for "subjective outcomes" (a third-person's evaluation of the patient (g = 0.563, p = 0.022 and "objective outcomes" (direct evaluation of the patient's abilities (g = 0.434, p = 0.036. Individuals with higher IQ had higher response to placebo (p = 0.02 and no placebo response was observed in ID patients with comorbid dementia. A significant effect of age (p = 0.02 was found, indicating higher placebo responses in treatment of younger patients.Results suggest that patients with genetically determined ID improve in the placebo arm of RCTs. Several mechanisms may contribute to placebo effects in ID, including expectancy, implicit learning and "placebo-by-proxy" induced by

  14. Determination of allele frequencies in nine short tandem repeat loci ...

    African Journals Online (AJOL)

    SERVER

    2008-04-17

    Apr 17, 2008 ... out the human genome. These loci are a rich source of highly polymorphic markers that may be detected using the polymerase chain reaction (PCR). PCR is a mimic of the normal cellular process of replication of DNA molecules. Each STR is distinguished by the number of times a sequence is repeated, ...

  15. Determining the response of African biota to climate change: using the past to model the future

    Science.gov (United States)

    Willis, K. J.; Bennett, K. D.; Burrough, S. L.; Macias-Fauria, M.; Tovar, C.

    2013-01-01

    Prediction of biotic responses to future climate change in tropical Africa tends to be based on two modelling approaches: bioclimatic species envelope models and dynamic vegetation models. Another complementary but underused approach is to examine biotic responses to similar climatic changes in the past as evidenced in fossil and historical records. This paper reviews these records and highlights the information that they provide in terms of understanding the local- and regional-scale responses of African vegetation to future climate change. A key point that emerges is that a move to warmer and wetter conditions in the past resulted in a large increase in biomass and a range distribution of woody plants up to 400–500 km north of its present location, the so-called greening of the Sahara. By contrast, a transition to warmer and drier conditions resulted in a reduction in woody vegetation in many regions and an increase in grass/savanna-dominated landscapes. The rapid rate of climate warming coming into the current interglacial resulted in a dramatic increase in community turnover, but there is little evidence for widespread extinctions. However, huge variation in biotic response in both space and time is apparent with, in some cases, totally different responses to the same climatic driver. This highlights the importance of local features such as soils, topography and also internal biotic factors in determining responses and resilience of the African biota to climate change, information that is difficult to obtain from modelling but is abundant in palaeoecological records. PMID:23878343

  16. Determining the response of African biota to climate change: using the past to model the future.

    Science.gov (United States)

    Willis, K J; Bennett, K D; Burrough, S L; Macias-Fauria, M; Tovar, C

    2013-01-01

    Prediction of biotic responses to future climate change in tropical Africa tends to be based on two modelling approaches: bioclimatic species envelope models and dynamic vegetation models. Another complementary but underused approach is to examine biotic responses to similar climatic changes in the past as evidenced in fossil and historical records. This paper reviews these records and highlights the information that they provide in terms of understanding the local- and regional-scale responses of African vegetation to future climate change. A key point that emerges is that a move to warmer and wetter conditions in the past resulted in a large increase in biomass and a range distribution of woody plants up to 400-500 km north of its present location, the so-called greening of the Sahara. By contrast, a transition to warmer and drier conditions resulted in a reduction in woody vegetation in many regions and an increase in grass/savanna-dominated landscapes. The rapid rate of climate warming coming into the current interglacial resulted in a dramatic increase in community turnover, but there is little evidence for widespread extinctions. However, huge variation in biotic response in both space and time is apparent with, in some cases, totally different responses to the same climatic driver. This highlights the importance of local features such as soils, topography and also internal biotic factors in determining responses and resilience of the African biota to climate change, information that is difficult to obtain from modelling but is abundant in palaeoecological records.

  17. Determination of the response time of pressure transducers using the direct method

    International Nuclear Information System (INIS)

    Perillo, S.R.P.

    1994-01-01

    The available methods to determine the response time of nuclear safety related pressure transducers are discussed, with emphasis to the direct method. In order to perform the experiments, a Hydraulic Ramp Generator was built. The equipment produces ramp pressure transients simultaneously to a reference transducer and to the transducer under test. The time lag between the output of the two transducers, when they reach a predetermined setpoint, is measured as the time delay of the transducer under test. Some results using the direct method to determine the time delay of pressure transducers (1 E Class Conventional) are presented. (author). 18 refs, 35 figs, 12 tabs

  18. Quantification of classical HLA class I mRNA by allele-specific, real-time polymerase chain reaction for most Han individuals.

    Science.gov (United States)

    Pan, N; Lu, S; Wang, W; Miao, F; Sun, H; Wu, S; Nan, D; Qiu, J; Xu, J; Zhang, J

    2018-02-01

    Recent studies have shown that expression levels of different alleles at the same HLA class I locus can vary dramatically, which might have a broad influence on human disease. However, precise quantification of the relative expression level of each HLA allele is challenging, because distinguishing different alleles on the same locus is difficult. Here, we developed a series of allele-specific, real-time polymerase chain reaction assays for quantifying HLA class I allele mRNA in most Han individuals. The alleles of almost all heterozygous genotypes with a frequency higher than 0.5% in our population (78 alleles on HLA-A locus, 124 alleles on HLA-B locus, and 74 alleles on HLA-C locus) were specifically amplified. The specificity of the amplification was strictly validated by setting the corresponding negative control for each allele of each genotype. The amplification efficiency of each reaction was determined, and the slopes of the reactions were compared. This study provides a tool for detecting the comprehensive expression profile of HLA class I alleles and will be useful not only for the investigation of the molecular mechanism underlying HLA allele expression regulation but also for exploration of immunological mechanisms involving HLA expression in the fields of tumour immune evasion, viral infection, auto-immune disorders, and graft vs host disease after haematopoietic stem cell transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Postprandial lipid responses to standard carbohydrates used to determine glycaemic index values.

    Science.gov (United States)

    Vega-López, Sonia; Ausman, Lynne M; Matthan, Nirupa R; Lichtenstein, Alice H

    2013-11-01

    Prior studies assessing the metabolic effects of different types of carbohydrates have focused on their glycaemic response. However, the response of postprandial cardiometabolic risk indicators has not been considered in these studies. The present study assessed postprandial lipid responses to two forms of carbohydrates used as reference foods for glycaemic index determinations, white bread (50 g available carbohydrate) and glucose (50 g), under controlled conditions and with intra-individual replicate determinations. A total of twenty adults (20–70 years) underwent two cycles of challenges with each pair of reference foods (four challenges/person), administered in a random order on separate days under standard conditions. Serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, TAG and NEFA), glucose and insulin were monitored for 5 h post-ingestion. Oral glucose resulted in greater glycaemic and insulinaemic responses than white bread for the first 90 min and a greater subsequent decline after 120 min (P =0·0001). The initial decline in serum NEFA concentrations was greater after the oral glucose than after the white bread challenge, as was the rebound after 150 min (P = 0·001). Nevertheless, the type of carbohydrate had no significant effect on postprandial total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. Following an initial modest rise in TAG concentrations in response to both challenges, the values dropped below the fasting values for oral glucose but not for the white bread challenge. These data suggest that the type of carbohydrate used to determine the glycaemic index, bread or glucose, has little or modest effects on postprandial plasma cholesterol concentrations. Differences in TAG and NEFA concentrations over the 5 h time period were modest, and their clinical relevance is unclear.

  20. Determinants of Private Long-Term Care Insurance Purchase in Response to the Partnership Program.

    Science.gov (United States)

    Lin, Haizhen; Prince, Jeffrey T

    2016-04-01

    To assess three possible determinants of individuals' response in their private insurance purchases to the availability of the Partnership for Long-Term Care (PLTC) insurance program: bequest motives, financial literacy, and program awareness. The health and retirement study (HRS) merged with data on states' implementation of the PLTC program. Individual-level decision on private long-term care insurance is regressed on whether the PLTC program is being implemented for a given state-year, asset dummies, policy determinant variable, two-way and three-way interactions of these variables, and other controls, using fixed effects panel regression. Analysis used a sample between 50 and 69 years of age from 2002 to 2010, resulting in 12,695 unique individuals with a total of 39,151 observations. We find mild evidence that intent to bequest influences individual purchase of insurance. We also find that program awareness is necessary for response, while financial literacy notably increases responsiveness. Increasing response to the PLTC program among the middle class (the stated target group) requires increased efforts to create awareness of the program's existence and increased education about the program's benefits, and more generally, about long-term care risks and needs. © Health Research and Educational Trust.

  1. Influence Determination of Social Responsibility to the Productivity Enterprise Activity Level

    Directory of Open Access Journals (Sweden)

    Sergii Kavun

    2016-07-01

    Full Text Available The purpose of this paper is to develop a scientific and methodical approach for determination of the comprehensive social responsibility indicator in this paper based on estimation of influence degree for the economical, ecological, social and labour, standard and legal components. There is allowance for determining of some level of enterprise social responsibility. In addition, there is a basis for development some ways of their increasing. The essence of the used approach is clotting of the individual indicators set to four intermediate indicators of the economic, ecological, social and labor, standard and legal components, which can be boiled down to the generalizing activity productivity indicator based on the matrix and range approach. An economical and mathematical model of the social responsibility influence level to the enterprise activity productivity level, which is based on enterprise propose harmonization with the participants’ interests, was being built. The paper proposes the mathematical model, which allows detecting a necessary time period for enterprise activity productivity ensuring due to social responsibility implementation.

  2. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation

    Science.gov (United States)

    Kadekaro, Ana Luisa; Leachman, Sancy; Kavanagh, Renny J.; Swope, Viki; Cassidy, Pamela; Supp, Dorothy; Sartor, Maureen; Schwemberger, Sandy; Babcock, George; Wakamatsu, Kazumasa; Ito, Shosuke; Koshoffer, Amy; Boissy, Raymond E.; Manga, Prashiela; Sturm, Richard A.; Abdel-Malek, Zalfa A.

    2010-01-01

    The melanocortin 1 receptor gene is a main determinant of human pigmentation, and a melanoma susceptibility gene, because its variants that are strongly associated with red hair color increase melanoma risk. To test experimentally the association between melanocortin 1 receptor genotype and melanoma susceptibility, we compared the responses of primary human melanocyte cultures naturally expressing different melanocortin 1 receptor variants to α-melanocortin and ultraviolet radiation. We found that expression of 2 red hair variants abolished the response to α-melanocortin and its photoprotective effects, evidenced by lack of functional coupling of the receptor, and absence of reduction in ultraviolet radiation-induced hydrogen peroxide generation or enhancement of repair of DNA photoproducts, respectively. These variants had different heterozygous effects on receptor function. Microarray data confirmed the observed differences in responses of melanocytes with functional vs. nonfunctional receptor to α-melanocortin and ultraviolet radiation, and identified DNA repair and antioxidant genes that are modulated by α-melanocortin. Our findings highlight the molecular mechanisms by which the melanocortin 1 receptor genotype controls genomic stability of and the mutagenic effect of ultraviolet radiation on human melanocytes.—Kadekaro, A. L., Leachman, S., Kavanagh, R. J., Swope, V., Cassidy, P., Supp, D., Sartor, M., Schwemberger, S., Babcock, G., Wakamatsu, K., Ito, S., Koshoffer, A., Boissy, R. E., Manga, P., Sturm, R. A., Abdel-Malek, Z. A. Melanocortin 1 receptor genotype: an important determinant of the damage response of melanocytes to ultraviolet radiation. PMID:20519635

  3. Rapid progressing allele HLA-B35 Px restricted anti-HIV-1 CD8+ T cells recognize vestigial CTL epitopes.

    Directory of Open Access Journals (Sweden)

    Christian B Willberg

    Full Text Available The HLA-B*35-Px allele has been associated with rapid disease progression in HIV-1 infection, in contrast to the HLA-B*35-Py allele.Immune responses to two HLA-B*35 restricted HIV-1 specific CTL epitopes and their variants were followed longitudinally during early HIV-1 infection in 16 HLA-B*35+ individuals. Subjects expressing HLA-B*35-Px alleles showed no difference in response to the consensus epitopes compared to individuals with HLA-B*35-Py alleles. Surprisingly, all the HLA-B*35-Px+ individuals responded to epitope-variants even in the absence of a consensus response. Sequencing of the viral population revealed no evidence of variant virus in any of the individuals.This demonstrates a novel phenomenon that distinguishes individuals with the HLA-B*35-Px rapid progressing allele and those with the HLA-B*35-Py slower progressing allele.

  4. Use of allele scores as instrumental variables for Mendelian randomization.

    Science.gov (United States)

    Burgess, Stephen; Thompson, Simon G

    2013-08-01

    An allele score is a single variable summarizing multiple genetic variants associated with a risk factor. It is calculated as the total number of risk factor-increasing alleles for an individual (unweighted score), or the sum of weights for each allele corresponding to estimated genetic effect sizes (weighted score). An allele score can be used in a Mendelian randomization analysis to estimate the causal effect of the risk factor on an outcome. Data were simulated to investigate the use of allele scores in Mendelian randomization where conventional instrumental variable techniques using multiple genetic variants demonstrate 'weak instrument' bias. The robustness of estimates using the allele score to misspecification (for example non-linearity, effect modification) and to violations of the instrumental variable assumptions was assessed. Causal estimates using a correctly specified allele score were unbiased with appropriate coverage levels. The estimates were generally robust to misspecification of the allele score, but not to instrumental variable violations, even if the majority of variants in the allele score were valid instruments. Using a weighted rather than an unweighted allele score increased power, but the increase was small when genetic variants had similar effect sizes. Naive use of the data under analysis to choose which variants to include in an allele score, or for deriving weights, resulted in substantial biases. Allele scores enable valid causal estimates with large numbers of genetic variants. The stringency of criteria for genetic variants in Mendelian randomization should be maintained for all variants in an allele score.

  5. Differences in the ability to suppress interferon β production between allele A and allele B NS1 proteins from H10 influenza A viruses

    Directory of Open Access Journals (Sweden)

    Zohari Siamak

    2010-12-01

    Full Text Available Abstract Background In our previous study concerning the genetic relationship among H10 avian influenza viruses with different pathogenicity in mink (Mustela vison, we found that these differences were related to amino acid variations in the NS1 protein. In this study, we extend our previous work to further investigate the effect of the NS1 from different gene pools on type I IFN promoter activity, the production of IFN-β, as well as the expression of the IFN-β mRNA in response to poly I:C. Results Using a model system, we first demonstrated that NS1 from A/mink/Sweden/84 (H10N4 (allele A could suppress an interferon-stimulated response element (ISRE reporter system to about 85%. The other NS1 (allele B, from A/chicken/Germany/N/49 (H10N7, was also able to suppress the reporter system, but only to about 20%. The differences in the abilities of the two NS1s from different alleles to suppress the ISRE reporter system were clearly reflected by the protein and mRNA expressions of IFN-β as shown by ELISA and RT-PCR assays. Conclusions These studies reveal that different non-structural protein 1 (NS1 of influenza viruses, one from allele A and another from allele B, show different abilities to suppress the type I interferon β expression. It has been hypothesised that some of the differences in the different abilities of the alleles to suppress ISRE were because of the interactions and inhibitions at later stages from the IFN receptor, such as the JAK/STAT pathway. This might reflect the additional effects of the immune evasion potential of different NS1s.

  6. What next after determinism in the ontology of technology? Distributing responsibility in the biofuel debate.

    Science.gov (United States)

    Boucher, Philip

    2011-09-01

    This article builds upon previous discussion of social and technical determinisms as implicit positions in the biofuel debate. To ensure these debates are balanced, it has been suggested that they should be designed to contain a variety of deterministic positions. Whilst it is agreed that determinism does not feature strongly in contemporary academic literatures, it is found that they have generally been superseded by an absence of any substantive conceptualisation of how the social shaping of technology may be related to, or occur alongside, an objective or autonomous reality. The problem of determinism emerges at an ontological level and must be resolved in situ. A critical realist approach to technology is presented which may provide a more appropriate framework for debate. In dialogue with previous discussion, the distribution of responsibility is revisited with reference to the role of scientists and engineers.

  7. PET/MRI of Hepatic 90Y Microsphere Deposition Determines Individual Tumor Response

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Kathryn J. [Washington University, Department of Radiology (United States); Maughan, Nichole M. [Washington University, Department of Biomedical Engineering (United States); Laforest, Richard [Washington University, Department of Nuclear Medicine (United States); Saad, Nael E. [Washington University, Department of Radiology (United States); Sharma, Akash [Washington University, Department of Nuclear Medicine (United States); Olsen, Jeffrey; Speirs, Christina K.; Parikh, Parag J., E-mail: parikh@wustl.edu [Washington University, Department of Radiation Oncology (United States)

    2016-06-15

    PurposeThe purpose of our study is to determine if there is a relationship between dose deposition measured by PET/MRI and individual lesion response to yttrium-90 ({sup 90}Y) microsphere radioembolization.Materials and Methods26 patients undergoing lobar treatment with {sup 90}Y microspheres underwent PET/MRI within 66 h of treatment and had follow-up imaging available. Adequate visualization of tumor was available in 24 patients, and contours were drawn on simultaneously acquired PET/MRI data. Dose volume histograms (DVHs) were extracted from dose maps, which were generated using a voxelized dose kernel. Similar contours to capture dimensional and volumetric change of tumors were drawn on follow-up imaging. Response was analyzed using both RECIST and volumetric RECIST (vRECIST) criteria.ResultsA total of 8 hepatocellular carcinoma (HCC), 4 neuroendocrine tumor (NET), 9 colorectal metastases (CRC) patients, and 3 patients with other metastatic disease met inclusion criteria. Average dose was useful in predicting response between responders and non-responders for all lesion types and for CRC lesions alone using both response criteria (p < 0.05). D70 (minimum dose to 70 % of volume) was also useful in predicting response when using vRECIST. No significant trend was seen in the other tumor types. For CRC lesions, an average dose of 29.8 Gy offered 76.9 % sensitivity and 75.9 % specificity for response.ConclusionsPET/MRI of {sup 90}Y microsphere distribution showed significantly higher DVH values for responders than non-responders in patients with CRC. DVH analysis of {sup 90}Y microsphere distribution following treatment may be an important predictor of response and could be used to guide future adaptive therapy trials.

  8. Allele specific expression and methylation in the bumblebee, Bombus terrestris

    Directory of Open Access Journals (Sweden)

    Zoë Lonsdale

    2017-09-01

    Full Text Available The social hymenoptera are emerging as models for epigenetics. DNA methylation, the addition of a methyl group, is a common epigenetic marker. In mammals and flowering plants methylation affects allele specific expression. There is contradictory evidence for the role of methylation on allele specific expression in social insects. The aim of this paper is to investigate allele specific expression and monoallelic methylation in the bumblebee, Bombus terrestris. We found nineteen genes that were both monoallelically methylated and monoallelically expressed in a single bee. Fourteen of these genes express the hypermethylated allele, while the other five express the hypomethylated allele. We also searched for allele specific expression in twenty-nine published RNA-seq libraries. We found 555 loci with allele-specific expression. We discuss our results with reference to the functional role of methylation in gene expression in insects and in the as yet unquantified role of genetic cis effects in insect allele specific methylation and expression.

  9. The A/G Allele of Rs16906252 Predicts for MGMT Methylation and Is Selectively Silenced in Premalignant Lesions from Smokers and in Lung Adenocarcinomas

    Science.gov (United States)

    Leng, Shuguang; Bernauer, Amanda M.; Hong, Chibo; Do, Kieu C.; Yingling, Christin M.; Flores, Kristina G.; Tessema, Mathewos; Tellez, Carmen S.; Willink, Randall P.; Burki, Elizabeth A.; Picchi, Maria A.; Stidley, Christine A.; Prados, Michael D.; Costello, Joseph F.; Gilliland, Frank D.; Crowell, Richard E.; Belinsky, Steven A.

    2011-01-01

    Purpose To address the association between sequence variants within the MGMT promoter-enhancer region and methylation of MGMT in premalignant lesions from smokers and lung adenocarcinomas, their biological effects on gene regulation, and targeting MGMT for therapy. Experimental Design SNPs identified through sequencing a 1.9kb fragment 5' of MGMT were examined in relation to MGMT methylation in 169 lung adenocarcinomas and 1731 sputum samples from smokers. The effect of promoter haplotypes on MGMT expression was tested using a luciferase reporter assay and cDNA expression analysis along with allele-specific sequencing for methylation. The response of MGMT methylated lung cancer cell lines to the alkylating agent temozolomide was assessed. Results The A allele of rs16906252 and the haplotype containing this SNP were strongly associated with increased risk for MGMT methylation in adenocarcinomas (ORs ≥ 94). This association was observed to a lesser extent in sputum samples in both smoker cohorts. The A allele was selectively methylated in primary lung tumors and cell lines heterozygous for rs16906252. With the most common haplotype as the reference, a 20–41% reduction in promoter activity was seen for the haplotype carrying the A allele that correlated with lower MGMT expression. The sensitivity of lung cancer cell lines to temozolamide was strongly correlated with levels of MGMT methylation and expression. Conclusions These studies provide strong evidence that the A allele of a MGMT promoter-enhancer SNP is a key determinant for MGMT methylation in lung carcinogenesis. Moreover, temozolamide treatment may benefit a subset of lung cancer patients methylated for MGMT. PMID:21355081

  10. Analysis of FBN1 allele expression by dermal fibroblasts from Marfan syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Putman, E.A.; Cao, S.N.; Milewicz, D.M. [Univ. of Texas Medical School, Houston, TX (United States)

    1994-09-01

    Screening for mutations in the FBN1 cDNA from Marfan patient cell strains has detected mutations in only 10-15% of patients. In an attempt to explain this poor detection rate, we examined FBN1 allele expression and fibrillin synthesis by 26 cell strains from Marfan patients. DNA from the patients and 10 controls was assessed for the presence of a polymorphic Rsa I restriction site in the 3{prime} untranslated region of the FBN1 gene. Twelve of 26 patient and 5 of 10 control DNAs were heterozygous. Fibroblast RNA from the heterozygous cell strains was reverse-transcribed and subsequently PCR amplified using a [{sup 32}P]-labelled primer, digested with Rsa I and analyzed. Although 3 samples showed no transcript from one allele by ethidium bromide staining, a Betagen scanner detected low levels (10-15%) of that allele. In addition, there was unequal expression of the two alleles in three other patients; for example, only 30% expression from one allele. The remaining patients and the controls had equal expression of each allele. Fibrillin protein synthesis by fibroblasts from these heterozygous patients was also examined. After a 30 minute pulse with [{sup 35}S]-cysteine, cell lysates were collected and proteins analyzed by SDS-PAGE. The amount of fibrillin produced relative to a reference protein was determined using a Betagen scanner. Fibrillin protein synthesis was reduced in 2 of the 3 patients with very low RNA production from one of the FBN1 alleles. All other Marfan and control cell strains showed normal amounts of fibrillin synthesized. The low expression levels from one allele may contribute to, but not fully account for, the low detection rate of FBN1 mutations. Interestingly, protein synthesis levels were not affected in 4 of 6 cell strains demonstrating low levels of RNA expression.

  11. Development of thermal response spectroscopy technique for determination of defect parameters

    Science.gov (United States)

    Sakagami, Takahide; Imanishi, Daisuke; Kubo, Shiro

    2007-04-01

    Thermal response spectroscopy method was newly developed for quantitative measurement of size and depth of the defects. In this method, sequential thermal response data observed on the surface of objective body under active step heating were processed by lock-in analysis scheme based on the Fourier series expansion, in which Fourier coefficients synchronizing with sine and cosine waves were calculated. Phase and amplitude were calculated using these coefficients for different thermal fluctuation periods and different defect parameters, such as size and depth of the defects. Obtained phase and amplitude were represented in spectroscopic diagram. It was found that plotted phase and amplitude data of certain defect depth obtained for various thermal fluctuation periods showed characteristic curves in the diagram. An inverse analysis method for the thermal response spectroscopy was proposed for quantitative measurement of size and depth of the defects. The least-squares residual inverse analysis scheme was applied to the defect parameter determination based on the Fourier coefficient values in the spectroscopic diagram. It was found that defect depth and size can be quantitatively determined by the inverse analyses.

  12. The response to ACTH is determined early in the treatment of infantile spasms.

    Science.gov (United States)

    Mytinger, John R; Weber, Amanda; Heyer, Geoffrey L

    2015-03-01

    Although adrenocorticotropic hormone is the most commonly used treatment for infantile spasms in the United States, the optimal regimen for this indication is not known. The purpose of this study was to elucidate the optimal adrenocorticotropic hormone treatment duration. We conducted a retrospective chart review of response to adrenocorticotropic hormone among all patients with infantile spasms managed at our institution from January 2009 to September 2013. Treatment response was defined as clinical remission for greater than or equal to 28 days starting at any point within the adrenocorticotropic hormone course and remission of hypsarrhythmia (or definite EEG improvement if hypsarrhythmia was absent at baseline). For responders, the diagnostic and post-treatment EEG tracings were reviewed. Electroclinical remission was achieved in 21 of 39 patients (54%) receiving adrenocorticotropic hormone, including 11/25 (44%) receiving a long course (typically 12 weeks) and 10/14 (71%) receiving a short course (typically four weeks). The mean time to clinical remission was 5.8 days (median: 5 days; range: 1-20 days). Only one patient responded beyond two weeks of treatment. This study provides Class IV evidence that among patients with infantile spasms, the response to adrenocorticotropic hormone is most often determined early in the treatment course. Given the importance of rapid remission, clinicians should consider adding or changing treatment if infantile spasms do not resolve within two weeks of adrenocorticotropic hormone initiation. Further study is needed to determine the optimal adrenocorticotropic hormone regimen for infantile spasms.

  13. Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts.

    Science.gov (United States)

    Bouwman, Aniek C; Hayes, Ben J; Calus, Mario P L

    2017-10-30

    Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of allele counts results in less shrinkage towards the mean for low minor allele frequency (MAF) variants. Scaling may become relevant for estimating ASE as more low MAF variants will be used in genomic evaluations. We show the impact of scaling on estimates of ASE using real data and a theoretical framework, and in terms of power, model fit and predictive performance. In a dairy cattle dataset with 630 K SNP genotypes, the correlation between DGV for stature from a random regression model using centered allele counts (RRc) and centered and scaled allele counts (RRcs) was 0.9988, whereas the overall correlation between ASE using RRc and RRcs was 0.27. The main difference in ASE between both methods was found for SNPs with a MAF lower than 0.01. Both the ratio (ASE from RRcs/ASE from RRc) and the regression coefficient (regression of ASE from RRcs on ASE from RRc) were much higher than 1 for low MAF SNPs. Derived equations showed that scenarios with a high heritability, a large number of individuals and a small number of variants have lower ratios between ASE from RRc and RRcs. We also investigated the optimal scaling parameter [from - 1 (RRcs) to 0 (RRc) in steps of 0.1] in the bovine stature dataset. We found that the log-likelihood was maximized with a scaling parameter of - 0.8, while the mean squared error of prediction was minimized with a scaling parameter of - 1, i.e., RRcs. Large differences in estimated ASE were observed for low MAF SNPs when allele counts were scaled or not scaled because there is less shrinkage towards the mean for scaled allele counts. We derived a theoretical framework that shows that the difference in ASE due to shrinkage is heavily influenced by the

  14. Spectrophotometric determination of anionic surfactants: optimization by response surface methodology and application to Algiers bay wastewater.

    Science.gov (United States)

    Sini, Karima; Idouhar, Madjid; Ahmia, Aida-Cherifa; Ferradj, Abdelhak; Tazerouti, Ammal

    2017-11-23

    A simple analytical method for quantitative determination of an anionic surfactant in aqueous solutions without liquid-liquid extraction is described. The method is based on the formation of a green-colored ion associate between sodium dodecylbenzenesulfonate (SDBS) and cationic dye, Brilliant Green (BG) in acidic medium. Spectral changes of the dye by addition of SDBS are studied by visible spectrophotometry at maximum wave length of 627 nm. The interactions and micellar properties of SDBS and cationic dye are also investigated using surface tension method. The pH, the molar ratio ([BG]/[SDBS]), and the shaking time of the solutions are considered as the main parameters which affect the formation of the ion pair. Determination of AS in distilled water gives a significant detection limit up to 3 × 10 -6  M. The response surface methodology (RSM) is applied to study the absorbance. A Box-Behnken is a model designed to the establishment of responses given by parameters with great probability. This model is set up by using the three main parameters at three levels. Analysis of variance shows that only two parameters affect the absorbance of the ion pair. The statistical results obtained are interesting and give us real possibility to reach optimum conditions for the formation of the ion pair. As the proposed method is free from interferences from major constituents of water, it has been successfully applied to the determination of anionic surfactant contents in wastewaters samples collected from Algiers bay.

  15. Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins.

    Science.gov (United States)

    Remington, David L

    2015-12-01

    Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  16. Geographically Distinct and Domain-Specific Sequence Variations in the Alleles of Rice Blast Resistance Gene Pib.

    Science.gov (United States)

    Vasudevan, Kumar; Vera Cruz, Casiana M; Gruissem, Wilhelm; Bhullar, Navreet K

    2016-01-01

    Rice blast is caused by Magnaporthe oryzae, which is the most destructive fungal pathogen affecting rice growing regions worldwide. The rice blast resistance gene Pib confers broad-spectrum resistance against Southeast Asian M. oryzae races. We investigated the allelic diversity of Pib in rice germplasm originating from 12 major rice growing countries. Twenty-five new Pib alleles were identified that have unique single nucleotide polymorphisms (SNPs), insertions and/or deletions, in addition to the polymorphic nucleotides that are shared between the different alleles. These partially or completely shared polymorphic nucleotides indicate frequent sequence exchange events between the Pib alleles. In some of the new Pib alleles, nucleotide diversity is high in the LRR domain, whereas, in others it is distributed among the NB-ARC and LRR domains. Most of the polymorphic amino acids in LRR and NB-ARC2 domains are predicted as solvent-exposed. Several of the alleles and the unique SNPs are country specific, suggesting a diversifying selection of alleles in various geographical locations in response to the locally prevalent M. oryzae population. Together, the new Pib alleles are an important genetic resource for rice blast resistance breeding programs and provide new information on rice-M. oryzae interactions at the molecular level.

  17. Transcriptional profiling identifies physicochemical properties of nanomaterials that are determinants of the in vivo pulmonary response.

    Science.gov (United States)

    Halappanavar, Sabina; Saber, Anne Thoustrup; Decan, Nathalie; Jensen, Keld Alstrup; Wu, Dongmei; Jacobsen, Nicklas Raun; Guo, Charles; Rogowski, Jacob; Koponen, Ismo K; Levin, Marcus; Madsen, Anne Mette; Atluri, Rambabu; Snitka, Valentinas; Birkedal, Renie K; Rickerby, David; Williams, Andrew; Wallin, Håkan; Yauk, Carole L; Vogel, Ulla

    2015-03-01

    We applied transcriptional profiling to elucidate the mechanisms associated with pulmonary responses to titanium dioxide (TiO2 ) nanoparticles (NPs) of different sizes and surface coatings, and to determine if these responses are modified by NP size, surface area, surface modification, and embedding in paint matrices. Adult C57BL/6 mice were exposed via single intratracheal instillations to free forms of TiO2 NPs (10, 20.6, or 38 nm in diameter) with different surface coatings, or TiO2 NPs embedded in paint matrices. Controls were exposed to dispersion medium devoid of NPs. TiO2 NPs were characterized for size, surface area, chemical impurities, and agglomeration state in the exposure medium. Pulmonary transcriptional profiles were generated using microarrays from tissues collected one and 28 d postexposure. Property-specific pathway effects were identified. Pulmonary protein levels of specific inflammatory cytokines and chemokines were confirmed by ELISA. The data were collapsed to 659 differentially expressed genes (P ≤ 0.05; fold change ≥ 1.5). Unsupervised hierarchical clustering of these genes revealed that TiO2 NPs clustered mainly by postexposure timepoint followed by particle type. A pathway-based meta-analysis showed that the combination of smaller size, large deposited surface area, and surface amidation contributes to TiO2 NP gene expression response. Embedding of TiO2 NP in paint dampens the overall transcriptional effects. The magnitude of the expression changes associated with pulmonary inflammation differed across all particles; however, the underlying pathway perturbations leading to inflammation were similar, suggesting a generalized mechanism-of-action for all TiO2 NPs. Thus, transcriptional profiling is an effective tool to determine the property-specific biological/toxicity responses induced by nanomaterials. © 2014 Wiley Periodicals, Inc.

  18. Knockdown resistance, Rdl alleles, and the annual entomological Inoculation rate of wild mosquito populations from Lower Moshi, Northern Tanzania

    Directory of Open Access Journals (Sweden)

    Aneth M Mahande

    2012-01-01

    Full Text Available Aim: Understanding vector behavioral response due to ecological factors is important in the control of disease vectors. This study was conducted to determine the knockdown resistance (kdr alleles, dieldrin resistance alleles, and entomological inoculation rates (EIRs of malaria vectors in lower Moshi irrigation schemes for the mitigation of disease transmission. Materials and Methods: The study was longitudinal design conducted for 14 months. Mosquitoes were collected fortnightly by using a CDC miniature light trap in 20 houses. Mosquitoes were identified morphologically in the field, of which 10% of this population was identified to species level by using molecular techniques. Samples from this study population were taken for kdr and resistance to dieldrin (rdl genes detection. Results: A total of 6220 mosquitoes were collected by using a light trap, of which 86.0% (n=5350 were Anopheles gambiae sensu lato and 14.0% (n=870 were Culex quinquefasciatus. Ten percent of the An. gambiae s.l. (n=535 collected were taken for species identification, of which 99.8% (n=534 were identified as An. arabiensis while 0.2% (n=1 were An. gambiae sensu stricto. Of the selected mosquitoes, 3.5% (n=19 were sporozoite positive. None of the mosquitoes tested had the kdr gene. The rdl resistant allele was detected at a frequency of 0.48 throughout the year. EIR was determined to be 0.54 ib/trap/year. Conclusion: The findings of this study suggest that the homozygous and the heterozygous resistance present in rdl genes demonstrated the effect of pesticide residues on resistance selection pressure in mosquitoes. A better insecticide usage protocol needs to be developed for farmers to use in order to avoid excessive use of pesticides. Key words: An. arabiensis, EIR, Knockdown mutation, Moshi, rdl locus, Tanzania

  19. Induction of tolerance to one determinant on a synthetic peptide does not affect the response to a second linked determinant. Implications for the mechanism of neonatal tolerance induction

    Science.gov (United States)

    1986-01-01

    To investigate the mechanism underlying neonatal T cell tolerance, we used synthetic peptides to induce tolerance. We found that induction of tolerance to one determinant on a 23-amino acid peptide did not affect the response to an adjacent determinant on the same peptide. There was no evidence of suppression of the response to the second determinant. Furthermore, even small peptides near the minimal size for a determinant, which would be very unlikely to possess a suppressor T cell-inducing determinant as well as a proliferative T cell-inducing determinant, could induce tolerance. These studies provide in vivo experiments supporting clonal inactivation as the mechanism of neonatal tolerance to immunogenic peptides. PMID:2425038

  20. Genotype 1 hepatitis C virus envelope features that determine antiviral response assessed through optimal covariance networks.

    Directory of Open Access Journals (Sweden)

    John M Murray

    Full Text Available The poor response to the combined antiviral therapy of pegylated alfa-interferon and ribavarin for hepatitis C virus (HCV infection may be linked to mutations in the viral envelope gene E1E2 (env, which can result in escape from the immune response and higher efficacy of viral entry. Mutations that result in failure of therapy most likely require compensatory mutations to achieve sufficient change in envelope structure and function. Compensatory mutations were investigated by determining positions in the E1E2 gene where amino acids (aa covaried across groups of individuals. We assessed networks of covarying positions in E1E2 sequences that differentiated sustained virological response (SVR from non-response (NR in 43 genotype 1a (17 SVR, and 49 genotype 1b (25 SVR chronically HCV-infected individuals. Binary integer programming over covariance networks was used to extract aa combinations that differed between response groups. Genotype 1a E1E2 sequences exhibited higher degrees of covariance and clustered into 3 main groups while 1b sequences exhibited no clustering. Between 5 and 9 aa pairs were required to separate SVR from NR in each genotype. aa in hypervariable region 1 were 6 times more likely than chance to occur in the optimal networks. The pair 531-626 (EI appeared frequently in the optimal networks and was present in 6 of 9 NR in one of the 1a clusters. The most frequent pairs representing SVR were 431-481 (EE, 500-522 (QA in 1a, and 407-434 (AQ in 1b. Optimal networks based on covarying aa pairs in HCV envelope can indicate features that are associated with failure or success to antiviral therapy.

  1. [An allelism test for quantitative trait genes].

    Science.gov (United States)

    Smiriaev, A V

    2011-04-01

    Analytical modeling has been used to test assumptions on the mode of inheritance of a quantitative trait in the course of diallel crossing between pure strains that are sufficient for adequacy of a simple regression model. This model frequently proved to be adequate in analysis of numerous data on diallel crossings of wheat and maize. An allelism test for quantitative trait genes has been suggested. Computer simulation has been used to estimate the effect of random experimental errors and deviations from the suggested model.

  2. Novel chromosome-encoded erm(47) determinant responsible for constitutive MLSB resistance in Helcococcus kunzii.

    Science.gov (United States)

    Guérin, François; Isnard, Christophe; Bucquet, Fiona; Fines-Guyon, Marguerite; Giard, Jean-Christophe; Burrus, Vincent; Cattoir, Vincent

    2016-11-01

    The aim of the study was to identify the determinant responsible for erythromycin resistance in Helcococcus kunzii clinical isolate UCN99 and to characterize the genetic support and environment of this novel gene. MICs were determined using the broth microdilution method according to EUCAST guidelines. The entire genome sequence of H. kunzii UCN99 was determined using a 454/Roche GS Junior sequencer. The fragment encompassing the new resistance gene and its own promoter was cloned into the pAT29 shuttle vector and the recombinant plasmid pAT29Ωerm(47) was expressed in both Staphylococcus aureus and Streptococcus agalactiae. The transcription start site (TSS) was experimentally determined by 5' RACE-PCR. UCN99 exhibited a constitutive macrolide/lincosamide/streptogramin B (MLS B ) resistance phenotype, suggesting the presence of an Erm protein. WGS allowed the identification of a novel gene, named erm(47), encoding a protein sharing 44%-48% amino acid identity with known Erm methylases. In both S. aureus and S. agalactiae, the introduction of pAT29Ωerm(47) conferred a significant increase (≥16-fold) in MICs of all macrolides and lincosamides tested, as well as a 4-fold increase in MICs of quinupristin (streptogramin B), confirming the MLS B resistance. The TSS identification revealed the presence of a short leader peptide, potentially implicated in a translational attenuation mechanism. It was also demonstrated that erm(47) was harboured by a 81 kb genomic island integrated into a chromosomal gene. This is the first description of a novel MLS B resistance determinant, named erm(47). The prevalence of this gene among Gram-positive cocci must be further investigated to determine its clinical significance. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome.

    Science.gov (United States)

    Byun, Hyang-Min; Heo, Kyu; Mitchell, Kasey J; Yang, Allen S

    2012-02-02

    Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability. we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation. We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression. The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.

  4. Determination of volatile organic compounds responsible for flavour in cooked river buffalo meat

    Directory of Open Access Journals (Sweden)

    A. Di Luccia

    2010-02-01

    Full Text Available Flavour is an important consumer attractive that directly influences the success of food products on the market. The determination of odorous molecules and their identification allows to useful knowledge for producers to valorise their own products. Buffalo meat has a different chemical composition from pork and beef and requires some cautions in cooking and processing. This work aims at the identification of volatile molecules responsible for flavours in river buffalo meat. The determination was carried out by solid phase micro-extraction (SPME technique and analysed by gas chromatography coupled to mass spectrometry (GC-MS. The most relevant results were the higher odorous impact of buffalo meat and the higher content of sulphide compounds responsible for wild aroma respect to pork and beef. These results were obtained comparing the total area of peaks detected in every chromatogram. We have also found significant differences concerning the contents of pentadecane, 1-hexanol-2 ethyl, butanoic acid, furano-2-penthyl. The origin of volatile organic compounds and their influence on the river buffalo aromas were discussed.

  5. Role of Smac in determining the chemotherapeutic response of esophageal squamous cell carcinoma.

    Science.gov (United States)

    Xu, Yang; Zhou, Lanping; Huang, Jing; Liu, Fang; Yu, Jian; Zhan, Qimin; Zhang, Lin; Zhao, Xiaohang

    2011-08-15

    Second mitochondria-derived activator of caspase (Smac) regulates chemotherapy-induced apoptosis. Smac mimetics have been tested in clinical trials as chemosensitizers. We determined the role of Smac in modulating the chemosensitivity of esophageal squamous cell carcinoma (ESCC). Smac expression was evaluated in tissues from ESCC patients with differential chemotherapeutic responses. The effects of Smac knockdown and Smac mimetics on the chemosensitivity of ESCC cells and the molecular mechanisms by which Smac and Smac mimetics modulate chemosensitivity were determined. The therapeutic responses of ESCC cells with different Smac statuses were compared using xenograft models. We found that Smac was significantly downregulated in most ESCC samples (36.8%, 25/68, P = 0.001), and Smac expression differed significantly (P Smac and cytochrome c were released from mitochondria, and caspase-3 and caspase-9 were activated. Knockdown of Smac abrogated cisplatin-induced apoptosis, mitochondrial dysfunction, cytochrome c release, and caspase activation. Smac deficiency also reduced the effect of cisplatin on long-term cell viability, and led to cisplatin resistance in xenograft tumors in vivo. LBW242, a small molecule Smac mimetic, enhanced cisplatin-induced apoptosis and caspase activation and restored cisplatin sensitivity in Smac-deficient cells. Our data suggested that downregulation of Smac may be a chemoresistance mechanism in ESCC. Combinations of Smac mimetics with chemotherapeutic agents may have therapeutic benefits for the treatment of esophageal cancer. ©2011 AACR.

  6. Determining dose rate with a semiconductor detector - Monte Carlo calculations of the detector response

    International Nuclear Information System (INIS)

    Nordenfors, C.

    1999-02-01

    To determine dose rate in a gamma radiation field, based on measurements with a semiconductor detector, it is necessary to know how the detector effects the field. This work aims to describe this effect with Monte Carlo simulations and calculations, that is to identify the detector response function. This is done for a germanium gamma detector. The detector is normally used in the in-situ measurements that is carried out regularly at the department. After the response function is determined it is used to reconstruct a spectrum from an in-situ measurement, a so called unfolding. This is done to be able to calculate fluence rate and dose rate directly from a measured (and unfolded) spectrum. The Monte Carlo code used in this work is EGS4 developed mainly at Stanford Linear Accelerator Center. It is a widely used code package to simulate particle transport. The results of this work indicates that the method could be used as-is since the accuracy of this method compares to other methods already in use to measure dose rate. Bearing in mind that this method provides the nuclide specific dose it is useful, in radiation protection, since knowing what the relations between different nuclides are and how they change is very important when estimating the risks

  7. Inbreeding and PKU allele frequency: Estimating by microsatellite approaches.

    Science.gov (United States)

    Santos, Luciana L; da Fonseca, Cleusa G; Vaintraub, Marco T; Vaintraub, Patricia; Januário, José N; de Aguiar, Marcos J B; Raquel Santos Carvalho, Maria

    2010-01-01

    Estimates of allele frequencies for recessive diseases are generally based on the frequency of affected individuals (q(2)). However, these estimates can be strongly biased due to inbreeding in the population. The purpose of this study was to gain a better understanding of how inbreeding in the Minas Gerais State population affects phenylketonuria (PKU) incidence in the state and to determine the inbreeding coefficient based on microsatellites. Inbreeding coefficients of samples of 104 controls and 76 patients with PKU were estimated through a microsatellite approach. Besides, the amount and distribution of genetic variation within and among patients with PKU and control samples were characterized. No genetic differentiation was observed between the samples. However, the Fis value found for samples of patients with PKU (0.042) was almost 15 times higher than that found among controls (0.003). When corrected by the inbreeding coefficient found among the controls, the PKU allele frequency decreased to 0.0057. The results enables us to infer that at least 35% of the PKU recessive homozygotes from the Minas Gerais population could be due to consanguineous marriages and suggest that microsatellites can be an useful approach to estimate inbreeding coefficients. (c) 2010 Wiley-Liss, Inc.

  8. Multilevel selection 2: Estimating the genetic parameters determining inheritance and response to selection.

    Science.gov (United States)

    Bijma, Piter; Muir, William M; Ellen, Esther D; Wolf, Jason B; Van Arendonk, Johan A M

    2007-01-01

    Interactions among individuals are universal, both in animals and in plants and in natural as well as domestic populations. Understanding the consequences of these interactions for the evolution of populations by either natural or artificial selection requires knowledge of the heritable components underlying them. Here we present statistical methodology to estimate the genetic parameters determining response to multilevel selection of traits affected by interactions among individuals in general populations. We apply these methods to obtain estimates of genetic parameters for survival days in a population of layer chickens with high mortality due to pecking behavior. We find that heritable variation is threefold greater than that obtained from classical analyses, meaning that two-thirds of the full heritable variation is hidden to classical analysis due to social interactions. As a consequence, predicted responses to multilevel selection applied to this population are threefold greater than classical predictions. This work, combined with the quantitative genetic theory for response to multilevel selection presented in an accompanying article in this issue, enables the design of selection programs to effectively reduce competitive interactions in livestock and plants and the prediction of the effects of social interactions on evolution in natural populations undergoing multilevel selection.

  9. Determination of the Timing and Level of Activities of Lumbopelvic Muscles in Response to Postural Perturbations

    Directory of Open Access Journals (Sweden)

    S Ebrahimi Takamjani

    2005-05-01

    Full Text Available Background: One of the most important concerns in orthopedic medicine is the low back. Considering the importance of muscle function in preventing LBT by controlling too much load and stress applied on the spinal joints and ligaments. Materials and Methods: The aim of this research was to determine the timing and level of activities of lumbopelvic muscles in response to postural perturbations caused by unexpected loading of the upper limbs in standing on three different supporting surfaces (neutral, positive slope, negative slope in 20 healthy females 18 to 30 years old ( = 23.20 SD = 2.55 . The electromyographic signals were recorded from the deltoid, gluteus maximus, internal oblique abdominis and lumbar paraspinal muscles of the dominant side of the body to evaluate the onset time, end time, level of muscle activity (RMS and duration of different muscles in one task and one muscle in different tasks. Results: The results showed that the agonists (posterior muscles activated at first to compensate the flexor torque caused by loading and then the antagonists (anterior muscles switched-on to compensate the reaction forces caused by agonist activities. With regards to continuous activity of internal oblique and its attachments via thoracalumbar fascia to the transverse processes of the lumbar vertebrae, it can be considered as one of the major stabilizer muscles of the trunk . Conclusion: Finally the results indicated that supporting surface type didn’t have any effect on timing and scaling of muscle activities in different tasks suggesting that probably spinal and trunk priprioceptors are just responsible for triggering postural responses and they don’t have any role in determining timing and scaling.

  10. Determination of tolerance dose uncertainties and optimal design of dose response experiments with small animal numbers

    International Nuclear Information System (INIS)

    Karger, C.P.; Hartmann, G.H.

    2001-01-01

    Background: Dose response experiments aim to determine the complication probability as a function of dose. Adjusting the parameters of the frequently used dose response model P(D)=1/[1+(D 50 /D) k ] to the experimental data, 2 intuitive quantities are obtained: The tolerance dose D 50 and the slope parameter k. For mathematical reasons, however, standard statistic software uses a different set of parameters. Therefore, the resulting fit parameters of the statistic software as well as their standard errors have to be transformed to obtain D 50 and k as well as their standard errors. Material and Methods: The influence of the number of dose levels on the uncertainty of the fit parameters is studied by a simulation for a fixed number of animals. For experiments with small animal numbers, statistical artifacts may prevent the determination of the standard errors of the fit parameters. Consequences on the design of dose response experiments are investigated. Results: Explicit formulas are presented, which allow to calculate the parameters D 50 and k as well as their standard errors from the output of standard statistic software. The simulation shows, that the standard errors of the resulting parameters are independent of the number of dose levels, as long as the total number of animals involved in the experiment, remains constant. Conclusion: Statistical artifacts in experiments containing small animal numbers may be prevented by an adequate design of the experiment. For this, it is suggested to select a higher number of dose levels, rather than using a higher number of animals per dose level. (orig.) [de

  11. Renal microvascular disease determines the responses to revascularization in experimental renovascular disease.

    Science.gov (United States)

    Chade, Alejandro R; Kelsen, Silvia

    2010-08-01

    Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.

  12. Exquisite allele discrimination by toehold hairpin primers

    Science.gov (United States)

    Byrom, Michelle; Bhadra, Sanchita; Jiang, Yu Sherry; Ellington, Andrew D.

    2014-01-01

    The ability to detect and monitor single nucleotide polymorphisms (SNPs) in biological samples is an enabling research and clinical tool. We have developed a surprising, inexpensive primer design method that provides exquisite discrimination between SNPs. The field of DNA computation is largely reliant on using so-called toeholds to initiate strand displacement reactions, leading to the execution of kinetically trapped circuits. We have now similarly found that the short toehold sequence to a target of interest can initiate both strand displacement within the hairpin and extension of the primer by a polymerase, both of which will further stabilize the primer:template complex. However, if the short toehold does not bind, neither of these events can readily occur and thus amplification should not occur. Toehold hairpin primers were used to detect drug resistance alleles in two genes, rpoB and katG, in the Mycobacterium tuberculosis genome, and ten alleles in the Escherichia coli genome. During real-time PCR, the primers discriminate between mismatched templates with Cq delays that are frequently so large that the presence or absence of mismatches is essentially a ‘yes/no’ answer. PMID:24990378

  13. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  14. Brazilian quilombos: A repository of Amerindian alleles.

    Science.gov (United States)

    Gontijo, Carolina Carvalho; Guerra Amorim, Carlos Eduardo; Godinho, Neide Maria Oliveira; Toledo, Rafaela Cesare Parmezan; Nunes, Adriana; Silva, Wellington; Da Fonseca Moura, Maria Manuela; De Oliveira, José Carlos Coutinho; Pagotto, Rubiani C; Klautau-Guimarães, Maria De Nazaré; De Oliveira, Silviene Fabiana

    2014-01-01

    As a consequence of colonization of the Americas and decimation of the native population, an important portion of autochthonous genetic variation has been lost. However, some alleles have been incorporated into the growing populations of admixed mestizos. In this study, we evaluated the potential of African-derived communities in Brazil to be repositories of Amerindian alleles and, by extension, a source of information on American prehistory. In this study, we describe the genetic variation of 15 ancestry informative markers (AIMs) of autosomal origin in two quilombos, Brazilian populations mainly of African descent, Santo Antônio do Guaporé (SAG; N = 31), and Santiago do Iguape (STI; N = 37). We compared the AIMs from these populations to those of other African-Brazilian populations, and to the Distrito Federal (N = 168), an urban population representative of Brazilian genetic diversity. By admixture analysis, we found that the SAG and STI communities have a much higher proportion (over 40%) of Amerindian contribution to their gene pools than other admixed Brazilian populations, in addition to marked African contributions. These results identify two living African-Brazilian populations that carry unique and important genetic information regarding Amerindian history. These populations will be extremely valuable in future investigations into American pre-history and Native American evolutionary dynamics. Copyright © 2014 Wiley Periodicals, Inc.

  15. allele of the noncoding hsrω gene of Drosophila melanogaster is not ...

    Indian Academy of Sciences (India)

    Drosophila melanogaster is not responsible for male sterility as reported earlier ... gene, the pl alleles were brought in trans with hsrω05241 or with the ... The progeny hsrω05241/ry. − females were crossed with TM3/TM6B males (for details of the var- ious mutant genes and balancer chromosomes, see Lindslay and Zimm ...

  16. Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis

    International Nuclear Information System (INIS)

    Moneo, Victoria; Serelde, Beatriz G; Blanco-Aparicio, Carmen; Diaz-Uriarte, Ramon; Avilés, Pablo; Santamaría, Gemma; Tercero, Juan C; Cuevas, Carmen; Carnero, Amancio

    2014-01-01

    Zalypsis® is a marine compound in phase II clinical trials for multiple myeloma, cervical and endometrial cancer, and Ewing’s sarcoma. However, the determinants of the response to Zalypsis are not well known. The identification of biomarkers for Zalypsis activity would also contribute to broaden the spectrum of tumors by selecting those patients more likely to respond to this therapy. Using in vitro drug sensitivity data coupled with a set of molecular data from a panel of sarcoma cell lines, we developed molecular signatures that predict sensitivity to Zalypsis. We verified these results in culture and in vivo xenograft studies. Zalypsis resistance was dependent on the expression levels of PDGFRα or constitutive phosphorylation of c-Kit, indicating that the activation of tyrosine kinase receptors (TKRs) may determine resistance to Zalypsis. To validate our observation, we measured the levels of total and active (phosphorylated) forms of the RTKs PDGFRα/β, c-Kit, and EGFR in a new panel of diverse solid tumor cell lines and found that the IC50 to the drug correlated with RTK activation in this new panel. We further tested our predictions about Zalypsis determinants for response in vivo in xenograft models. All cells lines expressing low levels of RTK signaling were sensitive to Zalypsis in vivo, whereas all cell lines except two with high levels of RTK signaling were resistant to the drug. RTK activation might provide important signals to overcome the cytotoxicity of Zalypsis and should be taken into consideration in current and future clinical trials

  17. Application of Response Surface Methods To Determine Conditions for Optimal Genomic Prediction

    Science.gov (United States)

    Howard, Réka; Carriquiry, Alicia L.; Beavis, William D.

    2017-01-01

    An epistatic genetic architecture can have a significant impact on prediction accuracies of genomic prediction (GP) methods. Machine learning methods predict traits comprised of epistatic genetic architectures more accurately than statistical methods based on additive mixed linear models. The differences between these types of GP methods suggest a diagnostic for revealing genetic architectures underlying traits of interest. In addition to genetic architecture, the performance of GP methods may be influenced by the sample size of the training population, the number of QTL, and the proportion of phenotypic variability due to genotypic variability (heritability). Possible values for these factors and the number of combinations of the factor levels that influence the performance of GP methods can be large. Thus, efficient methods for identifying combinations of factor levels that produce most accurate GPs is needed. Herein, we employ response surface methods (RSMs) to find the experimental conditions that produce the most accurate GPs. We illustrate RSM with an example of simulated doubled haploid populations and identify the combination of factors that maximize the difference between prediction accuracies of best linear unbiased prediction (BLUP) and support vector machine (SVM) GP methods. The greatest impact on the response is due to the genetic architecture of the population, heritability of the trait, and the sample size. When epistasis is responsible for all of the genotypic variance and heritability is equal to one and the sample size of the training population is large, the advantage of using the SVM method vs. the BLUP method is greatest. However, except for values close to the maximum, most of the response surface shows little difference between the methods. We also determined that the conditions resulting in the greatest prediction accuracy for BLUP occurred when genetic architecture consists solely of additive effects, and heritability is equal to one. PMID

  18. Association of LEI0258 microsatellite alleles with antibody response ...

    African Journals Online (AJOL)

    SERVER

    2008-03-18

    Mar 18, 2008 ... use of cheaper methods for the chicken MHC typing was recommended. Key words: Microsatellites, PCR, Newcastle-disease, body-weight, local-chicken. INTRODUCTION. Low genetic potential and high prevalence of diseases are among of the major factors limiting productivity of the local chickens in the ...

  19. A Maximum Likelihood Approach to Determine Sensor Radiometric Response Coefficients for NPP VIIRS Reflective Solar Bands

    Science.gov (United States)

    Lei, Ning; Chiang, Kwo-Fu; Oudrari, Hassan; Xiong, Xiaoxiong

    2011-01-01

    Optical sensors aboard Earth orbiting satellites such as the next generation Visible/Infrared Imager/Radiometer Suite (VIIRS) assume that the sensors radiometric response in the Reflective Solar Bands (RSB) is described by a quadratic polynomial, in relating the aperture spectral radiance to the sensor Digital Number (DN) readout. For VIIRS Flight Unit 1, the coefficients are to be determined before launch by an attenuation method, although the linear coefficient will be further determined on-orbit through observing the Solar Diffuser. In determining the quadratic polynomial coefficients by the attenuation method, a Maximum Likelihood approach is applied in carrying out the least-squares procedure. Crucial to the Maximum Likelihood least-squares procedure is the computation of the weight. The weight not only has a contribution from the noise of the sensor s digital count, with an important contribution from digitization error, but also is affected heavily by the mathematical expression used to predict the value of the dependent variable, because both the independent and the dependent variables contain random noise. In addition, model errors have a major impact on the uncertainties of the coefficients. The Maximum Likelihood approach demonstrates the inadequacy of the attenuation method model with a quadratic polynomial for the retrieved spectral radiance. We show that using the inadequate model dramatically increases the uncertainties of the coefficients. We compute the coefficient values and their uncertainties, considering both measurement and model errors.

  20. Experimental determination of thermal conductivity of soil with a thermal response test

    Directory of Open Access Journals (Sweden)

    Banjac Miloš J.

    2012-01-01

    Full Text Available Optimal design of a borehole heat exchanger, as the outer part of a ground source heat pump heating system, requires information on the thermal properties of the soil. Those data, the effective thermal conductivity of the soil λeff and the average temperature of the soil T0, enable us to determine the necessary number and depth of boreholes. The determination of thermal conductivity of the soil in laboratory experiments does not usually coincide with the data under in-situ conditions. Therefore, an in-situ method of experimental determination of these parameters, the so-called thermal response test, is presented in this paper. In addition to the description of the experimental procedure and installation overview, the paper describes methods based on theory and presents their basic limitations, through the presentation of experimental data. [Acknowledgment. This paper is made in a scope of the project TR 33047 “Intelligent climate control systems to achieve energy efficient regime in the complex conditions of exploitation” funded by the Ministry of Education and Science of the Republic of Serbia.

  1. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...

  2. JK null alleles identified from Japanese individuals with Jk(a−b−) phenotype.

    Science.gov (United States)

    Onodera, T; Sasaki, K; Tsuneyama, H; Isa, K; Ogasawara, K; Satake, M; Tadokoro, K; Uchikawa, M

    2014-05-01

    The Kidd blood group system consists of three common phenotypes: Jk(a+b−), Jk(a−b+) and Jk(a+b+), and one rare phenotype, Jk(a−b−). Jka/Jkb polymorphism is associated with c.838G>A (p.Asp280Asn) in exon 9 of the JK (SLC14A1) gene, and the corresponding alleles are named JK*01 and JK*02. The rare phenotype Jk(a−b−) was first found in a Filipina of Spanish and Chinese ancestry, and to date, several JK null alleles responsible for the Jk(a−b−) phenotype have been reported. We report seven novel JK null alleles, 4 with a JK*01 background and 3 with a JK*02 background, identified from Jk(a−b−) Japanese.

  3. Vocal similarity and familiarity determine response to potential flockmates in orange-fronted conures (Psittacidae)

    DEFF Research Database (Denmark)

    Balsby, Thorsten Johannes Skovbjerg; Adams, Danielle M.

    2011-01-01

    to discriminate others based on their vocalizations and associate knowledge with their vocal identity. Alternatively, this decision may be determined solely by the current interaction. In a playback experiment, we tested the ability of orange-fronted conures, Aratinga canicularis to discriminate between calls...... of familiar and unfamiliar females. Males were able to discriminate between familiar and unfamiliar calls from different females. Furthermore, test birds seemed to associate experience from the previous interaction with the vocal characteristics of the familiar call, but this result was marginally...... nonsignificant. The success of the playback in imitating the test bird’s contact call in the current interaction proved important, as high similarity between playback and the test bird’s contact calls elicited a stronger response from it. The importance of call imitation during current interactions probably...

  4. Fear of violence during armed conflict: Social roles and responsibilities as determinants of fear.

    Science.gov (United States)

    Williams, Nathalie E; Ghimire, Dirgha; Snedker, Karen A

    2018-03-01

    This article investigates the prevalence and determinants of fear as a consequence of living through armed conflict. We use survey data from Nepal during the armed conflict (1996-2006) to examine how trauma, sex and gender, age, marriage, and household size affect fear of violence. We also disaggregate types of worry, and find substantial variance on whether respondents were more concerned about livelihood consequences of conflict than physical danger. We supplement quantitative analyses with discussion of in-depth interviews from the study area on these same topics. Overall, our results highlight the enduring impact of gender roles in Nepal and that conflict might disproportionately affect those who are already vulnerable and have greater social responsibilities. This article provides a unique comparison between fear of violence during armed conflict in a low-income country to the fear of crime literature based in high-income countries. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. RNA-Seq using two populations reveals genes and alleles controlling wood traits and growth in Eucalyptus nitens.

    Directory of Open Access Journals (Sweden)

    Saravanan Thavamanikumar

    Full Text Available Eucalyptus nitens is a perennial forest tree species grown mainly for kraft pulp production in many parts of the world. Kraft pulp yield (KPY is a key determinant of plantation profitability and increasing the KPY of trees grown in plantations is a major breeding objective. To speed up the breeding process, molecular markers that can predict KPY are desirable. To achieve this goal, we carried out RNA-Seq studies on trees at extremes of KPY in two different trials to identify genes and alleles whose expression correlated with KPY. KPY is positively correlated with growth measured as diameter at breast height (DBH in both trials. In total, six RNA bulks from two treatments were sequenced on an Illumina HiSeq platform. At 5% false discovery rate level, 3953 transcripts showed differential expression in the same direction in both trials; 2551 (65% were down-regulated and 1402 (35% were up-regulated in low KPY samples. The genes up-regulated in low KPY trees were largely involved in biotic and abiotic stress response reflecting the low growth among low KPY trees. Genes down-regulated in low KPY trees mainly belonged to gene categories involved in wood formation and growth. Differential allelic expression was observed in 2103 SNPs (in 1068 genes and of these 640 SNPs (30% occurred in 313 unique genes that were also differentially expressed. These SNPs may represent the cis-acting regulatory variants that influence total gene expression. In addition we also identified 196 genes which had Ka/Ks ratios greater than 1.5, suggesting that these genes are under positive selection. Candidate genes and alleles identified in this study will provide a valuable resource for future association studies aimed at identifying molecular markers for KPY and growth.

  6. Frequency of the CCRdelta32 allele in Brazilians: a study in colorectal cancer and in HTLV-I infection

    OpenAIRE

    Pereira, Rinaldo W.; Pires, Edina R.; Duarte, Ana P.M.; Moura, Ricardo P. de; Monteiro, Elisangela; Torloni, Humberto; Proietti, Anna B.; Simpson, Andrew J.G.; Pena, Sérgio D.J.

    2000-01-01

    The identification of a 32-bp deletion in the cc-chemokine receptor-5 gene (CCR5delta32 allele) that renders homozygous individuals highly resistant to HIV infection has prompted worldwide investigations of the frequency of the CCR5delta32 allele in regional populations. It is important to ascertain if CCR5delta32 is a factor to be considered in the overall epidemiology of HIV in individual populations. With this in mind we determined the CCR5delta32 allele frequency in a large sample (907 in...

  7. An Analytical Method to Determine the Response of a Micro Capacitive Pressure Sensor

    Directory of Open Access Journals (Sweden)

    Ashwin Simha

    2011-07-01

    Full Text Available The response of a capacitive pressure sensor is generally represented by a fourth order partial differential equation which is complex to solve and does not possess an exact solution. Several attempts have been made earlier through various techniques such as the Galerkin method, Finite Difference Method etc. In this paper an attempt has been made to develop a simple approximate analytical approach to determine the response of a capacitive pressure sensor whose diaphragm is designed to undergo very small deflections (typically less than 25 % of the thickness. The non-uniform gap between the electrodes is mathematically expressed as a combination of the initial gap between the electrodes (in the undeformed state and a displacement function in (x, y. The proposed displacement function is then utilized in evaluating the capacitance as a function of the applied pressure. The results obtained from the analytical approach are benchmarked against those obtained from COMSOL Multiphysics®, a popular Finite Element Analysis tool in the MEMS industry. It is observed that the results obtained from COMSOL Multiphysics® and those from the analytical approach are in good agreement with a maximum deviation of about 3.38 %.

  8. Determining criminal responsibility: How relevant are insight and personal attitudes to mock jurors?

    Science.gov (United States)

    Jung, Sandy

    2015-01-01

    High levels of insight are interpreted as indications of a treatment compliance and good outcome by clinical professionals. However, it is unclear whether a defendant's insight plays a role in the decision-making of jurors when determining criminal responsibility. It may be the case that personal biases and attitudes toward the mentally ill and the insanity defense are more relevant in such decisions. This study examines the influence of two core dimensions of insight and personal attitudes on juror decision-making. Participants read trial scenarios describing a defendant who is accused of a violent crime and is diagnosed with schizophrenia. Assigning a verdict of not criminally responsible to the defendant was not influenced by insight, but instead, by supportive attitudes of the insanity defense and higher attributions of blame to external factors and to psychological factors. These findings highlight the need for continued investigation in the area of extra-legal factors that guide legal decision-making when defendants have a mental disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. ERBB2 regulation by Estrogen Receptor-Pax2 determines tamoxifen response

    Science.gov (United States)

    Hurtado, Antoni; Holmes, Kelly A.; Geistlinger, Timothy R.; Hutcheson, Iain R.; Nicholson, Robert I.; Brown, Myles; Jiang, Jie; Howat, William J.; Ali, Simak; Carroll, Jason S.

    2010-01-01

    Cross talk between the Estrogen Receptor (ER) and ErbB2/HER-2 pathways have long been implicated in breast cancer aetiology and drug response1, yet no direct connection at a transcriptional level has been shown. We now show that estrogen-ER and tamoxifen-ER complexes directly repress ErbB2 transcription via a cis-regulatory element within the ERBB2 gene. We implicate the Paired Box 2 gene product (Pax2), in a novel role, as a crucial mediator of ER repression of ErbB2 by the anti-cancer drug tamoxifen. We show that Pax2 and the ER co-activator AIB-1/SRC-3 compete for binding and regulation of ErbB2 transcription, the outcome of which determines tamoxifen response in breast cancer cells. The repression of ErbB2 by ER-Pax2 links these two important breast cancer subtypes and suggests that aggressive ErbB2 positive tumours can originate from ER positive luminal tumours by circumventing this repressive mechanism. These data provide mechanistic insight into the molecular basis of endocrine resistance in breast cancer. PMID:19005469

  10. Is cell survival a determinant of the in situ response of 9L tumours

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Wallen, C.A.

    1980-01-01

    The influence of growth rate, location, size and potential lethal damage (PLD) recovery on the cellular radiosensitivity and the tumour response was studied in 9L/Ro and 9L/SF rat tumours. The median day of death of rats bearing the intracerebral (i.c.) 9L/Ro tumours was 16-18 days; for i.c. 9L/SF tumours it was 23-25 days. The doubling time of 9L/Ro cells was slightly faster than for 9L/SF cells both in culture and in the brain. The cellular radiosensitivity of both i.c. tumour cell sublines was identical. However, subcutaneous (s.c.) 9L/Ro tumour cells were more resistant. There was no evidence of a substantial hypoxic fraction in either site. When i.c. 9L/Ro and 9L/SF tumours of similar size were treated with fractionated doses of BCNU, X-rays or combinations of the two, the responses of the two tumours were essentially identical. The rate of recovery from radiation-induced PLD was identical in the two sublines and the two sites. Increase in life-span of rats bearing i.c. 9L/Ro tumours appeared to be correlated with the tumour cell kill measured after completion of PLD recovery rather than with the tumour cell kill determined immediately after irradiation. (author)

  11. Determining a cost effective intervention response to HIV/AIDS in Peru

    Science.gov (United States)

    Aldridge, Robert W; Iglesias, David; Cáceres, Carlos F; Miranda, J Jaime

    2009-01-01

    Background The HIV epidemic in Peru is still regarded as concentrated - sentinel surveillance data shows greatest rates of infection in men who have sex with men, while much lower rates are found in female sex workers and still lower in the general population. Without an appropriate set of preventive interventions, continuing infections could present a challenge to the sustainability of the present programme of universal access to treatment. Determining how specific prevention and care strategies would impact on the health of Peruvians should be key in reshaping the national response. Methods HIV/AIDS prevalence levels for risk groups with sufficient sentinel survey data were estimated. Unit costs were calculated for a series of interventions against HIV/AIDS which were subsequently inputted into a model to assess their ability to reduce infection transmission rates. Interventions included: mass media, voluntary counselling and testing; peer counselling for female sex workers; peer counselling for men who have sex with men; peer education of youth in-school; condom provision; STI treatment; prevention of mother to child transmission; and highly active antiretroviral therapy. Impact was assessed by the ability to reduce rates of transmission and quantified in terms of cost per DALY averted. Results Results of the analysis show that in Peru, the highest levels of HIV prevalence are found in men who have sex with men. Cost effectiveness varied greatly between interventions ranging from peer education of female commercial sex workers at $US 55 up to $US 5,928 (per DALY averted) for prevention of mother to child transmission. Conclusion The results of this work add evidence-based clarity as to which interventions warrant greatest consideration when planning an intervention response to HIV in Peru. Cost effectiveness analysis provides a necessary element of transparency when facing choices about priority setting, particularly when the country plans to amplify its

  12. Determination of Wheat Yield Response Factor to Deficit Irrigation at Different Growth Stages

    Directory of Open Access Journals (Sweden)

    N. A. Ebrahimi Pak

    2012-12-01

    Full Text Available This study was conducted to determine the yield response factor (Ky of wheat with respect to deficit irrigation at different growth stages. The experiment was conducted in Shahrekord in three crop growing seasons using randomized complete blocks design with 3 replications. Treatments consisted of five levels of deficit irrigation: E0 (full irrigation, E1 (85%, E2 (70% and E3 (55% of potential evapotranspiration of wheat and E4 (no irrigation, and were assigned to six growth stages: T1 (establishment, T2 (tillering, T3 (head development, T4 (flowering, T5 (milk ripeness and T6 (maturity harvest. Potential evapotranspiration was measured using a lysimeter, which was in conditions (soil texture and structure and plant growth similar to the field. After harvesting the plants, grain yield was measured and wheat yield response factor was calculated. Results of combined analysis of variance showed that grain yield was significantly affected by deficit irrigation at establishment, tillering, head development, flowering and milk ripeness stages. The highest and the lowest grain yields (6354 and 2203 kg/ha, respectively were obtained in E0 and E4 treatments, respectively. Potential evapotranspiration of wheat was 641 mm in this area. Yield response factors (ky were 0.55-0.76 in T1 growth stage, 0.58-0.97 in T2, 0.70-1.43 in T3, 0.75-1.45 in T4, 0.68-0.95 in T5 and 0.52-0.58 in T6. In general, in all plant growth stages, actual and relative yields decrease as relative evapotranspiration decreases.

  13. Determining a cost effective intervention response to HIV/AIDS in Peru

    Directory of Open Access Journals (Sweden)

    Cáceres Carlos F

    2009-09-01

    Full Text Available Abstract Background The HIV epidemic in Peru is still regarded as concentrated - sentinel surveillance data shows greatest rates of infection in men who have sex with men, while much lower rates are found in female sex workers and still lower in the general population. Without an appropriate set of preventive interventions, continuing infections could present a challenge to the sustainability of the present programme of universal access to treatment. Determining how specific prevention and care strategies would impact on the health of Peruvians should be key in reshaping the national response. Methods HIV/AIDS prevalence levels for risk groups with sufficient sentinel survey data were estimated. Unit costs were calculated for a series of interventions against HIV/AIDS which were subsequently inputted into a model to assess their ability to reduce infection transmission rates. Interventions included: mass media, voluntary counselling and testing; peer counselling for female sex workers; peer counselling for men who have sex with men; peer education of youth in-school; condom provision; STI treatment; prevention of mother to child transmission; and highly active antiretroviral therapy. Impact was assessed by the ability to reduce rates of transmission and quantified in terms of cost per DALY averted. Results Results of the analysis show that in Peru, the highest levels of HIV prevalence are found in men who have sex with men. Cost effectiveness varied greatly between interventions ranging from peer education of female commercial sex workers at $US 55 up to $US 5,928 (per DALY averted for prevention of mother to child transmission. Conclusion The results of this work add evidence-based clarity as to which interventions warrant greatest consideration when planning an intervention response to HIV in Peru. Cost effectiveness analysis provides a necessary element of transparency when facing choices about priority setting, particularly when the country

  14. Response to enemies in the invasive plant Lythrum salicaria is genetically determined

    Science.gov (United States)

    Joshi, Srijana; Tielbörger, Katja

    2012-01-01

    Background and Aims The enemy release hypothesis assumes that invasive plants lose their co-evolved natural enemies during introduction into the new range. This study tested, as proposed by the evolution of increased competitive ability (EICA) hypothesis, whether escape from enemies results in a decrease in defence ability in plants from the invaded range. Two straightforward aspects of the EICA are examined: (1) if invasives have lost their enemies and their defence, they should be more negatively affected by their full natural pre-invasion herbivore spectrum than their native conspecifics; and (2) the genetic basis of evolutionary change in response to enemy release in the invasive range has not been taken sufficiently into account. Methods Lythrum salicaria (purple loosestrife) from several populations in its native (Europe) and invasive range (North America) was exposed to all above-ground herbivores in replicated natural populations in the native range. The experiment was performed both with plants raised from field-collected seeds as well as with offspring of these where maternal effects were removed. Key Results Absolute and relative leaf damage was higher for introduced than for native plants. Despite having smaller height growth rate, invasive plants attained a much larger final size than natives irrespective of damage, indicating large tolerance rather than effective defence. Origin effects on response to herbivory and growth were stronger in second-generation plants, suggesting that invasive potential through enemy release has a genetic basis. Conclusions The findings support two predictions of the EICA hypothesis – a genetically determined difference between native and invasive plants in plant vigour and response to enemies – and point to the importance of experiments that control for maternal effects and include the entire spectrum of native range enemies. PMID:22492331

  15. An allelic variant of congenital Salih myopathy

    Directory of Open Access Journals (Sweden)

    M. S. Belenikin

    2015-01-01

    Full Text Available The paper describes the steps and problems of diagnosing congenital myopathy with early respiratory disorders. While differentially diagnosing, the authors consider congenital myopathies, in which early cardiac involvement is encountered. Since the course of the disease in an observed female patient differed from that of such nosological entities and appeared as not only muscle weakness, but also as early respiratory disorders, we could not identify what nosological entity the disease belonged to in view of its clinical presentation and the results of muscle histological examination and we decided to perform exome sequencing. Molecular genetic testing could find heterozygous mutations in the titin (TTN gene. The findings are suggestive of congenital proximal myopathy with early respiratory failure, which is an allelic variant of Salih myopathy. This case is the first and so far only description of this disease in Russia. 

  16. Microsatellite polymorphism within pfcrt provides evidence of continuing evolution of chloroquine-resistant alleles in Papua New Guinea

    Directory of Open Access Journals (Sweden)

    Sharma Yagya D

    2007-03-01

    Full Text Available Abstract Background Polymorphism in the pfcrt gene underlies Plasmodium falciparum chloroquine resistance (CQR, as sensitive strains consistently carry lysine (K, while CQR strains carry threonine (T at the codon 76. Previous studies have shown that microsatellite (MS haplotype variation can be used to study the evolution of CQR polymorphism and to characterize intra- and inter-population dispersal of CQR in Papua New Guinea (PNG. Methods Here, following identification of new polymorphic MS in introns 2 and 3 within the pfcrt gene (msint2 and msint3, respectively, locus-by-locus and haplotype heterozygosity (H analyses were performed to determine the distribution of this intronic polymorphism among pfcrt chloroquine-sensitive and CQR alleles. Results For MS flanking the pfcrt CQR allele, H ranged from 0.07 (B5M77, -18 kb to 0.094 (9B12, +2 kb suggesting that CQ selection pressure was responsible for strong homogenisation of this gene locus. In a survey of 206 pfcrt-SVMNT allele-containing field samples from malaria-endemic regions of PNG, H for msint2 was 0.201. This observation suggests that pfcrt msint2 exhibits a higher level of diversity than what is expected from the analyses of pfcrt flanking MS. Further analyses showed that one of the three haplotypes present in the early 1980's samples has become the predominant haplotype (frequency = 0.901 in CQR parasite populations collected after 1995 from three PNG sites, when CQR had spread throughout malaria-endemic regions of PNG. Apparent localized diversification of pfcrt haplotypes at each site was also observed among samples collected after 1995, where minor CQR-associated haplotypes were found to be unique to each site. Conclusion In this study, a higher level of diversity at MS loci within the pfcrt gene was observed when compared with the level of diversity at pfcrt flanking MS. While pfcrt (K76T and its immediate flanking region indicate homogenisation in PNG CQR parasite populations

  17. The effect of wild card designations and rare alleles in forensic DNA database searches

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Bright, Jo-Anne; Buckleton, John S

    2015-01-01

    may be compromised in quantity or quality. When an individual's profile cannot be resolved from a DNA mixture, ambiguity is introduced. A wild card, F, may be used in place of an allele that has dropped out or when an ambiguous profile is resolved from a DNA mixture. Variant alleles that do...... not been determined. The F and R designation are treated as wild cards for searching, which results in increased chance of adventitious matches. We investigated the probability of adventitious matches given these two types of wild cards....

  18. Characterization of Tn6238 with a New Allele of aac(6′)-Ib-cr

    Science.gov (United States)

    Quiroga, María P.; Orman, Betina; Errecalde, Laura; Kaufman, Sara

    2015-01-01

    Here, we report that the genetic structure of Tn1331 remained conserved in Argentina from 1989 to 2013 (72 of 73 isolates), with the exception being the plasmid-borne Tn1331-like transposon Tn6238 containing a new aac(6′)-Ib-cr allele recovered from a colistin-resistant Klebsiella pneumoniae clinical isolate. A bioinformatic analysis of aac(6′)-Ib-like gene cassettes suggests that this new aac(6′)-Ib-cr allele emerged through mutation or homologous recombination in the Tn1331 genetic platform. Tn6238 is a novel platform for the dissemination of aminoglycoside and fluoroquinolone resistance determinants. PMID:25691640

  19. Genomic analyses of RH alleles to improve transfusion therapy in patients with sickle cell disease.

    Science.gov (United States)

    Reid, Marion E; Halter Hipsky, Christine; Hue-Roye, Kim; Hoppe, Carolyn

    2014-04-01

    Red cell (RBC) blood group alloimmunization remains a major problem in transfusion medicine. Patients with sickle cell disease (SCD) are at particularly high risk for developing alloantibodies to RBC antigens compared to other multiply transfused patient populations. Hemagglutination is the classical method used to test for blood group antigens, but depending on the typing methods and reagents used may result in discrepancies that preclude interpretation based on serologic reactivity alone. Molecular methods, including customized DNA microarrays, are increasingly used to complement serologic methods in predicting blood type. The purpose of this study was to determine the diversity and frequency of RH alleles in African Americans and to assess the performance of a DNA microarray for RH allele determination. Two sets of samples were tested: (i) individuals with known variant Rh types and (ii) randomly selected African American donors and patients with SCD. Standard hemagglutination tests were used to establish the Rh phenotype, and cDNA- and gDNA-based analyses (sequencing, PCR-RFLP, and customized RHD and RHCE microarrays were used to predict the genotype). In a total of 829 samples (1658 alleles), 72 different alleles (40 RHD and 32 RHCE) were identified, 22 of which are novel. DNA microarrays detected all nucleotides probed, allowing for characterization of over 900 alleles. High-throughput DNA testing platforms provide a means to test a relatively large number of donors and potentially prevent immunization by changing the way antigen-negative blood is provided to patients. Because of the high RH allelic diversity found in the African American population, determination of an accurate Rh phenotype often requires DNA testing, in conjunction with serologic testing. Allele-specific microarrays offer a means to perform high-throughput donor Rh typing and serve as a valuable adjunct to serologic methods to predict Rh type. Because DNA microarrays test for only a fixed

  20. The Spanish version of the Self-Determination Inventory Student Report: application of item response theory to self-determination measurement.

    Science.gov (United States)

    Mumbardó-Adam, C; Guàrdia-Olmos, J; Giné, C; Raley, S K; Shogren, K A

    2018-04-01

    A new measure of self-determination, the Self-Determination Inventory: Student Report (Spanish version), has recently been adapted and empirically validated in Spanish language. As it is the first instrument intended to measure self-determination in youth with and without disabilities, there is a need to further explore and strengthen its psychometric analysis based on item response patterns. Through item response theory approach, this study examined item observed distributions across the essential characteristics of self-determination. The results demonstrated satisfactory to excellent item functioning patterns across characteristics, particularly within agentic action domains. Increased variability across items was also found within action-control beliefs dimensions, specifically within the self-realisation subdomain. These findings further support the instrument's psychometric properties and outline future research directions. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  1. Predominance of N-acetyl transferase 2 slow acetylator alleles in ...

    African Journals Online (AJOL)

    Student

    The human N-acetyltransferase II (NAT2) gene may vary between individuals resulting in variability in the incidence of adverse drug reactions. We set out in this adhoc analysis to determine the distribution of allele frequencies of NAT2 gene variants among children less than ten years treated with artemisinin-based.

  2. Composition and functional analysis of low-molecular-weight glutenin alleles with Aroona near-isogenic lines of bread wheat

    Directory of Open Access Journals (Sweden)

    Zhang Xiaofei

    2012-12-01

    Full Text Available Abstract Background Low-molecular-weight glutenin subunits (LMW-GS strongly influence the bread-making quality of bread wheat. These proteins are encoded by a multi-gene family located at the Glu-A3, Glu-B3 and Glu-D3 loci on the short arms of homoeologous group 1 chromosomes, and show high allelic variation. To characterize the genetic and protein compositions of LMW-GS alleles, we investigated 16 Aroona near-isogenic lines (NILs using SDS-PAGE, 2D-PAGE and the LMW-GS gene marker system. Moreover, the composition of glutenin macro-polymers, dough properties and pan bread quality parameters were determined for functional analysis of LMW-GS alleles in the NILs. Results Using the LMW-GS gene marker system, 14–20 LMW-GS genes were identified in individual NILs. At the Glu-A3 locus, two m-type and 2–4 i-type genes were identified and their allelic variants showed high polymorphisms in length and nucleotide sequences. The Glu-A3d allele possessed three active genes, the highest number among Glu-A3 alleles. At the Glu-B3 locus, 2–3 m-type and 1–3 s-type genes were identified from individual NILs. Based on the different compositions of s-type genes, Glu-B3 alleles were divided into two groups, one containing Glu-B3a, B3b, B3f and B3g, and the other comprising Glu-B3c, B3d, B3h and B3i. Eight conserved genes were identified among Glu-D3 alleles, except for Glu-D3f. The protein products of the unique active genes in each NIL were detected using protein electrophoresis. Among Glu-3 alleles, the Glu-A3e genotype without i-type LMW-GS performed worst in almost all quality properties. Glu-B3b, B3g and B3i showed better quality parameters than the other Glu-B3 alleles, whereas the Glu-B3c allele containing s-type genes with low expression levels had an inferior effect on bread-making quality. Due to the conserved genes at Glu-D3 locus, Glu-D3 alleles showed no significant differences in effects on all quality parameters. Conclusions This work

  3. Determination of the response of a NaI(Tl) detector

    International Nuclear Information System (INIS)

    Vega C, H.R.; Manzanares A, E.; Hernandez D, V.M.; Chacon R, A.

    2006-01-01

    By means of Monte Carlo calculations it was determined the response of a scintillator of NaI (Tl) of 7.62 Φ x 7.62 cm to monoenergetic gamma rays of 0.2 to 3.5 MeV. The response allows to determine the spectra of height of pulses of the monoenergetic photons. This type of calculations was also carried out for photons emitted by sources of Cs-137, Co-60, Na-22, Na-24 and 239 PuBe, with the purpose of reproducing the gamma spectra obtained with this type of detecting. In the calculations the detector was modelled as a NaI cylinder with Al cover and the base of lucite; due to the absence of reliable information on the quantity of thallium in the calculations this information was omitted: for photons whose energy is greater to 1.022 MeV the presence of the gamma peak of the simple escape and twice is observed. The source was modelled as punctual and was located to 5 cm along the axial axis of the detector. To verify the calculations its were carried out measurements with a spectrometer with a scintillator of 7.62 Φ x 7.62 cm. In the measured spectra the sum peak is observed, while in those calculated it doesn't appear; because the simultaneous detection of photons of different energy doesn't happen each photon since, in single form, it is followed until its complete absorption in the scintillator or when it escapes from the volume of the detector. To reproduce the sum peak and to obtain height spectra of pulses similar to those measured, the sum photons were introduced in the calculations. With the purpose of that Monte Carlo calculation it reproduces the scattering around the photopeak it was used a gaussian function in each photopeak whose characteristics were obtained starting from the experimental data. The calculation of the response of a scintillator allows to establish the capacity of the measurement of the gamma radiation as well as to distinguish the real events of those that appear by the limitations of the detection process. (Author)

  4. Determination of the spatial response of neutron based analysers using a Monte Carlo based method

    Science.gov (United States)

    Tickner

    2000-10-01

    One of the principal advantages of using thermal neutron capture (TNC, also called prompt gamma neutron activation analysis or PGNAA) or neutron inelastic scattering (NIS) techniques for measuring elemental composition is the high penetrating power of both the incident neutrons and the resultant gamma-rays, which means that large sample volumes can be interrogated. Gauges based on these techniques are widely used in the mineral industry for on-line determination of the composition of bulk samples. However, attenuation of both neutrons and gamma-rays in the sample and geometric (source/detector distance) effects typically result in certain parts of the sample contributing more to the measured composition than others. In turn, this introduces errors in the determination of the composition of inhomogeneous samples. This paper discusses a combined Monte Carlo/analytical method for estimating the spatial response of a neutron gauge. Neutron propagation is handled using a Monte Carlo technique which allows an arbitrarily complex neutron source and gauge geometry to be specified. Gamma-ray production and detection is calculated analytically which leads to a dramatic increase in the efficiency of the method. As an example, the method is used to study ways of reducing the spatial sensitivity of on-belt composition measurements of cement raw meal.

  5. Determination of injection molding process windows for optical lenses using response surface methodology.

    Science.gov (United States)

    Tsai, Kuo-Ming; Wang, He-Yi

    2014-08-20

    This study focuses on injection molding process window determination for obtaining optimal imaging optical properties, astigmatism, coma, and spherical aberration using plastic lenses. The Taguchi experimental method was first used to identify the optimized combination of parameters and significant factors affecting the imaging optical properties of the lens. Full factorial experiments were then implemented based on the significant factors to build the response surface models. The injection molding process windows for lenses with optimized optical properties were determined based on the surface models, and confirmation experiments were performed to verify their validity. The results indicated that the significant factors affecting the optical properties of lenses are mold temperature, melt temperature, and cooling time. According to experimental data for the significant factors, the oblique ovals for different optical properties on the injection molding process windows based on melt temperature and cooling time can be obtained using the curve fitting approach. The confirmation experiments revealed that the average errors for astigmatism, coma, and spherical aberration are 3.44%, 5.62%, and 5.69%, respectively. The results indicated that the process windows proposed are highly reliable.

  6. Determinants of Corporate Social Responsibility Disclosure: An Empirical Study of Polish Listed Companies

    Directory of Open Access Journals (Sweden)

    Justyna Dyduch

    2017-10-01

    Full Text Available In this paper we explore whether a number of elements influence the levels of corporate social responsibility (CSR disclosure in the annual reports of Polish companies. These elements include the following: company size, profitability, financial leverage, industry environmental sensitivity, board size, women on the board, internationalization, and reputation. We use content analysis to determine the quality of CSR disclosures. We test our hypotheses using a Tobit regression analysis on a sample of 60 reports from Polish companies listed on the Warsaw Stock Exchange. We find industry environmental sensitivity to have significant influence on CSR disclosures. Our research findings also reveal a relationship between company turnover, duration of the stock exchange listing, inclusion in the Respect Index portfolio and foreign capital share, and the level of CSR disclosures. This study extends the scope of previous studies by including non-commonly used independent variables: the company’s internationalization and reputation. To the authors’ knowledge, it is the primary step to investigating CSR reporting practices coupled with the corporate characteristics in a Central and Eastern European country such as Poland. The paper contributes to the understanding of determinants of CSR disclosure and offers findings which are potentially useful for both theory and practice.

  7. Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study

    NARCIS (Netherlands)

    Gichohi-Wainaina, W.N.; Boonstra, A.; Feskens, E.J.M.; Demir, A.Y.; Veenemans, J.; Verhoef, H.

    2015-01-01

    Background Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study’s objectives were to assess TNF allele variants (TNF-1031 , TNF-308 ): (1) modulation of malaria rates

  8. A novel JK null allele associated with typing discrepancies among African Americans.

    Science.gov (United States)

    Billingsley, Katrina L; Posadas, Jeff B; Moulds, Joann M; Gaur, Lakshmi K

    2013-01-01

    The Jknun (Jk-3) phenotype, attributable to null or silenced alleles, has predominantly been found in persons of Polynesian descent. With the increased use of molecular genotyping, many new silencing mutations have been identified in persons of other ethnic backgrounds. To date, only two JK null alleles have been reported in African Americans, JK*01N.04 and JK*OlN.OS.A comparative study was undertaken to determine whether JK mutations were present in the regional African American population. Results of donor genotyping were compared with previously recorded results of serologic tests, and discrepant results were investigated. Although the two previously identified polymorphisms were not detected in the discrepant samples, a novel allele (191G>A) was identified and was assigned the ISBT number JK*02N.09. This study illustrates a limitation of using single-nucleotide polymorphisms for prediction of blood group antigens.

  9. Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Knudsen, T B; Kristiansen, T B; Katzenstein, T L

    2001-01-01

    HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A....... Genotypes were determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When including the concurrent effects of the CCR5 Delta32 and CCR2 64I mutations, homozygous carriers of the CCR5 promoter -2459A allele had a significantly faster progression towards death than heterozygous A/G individuals...... (P = 0.03), whereas this adverse effect was not significant when comparing A/A and G/G individuals. However, independent analysis revealed a significant adverse effect of the CCR5 promoter -2459A allele. Homozygous carriers of the -2459A allele that lack the protective effects of the CCR5 Delta32...

  10. Microsatellite D21D210 (GT-12) allele frequencies in sporadic Alzheimer's disease

    International Nuclear Information System (INIS)

    Lannfelt, L.; Lilius, L.; Viitanen, M.; Winblad, B.; Basun, H.; Houlden, H.; Rossor, M.; Hardy, J.

    1995-01-01

    Four disease-causing mutations have so far been described in the amyloid precursor protein gene on chromosome 21 in familial early-onset Alzheimer's disease. Linkage analysis with a fourteen-allele microsatellite at D21S210 named GT-12 has proven useful in the elucidation of amyloid presursor protein gene involvement in Alzheimer's disease families, as it is closely linked to the gene. Most cases of Alzheimer's disease are thought to be sporadic and not familial. However, evidence from earlier studies suggests an important genetic contribution also in sporadic cases, where gene-environment interaction may contribute to the disease. We have determined frequencies of the GT-12 alleles in 78 Swedish and 49 British sporadic Alzheimer's disease cases and 104 healthy elderly control subjects, to investigate if the disease associates with a particular genotype in GT-12. However, no differences in allele frequencies were observed between any of the groups. (au) (26 refs.)

  11. Important predictors of response determined by surgical staging prior to triple modality therapy for esophageal cancer

    International Nuclear Information System (INIS)

    Suntharalingam, M.; Vines, E.; Slawson, R.; Doyle, A.; Schuetz, J.; Greenwald, B.; Sonnet, J.; Krasna, M.

    1997-01-01

    Purpose/Objective: Since 1992, the University of Maryland has routinely performed preoperative surgical staging including thoracoscopy and laparoscopy on patients undergoing concurrent chemoradiation followed by surgical resection for esophageal carcinoma. We have performed an analysis of the pathologic pretreatment data in an attempt to identify possible predictors of response and outcome. Materials: Patients underwent thoracoscopy and laparoscopy in order to determine resectability of the primary lesion and pathologic nodal status prior to therapy. To date, 32 patients have completed triple modality therapy (28 men, 4 women, median age 59). Patients received 50.4 Gy in 1.8 Gy fractions in conjunction with two cycles of 5-FU (1 gm/m2) and Cisplatin (100 mg/m2) on days 1 and 28. Radiotherapy fields were determined by the extent of disease discovered at time of surgical staging. Ivor Lewis esophagectomy was performed 4 to 6 weeks after completion of chemo/RT. The median follow up is 24.8 months (range 4-49 mo.) Sixteen patients had squamous cell ca and 16 had adenocarcinoma. Univariate and multivariate analysis was performed in order to determine the influence of age, KPS, T stage, Lymph Nodes status and histology, on the likelihood of achieving a pathologic complete response and disease free survival. Results: Twenty-eight have undergone preoperative staging (2 refused, 2 medical contraindications.) All 32 patients are valuable for response to therapy and are included in the analysis. The three year cause specific and disease free survival is 46% and 41% respectively with a median CSS of 23 months and DFS of 19 months. The overall complete response rate assessed by histologic and immunohistologic evaluation at the time of esophagectomy is 31%. The DFS at 32 months is 72% (median not reached) for these patients versus 24% for those with residual disease at the time of surgery. The most significant predictor for the likelihood of achieving a pathologic CR was the

  12. Cost-effective genome-wide estimation of allele frequencies from pooled DNA in Atlantic salmon (Salmo salar L.

    Directory of Open Access Journals (Sweden)

    Ozerov Mikhail

    2013-01-01

    Full Text Available Abstract Background New sequencing technologies have tremendously increased the number of known molecular markers (single nucleotide polymorphisms; SNPs in a variety of species. Concurrently, improvements to genotyping technology have now made it possible to efficiently genotype large numbers of genome-wide distributed SNPs enabling genome wide association studies (GWAS. However, genotyping significant numbers of individuals with large number of SNPs remains prohibitively expensive for many research groups. A possible solution to this problem is to determine allele frequencies from pooled DNA samples, such ‘allelotyping’ has been presented as a cost-effective alternative to individual genotyping and has become popular in human GWAS. In this article we have tested the effectiveness of DNA pooling to obtain accurate allele frequency estimates for Atlantic salmon (Salmo salar L. populations using an Illumina SNP-chip. Results In total, 56 Atlantic salmon DNA pools from 14 populations were analyzed on an Atlantic salmon SNP-chip containing probes for 5568 SNP markers, 3928 of which were bi-allelic. We developed an efficient quality control filter which enables exclusion of loci showing high error rate and minor allele frequency (MAF close to zero. After applying multiple quality control filters we obtained allele frequency estimates for 3631 bi-allelic loci. We observed high concordance (r > 0.99 between allele frequency estimates derived from individual genotyping and DNA pools. Our results also indicate that even relatively small DNA pools (35 individuals can provide accurate allele frequency estimates for a given sample. Conclusions Despite of higher level of variation associated with array replicates compared to pool construction, we suggest that both sources of variation should be taken into account. This study demonstrates that DNA pooling allows fast and high-throughput determination of allele frequencies in Atlantic salmon enabling cost

  13. Using the distribution of the CCR5-Δ32 allele in third-generation Maltese citizens to disprove the Black Death hypothesis.

    Science.gov (United States)

    Baron, B; Schembri-Wismayer, P

    2011-04-01

    Malta was under Norman rule for over 400 years and has had three major documented plague outbreaks (and a number of minor ones) since the 14th century with death tolls of 5-15% of the population at the time. This makes the Maltese population ideal for testing the hypothesis that the Black Death (particularly that of 1346-52) was responsible for a genetic shift that spread the CCR5-Δ32 allele. By enrolling 300 blood donors to determine the percentage of the Maltese population resistant to HIV-1 (which uses the CCR5-receptor to infect cells), it was established that the CCR5-Δ32 allele frequency is almost zero in third-generation Maltese citizens and sequencing showed that the deletion observed in the region of interest is the 32-base deletion expected. Thus, despite the extensive Norman occupation and the repeated plague cullings, the CCR5-Δ32 allele frequency is extremely low. This provides a basis for the discussion of conflicting hypotheses regarding the possible origin, function and spread of the CCR5-Δ32 deletion. © 2010 Blackwell Publishing Ltd.

  14. The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.

    Science.gov (United States)

    Moskovitz, Jackob; Walss-Bass, Consuelo; Cruz, Dianne A; Thompson, Peter M; Hairston, Jenaqua; Bortolato, Marco

    2015-12-01

    The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulphoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion. COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects by using catechol and dabsyl-Met sulphoxide as substrates, respectively. Allelic discrimination of COMT Val(108/185) Met SNP was performed using the Taqman 5'nuclease assay. Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR was significantly correlated throughout all tested brain regions. These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulphoxidation and point to MSR as a key molecular determinant for the modulation of COMT activity. © 2015 British Neuropathological Society.

  15. Allele Frequency - JSNP | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available nd 39 SNPs are assayed in three (POP_*) and two (RIKEN_japanese_*) panels, respectively. Derived from Flat f... assay (JBIC-allele and RIKEN_japanese_*), TaqMan assay (RIKEN-allele) or direct sequencing / allelic discri...unteers under informed consent RIKEN_japanese_normal_weight - 711 unrelated japanese normal weight volunteer...s ( body mass index RIKEN_japanese_obese - 796 unrelated japanese obese patients

  16. Imputation of TPMT defective alleles for the identification of patients with high-risk phenotypes

    Directory of Open Access Journals (Sweden)

    Berta eAlmoguera

    2014-05-01

    Full Text Available Background: The activity of thiopurine methyltransferase (TPMT is subject to genetic variation. Loss-of-function alleles are associated with various degrees of myelosuppression after treatment with thiopurine drugs, thus genotype-based dosing recommendations currently exist. The aim of this study was to evaluate the potential utility of leveraging genomic data from large biorepositories in the identification of individuals with TPMT defective alleles. Material and methods: TPMT variants were imputed using the 1,000 Genomes Project reference panel in 87,979 samples from the biobank at The Children’s Hospital of Philadelphia. Population ancestry was determined by principal component analysis using HapMap3 samples as reference. Frequencies of the TPMT imputed alleles, genotypes and the associated phenotype were determined across the different populations. A sample of 630 subjects with genotype data from Sanger sequencing (N=59 and direct genotyping (N=583 (12 samples overlapping in the two groups was used to check the concordance between the imputed and observed genotypes, as well as the sensitivity, specificity and positive and negative predictive values of the imputation. Results: Two SNPs (rs1800460 and rs1142345 that represent three TPMT alleles (*3A, *3B, and *3C were imputed with adequate quality. Frequency for the associated enzyme activity varied across populations and 89.36-94.58% were predicted to have normal TPMT activity, 5.3-10.31% intermediate and 0.12-0.34% poor activities. Overall, 98.88% of individuals (623/630 were correctly imputed into carrying no risk alleles (553/553, heterozygous (45/46 and homozygous (25/31. Sensitivity, specificity and predictive values of imputation were over 90% in all cases except for the sensitivity of imputing homozygous subjects that was 80.64%. Conclusion: Imputation of TPMT alleles from existing genomic data can be used as a first step in the screening of individuals at risk of developing serious

  17. ABO locus O1 allele and risk of myocardial infarction.

    Science.gov (United States)

    von Beckerath, Nicolas; Koch, Werner; Mehilli, Julinda; Gorchakova, Olga; Braun, Siegmund; Schömig, Albert; Kastrati, Adnan

    2004-01-01

    An association between ABO blood group and myocardial infarction (MI) has been described. One probable mechanism underlying this association is the influence of ABO blood group on plasma von Willebrand factor (vWF) levels. We conducted this genetic study to test whether the ABO O1 allele is associated with low vWF plasma levels and with a reduced risk of MI. Cases consisted of 793 consecutive, angiographically examined patients with either acute or prior MI. As controls served 340 angiographically examined patients with neither coronary artery disease nor signs of MI. ABO1 locus alleles (A1, A2, B, O1, O2) were identified with polymerase chain reaction and fluorogenic probes. The distribution of O1 alleles in the MI group versus the control group was: no O1 allele (15.4%/10.0%), one O1 allele (49.7%/50.0%) and two O1 alleles (34.9%/40.0%) (P = 0.035). O1 allele carriage was associated with a 39% reduction in the risk of MI unadjusted odds ratio, 0.61; 95% confidence interval, 0.41-0.91). The significant association was maintained after adjustment for other cardiovascular risk factors. vWF antigen levels correlated with the number of O1 alleles (P = 0.00003) in a separate control group (n = 164). Carriage of the O1 allele is associated with a decreased risk of myocardial infarction, with homozygosity providing the greatest protection. Copyright 2004 Lippincott Williams and Wilkins

  18. A novel HLA-A allele: A*0257.

    Science.gov (United States)

    García-Ortiz, J E; Cox, S T; Sandoval-Ramirez, L; Little, A M; Marsh, S G E; Madrigal, J A; Argüello, J R

    2004-01-01

    A novel human leucocyte antigen-A*02 (HLA-A*02) allele was detected by reference strand-mediated conformation analysis (RSCA) of a DNA sample from a Tarahumara individual. Direct sequencing of HLA-A locus polymerase chain reaction products identified a mutation in one of the alleles. Cloning and sequencing confirmed the presence of a new allele, A*0257 which differed from A*0206 by two nucleotides at positions 355 and 362, inducing changes in residues 95 and 97, respectively, within the peptide-binding site. Those changes suggest that allele A*0257 may have resulted from an intralocus recombination event.

  19. Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences

    Energy Technology Data Exchange (ETDEWEB)

    Sachse, C.; Brockmoeller, J.; Bauer, S.; Roots, I. [Humboldt Univ., Berlin (Germany)

    1997-02-01

    Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324, .018, and .015, respectively. By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of.005 (*1 x 2), .013 (* 2 x 2), and .001 (*4 x 2). Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001 (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found. All 41 PMs (7.0%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity. Three novel variants of known CYP2D6 alleles were discovered: *1C (T{sub 1957}C), *2B (additional C{sub 2558}T), and *4E (additional C{sub 2938}T). Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EN/PM (mean MR = .006) and IM/PM (mean MR = .014) alleles and between carriers of one (mean MR = .009) and two (mean MR = .003) functional alleles. The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment. 35 refs., 4 figs., 5 tabs.

  20. Identification, genealogical structure and population genetics of S-alleles in Malus sieversii, the wild ancestor of domesticated apple.

    Science.gov (United States)

    Ma, X; Cai, Z; Liu, W; Ge, S; Tang, L

    2017-09-01

    The self-incompatibility (SI) gene that is specifically expressed in pistils encodes the SI-associated ribonuclease (S-RNase), functioning as the female-specificity determinant of a gametophytic SI system. Despite extensive surveys in Malus domestica, the S-alleles have not been fully investigated for Malus sieversii, the primary wild ancestor of the domesticated apple. Here we screened the M. sieversii S-alleles via PCR amplification and sequencing, and identified 14 distinct alleles in this species. By contrast, nearly 40 are present in its close wild relative, Malus sylvestris. We further sequenced 8 nuclear genes to provide a neutral reference, and investigated the evolution of S-alleles via genealogical and population genetic analyses. Both shared ancestral polymorphism and an excess of non-synonymous substitution were detected in the S-RNases of the tribe Maleae in Rosaceae, indicating the action of long-term balancing selection. Approximate Bayesian Computations based on the reference neutral loci revealed a severe bottleneck in four of the six studied M. sieversii populations, suggesting that the low number of S-alleles found in this species is mainly the result of diversity loss due to a drastic population contraction. Such a bottleneck may lead to ambiguous footprints of ongoing balancing selection detected at the S-locus. This study not only elucidates the constituents and number of S-alleles in M. sieversii but also illustrates the potential utility of S-allele number shifts in demographic inference for self-incompatible plant species.

  1. Development of a novel multiplex PCR assay to detect functional subtypes of KIR3DL1 alleles.

    Directory of Open Access Journals (Sweden)

    Jeanette E Boudreau

    Full Text Available Among NK cell receptor-ligand partnerships, KIR3DL1 and HLA-Bw4 demonstrate the greatest diversity; permutations of their allelic combinations titrate NK reactivity. Balancing selection has maintained distinct subtypes of KIR3DL1 alleles in global populations, implying that each may provide unique fitness advantages and variably influence disease processes. Though approaches exist for determining HLA-B allotypes, practical methods for identifying KIR3DL1 alleles are lacking. We have developed a PCR-based approach that identifies functional subtypes of KIR3DL1 alleles; it is suitable for research and may have clinical application. Six allele subsets were identified based on expression characteristics of the eleven most common KIR3DL1 alleles represented in reported populations. The remaining 62 low-frequency alleles were distributed into these groups based on sequence homology to coding regions. Subtype-specific SNPs were found in exons 3, 4, and 7, and used as priming sites for five multiplex PCR reactions. Genomic DNA derived from 175 unrelated donors and 52 related individuals from 6 families demonstrated >99.5% concordance between sequence-based typing and our novel approach. Finally, PCR-based typing accurately predicted NK phenotypes obtained by flow cytometry after staining with DX9 and Z27 monoclonal antibodies. This novel approach facilitates high-throughput analysis of KIR3DL1 allotypes to enable a broader understanding of KIR3DL1 and HLA-Bw4 interaction in health and disease.

  2. Development of a novel multiplex PCR assay to detect functional subtypes of KIR3DL1 alleles.

    Science.gov (United States)

    Boudreau, Jeanette E; Le Luduec, Jean-Benoît; Hsu, Katharine C

    2014-01-01

    Among NK cell receptor-ligand partnerships, KIR3DL1 and HLA-Bw4 demonstrate the greatest diversity; permutations of their allelic combinations titrate NK reactivity. Balancing selection has maintained distinct subtypes of KIR3DL1 alleles in global populations, implying that each may provide unique fitness advantages and variably influence disease processes. Though approaches exist for determining HLA-B allotypes, practical methods for identifying KIR3DL1 alleles are lacking. We have developed a PCR-based approach that identifies functional subtypes of KIR3DL1 alleles; it is suitable for research and may have clinical application. Six allele subsets were identified based on expression characteristics of the eleven most common KIR3DL1 alleles represented in reported populations. The remaining 62 low-frequency alleles were distributed into these groups based on sequence homology to coding regions. Subtype-specific SNPs were found in exons 3, 4, and 7, and used as priming sites for five multiplex PCR reactions. Genomic DNA derived from 175 unrelated donors and 52 related individuals from 6 families demonstrated >99.5% concordance between sequence-based typing and our novel approach. Finally, PCR-based typing accurately predicted NK phenotypes obtained by flow cytometry after staining with DX9 and Z27 monoclonal antibodies. This novel approach facilitates high-throughput analysis of KIR3DL1 allotypes to enable a broader understanding of KIR3DL1 and HLA-Bw4 interaction in health and disease.

  3. Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins.

    Science.gov (United States)

    Colin, Didier J; Hain, Karolina O; Allan, Lindsey A; Clarke, Paul R

    2015-03-01

    Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-xL by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

  4. Determinants of antigenicity and specificity in immune response for protein sequences

    Directory of Open Access Journals (Sweden)

    Li Cheng

    2011-06-01

    . Conclusions Together our results suggest that antigenicity is a local property of the protein sequences and that protein sequence properties of composition, secondary structure, solvent accessibility and evolutionary conservation are the determinants of antigenicity and specificity in immune response. Moreover, specificity in immune response could also be accurately predicted for large protein regions without the knowledge of the protein tertiary structure or the presence of discontinuous epitopes. The dataset prepared in this work and the classifier models are available for download at https://sites.google.com/site/oracleclassifiers/.

  5. Technical Approach Determines Inflammatory Response after Surgical and Transcatheter Aortic Valve Replacement.

    Directory of Open Access Journals (Sweden)

    Gabor Erdoes

    Full Text Available To investigate the periprocedural inflammatory response in patients with isolated aortic valve stenosis undergoing surgical aortic valve replacement (SAVR or transcatheter aortic valve implantation (TAVI with different technical approaches.Patients were prospectively allocated to one of the following treatments: SAVR using conventional extracorporeal circulation (CECC, n = 47 or minimized extracorporeal circulation (MECC, n = 15, or TAVI using either transapical (TA, n = 15 or transfemoral (TF, n = 24 access. Exclusion criteria included infection, pre-procedural immunosuppressive or antibiotic drug therapy and emergency indications. We investigated interleukin (IL-6, IL-8, IL-10, human leukocyte antigen (HLA-DR, white blood cell count, high-sensitivity C-reactive protein (hs-CRP and soluble L-selectin (sCD62L levels before the procedure and at 4, 24, and 48 h after aortic valve replacement. Data are presented for group interaction (p-values for inter-group comparison as determined by the Greenhouse-Geisser correction.SAVR on CECC was associated with the highest levels of IL-8 and hs-CRP (p<0.017, and 0.007, respectively. SAVR on MECC showed the highest descent in levels of HLA-DR and sCD62L (both p<0.001 in the perioperative period. TA-TAVI showed increased intraprocedural concentration and the highest peak of IL-6 (p = 0.017. Significantly smaller changes in the inflammatory markers were observed in TF-TAVI.Surgical and interventional approaches to aortic valve replacement result in inflammatory modulation which differs according to the invasiveness of the procedure. As expected, extracorporeal circulation is associated with the most marked pro-inflammatory activation, whereas TF-TAVI emerges as the approach with the most attenuated inflammatory response. Factors such as the pre-treatment patient condition and the extent of myocardial injury also significantly affect inflammatory biomarker patterns. Accordingly, TA-TAVI is to be classified not

  6. Recombinational micro-evolution of functionally different metallothionein promoter alleles from Orchesella cincta

    Directory of Open Access Journals (Sweden)

    van Straalen Nico M

    2007-06-01

    Full Text Available Abstract Background Metallothionein (mt transcription is elevated in heavy metal tolerant field populations of Orchesella cincta (Collembola. This suggests that natural selection acts on transcriptional regulation of mt in springtails at sites where cadmium (Cd levels in soil reach toxic values This study investigates the nature and the evolutionary origin of polymorphisms in the metallothionein promoter (pmt and their functional significance for mt expression. Results We sequenced approximately 1600 bp upstream the mt coding region by genome walking. Nine pmt alleles were discovered in NW-European populations. They differ in the number of some indels, consensus transcription factor binding sites and core promoter elements. Extensive recombination events between some of the alleles can be inferred from the alignment. A deviation from neutral expectations was detected in a cadmium tolerant population, pointing towards balancing selection on some promoter stretches. Luciferase constructs were made from the most abundant alleles, and responses to Cd, paraquat (oxidative stress inducer and moulting hormone were studied in cell lines. By using paraquat we were able to dissect the effect of oxidative stress from the Cd specific effect, and extensive differences in mt induction levels between these two stressors were observed. Conclusion The pmt alleles evolved by a number of recombination events, and exhibited differential inducibilities by Cd, paraquat and molting hormone. In a tolerant population from a metal contaminated site, promoter allele frequencies differed significantly from a reference site and nucleotide polymorphisms in some promoter stretches deviated from neutral expectations, revealing a signature of balancing selection. Our results suggest that the structural differences in the Orchesella cincta metallothionein promoter alleles contribute to the metallothionein -over-expresser phenotype in cadmium tolerant populations.

  7. Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks

    DEFF Research Database (Denmark)

    Dodds, Chris M; Henson, Richard N; Suckling, John

    2013-01-01

    It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation...... of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe....... In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results...

  8. Allele frequency distribution of CYP2C9 2 and CYP2C9 3 polymorphisms in six Mexican populations.

    Science.gov (United States)

    Castelán-Martínez, Osvaldo D; Hoyo-Vadillo, Carlos; Sandoval-García, Emmanuel; Sandoval-Ramírez, Lucila; González-Ibarra, Miriam; Solano-Solano, Gloria; Gómez-Díaz, Rita A; Parra, Esteban J; Cruz, Miguel; Valladares-Salgado, Adán

    2013-07-10

    Allele frequency differences of functional CYP2C9 polymorphisms are responsible for some of the variation in drug response observed in human populations. The most relevant CYP2C9 functional variants are CYP2C9*2 (rs1799853) and CYP2C9 3 (rs1057910). These polymorphisms show variation in allele frequencies among different population groups. The present study aimed to analyze these polymorphisms in 947 Mexican-Mestizo from Mexico City and 483 individuals from five indigenous Mexican populations: Nahua, Teenek, Tarahumara, Purepecha and Huichol. The CYP2C9*2 allele frequencies in the Mestizo, Nahua and Teenek populations were 0.051, 0.007 and 0.005, respectively. As for CYP2C9 3, the allelic frequencies in the Mestizo, Nahua and Teenek populations were 0.04, 0.005 and 0.005, respectively. The CYP2C9 2 and CYP2C9 3 alleles were not observed in the Tarahumara, Purepecha and Huichol populations. These findings are in agreement with previous studies reporting very low allele frequencies for these polymorphisms in American Indigenous populations. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Identification of the third/extra allele for forensic application in cases with TPOX tri-allelic pattern.

    Science.gov (United States)

    Picanço, Juliane Bentes; Raimann, Paulo Eduardo; Motta, Carlos Henrique Ares Silveira da; Rodenbusch, Rodrigo; Gusmão, Leonor; Alho, Clarice Sampaio

    2015-05-01

    Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. High allele frequency of CYP2C9*3 (rs1057910) in a Negrito's subtribe population in Malaysia; Aboriginal people of Jahai.

    Science.gov (United States)

    Rosdi, Rasmaizatul Akma; Mohd Yusoff, Narazah; Ismail, Rusli; Soo Choon, Tan; Saleem, Mohamed; Musa, Nurfadhlina; Yusoff, Surini

    2016-09-01

    CYP2C9 gene polymorphisms modulate inter-individual variations in the human body's responses to various endogenous and exogenous drug substrates. To date, little is known about the CYP2C9 gene polymorphisms among the aboriginal populations of the world, including those in Malaysia. To characterise and compare the CYP2C9 polymorphisms (CYP2C9*2, CYP2C9*3, CYP2C9*4 and CYP2C9*5) between one of Malaysia's aboriginal populations, Jahai, with the national major ethnic, Malay. To also compare the allele frequencies from these two populations with available data of other aboriginal populations around the world. The extracted DNA of 155 Jahais and 183 Malays was genotyped for CYP2C9 polymorphisms using a nested multiplex allele-specific polymerase chain reaction technique. The results were confirmed by DNA direct sequencing. Genotyping results revealed that CYP2C9*2, CYP2C9*4 and CYP2C9*5 were absent in Jahais, while only the latter two were absent in Malays. The CYP2C9*3 allelic frequency in Jahais was 36.2%, making them the most frequent carriers of the allele thus far reported in any ethnic group from Southeast Asia. The high frequency of CYP2C9*3 and the absence of CYP2C9*2 in Jahais suggest that genetic drift may be occurring in this ethnic group. This is the first study to determine the CYP2C9 polymorphisms in an aboriginal population in Malaysia.

  11. Determining whether observed eukaryotic cell migration indicates chemotactic responsiveness or random chemokinetic motion.

    Science.gov (United States)

    Szatmary, A C; Nossal, R

    2017-07-21

    Chemotaxis, the motion of cells directed by a gradient of chemoattractant molecules, guides cells in immune response, development, wound healing, and cancer. Unfortunately, this process is difficult to distinguish from chemokinesis, i.e., stimulated random cell motion. Chemotaxis is frequently inferred by determining how many cells cross a boundary in a chemotaxis assay, for example how many cells crawl into a chemoattractant-infused filter, or how many cells enter a defined region in an under-agarose assay or agarose spot assay. To mitigate possible ambiguity in whether motion observed in these assays is directed by the chemoattractant gradient or by chemokinesis, we developed a mathematical model to determine when such methods indeed indicate directed motion of cells. In contrast to previous analyses of chemotaxis assays, we report not just the gradients that arise in the assays but also resulting cell motion. We applied the model to data obtained from rigorous measurements and show, as examples, that MDA-MB-231 breast-cancer cells are at least 20 times less sensitive to gradients of EGF or CXCL12 than neutrophils are to formyl peptides; we then used this information to determine the extent to which gradient sensing increases the rate of boundary crossing relative to a random-motility control. Results show, for example, that in the filter assay, 2-4 times as many neutrophils pass through the filter when exposed to a gradient as when the gradient is absent. However, in the other combinations of cells and assays we considered, only 10-20% more cells are counted as having migrated in a directed, rather than random, motility condition. We also discuss the design of appropriate controls for these assays, which is difficult for the under-agarose and agarose spot assays. Moreover, although straightforward to perform with the filter assay, reliable controls are often not done. Consequently, we infer that chemotaxis is frequently over-reported, especially for cells like

  12. Switched voltammetric determination of ractopamine by using a temperature-responsive sensing film.

    Science.gov (United States)

    Chen, Chao; Zhang, Mingxuan; Li, Chunyan; Xie, Yixi; Fei, Junjie

    2018-02-03

    This study describes an electrochemical sensor for the animal growth promoter ractopamine. The method is based on the use of a glassy carbon electrode (GCE) modified with a temperature-responsive sensing film composed of reduced graphene oxide, C 60 fullerene, and the temperature-sensitive polymer poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO 2 MA). The modified GCE was characterized by scanning electron microscopy and electrochemical impedance spectroscopy. A large oxidation peak current can be observed (maximum typically at 0.57 V vs. Ag/AgCl) when the temperature is raised to above the lower critical solution temperature of PMEO 2 MA. This peak disappears at lower temperature. Under optimum conditions, the sensor has a detection range for ractopamine from 0.1 to 3.1 μM, with an 82 nM detection limit. The method was successfully applied to the determination of ractopamine in spiked pork samples. Graphical abstract Schematic presentation of the reversible, temperature-controlled "on/off" electrochemical behavior of ractopamine at a glassy carbon electrode modified with a film composed of reduced graphene oxide (rGO), C 60 fullerene and the poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA).

  13. Metal-organic semiconductor interfacial barrier height determination from internal photoemission signal in spectral response measurements

    Science.gov (United States)

    Kumar, Sandeep; Iyer, S. Sundar Kumar

    2017-04-01

    Accurate and convenient evaluation methods of the interfacial barrier ϕb for charge carriers in metal semiconductor (MS) junctions are important for designing and building better opto-electronic devices. This becomes more critical for organic semiconductor devices where a plethora of molecules are in use and standardised models applicable to myriads of material combinations for the different devices may have limited applicability. In this paper, internal photoemission (IPE) from spectral response (SR) in the ultra-violet to near infra-red range of different MS junctions of metal-organic semiconductor-metal (MSM) test structures is used to determine more realistic MS ϕb values. The representative organic semiconductor considered is [6, 6]-phenyl C61 butyric acid methyl ester, and the metals considered are Al and Au. The IPE signals in the SR measurement of the MSM device are identified and separated before it is analysed to estimate ϕb for the MS junction. The analysis of IPE signals under different bias conditions allows the evaluation of ϕb for both the front and back junctions, as well as for symmetric MSM devices.

  14. (GHRH Alleles in Iranian Sarabi Cows

    Directory of Open Access Journals (Sweden)

    mehdi khosravi

    2013-08-01

    Full Text Available Selection based on molecular markers is one of the new methods that may improve progress and accuracy of selection in animal breeding programs. The GHRH gene (Growth Hormone-releasing Hormone is a candidate gene for marker-assisted selection strategies. Polymorphs of GHRH gene are reported to be significantly associated with milk production and constituent traits. In order to study the polymorphism of GHRH gene, blood samples were collected from 112 Sarabi cows. Genomic DNA was extracted and a fragment of 297 bp in size was amplified using polymerase chain reaction. The amplified fragments were subjected to restriction digestion with HaeIII endonuclease enzyme and the resultant digested products were run on 2% Agarose gel. The results revealed the existence of two alleles of GHRH A and GHRH B for the examined locus with frequencies of 0.19 and 0.81 respectively. Three different genotypic variants including GHRH A GHRH A, GHRH A GHRH B and GHRH B GHRH B were identified with genotypic frequencies of 0.0357, 0.3037 and 0.6607 respectively. The χ2 test showed that population is in Hardy-Weinberg equilibrium (P

  15. Silvicultural management and the manipulation of rare alleles

    Science.gov (United States)

    Paul G. Schaberg; Gary J. Hawley; Donald H. DeHayes; Samuel E. Nijensohn

    2004-01-01

    Because rare alleles provide a means for adaptation to environmental change they are often considered important to long-term forest health. Through the selective removal of trees (and genes), silvicultural management may alter the genetic structure of forests, with rare alleles perhaps being uniquely vulnerable to manipulation due to their low frequencies or...

  16. Evolutionary dynamics of sporophytic self-incompatibility alleles in plants

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1997-01-01

    codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model...

  17. Novel alleles of 31-bp VNTR polymorphism in the human ...

    Indian Academy of Sciences (India)

    2010-12-06

    Dec 6, 2010 ... with age at onset of Alzheimer's disease (AD). Allele 19 is related to a three-fold increased risk for developing AD at 75 years of age or older, while allele 21 is related to an almost two-fold increased risk for developing AD before 64 years of age (Beyer et al. 2004, 2005). Keywords. cystathionine β-synthase ...

  18. Estimating and testing the effect of allelic recombination on the ...

    African Journals Online (AJOL)

    Jane

    2011-01-21

    Jan 21, 2011 ... The significance of the correlation coefficient as well as the fitted regression model was obtained using. Analysis of Variance method. Key words: Allele, genotype, regression, correlation, F-ratio, analysis of variance. INTRODUCTION .... while if the allelic replacement is being made on an Aa individual the ...

  19. Human minisatellite alleles detectable only after PCR amplification.

    Science.gov (United States)

    Armour, J A; Crosier, M; Jeffreys, A J

    1992-01-01

    We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

  20. Estimation of allelic frequencies for ABO and Rh blood groups

    African Journals Online (AJOL)

    Mostafa Saadat

    2015-02-18

    Feb 18, 2015 ... Estimation of allelic frequencies for ABO and Rh blood groups. Dear Editor. Estimation of the allelic frequencies for genetic markers is very important in genetic studies. Also investigation of the concordance between observed and expected value based on the Hardy–Weinberg equilibrium (HWE) is strongly ...

  1. Factors affecting the United Nations' response to natural disasters: what determines the allocation of the Central Emergency Response Fund?

    Science.gov (United States)

    Robinson, Tyler D; Oliveira, Thiago M; Kayden, Stephanie

    2017-10-01

    Natural disasters can overwhelm the domestic response of a country, leaving it dependent on external humanitarian relief. The Central Emergency Response Fund (CERF) of the United Nations centralises humanitarian funding and thus allows for a rapid response. This study combined data to analyse the factors that affected the allocation of CERF funding to countries that suffered a natural disaster between 2007 and 2013. It generated descriptive statistics and information on relative risks, and performed regressions of CERF funding across countries. There were 4,346 disasters in total in 188 countries between 2007 and 2013. CERF provided USD 2.98 billion to 87 countries, comprising 3.3 per cent of their total humanitarian funding. CERF more frequently supplied aid to countries in North Africa and the Middle East, and to those that had suffered geophysical disasters. Appropriately, it funds vulnerable countries experiencing severe natural disasters, yet its funding may be affected by variables beyond severity and vulnerability. Further investigation is warranted, therefore. © 2017 The Author(s). Disasters © Overseas Development Institute, 2017.

  2. Altered G{sub 1} checkpoint control determines adaptive survival responses to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi [Department of Human Oncology, University of Wisconsin-Madison, Madison, WI (United States)

    1996-11-04

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G{sub 0}/G{sub 1}) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G{sub 1} (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells.

  3. Altered G1 checkpoint control determines adaptive survival responses to ionizing radiation

    International Nuclear Information System (INIS)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi

    1996-01-01

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G 0 /G 1 ) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G 1 (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells

  4. Determinants of the Maternal 25-Hydroxyvitamin D Response to Vitamin D Supplementation During Pregnancy

    Science.gov (United States)

    Moon, Rebecca J.; Harvey, Nicholas C.; D'Angelo, Stefania; Crozier, Sarah R.; Inskip, Hazel M.; Schoenmakers, Inez; Prentice, Ann; Arden, Nigel K.; Bishop, Nicholas J.; Carr, Andrew; Dennison, Elaine M.; Eastell, Richard; Fraser, Robert; Gandhi, Saurabh V.; Godfrey, Keith M.; Kennedy, Stephen; Mughal, M. Zulf; Papageorghiou, Aris T.; Reid, David M.; Robinson, Sian M.; Javaid, M. Kassim

    2016-01-01

    Context: Current approaches to antenatal vitamin D supplementation do not account for interindividual differences in 25-hydroxyvitamin D (25(OH)D) response. Objective: We assessed which maternal and environmental characteristics were associated with 25(OH)D after supplementation with cholecalciferol. Design: Within-randomization-group analysis of participants in the Maternal Vitamin D Osteoporosis Study trial of vitamin D supplementation in pregnancy. Setting: Hospital antenatal clinics. Participants: A total of 829 pregnant women (422 placebo, 407 cholecalciferol). At 14 and 34 weeks of gestation, maternal anthropometry, health, and lifestyle were assessed and 25(OH)D measured. Compliance was determined using pill counts at 19 and 34 weeks. Interventions: 1000 IU/d of cholecalciferol or matched placebo from 14 weeks of gestation until delivery. Main Outcome Measure: 25(OH)D at 34 weeks, measured in a single batch (Diasorin Liaison). Results: 25(OH)D at 34 weeks of gestation was higher in the women randomized to vitamin D (mean [SD], 67.7 [21.3] nmol/L) compared with placebo (43.1 [22.5] nmol/L; P pregnancy weight gain from 14 to 34 weeks of gestation (kg) (β = −0.81 [95% confidence interval −1.39, −0.22]), lower compliance with study medication (%) (β = −0.28 [−0.072, −0.48]), lower early pregnancy 25(OH)D (nmol/L) (β = 0.28 [0.16, 0.40]), and delivery in the winter vs the summer (β = −10.5 [−6.4, −14.6]) were independently associated with lower 25(OH)D at 34 weeks of gestation. Conclusions: Women who gained more weight during pregnancy had lower 25(OH)D in early pregnancy and delivered in winter achieved a lower 25(OH)D in late pregnancy when supplemented with 1000 IU/d cholecalciferol. Future studies should aim to determine appropriate doses to enable consistent repletion of 25(OH)D during pregnancy. PMID:27788053

  5. Large allele frequency differences between human continental groups are more likely to have occurred by drift during range expansions than by selection.

    Science.gov (United States)

    Hofer, T; Ray, N; Wegmann, D; Excoffier, L

    2009-01-01

    Several studies have found strikingly different allele frequencies between continents. This has been mainly interpreted as being due to local adaptation. However, demographic factors can generate similar patterns. Namely, allelic surfing during a population range expansion may increase the frequency of alleles in newly colonised areas. In this study, we examined 772 STRs, 210 diallelic indels, and 2834 SNPs typed in 53 human populations worldwide under the HGDP-CEPH Diversity Panel to determine to which extent allele frequency differs among four regions (Africa, Eurasia, East Asia, and America). We find that large allele frequency differences between continents are surprisingly common, and that Africa and America show the largest number of loci with extreme frequency differences. Moreover, more STR alleles have increased rather than decreased in frequency outside Africa, as expected under allelic surfing. Finally, there is no relationship between the extent of allele frequency differences and proximity to genes, as would be expected under selection. We therefore conclude that most of the observed large allele frequency differences between continents result from demography rather than from positive selection.

  6. To be or not to be the odd one out - Allele-specific transcription in pentaploid dogroses (Rosa L. sect. Caninae (DC. Ser

    Directory of Open Access Journals (Sweden)

    Theißen Günter

    2011-02-01

    Full Text Available Abstract Background Multiple hybridization events gave rise to pentaploid dogroses which can reproduce sexually despite their uneven ploidy level by the unique canina meiosis. Two homologous chromosome sets are involved in bivalent formation and are transmitted by the haploid pollen grains and the tetraploid egg cells. In addition the egg cells contain three sets of univalent chromosomes which are excluded from recombination. In this study we investigated whether differential behavior of chromosomes as bivalents or univalents is reflected by sequence divergence or transcription intensity between homeologous alleles of two single copy genes (LEAFY, cGAPDH and one ribosomal DNA locus (nrITS. Results We detected a maximum number of four different alleles of all investigated loci in pentaploid dogroses and identified the respective allele with two copies, which is presumably located on bivalent forming chromosomes. For the alleles of the ribosomal DNA locus and cGAPDH only slight, if any, differential transcription was determined, whereas the LEAFY alleles with one copy were found to be significantly stronger expressed than the LEAFY allele with two copies. Moreover, we found for the three marker genes that all alleles have been under similar regimes of purifying selection. Conclusions Analyses of both molecular sequence evolution and expression patterns did not support the hypothesis that unique alleles probably located on non-recombining chromosomes are less functional than duplicate alleles presumably located on recombining chromosomes.

  7. KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406).

    Science.gov (United States)

    Peter, Barbara; Hadzijusufovic, Emir; Blatt, Katharina; Gleixner, Karoline V; Pickl, Winfried F; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Willmann, Michael; Valent, Peter

    2010-09-01

    Advanced systemic mastocytosis (SM) is characterized by uncontrolled growth of neoplastic mast cells (MC) and drug resistance. The tyrosine kinase receptor KIT is often mutated and activated and thus contributes to malignant growth of MC. Therefore, KIT-targeting drugs are currently tested for their ability to block growth of malignant MC. We determined the effects of the multikinase inhibitor INNO-406 (bafetinib) on primary neoplastic MC, the canine mastocytoma cell line C2, the human MC leukemia cell line HMC-1.1 bearing the KIT mutant V560G, and HMC-1.2 cells harboring KIT V560G and KIT D816V. INNO-406 was found to inhibit proliferation in HMC-1.1 cells (IC(50): 30-40 nM), but not in HMC-1.2 cells or primary neoplastic cells in patients with KIT D816V-positive SM. In canines, growth-inhibitory effects of INNO-406 were seen in C2 cells (IC(50): 50-100 nM) exhibiting a KIT exon 11 internal tandem-duplication and in primary neoplastic MC harboring wild-type exon 11, whereas no effects were seen in MC exhibiting a polymorphism at amino acid 581 in exon 11. INNO-406 was found to block KIT phosphorylation and expression in HMC-1.1 cells and C2 cells, but not in HMC-1.2 cells, whereas Lyn-phosphorylation was blocked by INNO-406 in all types of MC. In neoplastic MC, the major target of INNO-406 appears to be KIT. Drug responses may depend on the presence and type of KIT mutation. In human MC, the KIT D816V mutant introduces resistance, and in canine mastocytomas, an exon 11 polymorphism may be indicative of resistance against INNO-406.

  8. Outsider interference: no role for motor lateralization in determining the strength of avoidance responses during reaching.

    Science.gov (United States)

    Menger, Rudmer; Van der Stigchel, Stefan; Dijkerman, H Chris

    2013-09-01

    When reaches are performed toward target objects, the presence of other non-target objects influences kinematic parameters of the reach. A typical observation has been that non-targets positioned ipsilaterally to the acting limb interfere more with the trajectory of the hand than contralateral non-targets. Here, we investigate whether this effect is mediated by motor lateralization or by the relative positioning of the objects with reference to the acting limb. Participants were asked to perform reaches toward physical target objects with their preferred or non-preferred hands while physical non-targets were present in different possible positions in the workspace. We tested both left-handers and right-handers. Our results show that a participant's handedness does not influence reaching behavior in an obstacle avoidance paradigm. Furthermore, no statistically significant differences between the use of the preferred and non-preferred hand were observed on the kinematic parameters of the reaches. We found evidence that non-targets positioned on the outside of the reaching limb influenced the reaching behavior more strongly than non-targets on the inside. Moreover, the type of movement also appeared to play a role, as reaches that crossed the workspace had a stronger effect on avoidance behavior than reaches that were 'uncrossed.' We interpret these results as support for the hypothesis that the avoidance response is determined by keeping a preferred distance between the acting limb in all stages of its reach toward the target and the non-target position. This process is not biased by hand dominance or the hand preference of the actor.

  9. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.

    Science.gov (United States)

    Grucza, Richard A; Wang, Jen C; Stitzel, Jerry A; Hinrichs, Anthony L; Saccone, Scott F; Saccone, Nancy L; Bucholz, Kathleen K; Cloninger, C Robert; Neuman, Rosalind J; Budde, John P; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John I; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A; Edenberg, Howard J; Rice, John P; Goate, Alison M; Bierut, Laura J

    2008-12-01

    A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.

  10. Ethical guideposts for allelic variation databases.

    Science.gov (United States)

    Knoppers, B M; Laberge, C M

    2000-01-01

    Basically, a mutation database (MDB) is a repository where allelic variations are described and assigned within a specific gene locus. The purposes of an MDB may vary greatly and have different content and structure. The curator of an electronic and computer-based MDB will provide expert feedback (clinical and research). This requires ethical guideposts. Going to direct on-line public access for the content of an MDB or to interactive communication also raises other considerations. Currently, HUGO's MDI (Mutation Database Initiative) is the only integrated effort supporting and guiding the coordinated deployment of MDBs devoted to genetic diversity. Thus, HUGO's ethical "Statements" are applicable. Among the ethical principles, the obligation of preserving the confidentiality of information transferred by a collaborator to the curator is particularly important. Thus, anonymization of such data prior to transmission is essential. The 1997 Universal Declaration on the Human Genome and Human Rights of UNESCO addresses the participation of vulnerable persons. Researchers in charge of MDBs should ensure that information received on the testing of children or incompetent adults is subject to ethical review and approval in the country of origin. Caution should be taken against the involuntary consequences of public disclosure of results without complete explanation. Clear and enforceable regulations must be developed to protect the public against misuse of genetic databanks. Interaction with a databank could be seen as creating a "virtual" physician-patient relationship. However, interactive public MDBs should not give medical advice. We have identified new social ethical principles to govern different levels of complexity of genetic information. They are: reciprocity, mutuality, solidarity, and universality. Finally, precaution and prudence at this early stage of the MDI may not only avoid ethically inextricable conundrums but also provide for the respect for the rights

  11. Genetic analysis of allelic variants, single-step mutations, three allelic variants of the 15 STR loci in the population of Northeast Bosnia

    Directory of Open Access Journals (Sweden)

    Hadžiavdić Vesna

    2013-01-01

    Full Text Available Diversity of nuclear DNA microsatellite markers were analyzed in a reference sample of the population of northeast Bosnia. 437 samples taken from unrelated individuals were processed and three samples of paternity proof were shown. Detection effectiveness profile of the research, points to a valid choice of method of extraction, amplification and genotyping STR loci with PowerPlextm16. Genetic analysis of allelic variants of the 15 STR loci detected 17 samples determined as microvariants. Samples were divided into 15 different allelic variants at 7 different loci, and are: in locus D7S820, D16S539, D3S1358, D18S51, PENTA D, PENTA E and in locus vWA. Genetic analysis of mutations in cases of paternity determined three examples of single-step mutations in the loci FGA, Penta D and D3S1358. Genetic analysis of observed STR loci detected three allelic variant of genotype combination 7/10/11.3 in locus D7S820 Type II.

  12. HLA-class II alleles in patients with drug-resistant pulmonary tuberculosis in Kazakhstan.

    Science.gov (United States)

    Kuranov, A B; Kozhamkulov, U A; Vavilov, M N; Belova, E S; Bismilda, V L; Alenova, A H; Ismailov, S S; Momynaliev, K T

    2014-02-01

    The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P = 0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. HLA class I allelic sequence and conformation regulate leukocyte Ig-like receptor binding.

    Science.gov (United States)

    Jones, Des C; Kosmoliaptsis, Vasilis; Apps, Richard; Lapaque, Nicolas; Smith, Isobel; Kono, Azumi; Chang, Chiwen; Boyle, Louise H; Taylor, Craig J; Trowsdale, John; Allen, Rachel L

    2011-03-01

    Leukocyte Ig-like receptors (LILRs) are a family of innate immune receptors predominantly expressed by myeloid cells that can alter the Ag presentation properties of macrophages and dendritic cells. Several LILRs bind HLA class I. Altered LILR recognition due to HLA allelic variation could be a contributing factor in disease. We comprehensively assessed LILR binding to >90 HLA class I alleles. The inhibitory receptors LILRB1 and LILRB2 varied in their level of binding to different HLA alleles, correlating in some cases with specific amino acid motifs. LILRB2 displayed the weakest binding to HLA-B*2705, an allele genetically associated with several autoimmune conditions and delayed progression of HIV infection. We also assessed the effect of HLA class I conformation on LILR binding. LILRB1 exclusively bound folded β(2)-microglobulin-associated class I, whereas LILRB2 bound both folded and free H chain forms. In contrast, the activating receptor LILRA1 and the soluble LILRA3 protein displayed a preference for binding to HLA-C free H chain. To our knowledge, this is the first study to identify the ligand of LILRA3. These findings support the hypothesis that LILR-mediated detection of unfolded versus folded MHC modulates immune responses during infection or inflammation.

  14. Predictable allele frequency changes due to habitat fragmentation in the Glanville fritillary butterfly.

    Science.gov (United States)

    Fountain, Toby; Nieminen, Marko; Sirén, Jukka; Wong, Swee Chong; Lehtonen, Rainer; Hanski, Ilkka

    2016-03-08

    Describing the evolutionary dynamics of now extinct populations is challenging, as their genetic composition before extinction is generally unknown. The Glanville fritillary butterfly has a large extant metapopulation in the Åland Islands in Finland, but declined to extinction in the nearby fragmented southwestern (SW) Finnish archipelago in the 20th century. We genotyped museum samples for 222 SNPs across the genome, including SNPs from candidate genes and neutral regions. SW Finnish populations had significantly reduced genetic diversity before extinction, and their allele frequencies gradually diverged from those in contemporary Åland populations over 80 y. We identified 15 outlier loci among candidate SNPs, mostly related to flight, in which allele frequencies have changed more than the neutral expectation. At outlier loci, allele frequencies in SW Finland shifted in the same direction as newly established populations deviated from old local populations in contemporary Åland. Moreover, outlier allele frequencies in SW Finland resemble those in fragmented landscapes as opposed to continuous landscapes in the Baltic region. These results indicate selection for genotypes associated with good colonization capacity in the highly fragmented landscape before the extinction of the populations. Evolutionary response to habitat fragmentation may have enhanced the viability of the populations, but it did not save the species from regional extinction in the face of severe habitat loss and fragmentation. These results highlight a potentially common situation in changing environments: evolutionary changes are not strong enough to fully compensate for the direct adverse effects of environmental change and thereby rescue populations from extinction.

  15. Avaliação da concentração de alfa 1-antitripsina e da presença dos alelos S e Z em uma população de indivíduos sintomáticos respiratórios crônicos Determination of alpha 1-antitrypsin levels and of the presence of S and Z alleles in a population of patients with chronic respiratory symptoms

    Directory of Open Access Journals (Sweden)

    Heliane Guerra Serra

    2008-12-01

    Full Text Available OBJETIVO: Determinar a concentração de alfa 1-antitripsina (AAT e a prevalência dos alelos S e Z em indivíduos sintomáticos respiratórios crônicos. MÉTODOS: Pacientes com tosse crônica e dispnéia foram submetidos à avaliação clínica, espirometria, tomografia computadorizada de tórax, dosagem de AAT por nefelometria e pesquisa das mutações S e Z por reação em cadeia da polimerase. Foram consideradas como variáveis dependentes a concentração de AAT e o tabagismo. RESULTADOS: Dos 89 pacientes incluídos no estudo (44 mulheres; idade média, 51,3 ± 18,2 anos, os alelos S e Z foram detectados em 33,3% e 5,7%, respectivamente, com freqüência gênica dos alelos S e Z de 0,16 e 0,028. Dois pacientes tinham genótipo SZ (AAT 141 mg/dL (normal, Grupo 2, n = 57. A freqüência de fumantes foi igual nos dois grupos, com carga tabágica maior no Grupo 2. O alelo S estava presente em 13 e 14 pacientes dos Grupos 1 e 2, respectivamente, enquanto que o alelo Z estava presente em 2 e 1 paciente dos mesmos grupos. Não houve diferença nos testes de função pulmonar, nem na freqüência de bronquiectasias ou enfisema entre os dois grupos. Os valores espirométricos e as concentrações de AAT foram similares entre fumantes e não-fumantes. Bronquiectasias foram mais freqüentes entre os não fumantes, e enfisema foi mais freqüente entre os fumantes. CONCLUSÕES: Trinta pacientes apresentaram níveis de AAT abaixo da média esperada para os genótipos MM e MS, e este fato não pode ser explicado por uma freqüência maior dos alelos S e Z.OBJECTIVE: To determine the levels of alpha-1 antitrypsin (AAT and the presence of S and Z alleles in patients with chronic respiratory symptoms. METHODS: Patients with chronic cough and dyspnea were submitted to clinical evaluation, pulmonary function tests, high-resolution computed tomography, nephelometric determination of AAT and determination of S and Z alleles by polymerase chain reaction. Smoking

  16. Acknowledging Individual Responsibility while Emphasizing Social Determinants in Narratives to Promote Obesity-Reducing Public Policy: A Randomized Experiment

    Science.gov (United States)

    Niederdeppe, Jeff; Roh, Sungjong; Shapiro, Michael A.

    2015-01-01

    This study tests whether policy narratives designed to increase support for obesity-reducing public policies should explicitly acknowledge individual responsibility while emphasizing social, physical, and economic (social) determinants of obesity. We use a web-based, randomized experiment with a nationally representative sample of American adults (n = 718) to test hypotheses derived from theory and research on narrative persuasion. Respondents exposed to narratives that acknowledged individual responsibility while emphasizing obesity’s social determinants were less likely to engage in counterargument and felt more empathy for the story’s main character than those exposed to a message that did not acknowledge individual responsibility. Counterarguing and affective empathy fully mediated the relationship between message condition and support for policies to reduce rates of obesity. Failure to acknowledge individual responsibility in narratives emphasizing social determinants of obesity may undermine the persuasiveness of policy narratives. Omitting information about individual responsibility, a strongly-held American value, invites the public to engage in counterargument about the narratives and reduces feelings of empathy for a character that experiences the challenges and benefits of social determinants of obesity. PMID:25706743

  17. Acknowledging individual responsibility while emphasizing social determinants in narratives to promote obesity-reducing public policy: a randomized experiment.

    Science.gov (United States)

    Niederdeppe, Jeff; Roh, Sungjong; Shapiro, Michael A

    2015-01-01

    This study tests whether policy narratives designed to increase support for obesity-reducing public policies should explicitly acknowledge individual responsibility while emphasizing social, physical, and economic (social) determinants of obesity. We use a web-based, randomized experiment with a nationally representative sample of American adults (n = 718) to test hypotheses derived from theory and research on narrative persuasion. Respondents exposed to narratives that acknowledged individual responsibility while emphasizing obesity's social determinants were less likely to engage in counterargument and felt more empathy for the story's main character than those exposed to a message that did not acknowledge individual responsibility. Counterarguing and affective empathy fully mediated the relationship between message condition and support for policies to reduce rates of obesity. Failure to acknowledge individual responsibility in narratives emphasizing social determinants of obesity may undermine the persuasiveness of policy narratives. Omitting information about individual responsibility, a strongly-held American value, invites the public to engage in counterargument about the narratives and reduces feelings of empathy for a character that experiences the challenges and benefits of social determinants of obesity.

  18. Acknowledging individual responsibility while emphasizing social determinants in narratives to promote obesity-reducing public policy: a randomized experiment.

    Directory of Open Access Journals (Sweden)

    Jeff Niederdeppe

    Full Text Available This study tests whether policy narratives designed to increase support for obesity-reducing public policies should explicitly acknowledge individual responsibility while emphasizing social, physical, and economic (social determinants of obesity. We use a web-based, randomized experiment with a nationally representative sample of American adults (n = 718 to test hypotheses derived from theory and research on narrative persuasion. Respondents exposed to narratives that acknowledged individual responsibility while emphasizing obesity's social determinants were less likely to engage in counterargument and felt more empathy for the story's main character than those exposed to a message that did not acknowledge individual responsibility. Counterarguing and affective empathy fully mediated the relationship between message condition and support for policies to reduce rates of obesity. Failure to acknowledge individual responsibility in narratives emphasizing social determinants of obesity may undermine the persuasiveness of policy narratives. Omitting information about individual responsibility, a strongly-held American value, invites the public to engage in counterargument about the narratives and reduces feelings of empathy for a character that experiences the challenges and benefits of social determinants of obesity.

  19. Association of gliadin antibodies, HLA alleles, and schizophrenia in Cuban population patients

    Directory of Open Access Journals (Sweden)

    José A. Galván

    2016-05-01

    Full Text Available Introduction: Several lines of evidence have suggested an interesting link between gluten ingestion and schizophrenia. For example, increased levels of gliadin and transglutaminase antibodies have been observed in patients with schizophrenia. Methods: To verify these observations we compared the prevalence of gliadin and transglutaminse antibodies, as well as the presence of the HLA alleles, HLA DQA1*0501-DQB1*02 (DQ2 and HLA-DQA1*0301-DQB1*0302 (DQ8, among patients with schizophrenia and healthy controls. A total of 108 patients with schizophrenia and 60 healthy controls were evaluated. Gliadin antibodies were determined by a visual semiquantitative assay and tissue transglutaminase antibodies were determined both by one-step immunochromatografic assay and ELISA. HLA typing was performed by PCR amplification using sequence-specific primers for each allele. Results: We found a strong association between the presence of gliadin antibodies and schizophrenia (OR 3.488; 95% CI, 1.43-8.44. However, tissue transglutaminase antibodies were not detected in either group neither by immunochromatograpic or ELISA. No significant association was found for the DQ2 or DQ8 heterodimer and the disease, but a significant positive association between schizophrenia and HLA alleles DQA1*0301 and DQB1*02 was present (OR = 2.80; 95% CI, 1.27-6.17, and OR = 2.37, 95% CI, 1.24-4.53, respectively. Conclusions: The present study showed that the presence of gliadin antibodies was not correlated with the presence of HLA DQA1*0301 or DQB1*02 alleles within the group of patients with schizophrenia. Our study replicates the findings that anti-gliadin antibodies are associated with schizophrenia but also suggests that the presence of these antibodies and the HLA alleles DQB1*02 and DQA1*0301 are independently associated with susceptibility to schizophrenia.

  20. Allelic Variation, Aneuploidy, and Nongenetic Mechanisms Suppress a Monogenic Trait in Yeast

    OpenAIRE

    Sirr, Amy; Cromie, Gareth A.; Jeffery, Eric W.; Gilbert, Teresa L.; Ludlow, Catherine L.; Scott, Adrian C.; Dudley, Aim?e M.

    2014-01-01

    Clinically relevant features of monogenic diseases, including severity of symptoms and age of onset, can vary widely in response to environmental differences as well as to the presence of genetic modifiers affecting the trait?s penetrance and expressivity. While a better understanding of modifier loci could lead to treatments for Mendelian diseases, the rarity of individuals harboring both a disease-causing allele and a modifying genotype hinders their study in human populations. We examined ...

  1. Apolipoprotein E epsilon4 allele and outcomes of traumatic spinal cord injury.

    Science.gov (United States)

    Jha, Amitabh; Lammertse, Daniel P; Coll, Joseph R; Charlifue, Susan; Coughlin, Christopher T; Whiteneck, Gale G; Worley, Gordon

    2008-01-01

    To test the hypothesis that apolipoprotein E (APOE) polymorphisms are associated with outcomes after spinal cord injury (SCI). Retrospective cohort study, from rehabilitation admission to discharge. Convenience sample of 89 persons with cervical SCI (C3-C8) treated from 1995 through 2003. Median age was 30 years (range 14-70); 67 were male (75%) and 83 were white (93%). American Spinal Injury Association (ASIA) motor and sensory scores, ASIA Impairment Scale (AIS), time from injury to rehabilitation admission, and length of stay (LOS) in rehabilitation. Subjects with an APOE epsilon4 allele (n = 15; 17%) had significantly less motor recovery during rehabilitation than did individuals without an epsilon4 allele (median 3.0 vs 5.5; P rehabilitation LOS (median 106 vs 89 days; P = 0.04), but better sensory-pinprick recovery (median 5.0 vs 2.0; P= 0.03). There were no significant differences by APOE epsilon4 allele status in sensory-light touch recovery, likelihood of improving AIS Grade, or time from injury to rehabilitation admission. APOE epsilon4 allele was associated with differences in neurological recovery and longer rehabilitation LOS. Genetic factors may be among the determinants of outcome after SCI and warrant further study.

  2. The frequency of allelic lethals and complementation maps in natural populations of drosophila melanogaster from Mexico

    Directory of Open Access Journals (Sweden)

    Salceda Victor M.

    2004-01-01

    Full Text Available Departing from a previous study on the genetic loads affecting the second chromosome of Drosophila melanogaster in four natural populations, 171 lethal chromosomes were recovered and maintained as a balanced stocks in the condition Cy L / 1 (l=lethal; of those lethais 24 correspond to population A, 50 to populations B and C and 47 to population D. later on an intra-population allelism test for the four populations was performed for each one. A total of 3807 inter lethal crosses were done yielding a total of i 10 allelic combinations, from them the respective percentage of allelism for each population was calculated and they are as follow: 3.98 % for population A, 1.80 % for population B, 3.67 % for population C and 2.96 % for population D. the observed values for the frequency of allelism in these populations are not significantly different from those reported by other authors in similar studies in natural and/or experimental populations. Beside these values the frequency for singles, doubles, triplets and even quadruplets present in each population were determined, they shown the presence of various complementation maps due to the clustering of few different lethals: also a large complementation map formed by a large cluster involving the presence of 26 different lethals found in population D all of them combined constituting a single unit was found.

  3. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

    Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt

    2013-01-01

    In certain crime cases, information about a perpetrator's phenotype, including eye colour, may be a valuable tool if no DNA profile of any suspect or individual in the DNA database matches the DNA profile found at the crime scene. Often, the available DNA material is sparse and allelic drop......-out when the amount of DNA was greater than 125 pg for 29 cycles of PCR and greater than 62 pg for 30 cycles of PCR. With the use of a logistic regression model, we estimated the allele specific probability of drop-out in heterozygote systems based on the signal strength of the observed allele...

  4. Identification of the Rare, Four Repeat Allele of IL-4 Intron-3 VNTR Polymorphism in Indian Populations.

    Science.gov (United States)

    Verma, Henu Kumar; Jha, Aditya Nath; Khodiar, Prafulla Kumar; Patra, Pradeep Kumar; Bhaskar, Lakkakula Venkata Kameswara Subrahmanya

    2016-06-01

    Cytokines are cell signaling molecules which upon release by cells facilitate the recruitment of immune-modulatory cells towards the sites of inflammation. Genetic variations in cytokine genes are shown to regulate their production and affect the risk of infectious as well as autoimmune diseases. Intron-3 of interleukin-4 gene (IL-4) harbors 70-bp variable number of tandem repeats (VNTR) that may alter the expression level of IL-4 gene. To determine the distribution of IL-4 70-bp VNTR polymorphism in seven genetically heterogeneous populations of Chhattisgarh, India and their comparison with the finding of other Indian and world populations. A total of 371 healthy unrelated individuals from 5 caste and 2 tribal populations were included in the present study. The IL-4 70-bp VNTR genotyping was carried out using PCR and electrophoresis. Overall, 3 alleles of IL-4 70-bp VNTR (a2, a3 and a4) were detected. The results demonstrated the variability of the IL-4 70-bp VNTR polymorphism in Chhattisgarh populations. Allele a3 was the most common allele at the 70-bp VNTR locus in all populations followed by a2 allele. This study reports the presence four repeat allele a4 at a low frequency in the majority of the Chhattisgarh populations studied. Further, the frequency of the minor allele (a2) in Chhattisgarh populations showed similarity with the frequencies of European populations but not with the East Asian populations where the a2 allele is a major allele. Our study provides a baseline for future research into the role of the IL-4 locus in diseases linked to inflammation in Indian populations.

  5. A method to determine insulin responsiveness in synaptosomes isolated from frozen brain tissue.

    Science.gov (United States)

    Franklin, Whitney; Taglialatela, Giulio

    2016-03-01

    Studying the insulin signaling response at the synapse is an important approach to understand molecular mechanisms involved in disease-related neurodegenerative processes. We developed a method for studying the insulin responsiveness at the synaptic level by isolating functional synaptosomes from fresh or frozen tissue and exposing them to insulin in the presence of ATP (a critical step) to detect insulin receptor (IR) activation. We performed an ATP dose-response curve, insulin dose-response curve, and insulin response time course to optimize this method. We also demonstrated that our protocol reflects the degree of insulin responsiveness in vivo by using an animal model of known insulin resistance, AtENPP1-Tg mice. This method is advantageous over other methods detecting IR in total brain homogenates due to the ability to detect IR response without confounding contributions from other cell areas and cell types also expressing IR. Furthermore, ex vivo insulin stimulation can be compared to baseline synaptosomes obtained from the same animal which improves reliability and statistical power while decreasing the number of animals required to perform individual experiments. We have developed a reliable, efficient method to measure insulin-driven ex vivo phosphorylation of the synaptosomal insulin receptor that can reliably reflect the pre-existing insulin responsiveness status in the CNS of the animal. To the best of our knowledge, this is the first evidence of stimulation of isolated synaptosomes with insulin and a promising new technique to study the synaptic CNS insulin responsiveness under physiological or disease conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Major histocompatibility complex (MHC) class I and II alleles which confer susceptibility or protection in the Morphea in Adults and Children (MAC) cohort

    Science.gov (United States)

    Jacobe, Heidi; Ahn, Chul; Arnett, Frank; Reveille, John D.

    2014-01-01

    Objective To determine human leukocyte antigen class I (HLA-class I) and II (HLA-class II) alleles associated with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort by a nested case–control association study. Methods Morphea patients were included from MAC cohort and matched controls from the NIH/NIAMS Scleroderma Family Registry and DNA Repository and Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA- Class II genotyping and SSCP typing was performed of HLA-A, -B, -C alleles. Associations between HLA-Class I and II alleles and morphea as well as its subphenotypes were determined. Results There were 211 cases available for HLA-class I typing with 726 matched controls and 158 cases available for HLA Class-II typing with 1108 matched controls. The strongest associations were found with DRB1*04:04 (OR 2.3, 95% CI 1.4–4.0 P=0.002) and HLA-B*37 conferred the highest OR among Class I alleles (3.3, 95% CI 1.6–6.9, P= 0.0016). Comparison with risk alleles in systemic sclerosis determined using the same methods and control population revealed one common allele (DRB*04:04). Conclusion Results of the present study demonstrate specific HLA Class I and II alleles are associated with morphea and likely generalized and linear subtypes. The associated morphea alleles are different than in scleroderma, implicating morphea is also immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population based studies indicate patients with RA have increased risk of morphea, implicating a common susceptibility allele. PMID:25223600

  7. Development of a high resolution melting method for genotyping of risk HLA-DQA1 and PLA2R1 alleles and ethnic distribution of these risk alleles.

    Science.gov (United States)

    Cui, Guanglin; Zhang, Lina; Xu, Yujun; Cianflone, Katherine; Ding, Hu; Wang, Dao Wen

    2013-02-10

    Recent studies have demonstrated that alleles at single nucleotide polymorphisms (SNPs) rs2187668 and rs4664308 within genes HLA-DQA1 and PLA2R1, respectively, had a significant impact on the susceptibility to idiopathic membranous nephropathy (IMN). Analysis of the two genomic loci could identify alleles for individuals at risk for IMN. Conventional methods for genotyping are labor intensive, expensive or time consuming. High resolution melting (HRM) is a new technique for genotyping and has the advantages of simplicity, speed, high sensitivity and low cost. Here, we describe genotyping of SNPs rs2187668 and rs4664308 using HRM. In this study, we identified polymorphisms of rs2187668 and rs4664308 in 480 healthy unrelated Chinese volunteers of two ethnic groups from three different geographical areas in China. The two genomic loci were genotyped by HRM using a saturating fluorescent dye SYTO® 9 on 7900 HT and RG 6000 instruments, and were further confirmed by direct DNA sequencing. Three different SNP genotypes were sufficiently distinguished by HRM with mean sensitivity of 98.8% and mean error rate of 1.9%. In addition, the allele frequencies varied greatly based on ethnic or geographic origins. In conclusion, HRM is a rapid, cost efficient, sensitive, suitable technique for genotyping, and simple enough to be readily implemented in a diagnostic laboratory. We believe this will be a valuable technique for determining the genotype of rs2187668 and rs4664308 and for assessing individual susceptibility to IMN. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras

    Science.gov (United States)

    Hashimoto, Ken; Zúniga, Concepción; Romero, Eduardo; Morales, Zoraida; Maguire, James H.

    2015-01-01

    Background Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings. Methodology/Principal Findings We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort. Conclusions/Significance Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with

  9. Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras.

    Directory of Open Access Journals (Sweden)

    Ken Hashimoto

    Full Text Available Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings.We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4% was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort.Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with limited resources, countries can improve health

  10. Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras.

    Science.gov (United States)

    Hashimoto, Ken; Zúniga, Concepción; Romero, Eduardo; Morales, Zoraida; Maguire, James H

    2015-01-01

    Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings. We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort. Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with limited resources, countries can improve health service

  11. Response of Substituted Indoleacetic Acids in the Indolo-alpha-pyrone Fluorescence Determination

    DEFF Research Database (Denmark)

    Engvild, Kjeld Christensen; Böttger, M.; Kaiser, P.

    1978-01-01

    .-pyrones. Other halogenated indoleacetic acids show between zero and 60% of the fluorescence of IAA. Apparently the concentration of IAA cannot be determined in crude extracts in the presence of 4-chloro- or 5-hydroxy-indoleacetic acid, because separate determinations of each of these compounds are not possible...

  12. AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

    DEFF Research Database (Denmark)

    Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per

    2015-01-01

    the possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility......Background: One aspect in which RNA sequencing is more valuable than microarray-based methods is the ability to examine the allelic imbalance of the expression of a gene. This process is often a complex task that entails quality control, alignment, and the counting of reads over heterozygous single...

  13. Experiments to Demonstrate Change in Allelic Frequency by ...

    Indian Academy of Sciences (India)

    /fulltext/reso/014/11/1110-1118. Keywords. Population genetics; genetic drift; allele frequency. Author Affiliations. N B Ramachandra1 M S Ranjini1. Unit on Evolution and Genetics DOS in Zoology Manasagangotri University of Mysore, India.

  14. Evolutionary history and novel biotic interactions determine plant responses to elevated CO2 and nitrogen fertilization.

    Directory of Open Access Journals (Sweden)

    Rachel Wooliver

    Full Text Available A major frontier in global change research is predicting how multiple agents of global change will alter plant productivity, a critical component of the carbon cycle. Recent research has shown that plant responses to climate change are phylogenetically conserved such that species within some lineages are more productive than those within other lineages in changing environments. However, it remains unclear how phylogenetic patterns in plant responses to changing abiotic conditions may be altered by another agent of global change, the introduction of non-native species. Using a system of 28 native Tasmanian Eucalyptus species belonging to two subgenera, Symphyomyrtus and Eucalyptus, we hypothesized that productivity responses to abiotic agents of global change (elevated CO2 and increased soil N are unique to lineages, but that novel interactions with a non-native species mediate these responses. We tested this hypothesis by examining productivity of 1 native species monocultures and 2 mixtures of native species with an introduced hardwood plantation species, Eucalyptus nitens, to experimentally manipulated soil N and atmospheric CO2. Consistent with past research, we found that N limits productivity overall, especially in elevated CO2 conditions. However, monocultures of species within the Symphyomyrtus subgenus showed the strongest response to N (gained 127% more total biomass in elevated CO2 conditions, whereas those within the Eucalyptus subgenus did not respond to N. Root:shoot ratio (an indicator of resource use was on average greater in species pairs containing Symphyomyrtus species, suggesting that functional traits important for resource uptake are phylogenetically conserved and explaining the phylogenetic pattern in plant response to changing environmental conditions. Yet, native species mixtures with E. nitens exhibited responses to CO2 and N that differed from those of monocultures, supporting our hypothesis and highlighting that both

  15. Influence of PAH Genotype on Sapropterin Response in PKU: Results of a Single-Center Cohort Study.

    Science.gov (United States)

    Leuders, Sarah; Wolfgart, Eva; Ott, Torsten; du Moulin, Marcel; van Teeffelen-Heithoff, Agnes; Vogelpohl, Lydia; Och, Ulrike; Marquardt, Thorsten; Weglage, Josef; Feldmann, Reinhold; Rutsch, Frank

    2014-01-01

    Identifying phenylalanine hydroxylase (PAH) mutations associated with sapropterin response in phenylketonuria (PKU) would be an advantageous means to determine clinical benefit to sapropterin therapy. Sapropterin response, defined as a ≥30 % reduction in phenylalanine (Phe) levels after a dose of 10 mg/kg/day sapropterin for week one and 20 mg/kg/day for week two in 112 PKU patients aged 4-45 years, was assessed in an outpatient setting. PAH was sequenced in all patients. Mutations were correlated with sapropterin response. Dietary Phe intake was increased over a 6-week period in responsive patients. Forty-six of 112 patients were sapropterin responsive. Genotypes p.[L48S];[L48S] and p.[Y414C];[Y414C] were always associated with response at a low dose. The mutation Y414C (present on 16 alleles) was most frequently associated with response. Patients with presence of the mutation L48S on at least one allele (12 alleles in 7 patients) always showed response to sapropterin. Responsive patients had a mean Phe tolerance increase of 189 % (range 11-742 %). In the 66 nonresponders, mutations R408W (38 alleles) and IVS12+1G>A (18 alleles) were detected most frequently. Genotypes [IVS12+1G>A];[IVS12+1G>A], p.[L348V];[R408W], p.[P281L];[P281L], p.[R158Q];[R408W], and p.[R261Q];[R408W] were always associated with nonresponse. Data from the study contributes to growing evidence of the relationship between PAH genotype and PKU phenotype. In most cases, response to sapropterin therapy cannot be predicted based on the presence of a single mutation on one allele alone, although the complete PAH genotype may help to predict sapropterin responsiveness in PKU patients.

  16. An Allele of an Ancestral Transcription Factor Dependent on a Horizontally Acquired Gene Product

    OpenAIRE

    Chen, H. Deborah; Jewett, Mollie W.; Groisman, Eduardo A.

    2012-01-01

    Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription factor PmrA that requires the horizontally acquired pmrD gene product to promote gene expression. We determined that a single amino acid difference between the PmrA proteins from the...

  17. Variant RH alleles and Rh immunisation in patients with sickle cell disease.

    Science.gov (United States)

    Sippert, Emilia; Fujita, Claudia R; Machado, Debora; Guelsin, Glaucia; Gaspardi, Ane C; Pellegrino, Jordão; Gilli, Simone; Saad, Sara S T O; Castilho, Lilian

    2015-01-01

    Alloimmunisation is a major complication in patients with sickle cell disease (SCD) receiving red blood cell (RBC) transfusions and despite provision of Rh phenotyped RBC units, Rh antibodies still occur. These antibodies in patients positive for the corresponding Rh antigen are considered autoantibodies in many cases but variant RH alleles found in SCD patients can also contribute to Rh alloimmunisation. In this study, we characterised variant RH alleles in 31 SCD patients who made antibodies to Rh antigens despite antigen-positive status and evaluated the clinical significance of the antibodies produced. RHD and RHCE BeadChip™ from BioArray Solutions and/or amplification and sequencing of exons were used to identify the RH variants. The serological features of all Rh antibodies in antigen-positive patients were analysed and the clinical significance of the antibodies was evaluated by retrospective analysis of the haemoglobin (Hb) levels before and after transfusion; the change from baseline pre-transfusion Hb and the percentage of HbS were also determined. We identified variant RH alleles in 31/48 (65%) of SCD patients with Rh antibodies. Molecular analyses revealed the presence of partial RHD alleles and variant RHCE alleles associated with altered C and e antigens. Five patients were compound heterozygotes for RHD and RHCE variants. Retrospective analysis showed that 42% of antibodies produced by the patients with RH variants were involved in delayed haemolytic transfusion reactions or decreased survival of transfused RBC. In this study, we found that Rh antibodies in SCD patients with RH variants can be clinically significant and, therefore, matching patients based on RH variants should be considered.

  18. Frequency of CCR5Δ32 allele in healthy Bosniak population.

    Directory of Open Access Journals (Sweden)

    Grażyna Adler

    2014-08-01

    Full Text Available Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12% and lower in the regions of Southeast Mediterranean (about 5%. Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013.  Mean age of the cohort being 58.8 (±10.7 years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. 

  19. MHC Class II alleles in ulcerative colitis-associated colorectal cancer.

    Science.gov (United States)

    Garrity-Park, M M; Loftus, E V; Sandborn, W J; Bryant, S C; Smyrk, T C

    2009-09-01

    Patients with ulcerative colitis are at risk for colorectal cancer (CRC). Although prior studies have shown a link between HLA genotypes and ulcerative colitis (UC) susceptibility, none have investigated HLA genotypes and UC-CRC. We therefore investigated HLA-DR/DQ alleles in UC-CRC cases and UC-controls. Furthermore, since methylation of the Class II transactivator (CIITA) gene may silence HLA expression in tumours, we correlated HLA allele frequencies with CIITA gene methylation and HLA-DR expression. Cases and controls were matched for duration/extent of ulcerative colitis, age, ethnicity and gender, but not for primary sclerosing cholangitis (PSC). DNA was extracted from archived tissue blocks from 114 UC-CRC cases and 114 UC-controls. HLA-DR/DQ genotyping was performed using sequence-specific-oligonucleotide polymerase chain reaction (SSO-PCR). CIITA methylation was determined using methylation-specific PCR. HLA-DR immunohistochemistry was done following standard protocols. UC-CRC cases were more likely than UC-controls to carry the DR17 or DR13 alleles (passociated with CIITA methylation (p = 0.04 and 0.02, respectively). UC-controls more frequently carried the DR7, DR1 or DQ5 alleles (p = 0.002, 0.05 or 0.01, respectively). After adjusting for PSC, DR17 remained significantly associated with an increased risk for UC-CRC while DR7 and DQ5 remained protective. We report a significant association between specific HLA alleles and either the risk for (DR17) or protection from (DR7, DQ5) UC-CRC. This suggests a possible genetic predisposition for increased UC-CRC risk. In addition, DQ2 and DR17 were associated with CIITA methylation.

  20. Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals.

    Science.gov (United States)

    Reimann, Manja; Vilser, Walthard; Gruber, Matthias; Bornstein, Stefan R; Ziemssen, Tjalf

    2015-09-01

    Insulin may link metabolic disorders to retinal microvascular pathology. The aim of the present study was to investigate the impact of early insulin resistance on retinal microcirculation. Retinal diameter responses to flicker-light stimulation were investigated in 81 clinically healthy participants (32 ± 6 years [mean ± SD], 59% women) who were recruited according to their BMI. All participants underwent an OGTT and euglycaemic-hyperinsulinaemic clamp (40 mU/m(2) · min(-1) insulin dose). After stratification by low and high insulin sensitivity based on a clamp-derived glucose disposal rate of ≤ or >4.9 mg/kg body mass, respectively, baseline retinal diameters and their relative changes to flicker stimulation were compared while controlling for mean arterial pressure, BMI and sex. The arterial vasodilator response at the end of flicker stimulation (p = 0.044) and the area under the arterial reaction curve during flicker stimulation (p = 0.015) were significantly higher in individuals with low vs high insulin sensitivity. Vasodilatory responses of retinal veins to flicker stimulation and baseline retinal diameters did not differ between insulin-sensitive and insulin-resistant participants (p > 0.05). In a stepwise linear regression analysis, fasting insulin remained the only predictor of the arterial vasodilator response to flicker-light (p flicker response in insulin-resistant states is a result of higher circulating insulin levels.

  1. CD8+lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury.

    Science.gov (United States)

    Chakraborty, Rituparna; Chandra, Janin; Cui, Shuai; Tolley, Lynn; Cooper, Matthew A; Kendall, Mark; Frazer, Ian H

    2018-01-01

    The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage-associated molecular patterns (DAMPs), as opposed to pathogen-associated molecules (PAMPs), regulate the immune response to non-self-antigens presented at the site of a physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterized by local cell death and caspase-1 activation without demonstrably disrupting skin integrity. Co-delivery of ovalbumin (OVA) with heat injury induces OVA-specific CD8 + T-cell responses, and this is dependent on caspase-1 activation and MyD88 signalling. Using Id2flox/flox-CD11cCre+ mice, we demonstrate that CD8 + lineage DCs are required to induce OVA-specific CD8 + T-cell responses following heat injury. Consistent with this observation, intradermal administration of CD8 + lineage DCs but not CD11b + lineage DCs restores priming of CD8 + T-cell responses in Casp-1 -/- mice. Thus, we conclude that a sterile injury induces CD8 + T-cell immune responses to local antigen through caspase-1 activation and requires CD8 + lineage DCs, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Response of Substituted Indoleacetic Acids in the Indolo-alpha-pyrone Fluorescence Determination

    DEFF Research Database (Denmark)

    Engvild, Kjeld Christensen; Böttger, M.; Kaiser, P.

    1978-01-01

    The method of indolo-.alpha.-pyrone fluorescence-determination of IAA was investigated to study possible interference from 4-chloro-indoleacetic acid and 5-hydroxyindoleacetic acid, which occur naturally. Both compounds show about 40% of the fluorescence of IAA after conversion into their .alpha.......-pyrones. Other halogenated indoleacetic acids show between zero and 60% of the fluorescence of IAA. Apparently the concentration of IAA cannot be determined in crude extracts in the presence of 4-chloro- or 5-hydroxy-indoleacetic acid, because separate determinations of each of these compounds are not possible...

  3. Determinants of Behavioral Intention to Use South Korean Airline Services: Effects of Service Quality and Corporate Social Responsibility

    Directory of Open Access Journals (Sweden)

    Eunil Park

    2015-09-01

    Full Text Available Since the introduction of corporate social responsibility (CSR, it has become an important duty of companies and organizations. In addition, academic and industry researchers have attempted to explore the effects of corporate social responsibility on firm performance. To this end, this study examined how corporate social responsibility and service quality are notably associated with customer satisfaction and behavioral intention to use by employing a structural equation modeling method. A research model with nine constructs was introduced and the findings revealed that economic, social, and environmental responsibility, as well as in-flight service quality, significantly determined customer satisfaction, while there were notable connections between customer satisfaction and behavioral intention to use. However, service quality at airports did not have a significant effect on satisfaction. The practical and theoretical implications of the current study are discussed.

  4. SSR allelic variation in almond (Prunus dulcis Mill.).

    Science.gov (United States)

    Xie, Hua; Sui, Yi; Chang, Feng-Qi; Xu, Yong; Ma, Rong-Cai

    2006-01-01

    Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

  5. Simultaneous determination of electron beam profile and material response using self-consistent iterative method

    Science.gov (United States)

    Kandel, Yudhishthir; Denbeaux, Gregory

    2016-08-01

    We develop a novel iterative method to accurately measure electron beam shape (current density distribution) and monotonic material response as a function of position. A common method is to scan an electron beam across a knife edge along many angles to give an approximate measure of the beam profile, however such scans are not easy to obtain in all systems. The present work uses only an electron beam and multiple exposed regions of a thin film of photoresist to measure the complete beam profile for any beam shape, where the material response is characterized externally. This simplifies the setup of new experimental tools. We solve for self-consistent photoresist thickness loss response to dose and the electron beam profile simultaneously by optimizing a novel functional iteratively. We also show the successful implementation of the method in a real world data set corrupted by noise and other experimental variabilities.

  6. The glossyhead1 allele of acc1 reveals a principal role for multidomain acetyl-coenzyme a carboxylase in the biosynthesis of cuticular waxes by Arabidopsis

    KAUST Repository

    Lu, Shiyou

    2011-09-23

    A novel mutant of Arabidopsis (Arabidopsis thaliana), having highly glossy inflorescence stems, postgenital fusion in floral organs, and reduced fertility, was isolated from an ethyl methanesulfonate-mutagenized population and designated glossyhead1 (gsd1). The gsd1 locus was mapped to chromosome 1, and the causal gene was identified as a new allele of Acetyl-Coenzyme A Carboxylase1 (ACC1), a gene encoding the main enzyme in cytosolic malonyl-coenzyme A synthesis. This, to our knowledge, is the first mutant allele of ACC1 that does not cause lethality at the seed or early germination stage, allowing for the first time a detailed analysis of ACC1 function in mature tissues. Broad lipid profiling of mature gsd1 organs revealed a primary role for ACC1 in the biosynthesis of the very-long-chain fatty acids (C 20:0 or longer) associated with cuticular waxes and triacylglycerols. Unexpectedly, transcriptome analysis revealed that gsd1 has limited impact on any lipid metabolic networks but instead has a large effect on environmental stress-responsive pathways, especially senescence and ethylene synthesis determinants, indicating a possible role for the cytosolic malonyl-coenzyme A-derived lipids in stress response signaling. © 2011 American Society of Plant Biologists. All Rights Reserved.

  7. Determination of floor response spectra for the Brookhaven HFBR reactor building structure

    Energy Technology Data Exchange (ETDEWEB)

    Subudhi, M.; Goradia, H.

    1978-11-01

    In order to perform the dynamic analysis of various structural components of the HFBR reactor building at Brookhaven National Laboratory (BNL) subjected to seismic disturbances, it is necessary to obtain the floor response spectra of the primary structure. The mathematical model includes the four floor levels of the internal structure, the dome, and soil spring effects. The standard time history analysis is adopted to obtain the response spectrum for each floor of the internal structure. This report summarizes the results both in tabular and graphical form for various damping values.

  8. Determination of floor response spectra for the Brookhaven HFBR reactor building structure

    International Nuclear Information System (INIS)

    Subudhi, M.; Goradia, H.

    1978-11-01

    In order to perform the dynamic analysis of various structural components of the HFBR reactor building at Brookhaven National Laboratory (BNL) subjected to seismic disturbances, it is necessary to obtain the floor response spectra of the primary structure. The mathematical model includes the four floor levels of the internal structure, the dome, and soil spring effects. The standard time history analysis is adopted to obtain the response spectrum for each floor of the internal structure. This report summarizes the results both in tabular and graphical form for various damping values

  9. Bacterial-epithelial contact is a key determinant of host innate immune responses to enteropathogenic and enteroaggregative Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Lindsey A Edwards

    Full Text Available BACKGROUND: Enteropathogenic (EPEC and Enteroaggregative (EAEC E. coli have similar, but distinct clinical symptoms and modes of pathogenesis. Nevertheless when they infect the gastrointestinal tract, it is thought that their flagellin causes IL-8 release leading to neutrophil recruitment and gastroenteritis. However, this may not be the whole story as the effect of bacterial adherence to IEC innate response(s remains unclear. Therefore, we have characterized which bacterial motifs contribute to the innate epithelial response to EPEC and EAEC, using a range of EPEC and EAEC isogenic mutant strains. METHODOLOGY: Caco-2 and HEp-2 cell lines were exposed to prototypical EPEC strain E2348/69 or EAEC strain O42, in addition to a range of isogenic mutant strains. E69 [LPS, non-motile, non-adherent, type three secretion system (TTSS negative, signalling negative] or O42 [non-motile, non-adherent]. IL-8 and CCL20 protein secretion was measured. Bacterial surface structures were assessed by negative staining Transmission Electron Microscopy. The Fluorescent-actin staining test was carried out to determine bacterial adherence. RESULTS: Previous studies have reported a balance between the host pro-inflammatory response and microbial suppression of this response. In our system an overall balance towards the host pro-inflammatory response is seen with the E69 WT and to a greater extent O42 WT, which is in fit with clinical symptoms. On removal of the external EPEC structures flagella, LPS, BFP, EspA and EspC; and EAEC flagella and AAF, the host inflammatory response is reduced. However, removal of E69 lymphostatin increases the host inflammatory response suggesting involvement in the bacterial mediated anti-inflammatory response. CONCLUSION: Epithelial responses were due to combinations of bacterial agonists, with host-bacterial contact a key determinant of these innate responses. Host epithelial recognition was offset by the microbe's ability to down

  10. [Study on the correlation between chronic asymptomatic HBV carriers of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles].

    Science.gov (United States)

    Guo, Jian-chun; Xiao, Li-na; Xun, Yun-hao

    2012-08-01

    To study on the correlation between chronic asymptomatic HBV carriers (ASC) of yin asthenia constitution and genotypes of HLA-DRB1 and HLA DQA1 alleles. Totally 105 ASC were assigned to two groups according to their constitutions, i.e., the yin asthenia group (47 cases) and the non-yin asthenia group (58 cases). The genotypes of HLA-DRB1 and HLA DQA1 alleles were determined using PCR-SSP. The gene frequency of HLA-DRB1 * 09 allele and HLA-DQA1 * 0301 allele (being 12.1% and 19.1%) were obviously lower in the yin asthenia group than in the non-yin asthenia group (being 27.8% and 39.7%, P HLA-DQA1 * 0501 allele were obviously higher in the yin asthenia group (being 12.1% and 28.7%) than in the non-yin asthenia group (4.3% and 9.5%), showing statistical difference (P HLA-DQA1 * 0301 allele might be the molecular bases for non-yin asthenia patients with ASC. HLA-DRB1 * 11 allele and HLA-DQA1 * 0501 allele might be the molecular bases for yin asthenia patients with ASC.

  11. On determination of microphone response and other parameters by a hybrid experimental and numerical method

    DEFF Research Database (Denmark)

    Barrera Figueroa, Salvador; Jacobsen, Finn; Rasmussen, Knud

    2008-01-01

    Typically, numerical calculations of the pressure, free-field and random-incidence response of a condenser microphone are carried out on the basis of an assumed displacement distribution of the diaphragm of the microphone; the conventional assumption is that the displacement follows a Bessel...

  12. A rapid challenge protocol for determination of non-specific bronchial responsiveness

    DEFF Research Database (Denmark)

    Madsen, F; Nielsen, N H; Holstein-Rathlou, N H

    1986-01-01

    well to a non-cumulative standard protocol and could be terminated either within 10 min or within 20 inhalations. The results of this new challenge procedure enables us to predict the responsiveness to inhaled histamine precisely enough to separate patients into hyperreactive or normal reactive...

  13. 33 CFR 151.2030 - Who is responsible for determining when to use the safety exemption?

    Science.gov (United States)

    2010-07-01

    ... the safety exemption? (a) The master, operator, or person-in-charge of a vessel is responsible for the safety of the vessel, its crew, and its passengers. (b) The master, operator, or person-in-charge of a... management alternatives under extraordinary conditions); or (2) Vessel is on a voyage to any port other than...

  14. A Meta-Analysis To Determine the Dose Response for Strength Development.

    Science.gov (United States)

    Rhea, Matthew R.; Alvar, Brent A.; Burkett, Lee N.; Ball, Stephen D.

    2003-01-01

    Examined the quantitative dose-response relationship for strength development by calculating the magnitude of gains elicited by various levels of training intensity, frequency, and volume; thus clarifying the effort to benefit ratio. A meta-analysis of 140 studies with 1,433 effect sizes (ES) was conducted. ES demonstrated different responses…

  15. Offense type as determinant of revenge and forgiveness after victimization : Adolescents’ responses to injustice and aggression

    NARCIS (Netherlands)

    Gerlsma, Coby; Lugtmeyer, Valerie

    2018-01-01

    Victims of injustice and aggression may have strong feelings about the perpetrator(s) that may impede their efforts to cope with the victimizing experience. We examined to what extent adolescents’ interpersonal responses to victimization in terms of revenge and forgiveness depend on offense type. Of

  16. NF1 Is a Tumor Suppressor in Neuroblastoma that Determines Retinoic Acid Response and Disease Outcome

    NARCIS (Netherlands)

    Hölzel, Michael; Huang, Sidong; Koster, Jan; Ora, Ingrid; Lakeman, Arjan; Caron, Huib; Nijkamp, Wouter; Xie, Jing; Callens, Tom; Asgharzadeh, Shahab; Seeger, Robert C.; Messiaen, Ludwine; Versteeg, Rogier; Bernards, René

    2010-01-01

    Retinoic acid (RA) induces differentiation of neuroblastoma cells in vitro and is used with variable success to treat aggressive forms of this disease. This variability in clinical response to RA is enigmatic, as no mutations in components of the RA signaling cascade have been found. Using a

  17. Determination of the response function for the Portsmouth Gaseous Diffusion Plant criticality accident alarm system neutron detectors

    International Nuclear Information System (INIS)

    Tayloe, R.W. Jr.; Brown, A.S.; Dobelbower, M.C.; Woollard, J.E.

    1997-03-01

    Neutron-sensitive radiation detectors are used in the Portsmouth Gaseous Diffusion Plant's (PORTS) criticality accident alarm system (CAAS). The CAAS is composed of numerous detectors, electronics, and logic units. It uses a telemetry system to sound building evacuation horns and to provide remote alarm status in a central control facility. The ANSI Standard for a CAAS uses a free-in-air dose rate to define the detection criteria for a minimum accident-of-concern. Previously, the free-in-air absorbed dose rate from neutrons was used for determining the areal coverge of criticality detection within PORTS buildings handling fissile materials. However, the free-in-air dose rate does not accurately reflect the response of the neutron detectors in use at PORTS. Because the cost of placing additional CAAS detectors in areas of questionable coverage (based on a free-in-air absorbed dose rate) is high, the actual response function for the CAAS neutron detectors was determined. This report, which is organized into three major sections, discusses how the actual response function for the PORTS CAAS neutron detectors was determined. The CAAS neutron detectors are described in Section 2. The model of the detector system developed to facilitate calculation of the response function is discussed in Section 3. The results of the calculations, including confirmatory measurements with neutron sources, are given in Section 4

  18. HIV-1 Nef responsiveness is determined by Env variable regions involved in trimer association and correlates with neutralization sensitivity.

    Science.gov (United States)

    Usami, Yoshiko; Göttlinger, Heinrich

    2013-11-14

    HIV-1 Nef and the unrelated murine leukemia virus glycoGag similarly enhance the infectivity of HIV-1 virions. We now show that the effects of Nef and glycoGag are similarly determined by variable regions of HIV-1 gp120 that control Env trimer association and neutralization sensitivity. Whereas neutralization-sensitive X4-tropic Env proteins conferred high responsiveness to Nef and glycoGag, particles bearing neutralization-resistant R5-tropic Envs were considerably less affected. The profoundly different Nef/glycoGag responsiveness of a neutralization-resistant and a neutralization-sensitive R5-tropic Env could be switched by exchanging their gp120 V1/V2 regions, which also switches their neutralization sensitivity. Within V1/V2, the same determinants governed Nef/glycoGag responsiveness and neutralization sensitivity, indicating that these phenotypes are mechanistically linked. The V1/V2 and V3 regions, which form an apical trimer-association domain, together determined the Nef and glycoGag responsiveness of an X4-tropic Env. Our results suggest that Nef and glycoGag counteract the inactivation of Env spikes with relatively unstable apical trimer-association domains. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Seasonal not annual rainfall determines grassland biomass response to carbon dioxide.

    Science.gov (United States)

    Hovenden, Mark J; Newton, Paul C D; Wills, Karen E

    2014-07-31

    The rising atmospheric concentration of carbon dioxide (CO2) should stimulate ecosystem productivity, but to what extent is highly uncertain, particularly when combined with changing temperature and precipitation. Ecosystem response to CO2 is complicated by biogeochemical feedbacks but must be understood if carbon storage and associated dampening of climate warming are to be predicted. Feedbacks through the hydrological cycle are particularly important and the physiology is well known; elevated CO2 reduces stomatal conductance and increases plant water use efficiency (the amount of water required to produce a unit of plant dry matter). The CO2 response should consequently be strongest when water is limiting; although this has been shown in some experiments, it is absent from many. Here we show that large annual variation in the stimulation of above-ground biomass by elevated CO2 in a mixed C3/C4 temperate grassland can be predicted accurately using seasonal rainfall totals; summer rainfall had a positive effect but autumn and spring rainfall had negative effects on the CO2 response. Thus, the elevated CO2 effect mainly depended upon the balance between summer and autumn/spring rainfall. This is partly because high rainfall during cool, moist seasons leads to nitrogen limitation, reducing or even preventing biomass stimulation by elevated CO2. Importantly, the prediction held whether plots were warmed by 2 °C or left unwarmed, and was similar for C3 plants and total biomass, allowing us to make a powerful generalization about ecosystem responses to elevated CO2. This new insight is particularly valuable because climate projections predict large changes in the timing of rainfall, even where annual totals remain static. Our findings will help resolve apparent differences in the outcomes of CO2 experiments and improve the formulation and interpretation of models that are insensitive to differences in the seasonal effects of rainfall on the CO2 response.

  20. Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil

    OpenAIRE

    Russo, Rodrigo; Zillmer, Laura Russo; Nascimento, Oliver Augusto; Manzano, Beatriz; Ivanaga, Ivan Teruaki; Fritscher, Leandro; Lundgren, Fernando; Miravitlles, Marc; Gondim, Heicilainy Del Carlos; Santos Junior, Gildo; Alves, Marcela Amorim; Oliveira, Maria Vera; Souza, Altay Alves Lino de; Sales, Maria Penha Uchoa; Jardim, José Roberto

    2016-01-01

    ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of <...

  1. PCR-based allelic discrimination for glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ugandan umbilical cord blood.

    Science.gov (United States)

    Hsu, Jennifer; Fink, Deanna; Langer, Erica; Carter, Michelle L; Bengo, Derrik; Ndidde, Susan; Slusher, Tina; Ross, Julie A; Lund, Troy C

    2014-02-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked disorder in the world. G6PD deficiency puts children at risk for hyperbilirubinemia and kernicterus during the newborn period and an increased risk of severe hemolysis after exposure to many antimalarial medications. A laboratory diagnosis of G6PD deficiency is rare in the developing world due to limited resources. We developed a TaqMan-based allele-specific assay to rapidly determine rates of G6PD deficiency contributing alleles (G202A and A376G) in East Africa. We tested umbilical cord blood from 100 Ugandan newborns and found that the overall allele frequency of G202A was .13 and A376G was .32. The overall incidence of G6PD A- (G202A/A376G) was 6%; all A- variants were males. There was no correlation between G6PD deficiency and umbilical cord blood hemoglobin, white blood count, platelet count, or other hematologic parameters. Allele-specific PCR can serve as a rapid method to determine specific G6PD deficiency allele frequencies in a given population and as a diagnostic tool in a hospital setting in which laboratory resources are present.

  2. Apolipoprotein E epsilon 4 allele and outcomes of traumatic spinal cord injury in a Chinese Han population.

    Science.gov (United States)

    Sun, Chongyi; Ji, Guangrong; Liu, Qingpeng; Yao, Meng

    2011-10-01

    The association between apolipoprotein E (APOE) epsilon 4 (ε4) allele and outcomes of traumatic spinal cord injury (SCI) is still controversial and ambiguous. The objective of this study was to test the hypothesis that APOE polymorphisms are associated with outcomes after SCI in Chinese Han patients. APOE polymorphisms were determined in 100 patients with cervical SCI (C3-C8). The genotype frequency of this polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. Patients with an APOE ε4 allele had significantly less motor recovery during rehabilitation than did patients without an APOE ε4 allele (mean 3.7 vs. 6.1; P = 0.04) and a longer rehabilitation length of stay (LOS) (mean 117.4 vs. 94.5; P = 0.02), but better sensory-pinprick recovery (mean 6.1 vs. 4.0; P = 0.03). There were no significant differences by APOE ε4 allele status in sensory-light touch recovery or acute LOS. This study suggests that the APOE ε4 allele is associated with outcomes after SCI and longer rehabilitation LOS in Chinese Han patients.

  3. Alleles of Ppd-D1 gene in the collection of Aegilops tauschii accessions and bread wheat varieties

    Directory of Open Access Journals (Sweden)

    Babenko D. O.

    2012-04-01

    Full Text Available Light period significantly influences on the growth and development of plants. One of the major genes of photoperiod sensitivity is Ppd-D1, located on the chromosome 2D. The aim of the work was to determine the alleles and molecular structure of Ppd-D1 gene in samples from the collection of Ae. tauschii accessions, which have different flowering periods, and in 29 Ukrainian wheat varieties. Methods. We used methods of allele-specific PCR with primers to the Ppd-D1 gene, sequencing and Blast-analysis. Results. The collection of Ae. tauschii accessions and several varieties of winter and spring wheat was studied. The molecular structure of the allelic variants (414, 429 and 453 b. p. of Ppd-D1b gene was determined in the collection of Aegilops. tauschii accessions. Conclusions. The Ppd-D1a allele was present in all studied varieties of winter wheat. 60 % of spring wheat is characterized by Ppd-D1b allele (size of amplification products 414 b. p.. Blast-analysis of the sequence data banks on the basis of the reference sequence of sample k-1322 from the collection of Ae. tauschii accessions has shown a high homology (80 to 100 % between the nucleotide sequences of PRR genes, that characterize the A and D genomes of representatives of the genera Triticum and Aegilops.

  4. Abdominal adiposity is the main determinant of the C-reactive response to injury in subjects undergoing inguinal hernia repair

    Directory of Open Access Journals (Sweden)

    Irkulla Sashidhar

    2013-02-01

    Full Text Available Abstract Background Obesity and serum C-reactive protein (CRP (a sensitive marker of inflammatory activity are associated with most chronic diseases. Abdominal adiposity along with age is the strongest determinant of baseline CRP levels in healthy subjects. The mechanism of the association of serum CRP with disease is uncertain. We hypothesized that baseline serum CRP is a marker of inflammatory responsiveness to injury and that abdominal adiposity is the main determinant of this responsiveness. We studied the effect of abdominal adiposity, age and other environmental risk factors for chronic disease on the CRP response to a standardised surgical insult, unilateral hernia repair to not only test this hypothesis but to inform the factors which must be taken into account when assessing systemic inflammatory responses to surgery. Methods 102 male subjects aged 24-94 underwent unilateral hernia repair by a single operator. CRP was measured at 0, 6, 24 and 48 hrs. Response was defined as the peak CRP adjusted for baseline CRP. Results Age and waist:hip ratio (WHR were associated both with basal CRP and CRP response with similar effect sizes after adjustment for a wide-range of covariates. The adjusted proportional difference in CRP response per 10% increase in WHR was 1.50 (1.17-1.91 p = 0.0014 and 1.15(1.00-1.31 p = 0.05 per decade increase in age. There was no evidence of important effects of other environmental cardiovascular risk factors on CRP response. Conclusion Waist:hip ratio and age need to be considered when studying the inflammatory response to surgery. The finding that age and waist:hip ratio influence baseline and post-operative CRP levels to a similar extent suggests that baseline CRP is a measure of inflammatory responsiveness to casual stimuli and that higher age and obesity modulate the generic excitability of the inflammatory system leading to both higher baseline CRP and higher CRP response to surgery. The mechanism for

  5. Determination of heavy metals contamination using a silicon sensor with extended responsive to the UV

    International Nuclear Information System (INIS)

    Aceves-Mijares, M; Ramírez, J M; Pedraza, J; Román-López, S; Chávez, C

    2013-01-01

    Due to its potential risk to human health and ecology, the presence of heavy metals in water demands of techniques to determine them in a simple and economical way. Currently, new developments of light emitters and detectors open a window of opportunities to use optical properties to analyze contaminated water. In this paper, a silicon sensor developed to extend its sensitivity up to the UV range is used to determine heavy metals in water. Cadmium, Zinc, Lead, Copper and Manganese mixed in pure water at different concentrations were used as test samples. The photocurrent obtained by the light that passes through the samples was used to determine the optical transmittance of pure and contaminated water. Preliminary results show a good separability between samples, which can be used for qualitative and quantitative detection of such heavy metals in water.

  6. Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

    Science.gov (United States)

    Floquet, Célia; Hatin, Isabelle; Rousset, Jean-Pierre; Bidou, Laure

    2012-01-01

    The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable. PMID:22479203

  7. Experimental determination of thermal conductivity of soil with a thermal response test

    OpenAIRE

    Banjac Miloš J.; Todorović Maja N.; Ristanović Milan R.; Galić Radoslav D.

    2012-01-01

    Optimal design of a borehole heat exchanger, as the outer part of a ground source heat pump heating system, requires information on the thermal properties of the soil. Those data, the effective thermal conductivity of the soil λeff and the average temperature of the soil T0, enable us to determine the necessary number and depth of boreholes. The determination of thermal conductivity of the soil in laboratory experiments does not usually coincide with the data under in-situ conditions. T...

  8. No evidence of association between mutant alleles of the CYP27B1 gene and MS

    Science.gov (United States)

    Ban, Maria; Caillier, Stacy; Mero, Inger-Lise; Myhr, Kjell-Morten; Celius, Elisabeth G.; Aarseth, Jan; Torkildsen, Øivind; Harbo, Hanne F.; Oksenberg, Jorge; Hauser, Stephen L.; Sawcer, Stephen; Compston, Alastair

    2012-01-01

    An association has previously been reported between susceptibility to multiple sclerosis and the rare mutant alleles of the CYP27B1 gene responsible for autosomal recessive Vitamin D Dependent Rickets type 1 (VDDR1). In an attempt to replicate this finding, we screened 495 multiplex families and 2092 single affected families, together with 4594 cases and 3583 controls (a total of 17073 individuals) but were unable to find any evidence supporting this putative association. Our data do not indicate that mutations responsible for VDDR1 influence the risk of developing multiple sclerosis. PMID:23444327

  9. Identification of 48 full-length MHC-DAB functional alleles in miiuy croaker and evidence for positive selection.

    Science.gov (United States)

    Liu, Jiang; Sun, Yueyan; Xu, Tianjun

    2016-07-01

    Major histocompatibility complex (MHC) molecules play a vital role in the immune response and are a highly polymorphic gene superfamily in vertebrates. As the molecular marker associated with polymorphism and disease susceptibility/resistance, the polymorphism of MHC genes has been investigated in many tetrapods and teleosts. Most studies were focused on the polymorphism of the second exon, which encodes the peptide-binding region (PBR) in the α1- or β1-domain, but few studies have examined the full-length coding region. To comprehensive investigate the polymorphism of MHC gene, we identified 48 full-length miiuy croaker (Miichthys miiuy) MHC class IIB (Mimi-DAB) functional alleles from 26 miiuy croaker individuals. All of the alleles encode 34 amino acid sequences, and a high level of polymorphism was detected in Mimi-DAB alleles. The rate of non-synonymous substitutions (dN) occurred at a significantly higher frequency than that of synonymous substitutions (dS) in the PBR, and this result suggests that balancing selection maintains polymorphisms at the Mimi-DAB locus. Phylogenetic analysis based on the full-length and exon 2 sequences of Mimi-DAB alleles both showed that the Mimi-DAB alleles were clustered into two major groups. A total of 19 positive selected sites were identified on the Mimi-DAB alleles after testing for positive selection, and 14 sites were predicted to be associated with antigen-binding sites, which suggests that most of selected sites are significant for disease resistance. The polymorphism of Mimi-DAB alleles provides an important resource for analyzing the association between the polymorphism of MHC gene and disease susceptibility/resistance, and for researching the molecular selective breeding of miiuy croaker with enhanced disease resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Sensory determinants of the autonomous sensory meridian response (ASMR: understanding the triggers

    Directory of Open Access Journals (Sweden)

    Emma L. Barratt

    2017-10-01

    Full Text Available The autonomous sensory meridian response (ASMR is an atypical sensory phenomenon involving electrostatic-like tingling sensations in response to certain sensory, primarily audio-visual, stimuli. The current study used an online questionnaire, completed by 130 people who self-reported experiencing ASMR. We aimed to extend preliminary investigations into the experience, and establish key multisensory factors contributing to the successful induction of ASMR through online media. Aspects such as timing and trigger load, atmosphere, and characteristics of ASMR content, ideal spatial distance from various types of stimuli, visual characteristics, context and use of ASMR triggers, and audio preferences are explored. Lower-pitched, complex sounds were found to be especially effective triggers, as were slow-paced, detail-focused videos. Conversely, background music inhibited the sensation for many respondents. These results will help in designing media for ASMR induction.

  11. The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity

    DEFF Research Database (Denmark)

    Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta

    2016-01-01

    non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small...... effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates...... that differences in the acute transcriptional response to insulin are primarily driven by obesity per se, challenging the notion of healthy obese adipose tissue, at least in severe obesity....

  12. Genetically determined differences in brain response to a primary food reward

    OpenAIRE

    Felsted, Jennifer A.; Ren, Xueying; Chouinard-Decorte, Francois; Small, Dana M.

    2010-01-01

    Combining genetic and neuroimaging techniques may elucidate the biological underpinnings of individual differences in neurophysiology and potential vulnerabilities to disease. The TaqIA A1 variant is associated with diminished DRD2 receptor density, higher body mass, and food reinforcement. It also moderates the relationship between brain response to food and future weight gain. This suggests that the polymorphism is associated with a fundamental difference in the neurophysiology of food that...

  13. The severity of airways obstruction as a determinant of treatment response in COPD

    DEFF Research Database (Denmark)

    Calverley, Peter Ma; Pauwels, Romain A; Jones, Paul W

    2006-01-01

    /513 respectively). Treatment effects on clinical outcomes - lung function, exacerbations, health status, diary card symptoms, and adverse events - were investigated. Treatment responses based on a pre-specified analysis explored treatment differences by severity as a continuous variable. Lung function improved...... with active treatment irrespective of FEV1; Sal/FP had greatest effect. This improvement appeared additive in milder disease; synergistic in severe disease. Active therapy significantly reduced exacerbation rate in patients with FEV1 Health status and breathlessness...

  14. Statistical determination of significant curved I-girder bridge seismic response parameters

    Science.gov (United States)

    Seo, Junwon

    2013-06-01

    Curved steel bridges are commonly used at interchanges in transportation networks and more of these structures continue to be designed and built in the United States. Though the use of these bridges continues to increase in locations that experience high seismicity, the effects of curvature and other parameters on their seismic behaviors have been neglected in current risk assessment tools. These tools can evaluate the seismic vulnerability of a transportation network using fragility curves. One critical component of fragility curve development for curved steel bridges is the completion of sensitivity analyses that help identify influential parameters related to their seismic response. In this study, an accessible inventory of existing curved steel girder bridges located primarily in the Mid-Atlantic United States (MAUS) was used to establish statistical characteristics used as inputs for a seismic sensitivity study. Critical seismic response quantities were captured using 3D nonlinear finite element models. Influential parameters from these quantities were identified using statistical tools that incorporate experimental Plackett-Burman Design (PBD), which included Pareto optimal plots and prediction profiler techniques. The findings revealed that the potential variation in the influential parameters included number of spans, radius of curvature, maximum span length, girder spacing, and cross-frame spacing. These parameters showed varying levels of influence on the critical bridge response.

  15. Local geology determines responses of stream producers and fungal decomposers to nutrient enrichment: A field experiment.

    Science.gov (United States)

    Mykrä, Heikki; Sarremejane, Romain; Laamanen, Tiina; Karjalainen, Satu Maaria; Markkola, Annamari; Lehtinen, Sirkku; Lehosmaa, Kaisa; Muotka, Timo

    2018-04-16

    We examined how short-term (19 days) nutrient enrichment influences stream fungal and diatom communities, and rates of leaf decomposition and algal biomass accrual. We conducted a field experiment using slow-releasing nutrient pellets to increase nitrate (NO 3 -N) and phosphate (PO 4 -P) concentrations in a riffle section of six naturally acidic (naturally low pH due to catchment geology) and six circumneutral streams. Nutrient enrichment increased microbial decomposition rate on average by 14%, but the effect was significant only in naturally acidic streams. Nutrient enrichment also decreased richness and increased compositional variability of fungal communities in naturally acidic streams. Algal biomass increased in both stream types, but algal growth was overall very low. Diatom richness increased in response to nutrient addition by, but only in circumneutral streams. Our results suggest that primary producers and decomposers are differentially affected by nutrient enrichment and that their responses to excess nutrients are context dependent, with a potentially stronger response of detrital processes and fungal communities in naturally acidic streams than in less selective environments.

  16. Floristics and physiognomy determine migrant landbird response to Tamarisk (Tamarix ramosissima) invasion in riparian areas

    Science.gov (United States)

    Hira A. Walker

    2008-01-01

    I investigated the relative importance of floristics and physiognomy in determining community organization of autumn-migrating landbirds in a riparian corridor in New Mexico invaded by Tamarisk (Tamarix ramosissima). All six avian measures were associated with floristics, physiognomy, or both. However, usefulness in predicting migrant parameters...

  17. Size at hatching determines population dynamics and response to harvesting in cannibalistic fish

    NARCIS (Netherlands)

    Kooten, van T.; Andersson, J.; Bystrom, P.; Persson, L.; Roos, A.M.

    2010-01-01

    We hypothesize that size at hatching strongly affects population dynamics of cannibalistic fish species and is a crucial determinant of how populations respond to selective removal of large individuals (harvesting). We use a mechanistic mathematical model to study the relation between hatching size

  18. DETERMINANT VALUE OF THE CYTOGENETIC AND MOLECULAR IMATINIB THERAPEUTIC RESPONSE IN CHRONIC MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Angela Dascalescu

    2013-12-01

    Full Text Available The hallmark of chronic myeloid leukemia is the existence of the cytogenetic evidence of the Phyladelphia chromosome (reciprocal translocation between chromosome 9 and 22, and is specifically designated t(9;22(q34;q11. The result of the translocation is the oncogenic BCR-ABL gene fusion, located on the shorter derivative 22 chromosome. This gene encodes the Bcr-abl fusion protein the BCR-ABL tyrosine kinase - a protein that is continuously activated. The result of this unregulated  activation is an unregulated neoplastic type cell division - chronic myeloid leukemia.   The first targeted molecular treatment operating in cancer-  inhibitor of the BCR-ABL tyrosine kinase, Imatinib mesylate, is the standard of care for chronic myeloid leukemia (CML Methods. A retrospective review of patients in one department of hematology with a diagnosis of Ph/BCR-ABL positive CML and received imatinib.  Results. From 2002 to 2012, 66 patients in CML-CP received imatinib were introduced in the study. 22 (33% patients received imatinib as upfront therapy, the others as second or third line treatment. The cytogenetic response (CyR achieved was major in 62% with 56% complete cytogenetic response (CCR, no CyR in 17 patients (25%. The molecular response was complete in 13 (20% and major in 16 (24% patients. Better cytogenetic and molecular responses were achieved by those with low and intermediary risk (Sokal Seven patients developed under imatinib additional cytogenetic anomalies: supplemental chromosome 8 (6, duplication of Ph1 (2, trisomy 17 and 19 (1. The median of follow-up was 69 months (range 18-180 and under imatinib was 52 months (range 3-126. The Sokal score was a better predictor of survival than Hasford’s.  Conclusions. Imatinib remains the best  first line treatment, but there are still a significant number of patients who did not achieve a CyR. The responses and survival were not influenced by the previous treatments but the earlier introduction

  19. Determinants and repeatability of the specific dynamic response of the corn snake, Pantherophis guttatus.

    Science.gov (United States)

    Crocker-Buta, Sarah P; Secor, Stephen M

    2014-03-01

    Ingesting, digesting, absorbing, and assimilating a meal are all energy consuming processes that accumulate to form the specific dynamic action (SDA) of the meal. Sensitive to digestive demand, SDA is theoretically fixed to a given meal size and type. In this study, we altered relative meal size to explore the effects of digestive demand on the postprandial metabolic profile and SDA of the corn snake, Pantherophis guttatus. We also examined the effects of body temperature on the SDA response while controlling for meal size and type and assessed whether these responses are highly repeatable under the same conditions. Additionally, the effects of body mass on SDA were investigated by feeding snakes the same relative and absolute meal size. With increases in digestive demand (meals from 5% to 45% of body mass), P. guttatus responded with incremental increases in the postprandial peak in oxygen consumption (VO2), the duration of the significantly elevated VO2, and SDA. Body temperature had an observable impact on the postprandial metabolic profile, decreasing the duration and increasing the peak VO2, however, body temperature did not significantly alter SDA. Regardless of temperature, and hence duration, snakes expended the same amount of energy in digesting a given meal. This was additionally borne out when testing the individual repeatability of the SDA response, individual P. guttatus exhibited nearly identical postprandial responses to the same meal. Over a 90-fold range in body mass, and fed meals equaling 25% of body mass, P. guttatus exhibited an isometric relationship between SDA and body mass. When fed a set 10-gram meal, snakes regardless of body size expended the same amount of energy on digestion and assimilation. Characteristically, P. guttatus experience a rapid postprandial increase in metabolic rate that peaks and gradually descends to prefeeding levels. The magnitude of that response (quantified as SDA) varies as a function of digestive demand (i

  20. Identification and Molecular Analysis of Four New Alleles at the W1 Locus Associated with Flower Color in Soybean

    Science.gov (United States)

    Sundaramoorthy, Jagadeesh; Park, Gyu Tae; Chang, Jeong Ho; Lee, Jeong-Dong; Kim, Jeong Hoe; Seo, Hak Soo; Chung, Gyuhwa; Song, Jong Tae

    2016-01-01

    In soybean, flavonoid 3′5′-hydroxylase (F3′5′H) and dihydroflavonol-4-reductase (DFR) play a crucial role in the production of anthocyanin pigments. Loss-of-function of the W1 locus, which encodes the former, or W3 and W4, which encode the latter, always produces white flowers. In this study, we searched for new genetic components responsible for the production of white flowers in soybean and isolated four white-flowered mutant lines, i.e., two Glycine soja accessions (CW12700 and CW13381) and two EMS-induced mutants of Glycine max (PE1837 and PE636). F3′5′H expression in CW12700, PE1837, and PE636 was normal, whereas that in CW13381 was aberrant and missing the third exon. Sequence analysis of F3′5′H of CW13381 revealed the presence of an indel (~90-bp AT-repeat) in the second intron. In addition, the F3′5′H of CW12700, PE1837, and PE636 harbored unique single-nucleotide substitutions. The single nucleotide polymorphisms resulted in substitutions of amino acid residues located in or near the SRS4 domain of F3′5′H, which is essential for substrate recognition. 3D structure modeling of F3′5′H indicated that the substitutions could interfere with an interaction between the substrate and heme group and compromise the conformation of the active site of F3′5′H. Recombination analysis revealed a tight correlation between all of the mutant alleles at the W1 locus and white flower color. On the basis of the characterization of the new mutant alleles, we discussed the biological implications of F3′5′H and DFR in the determination of flower colors in soybean. PMID:27442124

  1. HLA-DQA1 and -DQB1 allele typing in southern Taiwanese women with breast cancer.

    Science.gov (United States)

    Chen, Po-Chih; Tsai, Eing-Mei; Er, Tze-Kiong; Chang, Su-Jen; Chen, Bai-Hsiun

    2007-01-01

    The pathogenesis of breast cancer is multifactorial. Genetic predisposition, environmental factors, hormones and even infection agents are thought to interact in the manifestation of breast cancer. In particular, human leukocyte antigen (HLA) alleles play a pivotal role in cellular immunity and may be an important genetically determined host trait. Regardless of the importance and functions of HLA genes in the evolution of cancer, the allele-specific association of HLA molecules in cancer patients has not been well established. Recently, a few studies have concentrated on the association between HLA and breast cancer, but the results of these studies are controversial. We designed a study to evaluate the association between the genotype of HLA class II genes and breast cancer. HLA-DQA1 and -DQB1 polymorphisms were determined by PCR with sequence-specific primers (PCR-SSP) in 101 Taiwanese women patients with breast cancer and 115 matched control subjects. Using PCR-SSP typing, HLA-DQA1 and -DQB1 locus comparison of allele frequencies between breast cancer patients and healthy controls showed no significant difference. We have established a significant lack of HLA-DQA1 and -DQB1 association with breast cancer in southern Taiwanese women. The results of this study may provide information for further clarification of the etiology of breast cancer in this region.

  2. Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome

    Directory of Open Access Journals (Sweden)

    Byun Hyang-Min

    2012-02-01

    Full Text Available Abstract Background Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability. Methods we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation. Results We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression. Conclusion The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.

  3. Association of baseline vitamin D level with genetic determinants and virologic response in patients with chronic hepatitis B.

    Science.gov (United States)

    Yu, Rui; Tan, Deming; Ning, Qin; Niu, Junqi; Bai, Xuefan; Chen, Shijun; Cheng, Jun; Yu, Yanyan; Wang, Hao; Xu, Min; Shi, Guangfeng; Wan, Mobin; Chen, Xinyue; Tang, Hong; Sheng, Jifang; Dou, Xiaoguang; Shi, Junping; Ren, Hong; Wang, Maorong; Zhang, Hongfei; Gao, Zhiliang; Chen, Chengwei; Ma, Hong; Jia, Jidong; Hou, Jinlin; Xie, Qing; Sun, Jian

    2018-02-01

    The role of vitamin D in individuals with chronic hepatitis B (CHB) is unclear. We aimed to explore the association of baseline vitamin D level with genetic determinants and week-104 treatment outcome in CHB patients. Baseline serum 25-hydroxycholecalciferol (25(OH)D) levels and genetic polymorphism within GC, DHCR7, and CYP2R1 were determined in stored serum of 560 patients who were enrolled into a multicenter, randomized, controlled study and completed 104 weeks of telbivudine monotherapy or telbivudine-based optimized therapy. Virologic response was defined as hepatitis B virus DNA <300 copies/mL (52 IU/mL) at week 104. The mean 25(OH)D value was 29.64 ng/mL. The percentage of patients with vitamin D insufficiency (<30 ng/mL) and vitamin D deficiency (<20 ng/mL) were 55.0% and 20.9%, respectively. Gender, season, latitude, and GC rs2282679 polymorphism were independent factors of vitamin D status. Patients with sufficient vitamin D (≥30 ng/mL) achieved a higher virologic response rate than those with vitamin D insufficiency (81.7% vs. 67.2%, P < 0.001). The area under the curve of 25(OH)D to predict virologic response was 0.65 (P < 0.001; 95% confidence interval, 0.62-0.67). On multivariate analysis, 25(OH)D level was an independent predictor of virologic response, but not associated with hepatitis B envelope antigen (HBeAg) seroconversion or alanine aminotransferase (ALT) normalization. Vitamin D insufficiency was highly prevalent in treatment-naïve CHB patients in mainland China. Latitude and genetic determinants affect vitamin D status. Baseline vitamin D level can predict week-104 virologic response, but not HBeAg seroconversion or ALT normalization. © 2017 The Japan Society of Hepatology.

  4. Delicate Metabolic Control and Coordinated Stress Response Critically Determine Antifungal Tolerance of Candida albicans Biofilm Persisters.

    Science.gov (United States)

    Li, Peng; Seneviratne, Chaminda J; Alpi, Emanuele; Vizcaino, Juan A; Jin, Lijian

    2015-10-01

    Candida infection has emerged as a critical health care burden worldwide, owing to the formation of robust biofilms against common antifungals. Recent evidence shows that multidrug-tolerant persisters critically account for biofilm recalcitrance, but their underlying biological mechanisms are poorly understood. Here, we first investigated the phenotypic characteristics of Candida biofilm persisters under consecutive harsh treatments of amphotericin B. The prolonged treatments effectively killed the majority of the cells of biofilms derived from representative strains of Candida albicans, Candida glabrata, and Candida tropicalis but failed to eradicate a small fraction of persisters. Next, we explored the tolerance mechanisms of the persisters through an investigation of the proteomic profiles of C. albicans biofilm persister fractions by liquid chromatography-tandem mass spectrometry. The C. albicans biofilm persisters displayed a specific proteomic signature, with an array of 205 differentially expressed proteins. The crucial enzymes involved in glycolysis, the tricarboxylic acid cycle, and protein synthesis were markedly downregulated, indicating that major metabolic activities are subdued in the persisters. It is noteworthy that certain metabolic pathways, such as the glyoxylate cycle, were able to be activated with significantly increased levels of isocitrate lyase and malate synthase. Moreover, a number of important proteins responsible for Candida growth, virulence, and the stress response were greatly upregulated. Interestingly, the persisters were tolerant to oxidative stress, despite highly induced intracellular superoxide. The current findings suggest that delicate metabolic control and a coordinated stress response may play a crucial role in mediating the survival and antifungal tolerance of Candida biofilm persisters. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. On-Line, Self-Learning, Predictive Tool for Determining Payload Thermal Response

    Science.gov (United States)

    Jen, Chian-Li; Tilwick, Leon

    2000-01-01

    This paper will present the results of a joint ManTech / Goddard R&D effort, currently under way, to develop and test a computer based, on-line, predictive simulation model for use by facility operators to predict the thermal response of a payload during thermal vacuum testing. Thermal response was identified as an area that could benefit from the algorithms developed by Dr. Jeri for complex computer simulations. Most thermal vacuum test setups are unique since no two payloads have the same thermal properties. This requires that the operators depend on their past experiences to conduct the test which requires time for them to learn how the payload responds while at the same time limiting any risk of exceeding hot or cold temperature limits. The predictive tool being developed is intended to be used with the new Thermal Vacuum Data System (TVDS) developed at Goddard for the Thermal Vacuum Test Operations group. This model can learn the thermal response of the payload by reading a few data points from the TVDS, accepting the payload's current temperature as the initial condition for prediction. The model can then be used as a predictive tool to estimate the future payload temperatures according to a predetermined shroud temperature profile. If the error of prediction is too big, the model can be asked to re-learn the new situation on-line in real-time and give a new prediction. Based on some preliminary tests, we feel this predictive model can forecast the payload temperature of the entire test cycle within 5 degrees Celsius after it has learned 3 times during the beginning of the test. The tool will allow the operator to play "what-if' experiments to decide what is his best shroud temperature set-point control strategy. This tool will save money by minimizing guess work and optimizing transitions as well as making the testing process safer and easier to conduct.

  6. Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses

    DEFF Research Database (Denmark)

    Schaeffer, E B; Sette, A; Johnson, D L

    1989-01-01

    -cell responses. Ia binding and Ia-restricted T-cell immunogenicity could be determined for a total of 54 peptide-MHC combinations. Only 30% of the 54 instances examined involved detectable Ia binding, but they represented almost all (12 of 13) of the immune responses found. However, binding to Ia......Using BALB/c and CBA/J mice, the I-region associated (Ia) binding capacity and T-cell immunogenicity of a panel of 14 overlapping peptides that span the entire sequence of the protein staphylococcal nuclease (Nase) was examined to evaluate major histocompatibility gene complex (MHC) control of T...... was not sufficient to ensure T-cell immunogenicity, since only 70% of the binding events were productive--i.e., were associated with an immune response. Thus, Ia molecules have the expected characteristics of a highly permissive capacity for antigen interaction that allows them to function as restriction elements...

  7. Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria

    DEFF Research Database (Denmark)

    Abdulla, S.; Adam, I.; Adjei, G. O.

    2015-01-01

    early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included.......020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides...

  8. Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms

    Directory of Open Access Journals (Sweden)

    Salsano Ettore

    2012-01-01

    Full Text Available Abstract Background Approximately 20% of adrenoleukodystrophy (X-ALD female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI, leading to the preferential expression of the X chromosome carrying the mutant ABCD1 allele, has been proposed as a mechanism influencing X-linked adrenoleukodystrophy (X-ALD carrier phenotype, but reported data so far are conflicting. Methods To shed light into this topic we assessed the XCI pattern in peripheral blood mononuclear cells (PBMCs of 30 X-ALD carriers. Since a frequent problem with XCI studies is the underestimation of skewing due to an incomplete sample digestion by restriction enzymes, leading to variable results, we developed a pyrosequencing assay to identify samples completely digested, on which to perform the XCI assay. Pyrosequencing was also used to quantify ABCD1 allele-specific expression. Moreover, very long-chain fatty acid (VLCFA levels were determined in the same patients. Results We found severely (≥90:10 or moderately (≥75:25 skewed XCI in 23 out of 30 (77% X-ALD carriers and proved that preferential XCI is mainly associated with the preferential expression of the mutant ABCD1 allele, irrespective of the manifestation of symptoms. The expression of mutant ABCD1 allele also correlates with plasma VLCFA concentrations. Conclusions Our results indicate that preferential XCI leads to the favored expression of the mutant ABCD1 allele. This emerges as a general phenomenon in X-ALD carriers not related to the presence of symptoms. Our data support the postulated growth advantage of cells with the preferential expression of the mutant ABCD1 allele, but argue against the use of XCI pattern, ABCD1 allele-specific expression pattern and VLCFA plasma concentration as biomarkers to predict the development of symptoms in X-ALD carriers.

  9. Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms.

    Science.gov (United States)

    Salsano, Ettore; Tabano, Silvia; Sirchia, Silvia M; Colapietro, Patrizia; Castellotti, Barbara; Gellera, Cinzia; Rimoldi, Marco; Pensato, Viviana; Mariotti, Caterina; Pareyson, Davide; Miozzo, Monica; Uziel, Graziella

    2012-01-26

    Approximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI), leading to the preferential expression of the X chromosome carrying the mutant ABCD1 allele, has been proposed as a mechanism influencing X-linked adrenoleukodystrophy (X-ALD) carrier phenotype, but reported data so far are conflicting. To shed light into this topic we assessed the XCI pattern in peripheral blood mononuclear cells (PBMCs) of 30 X-ALD carriers. Since a frequent problem with XCI studies is the underestimation of skewing due to an incomplete sample digestion by restriction enzymes, leading to variable results, we developed a pyrosequencing assay to identify samples completely digested, on which to perform the XCI assay. Pyrosequencing was also used to quantify ABCD1 allele-specific expression. Moreover, very long-chain fatty acid (VLCFA) levels were determined in the same patients. We found severely (≥90:10) or moderately (≥75:25) skewed XCI in 23 out of 30 (77%) X-ALD carriers and proved that preferential XCI is mainly associated with the preferential expression of the mutant ABCD1 allele, irrespective of the manifestation of symptoms. The expression of mutant ABCD1 allele also correlates with plasma VLCFA concentrations. Our results indicate that preferential XCI leads to the favored expression of the mutant ABCD1 allele. This emerges as a general phenomenon in X-ALD carriers not related to the presence of symptoms. Our data support the postulated growth advantage of cells with the preferential expression of the mutant ABCD1 allele, but argue against the use of XCI pattern, ABCD1 allele-specific expression pattern and VLCFA plasma concentration as biomarkers to predict the development of symptoms in X-ALD carriers.

  10. Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms

    Science.gov (United States)

    2012-01-01

    Background Approximately 20% of adrenoleukodystrophy (X-ALD) female carriers may develop clinical manifestations, typically consisting of progressive spastic gait, sensory deficits and bladder dysfunctions. A skewing in X Chromosome Inactivation (XCI), leading to the preferential expression of the X chromosome carrying the mutant ABCD1 allele, has been proposed as a mechanism influencing X-linked adrenoleukodystrophy (X-ALD) carrier phenotype, but reported data so far are conflicting. Methods To shed light into this topic we assessed the XCI pattern in peripheral blood mononuclear cells (PBMCs) of 30 X-ALD carriers. Since a frequent problem with XCI studies is the underestimation of skewing due to an incomplete sample digestion by restriction enzymes, leading to variable results, we developed a pyrosequencing assay to identify samples completely digested, on which to perform the XCI assay. Pyrosequencing was also used to quantify ABCD1 allele-specific expression. Moreover, very long-chain fatty acid (VLCFA) levels were determined in the same patients. Results We found severely (≥90:10) or moderately (≥75:25) skewed XCI in 23 out of 30 (77%) X-ALD carriers and proved that preferential XCI is mainly associated with the preferential expression of the mutant ABCD1 allele, irrespective of the manifestation of symptoms. The expression of mutant ABCD1 allele also correlates with plasma VLCFA concentrations. Conclusions Our results indicate that preferential XCI leads to the favored expression of the mutant ABCD1 allele. This emerges as a general phenomenon in X-ALD carriers not related to the presence of symptoms. Our data support the postulated growth advantage of cells with the preferential expression of the mutant ABCD1 allele, but argue against the use of XCI pattern, ABCD1 allele-specific expression pattern and VLCFA plasma concentration as biomarkers to predict the development of symptoms in X-ALD carriers. PMID:22280810

  11. Determinants of Skeletal Muscle Hypertrophy and the Attenuated Hypertrophic Response at Old Age

    OpenAIRE

    Degens, Hans

    2012-01-01

    In 2012 we will again see the impressive achievements of many athletes during the London Olympic Games. In particular for weightlifters success is dependent on the power- and force-generating capacity of their muscles, which in turn are strongly determined by muscle mass. Many athletes and bodybuilders therefore train intensively to develop as much muscle hypertrophy as possible. Unlimited hypertrophy, however, is impossible. Limitations may be imposed by the peak forces that the ...

  12. Determination of non-stationary stochastic processes compatible with seismic response/design spectra

    OpenAIRE

    Giaralis, A.; Spanos, P. D.

    2011-01-01

    In this paper the problem of deriving non-stationary stochastic processes defined by a parametric evolutionary power spectrum (EPS) compatible with a given (target) design spectrum is addressed. An inverse stochastic dynamics problem is formulated and solved in a least-square sense to determine the requisite EPS. This involves the incorporation of a “peak factor” which is used to relate statistically the target spectrum to the EPS. Special attention is focused on deriving design spectrum comp...

  13. DETERMINATION OF THERMAL RESPONSE OF CARRARA AND SNEZNIKOVSKY MARBLE USED AS A BUILDING MATERIALS

    Directory of Open Access Journals (Sweden)

    Veronika Petráňová

    2016-02-01

    Full Text Available Physical weathering of marble, widely used as a cladding material on buildings, is one of the most common damaging mechanism caused by anisotropic thermal expansion of calcite grains. The extent of marble deterioration depends mainly on stone fabric and texture. Dry cuboids of Carrara marble and marble from Dolni Morava quarry were subjected to microscopic analysis and thermal cycling, to determine the thermal expansion related to stone fabric and predominant lattice orientation of grains (i.e. texture.

  14. An allele associated with a non-detectable amount of alpha s2 casein in goat milk.

    Science.gov (United States)

    Ramunno, L; Longobardi, E; Pappalardo, M; Rando, A; Di Gregorio, P; Cosenza, G; Mariani, P; Pastore, N; Masina, P

    2001-02-01

    The goat CSN1S2 locus is characterized by the presence of three alleles, A, B and C, all associated with about 2.5 g/l of protein per allele. The SDS-PAGE analysis of 441 individual milk samples obtained from goats belonging to a population reared in Southern Italy showed that the milk produced by three goats did not apparently contain alpha s2-casein, whereas milk produced by 37 goats showed a less intense electrophoretic band of this casein fraction (about 50%). These results can be explained by hypothesizing the presence of another allele at this locus, CSN1S2o, associated with a 'null' content of alpha s2-casein. Southern blot, PCR and PCR-RFLP analyses of the DNA region containing the CSN1S2 gene of individuals producing milk with and without alpha s2-casein did not show differences between the two groups. As a consequence, goats producing milk without alpha s2-casein carry an apparently intact gene. The first results obtained by sequencing part of the CSN1S2o allele revealed a G-->A transition at nucleotide 80 of the 11th exon which creates a stop codon and could be responsible for the absence of the alpha s2-casein in goat milk. This mutation eliminates a NcoI restriction site. A test based on this polymorphism has been established in order to identify carriers of the CSN1S2o allele.

  15. Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

    Science.gov (United States)

    Turnbull, Matthew L; Wise, Helen M; Nicol, Marlynne Q; Smith, Nikki; Dunfee, Rebecca L; Beard, Philippa M; Jagger, Brett W; Ligertwood, Yvonne; Hardisty, Gareth R; Xiao, Haixia; Benton, Donald J; Coburn, Alice M; Paulo, Joao A; Gygi, Steven P; McCauley, John W; Taubenberger, Jeffery K; Lycett, Samantha J; Weekes, Michael P; Dutia, Bernadette M; Digard, Paul

    2016-10-15

    Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia transmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses. Influenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a great socioeconomic

  16. The role of isohydric and anisohydric species in determining ecosystem-scale response to severe drought.

    Science.gov (United States)

    Roman, D T; Novick, K A; Brzostek, E R; Dragoni, D; Rahman, F; Phillips, R P

    2015-11-01

    Ongoing shifts in the species composition of Eastern US forests necessitate the development of frameworks to explore how species-specific water-use strategies influence ecosystem-scale carbon (C) cycling during drought. Here, we develop a diagnostic framework to classify plant drought-response strategies along a continuum of isohydric to anisohydric regulation of leaf water potential (Ψ(L)). The framework is applied to a 3-year record of weekly leaf-level gas exchange and Ψ measurements collected in the Morgan-Monroe State Forest (Indiana, USA), where continuous observations of the net ecosystem exchange of CO2 (NEE) have been ongoing since 1999. A severe drought that occurred in the middle of the study period reduced the absolute magnitude of NEE by 55%, though species-specific responses to drought conditions varied. Oak species were characterized by anisohydric regulation of Ψ(L) that promoted static gas exchange throughout the study period. In contrast, Ψ(L) of the other canopy dominant species was more isohydric, which limited gas exchange during the drought. Ecosystem-scale estimates of NEE and gross ecosystem productivity derived by upscaling the leaf-level data agreed well with tower-based observations, and highlight how the fraction of isohydric and anisohydric species in forests can mediate net ecosystem C balance.

  17. Water quality changes in response to urban expansion: spatially varying relations and determinants.

    Science.gov (United States)

    Zhao, Wenjun; Zhu, Xiaodong; Sun, Xiang; Shu, Yunqiao; Li, Yangfan

    2015-11-01

    Urban expansion is an important stressor to water bodies, and the spatial variations of their relations are increasingly highlighted by recent studies. What remain unclear, however, are the underlying drivers to the spatial variability. The paper was not limited to modeling spatially varying linkages but also drew attention to the local anthropogenic influential factors that shape land-water relations. We employed geographically weighted regression to examine the relationships between urban expansion (measured by land use change intensity) and water quality changes (focusing on six water quality indicators) in a recently fast-growing Chinese city, Lianyungang. Specifically, we analyzed how the local characteristics including urbanization level, environmental management, industrial zone expansion, and land use composition, attributed to the varying responses of water quality changes. Results showed that urbanization level significantly affects land-water linkages. Remarkable water quality improvement was accompanied by urbanization in highly developed watersheds, primarily due to strong influence from extensive water management practices (particularly for COD, BOD, NH3-N, and TP). By contrast, water qualities of less-urbanized watersheds were more sensitive and negatively responsive to land use changes. Clustering industrial activities acted as distinct contributor to Hg contamination, while boosted organic pollution control in highly urbanized areas. The approach proposed in the study can locate and further zoom into the hot-spots of human-water interactions, thereby contributing to better solutions for mitigating undesirable impacts of urbanization on water environment.

  18. Virulence Attributes and Host Response Assays for Determining Pathogenic Potential of Pseudomonas Strains Used in Biotechnology.

    Directory of Open Access Journals (Sweden)

    Azam F Tayabali

    Full Text Available Pseudomonas species are opportunistically pathogenic to humans, yet closely related species are used in biotechnology applications. In order to screen for the pathogenic potential of strains considered for biotechnology applications, several Pseudomonas strains (P.aeruginosa (Pa, P.fluorescens (Pf, P.putida (Pp, P.stutzeri (Ps were compared using functional virulence and toxicity assays. Most Pa strains and Ps grew at temperatures between 28°C and 42°C. However, Pf and Pp strains were the most antibiotic resistant, with ciprofloxacin and colistin being the most effective of those tested. No strain was haemolytic on sheep blood agar. Almost all Pa, but not other test strains, produced a pyocyanin-like chromophore, and caused cytotoxicity towards cultured human HT29 cells. Murine endotracheal exposures indicated that the laboratory reference strain, PAO1, was most persistent in the lungs. Only Pa strains induced pro-inflammatory and inflammatory responses, as measured by elevated cytokines and pulmonary Gr-1 -positive cells. Serum amyloid A was elevated at ≥ 48 h post-exposure by only some Pa strains. No relationship was observed between strains and levels of peripheral leukocytes. The species designation or isolation source may not accurately reflect pathogenic potential, since the clinical strain Pa10752 was relatively nonvirulent, but the industrial strain Pa31480 showed comparable virulence to PAO1. Functional assays involving microbial growth, cytotoxicity and murine immunological responses may be most useful for identifying problematic Pseudomonas strains being considered for biotechnology applications.

  19. Virulence Attributes and Host Response Assays for Determining Pathogenic Potential of Pseudomonas Strains Used in Biotechnology

    Science.gov (United States)

    Tayabali, Azam F.; Coleman, Gordon; Nguyen, Kathy C.

    2015-01-01

    Pseudomonas species are opportunistically pathogenic to humans, yet closely related species are used in biotechnology applications. In order to screen for the pathogenic potential of strains considered for biotechnology applications, several Pseudomonas strains (P.aeruginosa (Pa), P.fluorescens (Pf), P.putida (Pp), P.stutzeri (Ps)) were compared using functional virulence and toxicity assays. Most Pa strains and Ps grew at temperatures between 28°C and 42°C. However, Pf and Pp strains were the most antibiotic resistant, with ciprofloxacin and colistin being the most effective of those tested. No strain was haemolytic on sheep blood agar. Almost all Pa, but not other test strains, produced a pyocyanin-like chromophore, and caused cytotoxicity towards cultured human HT29 cells. Murine endotracheal exposures indicated that the laboratory reference strain, PAO1, was most persistent in the lungs. Only Pa strains induced pro-inflammatory and inflammatory responses, as measured by elevated cytokines and pulmonary Gr-1 -positive cells. Serum amyloid A was elevated at ≥ 48 h post-exposure by only some Pa strains. No relationship was observed between strains and levels of peripheral leukocytes. The species designation or isolation source may not accurately reflect pathogenic potential, since the clinical strain Pa10752 was relatively nonvirulent, but the industrial strain Pa31480 showed comparable virulence to PAO1. Functional assays involving microbial growth, cytotoxicity and murine immunological responses may be most useful for identifying problematic Pseudomonas strains being considered for biotechnology applications. PMID:26619347

  20. Mitogen-activated protein kinase (MAPK) dynamics determine cell fate in the yeast mating response.

    Science.gov (United States)

    Li, Yang; Roberts, Julie; AkhavanAghdam, Zohreh; Hao, Nan

    2017-12-15

    In the yeast Saccharomyces cerevisiae , the exposure to mating pheromone activates a prototypic mitogen-activated protein kinase (MAPK) cascade and triggers a dose-dependent differentiation response. Whereas a high pheromone dose induces growth arrest and formation of a shmoo-like morphology in yeast cells, lower pheromone doses elicit elongated cell growth. Previous population-level analysis has revealed that the MAPK Fus3 plays an important role in mediating this differentiation switch. To further investigate how Fus3 controls the fate decision process at the single-cell level, we developed a specific translocation-based reporter for monitoring Fus3 activity in individual live cells. Using this reporter, we observed strikingly different dynamic patterns of Fus3 activation in single cells differentiated into distinct fates. Cells committed to growth arrest and shmoo formation exhibited sustained Fus3 activation. In contrast, most cells undergoing elongated growth showed either a delayed gradual increase or pulsatile dynamics of Fus3 activity. Furthermore, we found that chemically perturbing Fus3 dynamics with a specific inhibitor could effectively redirect the mating differentiation, confirming the causative role of Fus3 dynamics in driving cell fate decisions. MAPKs mediate proliferation and differentiation signals in mammals and are therapeutic targets in many cancers. Our results highlight the importance of MAPK dynamics in regulating single-cell responses and open up the possibility that MAPK signaling dynamics could be a pharmacological target in therapeutic interventions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Hemodynamic, catecholamine, vasomotor and vascular responses: Determinants of myocardial ischemia during mental stress.

    Science.gov (United States)

    Hammadah, Muhammad; Alkhoder, Ayman; Al Mheid, Ibhar; Wilmot, Kobina; Isakadze, Nino; Abdulhadi, Naser; Chou, Danielle; Obideen, Malik; O'Neal, Wesley T; Sullivan, Samaah; Tahhan, Ayman Samman; Kelli, Heval Mohamed; Ramadan, Ronnie; Pimple, Pratik; Sandesara, Pratik; Shah, Amit J; Ward, Laura; Ko, Yi-An; Sun, Yan; Uphoff, Irina; Pearce, Brad; Garcia, Ernest V; Kutner, Michael; Bremner, J Douglas; Esteves, Fabio; Sheps, David S; Raggi, Paolo; Vaccarino, Viola; Quyyumi, Arshed A

    2017-09-15

    Mental stress-induced myocardial ischemia (MSIMI) in patients with coronary artery disease (CAD) is associated with adverse cardiovascular outcomes. We aim to assess hemodynamic, neuro-hormonal, endothelial, vasomotor and vascular predictors of MSIMI. We subjected 660 patients with stable CAD to 99mTc sestamibi myocardial perfusion imaging at rest, with mental (speech task) and with conventional (exercise/pharmacological) stress. Endothelium-dependent flow-mediated dilation (FMD), microvascular reactivity [reactive hyperemia index (RHI)] and arterial stiffness [pulse wave velocity (PWV)] were measured at rest and 30-min after mental stress. The digital microvascular vasomotor response during mental stress was assessed using peripheral arterial tonometry (PAT). A total of 106(16.1%) patients had MSIMI. Mental stress was accompanied by significant increases in rate-pressure-product (heart rate x systolic blood pressure; RPP), epinephrine levels and PWV, and significant decreases in FMD and PAT ratio denoting microvascular constriction. In comparison to those with no MSIMI, patients with MSIMI had higher hemodynamic and digital vasoconstrictive responses (pmental stress can help predict subjects with CAD at greater risk of developing MSIMI. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Standard practice for determining relative image quality response of industrial radiographic imaging systems

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2007-01-01

    1.1 This standard provides a practice whereby industrial radiographic imaging systems may be comparatively assessed using the concept of relative image quality response (RIQR). The RIQR method presented within this practice is based upon the use of equivalent penetrameter sensitivity (EPS) described within Practice E 1025 and subsection 5.2 of this practice. Figure 1 illustrates a relative image quality indicator (RIQI) that has four different steel plaque thicknesses (.015, .010, .008, and .005 in.) sequentially positioned (from top to bottom) on a ¾-in. thick steel plate. The four plaques contain a total of 14 different arrays of penetrameter-type hole sizes designed to render varied conditions of threshold visibility ranging from 1.92 % EPS (at the top) to .94 % EPS (at the bottom) when exposed to nominal 200 keV X-ray radiation. Each “EPS” array consists of 30 identical holes; thus, providing the user with a quantity of threshold sensitivity levels suitable for relative image qualitative response com...

  3. Single isolated hadron response and determination of the jet energy scale uncertainty with the ATLAS detector

    CERN Document Server

    Vivarelli, I; The ATLAS collaboration

    2010-01-01

    The response of single isolated hadrons in the ATLAS calorimeter is measured in proton-proton collisions at a centre-of-mass energy of 7 TeV at the LHC. Isolated tracks with a momentum between 0.5 to 10-20 GeV are selected in the rapidity region up to 2.3. Adjacent energy deposits collected in calorimeter clusters are summed together in a cone of size R=0.2. The measured calorimeter cluster energy sum is compared to the track momentum. Data are in compared in detail to Monte Carlo simulation based on the Geant4 tool-kit and to test-beam measurements. The response to hadrons at low momenta is described by the Monte Carlo simulation with an accuracy of a few percent. Together with test-beam data the results of the single isolated hadron analysis can be used to get a first estimate of the jet energy scale uncertainty in the ATLAS detector.

  4. IBC CARe microarray allelic population prevalences in an American Indian population.

    Directory of Open Access Journals (Sweden)

    Lyle G Best

    Full Text Available BACKGROUND: The prevalence of variant alleles among single nucleotide polymorphisms (SNPs is not well known for many minority populations. These population allele frequencies (PAFs are necessary to guide genetic epidemiology studies and to understand the population specific contribution of these variants to disease risk. Large differences in PAF among certain functional groups of genes could also indicate possible selection pressure or founder effects of interest. The 50K SNP, custom genotyping microarray (CARe was developed, focusing on about 2,000 candidate genes and pathways with demonstrated pathophysiologic influence on cardiovascular disease (CVD. METHODS: The CARe microarray was used to genotype 216 unaffected controls in a study of pre-eclampsia among a Northern Plains, American Indian tribe. The allelic prevalences of 34,240 SNPs suitable for analysis, were determined and compared with corresponding HapMap prevalences for the Caucasian population. Further analysis was conducted to compare the frequency of statistically different prevalences among functionally related SNPs, as determined by the DAVID Bioinformatics Resource. RESULTS: Of the SNPs with PAFs in both datasets, 9.8%,37.2% and 47.1% showed allele frequencies among the American Indian population greater than, less than and either greater or less than (respectively the HapMap Caucasian population. The 2,547 genes were divided into 53 functional groups using the highest stringency criteria. While none of these groups reached the Bonferroni corrected p value of 0.00094, there were 7 of these 53 groups with significantly more or less differing PAFs, each with a probability of less than 0.05 and an overall probability of 0.0046. CONCLUSION: In comparison to the HapMap Caucasian population, there are substantial differences in the prevalence among an American Indian community of SNPs related to CVD. Certain functional groups of genes and related SNPs show possible evidence of

  5. First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele.

    Science.gov (United States)

    O'Brien, Travis J; Kidd, Robert S; Richard, Craig A H; Ha, Ngoc-Han; Witcher, Preston; Tran, Linda V; Barbour, April; Tuck, Matthew; McIntosh, Samantha D; Douglas, Jacqueline N; Harralson, Arthur F

    2013-09-23

    Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4±7.94 mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2±12.65 mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Unique Clones of Vibrio cholerae O1 El Tor with Haitian Type ctxB Allele Implicated in the Recent Cholera Epidemics from Nigeria, Africa.

    Science.gov (United States)

    Adewale, Akinsinde Kehinde; Pazhani, Gururaja Perumal; Abiodun, Iwalokun Bamidele; Afolabi, Oluwadun; Kolawole, Olukoya Daniel; Mukhopadhyay, Asish K; Ramamurthy, Thanadarayan

    2016-01-01

    The antimicrobial susceptibility patterns and genetic characteristics of Vibrio cholerae O1, which is responsible for several cholera epidemics in Nigeria, are not reported in detail since 2007. In this study, we screened V. cholerae O1 El Tor biotype isolates from cholera cases and water samples from different states to investigate their phenotypic and genetic attributes with special reference to their clonality. All the V. cholerae O1 biotype El Tor isolates isolated during 2007-2013 were susceptible to fluoroquinolones and tetracycline, the drugs currently used in the treatment of cholera cases in Nigeria. Emergence of CT genotype 7 (Haitian type of ctxB allele) was predominantly seen among Ogawa serotype and the CT genotype 1 (classical ctxB allele) was mostly found in Inaba serotype. Overall, V. cholerae O1 from clinical and water samples were found to be closely related as determined by the pulsed-field gel electrophoresis. V. cholerae isolates from Abia, Kano and Bauchi were found to be genetically distinct from the other states of Nigeria. Fecal contamination of the water sources may be the possible source of the cholera infection. Combined prevalence of Haitian and classical ctxB alleles were detected in Ogawa and Inaba serotypes, respectively. This study further demonstrated that V. cholerae O1 with the ctxB has been emerged similar to the isolates reported in Haiti. Our findings suggest that the use of fluoroquinolones or tetracycline/doxycycline may help in the effective management of acute cholera in the affected Nigerian states. In addition, strengthening the existing surveillance in the hospitals of all the states and supply of clean drinking water may control cholera outbreaks in the future.

  7. Chromatin Configuration Determines Cell Responses to Hormone Stimuli | Center for Cancer Research

    Science.gov (United States)

    Ever since selective gene expression was established as the central driver of cell behavior, researchers have been working to understand the forces that control gene transcription. Aberrant gene expression can cause or promote many diseases, including cancer, and alterations in gene expression are the goal of many therapeutic agents. Recent work has focused on the potential role of chromatin structure as a contributor to gene regulation. Chromatin can exist in a tightly packed/inaccessible or loose/accessible configuration depending on the interactions between DNA and its associated proteins. Patterns of chromatin structure can differ between cell types and can also change within cells in response to certain signals. Cancer researchers are particularly interested in the role of chromatin in gene regulation because many of the genomic regions found to be associated with cancer risk are in open chromatin structures.

  8. The severity of airways obstruction as a determinant of treatment response in COPD

    DEFF Research Database (Denmark)

    Calverley, Peter Ma; Pauwels, Romain A; Jones, Paul W

    2006-01-01

    Abstract: Guidelines recommend that patients with COPD are stratified arbitrarily by baseline severity (FEV1) to decide when to initiate combination treatment with a long-acting ß2-agonist and an inhaled corticosteroid. Assessment of baseline FEV1 as a continuous variable may provide a more...... reliable prediction of treatment effects. Patients from a 1-year, parallel-group, randomized controlled trial comparing 50 µg salmeterol (Sal), 500 µg fluticasone propionate (FP), the combination (Sal/FP) and placebo, (bid), were categorized post hoc into FEV1 .../513 respectively). Treatment effects on clinical outcomes - lung function, exacerbations, health status, diary card symptoms, and adverse events - were investigated. Treatment responses based on a pre-specified analysis explored treatment differences by severity as a continuous variable. Lung function improved...

  9. Physiological responses and characteristics of table tennis matches determined in official tournaments.

    Science.gov (United States)

    Zagatto, Alessandro M; Morel, Erika A; Gobatto, Claudio A

    2010-04-01

    The purpose of this study was to verify the physiological responses and the match characteristics of table tennis and also to compare these responses in 2 different performance-level athletes from official tournaments. Twenty male table tennis players (12 regional experience-RP and 8 national and international experience-NP) were participants in the study. Blood lactate concentration ([LAC]) and heart rate (HR) were measured as physiological parameters in 21 official table tennis matches, and other 12 matches had recorded the duration of rally (DR), rest time, effort and rest ratio (E:R), total playing time (TPT), effective playing time (EPT), and frequency of shots by video analyses. The [LAC] verified in all matches was 1.8 mmol.L (+/-0.8), whereas the [LAC] peak was 2.2 mmol.L (+/-0.8). There were no significant differences between the 2 groups (p > 0.05) in both parameters. The HR was 164 b.min (+/-14), corresponding to 81.2% (+/-7.4) of the predicted maximum HR. As characteristics of the matches, the DR corresponded to 3.4 seconds (+/-1.7), rest time to 8.1 seconds (+/-5.1), E:R to 0.4 (+/-0.2), TPT to 970.5 seconds (+/-336.1), EPT to 44.3% (+/-23.7), and frequency of shots to 35.3 balls.min (+/-7.7). Among groups, the rest time was lower in RP than in NP. Consistently, the E:R and EPT were higher in RP than in NP (p table tennis matches present the aerobic system as a principal output energy, the phosphagenic system being the most important during efforts. The information pertaining to the physiological profile and the characteristics of table tennis should be used by coaches planning physical training and specific exercise prescriptions aiming at achieving maximal sport performance.

  10. Using temporal coherence to determine the response to climate change in Boreal Shield lakes.

    Science.gov (United States)

    Arnott, Shelley E; Keller, Bill; Dillon, Peter J; Yan, Norman; Paterson, Michael; Findlay, David

    2003-01-01

    Climate change is expected to have important impacts on aquatic ecosystems. On the Boreal Shield, mean annual air temperatures are expected to increase 2 to 4 degrees C over the next 50 years. An important challenge is to predict how changes in climate and climate variability will impact natural systems so that sustainable management policies can be implemented. To predict responses to complex ecosystem changes associated with climate change, we used long-term biotic databases to evaluate how important elements of the biota in Boreal Shield lakes have responded to past fluctuations in climate. Our long-term records span a two decade period where there have been unusually cold years and unusually warm years. We used coherence analyses to test for regionally operating controls on climate, water temperature, pH, and plankton richness and abundance in three regions across Ontario: the Experimental Lakes Area, Sudbury, and Dorset. Inter-annual variation in air temperature was similar among regions, but there was a weak relationship among regions for precipitation. While air temperature was closely related to lake surface temperatures in each of the regions, there were weak relationships between lake surface temperature and richness or abundance of the plankton. However, inter-annual changes in lake chemistry (i.e., pH) were correlated with some biotic variables. In some lakes in Sudbury and Dorset, pH was dependent on extreme events. For example, El Nino related droughts resulted in acidification pulses in some lakes that influenced phytoplankton and zooplankton richness. These results suggest that there can be strong heterogeneity in lake ecosystem responses within and across regions.

  11. Application of response surface methodology for determination of methyl red in water samples by spectrophotometry method.

    Science.gov (United States)

    Khodadoust, Saeid; Ghaedi, Mehrorang

    2014-12-10

    In this study a rapid and effective method (dispersive liquid-liquid microextraction (DLLME)) was developed for extraction of methyl red (MR) prior to its determination by UV-Vis spectrophotometry. Influence variables on DLLME such as volume of chloroform (as extractant solvent) and methanol (as dispersive solvent), pH and ionic strength and extraction time were investigated. Then significant variables were optimized by using a Box-Behnken design (BBD) and desirability function (DF). The optimized conditions (100μL of chloroform, 1.3mL of ethanol, pH 4 and 4% (w/v) NaCl) resulted in a linear calibration graph in the range of 0.015-10.0mgmL(-1) of MR in initial solution with R(2)=0.995 (n=5). The limits of detection (LOD) and limit of quantification (LOQ) were 0.005 and 0.015mgmL(-1), respectively. Finally, the DLLME method was applied for determination of MR in different water samples with relative standard deviation (RSD) less than 5% (n=5). Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Application of response surface methodology for determination of methyl red in water samples by spectrophotometry method

    Science.gov (United States)

    Khodadoust, Saeid; Ghaedi, Mehrorang

    2014-12-01

    In this study a rapid and effective method (dispersive liquid-liquid microextraction (DLLME) was developed for extraction of methyl red (MR) prior to its determination by UV-Vis spectrophotometry. Influence variables on DLLME such as volume of chloroform (as extractant solvent) and methanol (as dispersive solvent), pH and ionic strength and extraction time were investigated. Then significant variables were optimized by using a Box-Behnken design (BBD) and desirability function (DF). The optimized conditions (100 μL of chloroform, 1.3 mL of ethanol, pH 4 and 4% (w/v) NaCl) resulted in a linear calibration graph in the range of 0.015-10.0 mg mL-1 of MR in initial solution with R2 = 0.995 (n = 5). The limits of detection (LOD) and limit of quantification (LOQ) were 0.005 and 0.015 mg mL-1, respectively. Finally, the DLLME method was applied for determination of MR in different water samples with relative standard deviation (RSD) less than 5% (n = 5).

  13. Type I plasminogen activator inhibitor 4G allele frequency is associated with chronic venous insufficiency.

    Science.gov (United States)

    Katrancioglu, N; Manduz, S; Ozen, F; Yilmaz, M Birhan; Karahan, O; Ozdemir, O; Berkan, O

    2010-01-01

    Chronic venous insufficiency (CVI) is a common disease associated with poor quality of life. Genetic polymorphisms causing coagulation abnormalities may account for some of the CVI pathogenesis. Type I plasminogen activator inhibitor (PAI-1) is responsible for fibrinolytic system regulation, and plasma levels of PAI-1 are strongly correlated with PAI-1 4G/5G gene polymorphism. The association between PAI-1 4G/5G gene polymorphism and CVI was investigated. In 34 consecutive patients with clinically overt CVI, the PAI-1 4G/4G polymorphism was detected in three cases (8.8%); the 4G/5G polymorphism was detected in 28 (82.4%). In 34 age- and sex-matched controls, the PAI-1 4G/4G polymorphism was detected in one case (2.9%) and the 4G/5G polymorphism was detected in 14 cases (41.2%). The PAI-1 4G allele was found significantly more frequently in CVI patients than in controls. The 4G allele was associated with a 3.25-fold increase in CVI risk. Thus, a relationship between CVI and the PAI-1 4G allele is apparent.

  14. Prevalence of Helicobacter pylori vacuolating cytotoxin and its allelic mosaicism as a predictive marker for Iranian dyspeptic patients

    DEFF Research Database (Denmark)

    Mohammadi, M; Oghalaie, A; Mohajerani, N

    2003-01-01

    can serve as screening markers for such a population, H. pylori strains were isolated from one hundred and thirty two dyspeptic patients. H. pylori genomic DNA was extracted and underwent PCR-amplification for the cytotoxin alleles. Genotyping of the signal sequence region of the vacA gene identified......Helicobacter pylori infects the majority of the population in the developing countries. However, the rate of gastrointestinal complications such as peptic ulcers and gastric malignancies has no parallel with the infection. In order to determine whether cytotoxin (vacA) and its allelic polymorphism...

  15. Prevalence of Helicobacter pylori vacuolating cytotoxin and its allelic mosaicism as a predictive marker for Iranian dyspeptic patients

    DEFF Research Database (Denmark)

    Mohammadi, M; Oghalaie, A; Mohajerani, N

    2003-01-01

    Helicobacter pylori infects the majority of the population in the developing countries. However, the rate of gastrointestinal complications such as peptic ulcers and gastric malignancies has no parallel with the infection. In order to determine whether cytotoxin (vacA) and its allelic polymorphism...... can serve as screening markers for such a population, H. pylori strains were isolated from one hundred and thirty two dyspeptic patients. H. pylori genomic DNA was extracted and underwent PCR-amplification for the cytotoxin alleles. Genotyping of the signal sequence region of the vacA gene identified...

  16. Deep resequencing reveals allelic variation in Sesamum indicum.

    Science.gov (United States)

    Wang, Linhai; Han, Xuelian; Zhang, Yanxin; Li, Donghua; Wei, Xin; Ding, Xia; Zhang, Xiurong

    2014-08-20

    Characterization of genome-wide patterns of allelic variation and linkage disequilibrium can be used to detect reliable phenotype-genotype associations and signatures of molecular selection. However, the use of Sesamum indicum germplasm for breeding is limited by the lack of polymorphism data. Here we describe the massively parallel resequencing of 29 sesame strains from 12 countries at a depth of ≥ 13-fold coverage for each of the samples tested. We detected an average of 127,347 SNPs, 17,961 small InDels, and 9,266 structural variants per sample. The population SNP rate, population diversity (π) and Watterson's estimator of segregating sites (θw) were estimated at 8.6 × 10⁻³, 2.5 × 10⁻³ and 3.0 × 10⁻³ bp⁻¹, respectively. Of these SNPs, 23.2% were located within coding regions. Polymorphism patterns were nonrandom among gene families, with genes mediating interactions with the biotic or abiotic environment exhibiting high levels of polymorphism. The linkage disequilibrium (LD) decay distance was estimated at 150 kb, with no distinct structure observed in the population. Phylogenetic relationships between each of the 29 sesame strains were consistent with the hypothesis of sesame originating on the Indian subcontinent. In addition, we proposed novel roles for adenylate isopentenyltransferase (ITP) genes in determining the number of flowers per leaf axil of sesame by mediating zeatin biosynthesis. This study represents the first report of genome-wide patterns of genetic variation in sesame. The high LD distance and abundant polymorphisms described here increase our understanding of the forces shaping population-wide sequence variation in sesame and will be a valuable resource for future gene-phenotype and genome-wide association studies (GWAS).

  17. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  18. Common breast cancer risk alleles and risk assessment

    DEFF Research Database (Denmark)

    Näslund-Koch, C; Nordestgaard, B G; Bojesen, S E

    2017-01-01

    mammography in Denmark, the average 5-year breast cancer risk was 1.5%, overall and 1.1%, 1.4%, 1.6%, 1.7%, 2.1%, for the 1(st) through 5(th) quintile, respectively. Based on age, nulliparity, familial history, and allele sum, 25% of women aged 50-69, and 94% of women aged 40-49, had absolute 5-year breast...... cancer risks ≤ 1.5%. Using polygenic risk score led to similar results. CONCLUSION: Common breast cancer risk alleles are associated with incidence and mortality of breast cancer in the general population, but not with other cancers. After including breast cancer allele sum in risk assessment, 25...

  19. Allele-sharing statistics using information on family history.

    Science.gov (United States)

    Callegaro, A; Meulenbelt, I; Kloppenburg, M; Slagboom, P E; Houwing-Duistermaat, J J

    2010-11-01

    When conducting genetic studies for complex traits, large samples are commonly required to detect new genetic factors. A possible strategy to decrease the sample size is to reduce heterogeneity using available information. In this paper we propose a new class of model-free linkage analysis statistics which takes into account the information given by the ungenotyped affected relatives (positive family history). This information is included into the scoring function of classical allele-sharing statistics. We studied pedigrees of affected sibling pairs with one ungenotyped affected relative. We show that, for rare allele common complex diseases, the proposed method increases the expected power to detect linkage. Allele-sharing methods were applied to the symptomatic osteoarthritis GARP study where taking into account the family-history increased considerably the evidence of linkage in the region of the DIO2 susceptibility locus. © 2010 The Authors Annals of Human Genetics © 2010 Blackwell Publishing Ltd/University College London.

  20. A study of the association of childhood asthma with HLA alleles in the population of Siliguri, West Bengal, India.

    Science.gov (United States)

    Lama, M; Chatterjee, M; Chaudhuri, T K

    2014-09-01

    Asthma is a heterogeneous disease for which a strong genetic basis is firmly established. It is a complex disorder influenced by gene-environment interaction. Human leukocyte antigen (HLA) genes have been shown to be consistently associated with asthma and its related phenotypes in various populations. The aim of this study was to determine the frequency of the selected HLA classes I and II allelic groups in asthmatic and control groups. HLA typing was performed using polymerase chain reaction-sequence-specific typing (PCR-SSP) method. The allele frequency was estimated by direct counting. Frequency of each HLA allelic group was compared between asthmatic group and control group using χ(2) test. P-value was corrected by multiplying with the number of the allelic groups studied. Odds ratio (OR) and its corresponding 95% confidence interval (CI) for each allelic group were calculated using graphpad instat 3.10. The results of this study showed a significantly higher frequency of HLA-DRB1*03 in asthmatics than in controls (11.43% vs 3.64%, OR = 3.78, 95% CI = 1.61-8.85, P = 0.0025, Pcorr  population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Determination of histone epigenetic marks in Arabidopsis and tomato genes in the early response to Botrytis cinerea.

    Science.gov (United States)

    Crespo-Salvador, Óscar; Escamilla-Aguilar, Mónica; López-Cruz, Jaime; López-Rodas, Gerardo; González-Bosch, Carmen

    2018-01-01

    Determination of histone epigenetic marks in Arabidopsis and tomato genes in the early response to Botrytis cinerea may contribute to find biomarkers of the early detection of this devastating pathogen. Recent studies have linked epigenetic modifications with plant responses to biotic stresses. Information about specific histone marks upon necrotrophic pathogens is scarce. Here we wondered whether the altered responsiveness of specific genes in plants infected with Botrytis cinerea was associated with changes in chromatin structure. We performed a chromatin immunoprecipitation analysis that obtained differential epigenetic signature of activating marks H3K4me3, H3K9ac, and the repressor one H3K27me3 on both the promoter and the body of the highly induced PR1 in Arabidopsis plants infected with B. cinerea at 24 and 33 h after inoculation. We also determined the histone marks' profile in two differentially expressed genes in response to B. cinerea, as well as to oxidative stress, given its relevance in this infection. These are both the induced CYP71A13, which encodes a cytochrome P450 involved in camalexin synthesis, and is essential against this necrotroph and the repressed EXL7 (Exordium-like 1). We also adapted our protocol in tomato plants infected with B. cinerea. At 24 hpi, H3K4me3 level increased on the promoter and at different locations of the body of the genes induced upon B. cinerea, including DES (divinyl ethyl synthase), LoxD (lipoxygenase D), DOX1 (α-dioxygenase 1), PR2 (pathogenesis-related protein2), WRKY53 and WRKY33. The histone modifications determined herein will allow future studies on epigenetic marks and their transgenerational inheritance in plants infected with B. cinerea. In addition, the analyzed genes are potential biomarkers of B. cinerea infection that could contribute to its early detection in tomato and related crops.

  2. An update on HLA alleles associated with adverse drug reactions.

    Science.gov (United States)

    Fricke-Galindo, Ingrid; LLerena, Adrián; López-López, Marisol

    2017-05-24

    Adverse drug reactions (ADRs) are considered as an important cause of morbidity and mortality. The hypersensitivity reactions are immune-mediated ADRs, which are dose-independent, unpredictable and have been associated with several HLA alleles. The present review aimed to describe HLA alleles that have been associated with different ADRs in populations worldwide, the recommendations of regulatory agencies and pharmacoeconomic information and databases for the study of HLA alleles in pharmacogenetics. A systematic search was performed in June 2016 of articles relevant to this issue in indexed journals and in scientific databases (PubMed and PharmGKB). The information of 95 association studies found was summarized. Several HLA alleles and haplotypes have been associated with ADRs induced mainly by carbamazepine, allopurinol, abacavir and nevirapine, among other drugs. Years with the highest numbers of publications were 2013 and 2014. The majority of the reports have been performed on Asians and Caucasians, and carbamazepine was the most studied ADR drug inducer. Two HLA alleles' databases are described, as well as the recommendations of the U.S. Food and Drug Administration, the European Medicine Agency and the Clinical Pharmacogenetics Implementation Consortium. Pharmacoeconomic studies on this issue are also mentioned. The strongest associations remain for HLA-B*58:01, HLA-B*57:01, HLA-B*15:02 and HLA-A*31:01 but only in certain populations; therefore, studies on different ethnic groups would be useful. Due to the improvement of drug therapy and the economic benefit that HLA screening represents, investigations on HLA alleles associated with ADR should continue.

  3. Reduced Height (Rht) Alleles Affect Wheat Grain Quality.

    Science.gov (United States)

    Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

    2016-01-01

    The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (Pdirect pleiotropic effect of GA-insensitivity, rather than an effect consequential to yield and/or height.

  4. The Use of Critical Levels for Determining Plant Response to Ozone in Europe and in North America

    Directory of Open Access Journals (Sweden)

    Robert C. Musselman

    2007-01-01

    Full Text Available Critical levels to determine plant response to ozone (O3 have been used in Europe since the 1980s, utilizing the concentration-based AOT40 to relate plant response to ambient O3 exposure. More recently, there has been progress in Europe toward utilizing flux-based critical levels, because plant response is more closely related to O3 uptake than to the amount of O3 in ambient air. Flux-based critical levels are plant species specific; data for parameterization of flux-based critical levels models are lacking for most plant species. Although flux-based critical levels are now being used for a limited number of agricultural crops and tree species where data are available, the use of flux-based critical levels is limited by the lack of adequate consideration and incorporation of plant internal detoxification mechanisms in flux modeling. Critical levels have not been used in North America; however, recent interest in the U.S. and Canada for using critical loads for nitrogen and sulfur has generated interest in using critical levels for O3. A major obstacle for utilization of critical levels in North America is that ambient air quality standards for O3 in the U.S. and Canada are concentration based. It appears that cumulative exposure-based metrics, particularly when implemented with a quantification of peak concentrations and environmental variables, such as a drought index, are currently the most useful to relate O3 to vegetation response. Because data are unavailable to quantify detoxification potential of vegetation, effective flux models are not available to determine plant response to O3.

  5. Molecular genetic analysis of the Jk(a-b-) phenotype in Chinese: A novel silent recessive JK allele.

    Science.gov (United States)

    Zhang, Ai; Chi, Quan; Lin, Hongkeng; She, Yimin

    2016-04-01

    The Jk(a-b-) phenotype, referred to as Jknull, is rare in most populations. This blood type is characterized by the absence of Kidd glycoprotein on the surface of red blood cells (RBCs) and moderately reduced ability to concentrate urine. The molecular basis for Jknull phenotype includes splice-site mutations, missense mutations, and a partial gene deletion in the JK(SLC14A1) gene that encodes the human urea transporter protein. In this study, we have analyzed 10 Chinese Jknull samples to determine their molecular bases. In addition to the well known Polynesian Jknull allele, three Jknull alleles were detected including one novel Jknull allele: JKA (130A, 220G). Copyright © 2016. Published by Elsevier Ltd.

  6. Simultaneous inference of haplotypes and alleles at a causal gene

    Directory of Open Access Journals (Sweden)

    Fabrice eLarribe

    2015-10-01

    Full Text Available We present a new methodology which jointly infers haplotypes and the causal alleles at a gene influencing a given trait. Often in human genetic studies, the available data consists of genotypes (series of genetic markers along the chromosomes and a phenotype. However, for many genetic analyses, one needs haplotypes instead of genotypes. Our methodology is not only able to estimate haplotypes conditionally on the disease status, but is also able to infer the alleles at the unknown disease locus. Some applications of our methodology are in genetic mapping and in genetic counselling.

  7. A common allele on chromosome 9 associated with coronary heartdisease

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R.; Hinds, David; Pennachio, Len; Tybjaerg-Hansen, Anne; Folsom, Aaron R.; Boerwinkle,Eric; Hobbs, Helen H.; Cohen, Jonathan C.

    2007-03-01

    Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

  8. Reduced Height (Rht Alleles Affect Wheat Grain Quality.

    Directory of Open Access Journals (Sweden)

    Richard Casebow

    Full Text Available The effects of dwarfing alleles (reduced height, Rht in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c as well as those that retained GA-sensitivity (rht(tall, Rht8, Rht8 + Ppd-D1a, Rht12. Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05 reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there

  9. Trait variation within a species determines warming responses at different scales

    Energy Technology Data Exchange (ETDEWEB)

    Karve, Abhijit A [ORNL; Weston, David [ORNL; Souza, Lara [University of Tennessee, Knoxville (UTK); Classen, Aimee T [University of Tennessee, Knoxville (UTK)

    2011-01-01

    Plant species, and the traits associated with them, can help buffer ecosystems to environmental perturbations. Few studies have examined whether within species variation, both among and within populations, can similarly buffer ecosystems to environmental perturbations, such as climatic warming, across levels of organization. Using a dominant plant species in the eastern US, Solidago altissima, we examined whether genotypes of the same species from both southern and northern latitude populations exhibited differential short-term responses to temperature at the cell, leaf, and plant level. At the cell level we quantified the production of reactive oxygen species (by-product of temperature stress) and total oxygen radical antioxidant capacity (which ameliorates temperature stress by-products). At the leaf and plant levels, we measured CO2 assimilation. Increasing temperatures had strong negative impacts on plant-level carbon gain, but weak impacts on cell-level antioxidant capacity. Southern latitude genotypes had greater total antioxidant capacity, but lower leaf-level carbon gain, than did northern genotypes under elevated temperature. At the plant level, northern and southern genotypes exhibited similar declines in carbon gain under elevated temperature, likely because total plant leaf area was higher for southern genotypes than northern genotypes, which compensated for their lower per unit area leaf-level carbon gain. Overall, short-term temperature-induced declines in carbon gain at the plant level may scale to reduce within species variation, both across and within populations, potentially altering ecosystem carbon cycling.

  10. Developmental stage of oligodendrocytes determines their response to activated microglia in vitro

    Directory of Open Access Journals (Sweden)

    Bresnahan Jacqueline C

    2007-11-01

    Full Text Available Abstract Background Oligodendrocyte progenitor cells (OPCs and mature oligodendrocytes are both lost in central nervous system injury and disease. Activated microglia may play a role in OPC and oligodendrocyte loss or replacement, but it is not clear how the responses of OPCs and oligodendrocytes to activated microglia differ. Methods OPCs and microglia were isolated from rat cortex. OPCs were induced to differentiate into oligodendrocytes with thyroid hormone in defined medium. For selected experiments, microglia were added to OPC or oligodendrocyte cultures. Lipopolysaccharide was used to activate microglia and microglial activation was confirmed by TNFα ELISA. Cell survival was assessed with immunocytochemistry and cell counts. OPC proliferation and oligodendrocyte apoptosis were also assessed. Results OPCs and oligodendrocytes displayed phenotypes representative of immature and mature oligodendrocytes, respectively. Activated microglia reduced OPC survival, but increased survival and reduced apoptosis of mature oligodendrocytes. Activated microglia also underwent cell death themselves. Conclusion Activated microglia may have divergent effects on OPCs and mature oligodendrocytes, reducing OPC survival and increasing mature oligodendrocyte survival. This may be of importance because activated microglia are present in several disease states where both OPCs and mature oligodendrocytes are also reacting to injury. Activated microglia may simultaneously have deleterious and helpful effects on different cells after central nervous system injury.

  11. BCG-mediated bladder cancer immunotherapy: identifying determinants of treatment response using a calibrated mathematical model.

    Directory of Open Access Journals (Sweden)

    Cyrill A Rentsch

    Full Text Available Intravesical Bacillus Calmette Guérin (BCG immunotherapy is considered the standard of care for treatment of non-muscle invasive bladder cancer; however the treatment parameters were established empirically. In order to evaluate potential optimization of clinical parameters of BCG induction therapy, we constructed and queried a new mathematical model. Specifically, we assessed the impact of (1 duration between resection and the first instillation; (2 BCG dose; (3 indwelling time; and (4 treatment interval of induction therapy - using cure rate as the primary endpoint. Based on available clinical and in vitro experimental data, we constructed and parameterized a stochastic mathematical model describing the interactions between BCG, the immune system, the bladder mucosa and tumor cells. The primary endpoint of the model was the probability of tumor extinction following BCG induction therapy in patients with high risk for tumor recurrence. We theoretically demonstrate that extending the duration between the resection and the first BCG instillation negatively influences treatment outcome. Simulations of higher BCG doses and longer indwelling times both improved the probability of tumor extinction. A remarkable finding was that an inter-instillation interval two times longer than the seven-day interval used in the current standard of care would substantially improve treatment outcome. We provide insight into relevant clinical questions using a novel mathematical model of BCG immunotherapy. Our model predicts an altered regimen that may decrease side effects of treatment while improving response to therapy.

  12. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

    2014-01-01

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  13. Multinomial Response Models, for Modeling and Determining Important Factors in Different Contraceptive Methods in Women

    Directory of Open Access Journals (Sweden)

    E Haji Nejad

    2001-06-01

    Full Text Available Difference aspects of multinomial statistical modelings and its classifications has been studied so far. In these type of problems Y is the qualitative random variable with T possible states which are considered as classifications. The goal is prediction of Y based on a random Vector X ? IR^m. Many methods for analyzing these problems were considered. One of the modern and general method of classification is Classification and Regression Trees (CART. Another method is recursive partitioning techniques which has a strange relationship with nonparametric regression. Classical discriminant analysis is a standard method for analyzing these type of data. Flexible discriminant analysis method which is a combination of nonparametric regression and discriminant analysis and classification using spline that includes least square regression and additive cubic splines. Neural network is an advanced statistical method for analyzing these types of data. In this paper properties of multinomial logistics regression were investigated and this method was used for modeling effective factors in selecting contraceptive methods in Ghom province for married women age 15-49. The response variable has a tetranomial distibution. The levels of this variable are: nothing, pills, traditional and a collection of other contraceptive methods. A collection of significant independent variables were: place, age of women, education, history of pregnancy and family size. Menstruation age and age at marriage were not statistically significant.

  14. Molecular responses of genetically modified maize to abiotic stresses as determined through proteomic and metabolomic analyses.

    Directory of Open Access Journals (Sweden)

    Rafael Fonseca Benevenuto

    Full Text Available Some genetically modified (GM plants have transgenes that confer tolerance to abiotic stressors. Meanwhile, other transgenes may interact with abiotic stressors, causing pleiotropic effects that will affect the plant physiology. Thus, physiological alteration might have an impact on the product safety. However, routine risk assessment (RA analyses do not evaluate the response of GM plants exposed to different environmental conditions. Therefore, we here present a proteome profile of herbicide-tolerant maize, including the levels of phytohormones and related compounds, compared to its near-isogenic non-GM variety under drought and herbicide stresses. Twenty differentially abundant proteins were detected between GM and non-GM hybrids under different water deficiency conditions and herbicide sprays. Pathway enrichment analysis showed that most of these proteins are assigned to energetic/carbohydrate metabolic processes. Among phytohormones and related compounds, different levels of ABA, CA, JA, MeJA and SA were detected in the maize varieties and stress conditions analysed. In pathway and proteome analyses, environment was found to be the major source of variation followed by the genetic transformation factor. Nonetheless, differences were detected in the levels of JA, MeJA and CA and in the abundance of 11 proteins when comparing the GM plant and its non-GM near-isogenic variety under the same environmental conditions. Thus, these findings do support molecular studies in GM plants Risk Assessment analyses.

  15. The lancet weight determines wheal diameter in response to skin prick testing with histamine

    DEFF Research Database (Denmark)

    Andersen, Hjalte Holm; Lundgaard, Anna Charlotte; Sohrt Petersen, Anne

    2016-01-01

    BACKGROUND: Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in suboptimal diagnosis of sensitization. OBJECTIVE: Although not previously assessed qualitativ......BACKGROUND: Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in suboptimal diagnosis of sensitization. OBJECTIVE: Although not previously assessed...... qualitatively, lancet weight is hypothesized to be important when performing SPT to minimize the frequency of false positives, false negatives, and unwanted discomfort. METHODS: Accurate weight-controlled SPT was performed on the volar forearms and backs of 20 healthy subjects. Four predetermined lancet weights...... of bleeding, and the lancet provoked pain response. RESULTS: The mean wheal diameter increased significantly as higher weights were applied to the SPT lancet, e.g. from 3.2 ± 0.28 mm at 25 g to 5.4 ± 1.7 mm at 265 g (p

  16. The diagnostic utility of sonographic carotid flow time in determining volume responsiveness.

    Science.gov (United States)

    Shokoohi, Hamid; Berry, Grant W; Shahkolahi, Murteza; King, Jackson; King, Jordan; Salimian, Mohammad; Poshtmashad, Ameneh; Pourmand, Ali

    2017-04-01

    We aimed to predict volume responsiveness and to assess the diagnostic accuracy of carotid flow time (FTc) with the change in hydration status before and after a passive leg raise (PLR) maneuver. Participants who presented at a community health fair in a dehydrated state following a prolonged fast while observing the month of Ramadan were recruited. Sonographic FTc measurements were obtained in the semi-Fowler position and after a PLR maneuver while participants were in a fasting state and repeated approximately 3 hours after breaking their fast. In total, 123 participants with mean age of 47±14 years, 55% male, were enrolled. Participants had fasted for an average of 16.9 hours and consumed an average of 933 mL between the 2 ultrasound measurements. Mean FTc values were significantly lower in the fasting state compared with the nonfasting state (312±22 vs 345±25milliseconds, P value change in FTc of ≥5% provides a reliable diagnostic accuracy for predicting fluid status. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Site specific seismic hazard analysis and determination of response spectra of Kolkata for maximum considered earthquake

    Science.gov (United States)

    Shiuly, Amit; Sahu, R. B.; Mandal, Saroj

    2017-06-01

    This paper presents site specific seismic hazard analysis of Kolkata city, former capital of India and present capital of state West Bengal, situated on the world’s largest delta island, Bengal basin. For this purpose, peak ground acceleration (PGA) for a maximum considered earthquake (MCE) at bedrock level has been estimated using an artificial neural network (ANN) based attenuation relationship developed on the basis of synthetic ground motion data for the region. Using the PGA corresponding to the MCE, a spectrum compatible acceleration time history at bedrock level has been generated by using a wavelet based computer program, WAVEGEN. This spectrum compatible time history at bedrock level has been converted to the same at surface level using SHAKE2000 for 144 borehole locations in the study region. Using the predicted values of PGA and PGV at the surface, corresponding contours for the region have been drawn. For the MCE, the PGA at bedrock level of Kolkata city has been obtained as 0.184 g, while that at the surface level varies from 0.22 g to 0.37 g. Finally, Kolkata has been subdivided into eight seismic subzones, and for each subzone a response spectrum equation has been derived using polynomial regression analysis. This will be very helpful for structural and geotechnical engineers to design safe and economical earthquake resistant structures.

  18. Placental responses to changes in the maternal environment determine fetal growth

    Directory of Open Access Journals (Sweden)

    Kris Genelyn eDimasuay

    2016-01-01

    Full Text Available Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus.

  19. Accurate Determination of the Frequency Response Function of Submerged and Confined Structures by Using PZT-Patches†.

    Science.gov (United States)

    Presas, Alexandre; Valentin, David; Egusquiza, Eduard; Valero, Carme; Egusquiza, Mònica; Bossio, Matias

    2017-03-22

    To accurately determine the dynamic response of a structure is of relevant interest in many engineering applications. Particularly, it is of paramount importance to determine the Frequency Response Function (FRF) for structures subjected to dynamic loads in order to avoid resonance and fatigue problems that can drastically reduce their useful life. One challenging case is the experimental determination of the FRF of submerged and confined structures, such as hydraulic turbines, which are greatly affected by dynamic problems as reported in many cases in the past. The utilization of classical and calibrated exciters such as instrumented hammers or shakers to determine the FRF in such structures can be very complex due to the confinement of the structure and because their use can disturb the boundary conditions affecting the experimental results. For such cases, Piezoelectric Patches (PZTs), which are very light, thin and small, could be a very good option. Nevertheless, the main drawback of these exciters is that the calibration as dynamic force transducers (relationship voltage/force) has not been successfully obtained in the past. Therefore, in this paper, a method to accurately determine the FRF of submerged and confined structures by using PZTs is developed and validated. The method consists of experimentally determining some characteristic parameters that define the FRF, with an uncalibrated PZT exciting the structure. These parameters, which have been experimentally determined, are then introduced in a validated numerical model of the tested structure. In this way, the FRF of the structure can be estimated with good accuracy. With respect to previous studies, where only the natural frequencies and mode shapes were considered, this paper discuss and experimentally proves the best excitation characteristic to obtain also the damping ratios and proposes a procedure to fully determine the FRF. The method proposed here has been validated for the structure vibrating

  20. Exploring models for the roles of health systems’ responsiveness and social determinants in explaining universal health coverage and health outcomes

    Directory of Open Access Journals (Sweden)

    Nicole Britt Valentine

    2016-03-01

    Full Text Available Background: Intersectoral perspectives of health are present in the rhetoric of the sustainable development goals. Yet its descriptions of systematic approaches for an intersectoral monitoring vision, joining determinants of health, and barriers or facilitators to accessing healthcare services are lacking. Objective: To explore models of associations between health outcomes and health service coverage, and health determinants and health systems responsiveness, and thereby to contribute to monitoring, analysis, and assessment approaches informed by an intersectoral vision of health. Design: The study is designed as a series of ecological, cross-country regression analyses, covering between 23 and 57 countries with dependent health variables concentrated on the years 2002–2003. Countries cover a range of development contexts. Health outcome and health service coverage dependent variables were derived from World Health Organization (WHO information sources. Predictor variables representing determinants are derived from the WHO and World Bank databases; variables used for health systems’ responsiveness are derived from the WHO World Health Survey. Responsiveness is a measure of acceptability of health services to the population, complementing financial health protection. Results: Health determinants’ indicators – access to improved drinking sources, accountability, and average years of schooling – were statistically significant in particular health outcome regressions. Statistically significant coefficients were more common for mortality rate regressions than for coverage rate regressions. Responsiveness was systematically associated with poorer health and health service coverage. With respect to levels of inequality in health, the indicator of responsiveness problems experienced by the unhealthy poor groups in the population was statistically significant for regressions on measles vaccination inequalities between rich and poor. For the

  1. Trivalent adenovirus type 5 HIV recombinant vaccine primes for modest cytotoxic capacity that is greatest in humans with protective HLA class I alleles.

    Directory of Open Access Journals (Sweden)

    Stephen A Migueles

    2011-02-01

    Full Text Available If future HIV vaccine design strategies are to succeed, improved understanding of the mechanisms underlying protection from infection or immune control over HIV replication remains essential. Increased cytotoxic capacity of HIV-specific CD8+ T-cells associated with efficient elimination of HIV-infected CD4+ T-cell targets has been shown to distinguish long-term nonprogressors (LTNP, patients with durable control over HIV replication, from those experiencing progressive disease. Here, measurements of granzyme B target cell activity and HIV-1-infected CD4+ T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5 HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP. We observed readily detectable HIV-specific CD8+ T-cell recall cytotoxic responses in vaccinees at a median of 331 days following the last immunization. The magnitude of these responses was not related to the number of vaccinations, nor did it correlate with the percentages of cytokine-secreting T-cells determined by ICS assays. Although the recall cytotoxic capacity of the CD8+ T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection. These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8+ T-cell cytotoxic responses.

  2. Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.

    Science.gov (United States)

    Stanescu, Horia C; Arcos-Burgos, Mauricio; Medlar, Alan; Bockenhauer, Detlef; Kottgen, Anna; Dragomirescu, Liviu; Voinescu, Catalin; Patel, Naina; Pearce, Kerra; Hubank, Mike; Stephens, Henry A F; Laundy, Valerie; Padmanabhan, Sandosh; Zawadzka, Anna; Hofstra, Julia M; Coenen, Marieke J H; den Heijer, Martin; Kiemeney, Lambertus A L M; Bacq-Daian, Delphine; Stengel, Benedicte; Powis, Stephen H; Brenchley, Paul; Feehally, John; Rees, Andrew J; Debiec, Hanna; Wetzels, Jack F M; Ronco, Pierre; Mathieson, Peter W; Kleta, Robert

    2011-02-17

    Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population. We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients). The patients were compared with racially matched control subjects; population stratification and quality controls were carried out according to standard criteria. Associations were calculated by means of a chi-square basic allele test; the threshold for significance was adjusted for multiple comparisons (with the Bonferroni method). In a joint analysis of data from the 556 patients studied (398 men), we identified significant alleles at two genomic loci associated with idiopathic membranous nephropathy. Chromosome 2q24 contains the gene encoding M-type phospholipase A(2) receptor (PLA(2)R1) (SNP rs4664308, P=8.6×10(-29)), previously shown to be the target of an autoimmune response. Chromosome 6p21 contains the gene encoding HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1) (SNP rs2187668, P=8.0×10(-93)). The association with HLA-DQA1 was significant in all three populations (P=1.8×10(-9), P=5.6×10(-27), and P=5.2×10(-36) in the French, Dutch, and British groups, respectively). The odds ratio for idiopathic membranous nephropathy with homozygosity for both risk alleles was 78.5 (95% confidence interval, 34.6 to 178.2). An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. Our findings suggest a basis for understanding this disease and illuminate how adaptive immunity is regulated by HLA.

  3. Ultra-high resolution HLA genotyping and allele discovery by highly multiplexed cDNA amplicon pyrosequencing

    Directory of Open Access Journals (Sweden)

    Lank Simon M

    2012-08-01

    Full Text Available Abstract Background High-resolution HLA genotyping is a critical diagnostic and research assay. Current methods rarely achieve unambiguous high-resolution typing without making population-specific frequency inferences due to a lack of locus coverage and difficulty in exon-phase matching. Achieving high-resolution typing is also becoming more challenging with traditional methods as the database of known HLA alleles increases. Results We designed a cDNA amplicon-based pyrosequencing method to capture 94% of the HLA class I open-reading-frame with only two amplicons per sample, and an analogous method for class II HLA genes, with a primary focus on sequencing the DRB loci. We present a novel Galaxy server-based analysis workflow for determining genotype. During assay validation, we performed two GS Junior sequencing runs to determine the accuracy of the HLA class I amplicons and DRB amplicon at different levels of multiplexing. When 116 amplicons were multiplexed, we unambiguously resolved 99%of class I alleles to four- or six-digit resolution, as well as 100% unambiguous DRB calls. The second experiment, with 271 multiplexed amplicons, missed some alleles, but generated high-resolution, concordant typing for 93% of class I alleles, and 96% for DRB1 alleles. In a third, preliminary experiment we attempted to sequence novel amplicons for other class II loci with mixed success. Conclusions The presented assay is higher-throughput and higher-resolution than existing HLA genotyping methods, and suitable for allele discovery or large cohort sampling. The validated class I and DRB primers successfully generated unambiguously high-resolution genotypes, while further work is needed to validate additional class II genotyping amplicons.

  4. ADHD in childhood epilepsy: Clinical determinants of severity and of the response to methylphenidate.

    Science.gov (United States)

    Rheims, Sylvain; Herbillon, Vania; Villeneuve, Nathalie; Auvin, Stéphane; Napuri, Silvia; Cances, Claude; Berquin, Patrick; Castelneau, Pierre; Nguyen The Tich, Sylvie; Villega, Frédéric; Isnard, Hervé; Nabbout, Rima; Gaillard, Ségolène; Mercier, Catherine; Kassai, Behrouz; Arzimanoglou, Alexis

    2016-07-01

    Attention-deficit/hyperactivity disorder (ADHD) is commonly observed in children with epilepsy. However, factors associated with the development of ADHD and which might help to guide its therapeutic management, remain an issue of debate. We conducted a multicenter prospective observational study that included children, aged 6-16 years, with both epilepsy and ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. After inclusion, patients entered a 12-16 week follow-up period during which they were either treated with methylphenidate or they did not receive specific ADHD treatment. ADHD was evaluated with the ADHD Rating Scale-IV. One hundred sixty-seven patients were included, of which 91 were seizure-free during the preinclusion baseline period. At inclusion, the ADHD Rating Scale-IV total score was 30.4 ± (standard deviation) 9.2, the inattentive subscore was 17.3 ± 4.4, and the hyperactive subscore was 13.2 ± 6.6. We did not detect any difference of ADHD Rating Scale-IV scores across patients' age or gender, age at epilepsy onset, epilepsy syndrome, seizure frequency, or number of ongoing antiepileptic drugs. Methylphenidate was initiated in 61 patients, including 55 in whom a follow-up evaluation was available. At the last follow-up, 41 patients (75%) treated with methylphenidate and 39 (42%) of those who did not received ADHD therapy demonstrated ≥25% decrease of ADHD Rating Scale-IV total score (p < 0.001). Response to methylphenidate was greater in girls but was not influenced by any epilepsy-related variables. We did not detect any epilepsy-related factor associated with the severity of ADHD. Twenty-five percent of patients did not respond to methylphenidate. A better understanding of the pathologic process that underlies ADHD development in childhood epilepsy might be required to improve therapeutic strategies. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  5. DETERMINANTS OF SOCIAL RESPONSIBILITY EXPENDITURES OF SMALL AND MEDIUM ENTERPRISES FROM BIHOR COUNTY

    Directory of Open Access Journals (Sweden)

    Saveanu Tomina Gabriela

    2015-07-01

    Full Text Available This paper investigates the social responsibility expenditures of small and medium enterprises (SME in Bihor County. In line with the literature we consider donations and sponsorship the expression of philanthropic behavior of companies. Positioned at the top of the CSR pyramid such actions are some of the few on which there is consensus in considering forms of CSR. Explaining the factors that drive such expenditures at the level of small and medium enterprises fills in a gap in the scientific knowledge both at international and national level. Particularly in Romania, the CSR processes are less studied and seem developed mimetically by large companies from the example of multinational companies. However the data provided in this paper reveals that a significant number of small and medium enterprises are engaged in CSR actions, as almost 20% of SME with registered profit donate money. The factors explaining this orientation are in line with the literature as the size of the enterprise influences both the decision to donate and the amounts donated. The larger a company in terms of profit, turnover and number of employees the bigger the chances it donates money and the amounts donated are larger. The data was extracted from the National Agency of Fiscal Administration regarding expenditures of small and medium enterprises in 2013. Future studies should include information regarding the destination of these expenditures. More, in order to fully explain CSR at SMEs level qualitative data is needed regarding the motivations of managers for such actions and the reasons behind the choice for a specific area or action.

  6. Characterization of Sr9h, a wheat stem rust resistance allele effective to Ug99.

    Science.gov (United States)

    Rouse, Matthew N; Nirmala, Jayaveeramuthu; Jin, Yue; Chao, Shiaoman; Fetch, Thomas G; Pretorius, Zacharias A; Hiebert, Colin W

    2014-08-01

    Wheat stem rust resistance gene SrWeb is an allele at the Sr9 locus that confers resistance to Ug99. Race TTKSK (Ug99) of Puccinia graminis f. sp. tritici, the causal fungus of stem rust, threatens global wheat production because of its broad virulence to current wheat cultivars. A recently identified Ug99 resistance gene from cultivar Webster, temporarily designated as SrWeb, mapped near the stem rust resistance gene locus Sr9. We determined that SrWeb is also present in Ug99 resistant cultivar Gabo 56 by comparative mapping and an allelism test. Analysis of resistance in a population segregating for both Sr9e and SrWeb demonstrated that SrWeb is an allele at the Sr9 locus, which subsequently was designated as Sr9h. Webster and Gabo 56 were susceptible to the Ug99-related race TTKSF+ from South Africa. Race TTKSF+ possesses unique virulence to uncharacterized Ug99 resistance in cultivar Matlabas. This result validated that resistance to Ug99 in Webster and Gabo 56 is conferred by the same gene: Sr9h. The emergence of pathogen virulence to several resistance genes that are effective to the original Ug99 race TTKSK, including Sr9h, suggests that resistance genes should be used in combinations in order to increase resistance durability.

  7. Genetic Variability and Distribution of Mating Type Alleles in Field Populations of Leptosphaeria maculans from France

    Science.gov (United States)

    Gout, Lilian; Eckert, Maria; Rouxel, Thierry; Balesdent, Marie-Hélène

    2006-01-01

    Leptosphaeria maculans is the most ubiquitous fungal pathogen of Brassica crops and causes the devastating stem canker disease of oilseed rape worldwide. We used minisatellite markers to determine the genetic structure of L. maculans in four field populations from France. Isolates were collected at three different spatial scales (leaf, 2-m2 field plot, and field) enabling the evaluation of spatial distribution of the mating type alleles and of genetic variability within and among field populations. Within each field population, no gametic disequilibrium between the minisatellite loci was detected and the mating type alleles were present at equal frequencies. Both sexual and asexual reproduction occur in the field, but the genetic structure of these populations is consistent with annual cycles of randomly mating sexual reproduction. All L. maculans field populations had a high level of gene diversity (H = 0.68 to 0.75) and genotypic diversity. Within each field population, the number of genotypes often was very close to the number of isolates. Analysis of molecular variance indicated that >99.5% of the total genetic variability was distributed at a small spatial scale, i.e., within 2-m2 field plots. Population differentiation among the four field populations was low (GST < 0.02), suggesting a high degree of gene exchange between these populations. The high gene flow evidenced here in French populations of L. maculans suggests a rapid countrywide diffusion of novel virulence alleles whenever novel resistance sources are used. PMID:16391041

  8. Allele frequency distribution for 15 autosomal STR loci in Afridi Pathan population of Uttar Pradesh, India.

    Science.gov (United States)

    Noor, Sabahat; Ali, Shahnaz; Eaaswarkhanth, Muthukrishnan; Haque, Ikramul

    2009-11-01

    Allele frequencies of the 15 autosomal short tandem repeat (STR) loci D8S1179, D21S11, D7S820, CSF1PO D19S433, vWA, TPOX, D18S51, D3S1358, THO1, D13S317, D16S539, D2S1338, D5S818 and FGA were determined in Afridi Pathan population of Uttar Pradesh, India. All the 15 STR loci studied were found to be highly polymorphic with respect to observed heterozygosity values. Adherence to the expectations of the Hardy-Weinberg equilibrium (HWE) was confirmed for all the loci with an exception of TPOX and FGA. The allele 12 in CSF1PO was found to be most frequent. The power of discrimination was found to be high ranging from a minimum of 0.858 for the locus CSFIPO to maximum of 0.962 for the locus FGA, thereby facilitating the validation and efficiency of these STR markers in human identification. Population differentiation test between the studied and neighboring populations revealed significant differences at several loci suggesting the endogamous nature of the studied population. To the best of our knowledge, Afridi Pathan population has not been explored genetically for generating forensic data on STR markers. Therefore, STR allele frequency data of this unique population is a valuable contribution to the existing DNA database on Indian populations.

  9. Allelic polymorphism in introns 1 and 2 of the HLA-DQA1 gene.

    Science.gov (United States)

    Voorter, C E M; de Groot, N G; Meertens, C M H; Bontrop, R E; van den Berg-Loonen, E M

    2005-01-01

    Human leukocyte antigen (HLA) class II antigens are highly polymorphic membrane glycoproteins, encoded by the A and B genes of DR, DQ, and DP. The polymorphism is mainly located in exon 2, with the exception of DQA1. Of the 27 DQA1 alleles presently known, 18 cannot be identified on the basis of exon 2 alone, but need additional information from the other exons. DQA1 has been reported to be the most ancient class II gene. For evolutionary comparison and to assess the degree of polymorphism outside the exons, the sequences of introns 1 and 2 were determined from 30 different cell lines, encompassing 15 different DQA1 alleles. The sequences revealed major nucleotide differences between the different lineages, whereas within each lineage few differences were present. Phylogenetic analysis of intron and exon sequences confirmed this lineage specificity. Altogether, the present data indicate that the HLA-DQA1 lineages represent ancient entities. The observed variation of the introns in alleles with identical exon sequences implicates conservative selection of the exons within a given lineage. Intron sequences may provide the means to set up an accurate typing system.

  10. Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders.

    Science.gov (United States)

    Stetler, Dean A; Davis, Chad; Leavitt, Kathryn; Schriger, Ilana; Benson, Katie; Bhakta, Samir; Wang, Lam Chee; Oben, Cynthia; Watters, Matthew; Haghnegahdar, Tara; Bortolato, Marco

    2014-11-01

    The main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n = 49) and non-violent (n = 40) male Caucasian and African-American convicts in a correctional facility. All participants were also tested with the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11) and Buss-Perry Aggression Questionnaire (BPAQ) to assess their levels of childhood trauma exposure, impulsivity and aggression, respectively. Our results revealed a robust (P crime. This association was replicated in the group of Caucasian violent offenders (P crime charges were not associated with CTQ, BIS-11 and BPAQ scores, carriers of low-activity alleles exhibited a mild, yet significant (P < 0.05) increase in BIS-11 total and attentional-impulsiveness scores. In summary, these findings support the role of MAOA gene as a prominent genetic determinant for criminal violence. Further studies are required to confirm these results in larger samples of inmates and evaluate potential interactions between MAOA alleles and environmental vulnerability factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Identification of Alleles of Puroindoline Genes and Their Effect on Wheat (Triticum aestivum L. Grain Texture

    Directory of Open Access Journals (Sweden)

    Klára Štiasna

    2016-01-01

    Full Text Available Grain hardness is one of the most important quality characteristics of wheat (Triticum aestivum L.. It is a significant property of wheat grains and relates to milling quality and end product quality. Grain hardness is caused by the presence of puroindoline genes (Pina and Pinb. A collection of 25 genotypes of wheat with unusual grain colour (blue aleurone, purple and white pericarp, yellow endosperm was studied by polymerase chain reaction (PCR for the diversity within Pina and Pinb (alleles: Pina-D1a, Pina-D1b, Pinb-D1a, Pinb- -D1b, Pinb-D1c and Pinb-D1d. The endosperm structure was determined by a non-destructive method using light transfl ectance meter and grain hardness by a texture analyser. Genotype Novosibirskaya 67 and isogenic ANK lines revealed hitherto unknown alleles at the locus for the annealing of primers of Pinb-D1. Allele Pinb-D1c was found to be absent from each genotype. The mealy endosperm ranged from 0 to 100 % and grain hardness from 15.10 to 26.87 N per sample.

  12. Inferring modes of colonization for pest species using heterozygosity comparisons and a shared-allele test.

    Science.gov (United States)

    Sved, J A; Yu, H; Dominiak, B; Gilchrist, A S

    2003-02-01

    Long-range dispersal of a species may involve either a single long-distance movement from a core population or spreading via unobserved intermediate populations. Where the new populations originate as small propagules, genetic drift may be extreme and gene frequency or assignment methods may not prove useful in determining the relation between the core population and outbreak samples. We describe computationally simple resampling methods for use in this situation to distinguish between the different modes of dispersal. First, estimates of heterozygosity can be used to test for direct sampling from the core population and to estimate the effective size of intermediate populations. Second, a test of sharing of alleles, particularly rare alleles, can show whether outbreaks are related to each other rather than arriving as independent samples from the core population. The shared-allele statistic also serves as a genetic distance measure that is appropriate for small samples. These methods were applied to data on a fruit fly pest species, Bactrocera tryoni, which is quarantined from some horticultural areas in Australia. We concluded that the outbreaks in the quarantine zone came from a heterogeneous set of genetically differentiated populations, possibly ones that overwinter in the vicinity of the quarantine zone.

  13. Superstitious perception: response-independent reinforcement and punishment as determinants of recurring eccentric interpretations.

    Science.gov (United States)

    Mellon, Robert C

    2009-10-01

    This study provided controlled observations of a potential mechanism for the determination of the repetitive, aberrant perceptions or interpretations of everyday events that figure prominently in a range of psychological disorders: the adventitious reinforcement of acts of cognition by the actual consequences of concurrent motor acts. Adults made a series of two-choice brightness discriminations; on 60% of trials, choosing the brighter stimulus produced a "correct" signal while errors produced an aversive sound. On 40% of trials, the choice stimuli did not in fact differ in brightness; the consequences of responding on these "identical stimuli" trials differed across blocks of trials. Thus, on these trials perceptual judgments were directly followed by events that they did not produce. When all choices on identical stimuli trials were punished with the "error" sound, subjects showed little preference for the left-side or right-side identical stimuli, but when all choices of identical stimuli were reinforced with the "correct" light, individual preferences for the left-side or the right-side stimuli substantially increased. As the consequences of responding on identical stimuli trials were independent of the stimuli chosen, these findings provide evidence for superstitious perception, the reinforcement of perceptual acts by events that do not depend upon their occurrence.

  14. Determinants of a positive response to carotid sinus massage and head-up tilt testing.

    Science.gov (United States)

    Milton, James C; Lee, Thomas C; Jackson, Stephen H D

    2009-11-01

    Orthostatic hypotension (OH) and carotid sinus hypersensitivity (CSH) are common causes of syncope in older people. The aim of this study was to determine if patient's age, sex and presenting symptoms influence the result of carotid sinus massage and head-up tilt testing. Retrospective analysis of the database and reports was carried out between 1995 and 2006 at a tertiary referral centre. Patient's age, sex, presenting symptoms and test result were examined. Presenting symptoms were classified as syncope, falls or dizzy spells. Of the 1583 tests reported, OH was present in 402 patients (25.4%), of whom 175 (11.1%) were symptomatic. 188 of 1464 (12.8%) patients undergoing carotid sinus massage had evidence of CSH, of which 156 were symptomatic. Male patients were significantly more likely to have symptomatic CSH than female patients (odds ratio 2.28, 95% CI 1.54 to 3.04, p<0.01). There were non-significant trends to increased diagnosis of symptomatic OH with increasing age, male sex and referral with syncope. There were non-significant trends to increased diagnosis of symptomatic CSH with increasing age and referral with syncope. Male sex, increasing age and being referred with syncope were all associated with an increased likelihood of receiving a diagnosis of either OH or CSH. The overall prevalence of CSH was lower than in previous studies, which may reflect different patient populations.

  15. Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis.

    Science.gov (United States)

    Steiger, Stefanie; Kumar, Santhosh V; Honarpisheh, Mohsen; Lorenz, Georg; Günthner, Roman; Romoli, Simone; Gröbmayr, Regina; Susanti, Heni-Eka; Potempa, Jan; Koziel, Joanna; Lech, Maciej

    2017-08-15

    Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD). Our study assessed the contribution of macrophages in CKD and the role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK-M in chronic renal injury in vivo, a mouse model of unilateral ureteral obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d after UUO in obstructed compared with unobstructed kidneys. Mice deficient in IRAK-M were protected from fibrosis and displayed a diminished number of alternatively activated macrophages. Compared to wild-type mice, IRAK-M-deficient mice showed reduced tubular injury, leukocyte infiltration, and inflammation following renal injury as determined by light microscopy, immunohistochemistry, and intrarenal mRNA expression of proinflammatory and profibrotic mediators. Taken together, these results strongly support a role for IRAK-M in renal injury and identify IRAK-M as a possible modulator in driving an alternatively activated profibrotic macrophage phenotype in UUO-induced CKD. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. Higher frequency of septic shock in septic patients with the 47C allele (rs4880) of the SOD2 gene.

    Science.gov (United States)

    Paludo, Francis Jackson de Oliveira; Picanço, Juliane Bentes; Fallavena, Paulo Roberto Vargas; Fraga, Lucas da Rosa; Graebin, Pietra; Nóbrega, Otávio de Toledo; Dias, Fernando Suparregui; Alho, Clarice Sampaio

    2013-03-15

    To analyze the effect of the two different versions of the manganese superoxide dismutase gene (SOD2) on sepsis. The SOD2 gene presents the 47C>T single nucleotide polymorphism (SNP; ID: rs4880) which produces MnSOD with different activities. The -9Val MnSOD (47T allele) is less efficient than the -9Ala version (47C allele). During sepsis there are abundance of ROS, high SOD2 expression and excess of H(2)O(2) synthesis. High concentrations of H(2)O(2) could affect the sepsis scenario and/or the sepsis outcome. We determined the 47C>T single nucleotide polymorphism (SNP) frequencies in 529 critically ill patients with or without sepsis, facing outcome. To collect information on population frequencies, we obtained a pilot 47C>T genotypic and allelic frequencies in a random group of 139 healthy subjects. We compared the 47C allele carriers (47CC+47CT genotypes) with 47TT homozygotes and noticed a significant association between 47C allele carriers and septic shock in septic patients (P=0.025). With an adjusted binary multivariate logistic regression, incorporating 47C>T SNP and the main clinical predictors, we showed high SOFA scores [P<0.001, OR=9.107 (95% CI=5.319-15.592)] and 47C allele [P=0.011, OR=2.125 (95% CI=1.190-3.794)] were significantly associated with septic shock outcome. With this information we presented a hypothesis suggesting that this negative outcome from sepsis is possibly explained by effects on cellular stress caused by 47C allele. In our population there was a significant higher frequency of septic shock in septic patients with the 47C allele of the SOD2 gene. This higher 47C allele frequency in septic patients with negative outcome could be explained by effects of higher activity MnSOD on cellular stress during the sepsis. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Determinants associated with bone mineral density increase in response to daily teriparatide treatment in patients with osteoporosis.

    Science.gov (United States)

    Niimi, Rui; Kono, Toshibumi; Nishihara, Atsushi; Hasegawa, Masahiro; Matsumine, Akihiko; Kono, Toshihiko; Sudo, Akihiro

    2014-09-01

    Several factors associated with bone mineral density (BMD) increase are reported with daily teriparatide treatment, but there has been no systematic analysis to summarize these associations. The purpose of this study was to investigate the clinical determinants associated with BMD increase to daily teriparatide treatment. This was a retrospective study. We performed an analysis of 306 patients diagnosed with osteoporosis. Teriparatide was administered at 20μg/day for 12months. The primary efficacy measure was a change in lumbar spine (LS) BMD from baseline at 12months. To determine the response variables of BMD changes, we investigated the clinical determinants using univariate and multivariate analyses. There was a 9.8±8.2% increase in LS BMD after 12months. Prior bisphosphonate treatment and baseline procollagen type I N-terminal propeptide (PINP) concentration were significantly associated with LS BMD absolute response by univariate analyses. In the multiple regression model, patients with higher baseline PINP concentration had a significantly greater LS BMD absolute increase. Prior bisphosphonate use lost its correlation in the multiple regression models. Our results showed that baseline PINP concentration was a useful predictor of LS BMD absolute increase regardless of prior treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. An Allele Real-Coded Quantum Evolutionary Algorithm Based on Hybrid Updating Strategy

    OpenAIRE

    Zhang, Yu-Xian; Qian, Xiao-Yi; Peng, Hui-Deng; Wang, Jian-Hui

    2016-01-01

    For improving convergence rate and preventing prematurity in quantum evolutionary algorithm, an allele real-coded quantum evolutionary algorithm based on hybrid updating strategy is presented. The real variables are coded with probability superposition of allele. A hybrid updating strategy balancing the global search and local search is presented in which the superior allele is defined. On the basis of superior allele and inferior allele, a guided evolutionary process as well as updating alle...

  19. Determinants of long-term response to group therapy for dysfunctional fear of progression in chronic diseases.

    Science.gov (United States)

    Dinkel, Andreas; Herschbach, Peter; Berg, Petra; Waadt, Sabine; Duran, Gabriele; Engst-Hastreiter, Ursula; Henrich, Gerhard; Book, Katrin

    2012-01-01

    Prior work demonstrated that cognitive-behavioral (CBT) and supportive-experiential (SET) group interventions can reduce dysfunctional fear of progression (FoP) in patients with chronic diseases. In this secondary analysis of a randomized controlled study, we investigated determinants of long-term response to group therapy for FoP. Response to therapy after 12 months was assessed using the Reliable Change Index (RCI). Outcome data were available for 129 patients with cancer and 116 patients with chronic arthritis. 37.9% of the patients in the CBT group and 32.7% of those attending the SET group indicated response to therapy (p=.402). Educational level predicted long-term response to therapy (OR 2.53, 95% CI 1.33-4.81; p=.005). Medical patients with lower education may need additional attention in order to gain long-lasting benefit from brief group psychotherapy. However, this investigation needs to be replicated in a study that includes a broader range of psychological predictors.

  20. Mitigation/adaptation and health: health policymaking in the global response to climate change and implications for other upstream determinants.

    Science.gov (United States)

    Wiley, Lindsay F

    2010-01-01

    The time is ripe for innovation in global health governance if we are to achieve global health and development objectives in the face of formidable challenges. Integration of global health concerns into the law and governance of other, related disciplines should be given high priority. This article explores opportunities for health policymaking in the global response to climate change. Climate change and environmental degradation will affect weather disasters, food and water security, infectious disease patterns, and air pollution. Although scientific research has pointed to the interdependence of the global environment and human health, policymakers have been slow to integrate their approaches to environmental and health concerns. A robust response to climate change will require improved integration on two fronts: health concerns must be given higher priority in the response to climate change and threats associated with climate change and environmental degradation must be more adequately addressed by global health law and governance. The mitigation/adaptation response paradigm developing within and beyond the United Nations Framework Convention on Climate Change provides a useful framework for thinking about global health law and governance with respect to climate change, environmental degradation, and possibly other upstream determinants of health as well. © 2010 American Society of Law, Medicine & Ethics, Inc.

  1. Electromechanical response of articular cartilage in indentation--considerations on the determination of cartilage properties during arthroscopy.

    Science.gov (United States)

    Li, L P; Herzog, W

    2005-04-01

    A finite element formulation of streaming potentials in articular cartilage was incorporated into a fibril-reinforced model using the commercial software ABAQUS. This model was subsequently used to simulate interactions between an arthroscopic probe and articular cartilage in a knee joint. Fibril reinforcement was found to account for large fluid pressure at considerable strain rates, as has been observed in un-confined compression. Furthermore, specific electromechanical responses were associated with specific changes in tissue properties that occur with cartilage degeneration. For example, the strong strain-rate dependence of the load response was only observed when the collagen network was intact. Therefore, it is possible to use data measured during arthroscopy to evaluate the degree of cartilage degeneration and the source causing changed properties. However, practical problems, such as the difficulty of controlling the speed of the hand-held probe, may greatly reduce the reliability of such evaluations. The fibril-reinforced electromechanical model revealed that high-speed transient responses were associated with the collagen network, and equilibrium response was primarily determined by proteoglycan matrix. The results presented here may be useful in the application of arthroscopic tools for evaluating cartilage degeneration, for the proper interpretation of data, and for the optimization of data collection during arthroscopy.

  2. A novel ABO O allele caused by a large deletion covering two exons of the ABO gene identified in a Caucasian family showing discrepant ABO blood typing results.

    Science.gov (United States)

    Matzhold, Eva M; Drexler, Camilla; Wagner, Thomas

    2016-11-01

    The presence of ABO subgroup alleles and unusual O alleles often is associated with discrepant serologic findings in ABO blood group typing. In the ABO gene of a Caucasian female and her daughters who had aberrant ABO phenotypes, a novel ABO O allele characterized by a large deletion that included two exons was identified. ABO phenotypes were determined by standard agglutination tests and adsorption-elution studies. Allele-specific sequencing analyses of the ABO gene as well as messenger RNA transcripts were carried out. All three samples showed the same discrepant ABO blood typing results lacking A and B antigens, indicating Blood Group O, whereas anti-A1 and anti-A2 isoagglutinins were not detectable in reverse typing. Analyses of the ABO gene revealed a novel allele characterized by a deletion of 2169 base pairs, including sequences of Intron 1, Exon 2, Intron 2, Exon 3, and Intron 3. Exon 1 was directly joined to Exon 4 in the ABO transcript. Because the novel allele was associated with a well-described O allele, the absence of A-antigens in the inherited ABO subtype phenotype may be due to the identified mutation affecting the transmembrane-spanning domain of the encoded protein and impairing the transferase activity. © 2016 AABB.

  3. Comparative analysis of gene sequence of goat CSN1S1 F and N alleles and characterization of CSN1S1 transcript variants in mammary gland.

    Science.gov (United States)

    Ramunno, Luigi; Cosenza, Gianfranco; Rando, Andrea; Pauciullo, Alfredo; Illario, Rosa; Gallo, Daniela; Di Berardino, Dino; Masina, Piero

    2005-01-31

    In this paper, we report the full characterization, at DNA and RNA level, of the defective goat CSN1S1 F and N alleles and an extensive comparison with the A allele counterpart. By utilizing genomic DNA as template, we amplified the whole CSN1S1 gene plus 1972/3 nucleotides of the 5' region plus 610 nucleotides of the 3' region of the goat CSN1S1 N and CSN1S1 F alleles. Comparison of sequences of the N, F and A CSN1S1 alleles showed a total of 118 polymorphic sites. In particular, both the N and the F alleles are characterized by a deletion of the cytosine at the 23rd nucleotide of the 9th exon. The resulting one-nucleotide frameshift determines a premature stop codon (TGA, nucleotides 17-19 of the 12th exon). On the basis of the information so far available, it seems reasonable to hypothesize that the CSN1S1 N allele might be originated by interallelic recombination events. Comparison of transcripts produced by the N and F alleles shows a remarkable variability in alternative splicing events which concern, even though with different percentage ratios, mainly the lack of the 9th exon, the deletion of the last 5 nucleotides of the 9th exon and the contemporary deletion of exons 10 and 11.

  4. MHC genotyping of non-model organisms using next-generation sequencing: a new methodology to deal with artefacts and allelic dropout.

    Science.gov (United States)

    Sommer, Simone; Courtiol, Alexandre; Mazzoni, Camila J

    2013-08-09

    The Major Histocompatibility Complex (MHC) is the most important genetic marker to study patterns of adaptive genetic variation determining pathogen resistance and associated life history decisions. It is used in many different research fields ranging from human medical, molecular evolutionary to functional biodiversity studies. Correct assessment of the individual allelic diversity pattern and the underlying structural sequence variation is the basic requirement to address the functional importance of MHC variability. Next-generation sequencing (NGS) technologies are likely to replace traditional genotyping methods to a great extent in the near future but first empirical studies strongly indicate the need for a rigorous quality control pipeline. Strict approaches for data validation and allele calling to distinguish true alleles from artefacts are required. We developed the analytical methodology and validated a data processing procedure which can be applied to any organism. It allows the separation of true alleles from artefacts and the evaluation of genotyping reliability, which in addition to artefacts considers for the first time the possibility of allelic dropout due to unbalanced amplification efficiencies across alleles. Finally, we developed a method to assess the confidence level per genotype a-posteriori, which helps to decide which alleles and individuals should be included in any further downstream analyses. The latter method could also be used for optimizing experiment designs in the future. Combining our workflow with the study of amplification efficiency offers the chance for researchers to evaluate enormous amounts of NGS-generated data in great detail, improving confidence over the downstream analyses and subsequent applications.

  5. Polyphosphate kinase 2: a novel determinant of stress responses and pathogenesis in Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Dharanesh Gangaiah

    Full Text Available BACKGROUND: Inorganic polyphosphate (poly P plays an important role in stress tolerance and virulence in many bacteria. PPK1 is the principal enzyme involved in poly P synthesis, while PPK2 uses poly P to generate GTP, a signaling molecule that serves as an alternative energy source and a precursor for various physiological processes. Campylobacter jejuni, an important cause of foodborne gastroenteritis in humans, possesses homologs of both ppk1 and ppk2. ppk1 has been previously shown to impact the pathobiology of C. jejuni. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate for the first time that the deletion of ppk2 in C. jejuni resulted in a significant decrease in poly P-dependent GTP synthesis, while displaying an increased intracellular ATP:GTP ratio. The Deltappk2 mutant exhibited a significant survival defect under osmotic, nutrient, aerobic, and antimicrobial stresses and displayed an enhanced ability to form static biofilms. However, the Deltappk2 mutant was not defective in poly P and ppGpp synthesis suggesting that PPK2-mediated stress tolerance is not ppGpp-mediated. Importantly, the Deltappk2 mutant was significantly attenuated in invasion and intracellular survival within human intestinal epithelial cells as well as in chicken colonization. CONCLUSIONS/SIGNIFICANCE: Taken together, we have highlighted the role of PPK2 as a novel pathogenicity determinant that is critical for C. jejuni survival, adaptation, and persistence in the host environments. PPK2 is absent in humans and animals; therefore, can serve as a novel target for therapeutic intervention of C. jejuni infections.

  6. Extent and determinants of thermogenic responses to 24 hours of fasting, energy balance, and five different overfeeding diets in humans.

    Science.gov (United States)

    Thearle, Marie S; Pannacciulli, Nicola; Bonfiglio, Susan; Pacak, Karel; Krakoff, Jonathan

    2013-07-01

    Individual variation in the ability to convert excess calories to heat and the effects of dietary macronutrient composition are unclear. Stability and determinants of the energy expenditure (EE) response to overconsumption were assessed. Twenty subjects (75% male) with normal glucose regulation were evaluated during 24 hours each of energy balance, fasting, and 5 different diets with 200% energy requirements in a clinical research unit. Five 1-day overfeeding diets were given in random order: high carbohydrate (75%) and low protein (3%); high carbohydrate and normal protein (20%); high fat (46%) and low protein; high fat (60%) and normal protein; and balanced (50% carbohydrates, 20% protein). The 24-hour EE, sleeping EE, and thermic effect of food (TEF) during each diet were measured with a metabolic chamber. Appetitive hormones were measured before and after the diets. The EE response to overfeeding exhibited good intraindividual reproducibility. Similar increases above eucaloric feeding in 24-hour EE (mean 10.7 ± 5.7%, P calories.

  7. Allele-specific marker generation and linkage mapping on the Xiphophorus sex chromosomes.

    Science.gov (United States)

    Woolcock, B; Kazianis, S; Lucito, R; Walter, R B; Kallman, K D; Morizot, D C; Vielkind, J R

    2006-01-01

    There is great interest in the sex chromosomes of Xiphophorus fishes because both WY/YY and XX/XY sex-determining mechanisms function in these species, with at least one taxon possessing all three types of sex chromosomes, and because in certain interspecific hybrids melanoma arises as a consequence of inheritance of the sex-linked macromelanophore determining locus (MDL). Representational difference analysis (RDA) has been used to clone two sequences from the sex-determining region of X. maculatus, including a cholinergic receptor, nicotinic, delta polypeptide (CHRND) orthologue. Allele-specific assays for these sequences, as well as for the sex-linked XMRK1 and XMRK2 genes, were developed to distinguish W, X, and Y chromosomes derived from a X. maculatus (XX/XY) strain and a X. helleri (WY/YY) strain. Linkage mapping localized these markers to linkage group (LG) 24. No recombinants were observed between XMRK2 and MDL, confirming a role for XMRK2 in macromelanophore development. Although the master sex-determining (SD) locus certainly resides on Xiphophorus LG 24, autosomal loci are probably involved in sex determination as well, as indicated by the abnormal sex ratios in the backcross hybrids that contrast theoretical predictions based on LG 24 genotyping. Marker development and allelic discrimination on the Xiphophorus sex chromosomes should prove highly useful for studies that utilize this genus as an animal model.

  8. Determinants of responsiveness to botulinum toxin, casting, and bracing in the treatment of spastic equinus in children with cerebral palsy.

    Science.gov (United States)

    Yap, Rita; Majnemer, Annette; Benaroch, Thierry; Cantin, Marie-Andree

    2010-02-01

    The objective was to determine whether specific intrinsic (age, pattern of cerebral palsy [CP], child's motivation) and extrinsic (number of treatments, parenting stress) characteristics were associated with responsiveness to botulinum toxin A (BoNT-A) injections in children with CP 3 months after injection into the gastrocnemius muscle. Children with hemiplegia or diplegia recruited from a BoNT-A programme were evaluated before and 3 months following injection of BoNT-A into the gastrocnemius. Outcome measures included muscle tone, range of motion, gait pattern, level of ambulation, gross motor function, and functional independence. Determinants of responsiveness to BoNT-A considered were age, number of treatments, distribution of CP, parenting stress, and motivation. Thirty-one children were recruited (17 males, 14 females)--22 with hemiplegia and nine with diplegia. Twenty-eight were classified at Gross Motor Function Classification System (GMFCS) level I and three at level III. The mean age was 6 years 4 months (SD 2y 11mo). Younger age (p=0.015) and fewer number (p=0.024) of BoNT-A treatments were associated with greater change in gross motor function. Child's motivation and parenting stress were significantly associated with improvements in muscle tone (p=0.006-0.017), passive range of motion (p=0.008-0.033), gait pattern (p=0.005-0.042), level of ambulation (p=0.001-0.043), and functional independence (p=0.004-0.027). The results indicate that child, family, and treatment characteristics influence the degree of responsiveness to BoNT-A treatment. The contribution of contextual factors (personal and environmental) on responsiveness may be underappreciated in children with CP.

  9. Foliar Reflectance and Fluorescence Responses for Plants Under Nitrogen Stress Determined with Active and Passive Systems

    Science.gov (United States)

    Middleton, E. M.; McMurtrey, J. E.; Campbell, P. K. Entcheva; Corp, L. A.; Butcher, L. M.; Chappelle, E. W.

    2003-01-01

    Vegetation productivity is driven by nitrogen (N) availability in soils. Both excessive and low soil N induce physiological changes in plant foliage. In 2001, we examined the use of spectral fluorescence and reflectance measurements to discriminate among plants provided different N fertilizer application rates: 20%, 50%, 100% and 150% of optimal N levels. A suite of optical, fluorescence, and biophysical measurements were collected on leaves from field grown corn (Zea mays L.) and soybean plants (Glycine max L.) grown in pots (greenhouse + ambient sunlight daily). Three types of steady state laser-induced fluorescence measurements were made on adaxial and abaxial surfaces: 1) fluorescence images in four 10 nm bands (blue, green, red, far-red) resulting from broad irradiance excitation; 2) emission spectra (5 nm resolution) produced by excitation at single wavelengths (280,380 or 360, and 532 nm); and 3) excitation spectra (2 nm resolution), with emission wavelengths fixed at wavelengths centered on selected solar Fraunhofer lines (532,607,677 and 745 nm). Two complementary sets of high resolution (less than 2 nm) optical spectra were acquired for both adaxial and abaxial leaf surfaces: 1) optical properties (350-2500 nm) for reflectance, transmittance, and absorptance; and 2) reflectance spectra (500-1000 nm) acquired with and without a short pass filter at 665 nm to determine the fluorescence contribution to apparent reflectance in the 650-750 spectrum, especially at the 685 and 740 nm chlorophyll fluorescence (ChIF) peaks. The strongest relationships between foliar chemistry and optical properties were demonstrated for C/N content and two optical parameters associated with the red edge inflection point. Select optical properties and ChIF parameters were highly correlated for both species. A significant contribution of ChIF to apparent reflectance was observed, averaging 10-25% at 685 nm and 2 - 6% at 740 nm over all N treatments. Discrimination of N treatment

  10. [Regulation of the expression of plasmid determination responsible for caprolactam degradation by bacteria of the genus Pseudomonas].

    Science.gov (United States)

    Esikova, T Z; Grishchenkov, V G

    1992-01-01

    On the basis of the study of some Tn5 induced mutants in Pseudomonas putida strain BS836 containing the plasmid pBS268 coding caprolactam degradation, growth on caprolactam and its intermediates, and the data on the induction of oxidative activities in plasmid containing P. putida strain BS831 it was shown that plasmid and chromosome genes regulated the expression of CAP-determinants. The regulation has some elements of the negative control mechanism. Caprolactam is the inducer of the synthesis of key enzymes cleaving it and its intermediates (aminocaproic and adipic acids). At the same time each of its intermediates induced the synthesis of enzymes responsible for its cleavage.

  11. Ploidy mosaicism and allele-specific gene expression differences in the allopolyploid Squalius alburnoides

    Directory of Open Access Journals (Sweden)

    Matos Isa

    2011-12-01

    Full Text Available Abstract Background Squalius alburnoides is an Iberian cyprinid fish resulting from an interspecific hybridisation between Squalius pyrenaicus females (P genome and males of an unknown Anaecypris hispanica-like species (A genome. S. alburnoides is an allopolyploid hybridogenetic complex, which makes it a likely candidate for ploidy mosaicism occurrence, and is also an interesting model to address questions about gene expression regulation and genomic interactions. Indeed, it was previously suggested that in S. alburnoides triploids (PAA composition silencing of one of the three alleles (mainly of the P allele occurs. However, not a whole haplome is inactivated but a more or less random inactivation of alleles varying between individuals and even between organs of the same fish was seen. In this work we intended to correlate expression differences between individuals and/or between organs to the occurrence of mosaicism, evaluating if mosaics could explain previous observations and its impact on the assessment of gene expression patterns. Results To achieve our goal, we developed flow cytometry and cell sorting protocols for this system generating more homogenous cellular and transcriptional samples. With this set-up we detected 10% ploidy mosaicism within the S. alburnoides complex, and determined the allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin in cells from liver and kidney of mosaic and non-mosaic individuals coming from different rivers over a wide geographic range. Conclusions Ploidy mosaicism occurs sporadically within the S. alburnoides complex, but in a frequency significantly higher than reported for other organisms. Moreover, we could exclude the influence of this phenomenon on the detection of variable allelic expression profiles of ubiquitously expressed genes (rpl8; gapdh and β-actin in cells from liver and kidney of triploid individuals. Finally, we determined that the expression patterns

  12. Experiments to Demonstrate Change in Allelic Frequency by ...

    Indian Academy of Sciences (India)

    Admin

    a number of factors such as migration from or to other populations, mutation, selection and random ... beneficial, neutral, or detrimental to reproductive success. The statistical effect of sampling error ... original population, and through the random sampling of alleles during reproduction of sub- sequent generations, continue ...

  13. Estimating and testing the effect of allelic recombination on the ...

    African Journals Online (AJOL)

    Jane

    2011-01-21

    Jan 21, 2011 ... The significance of the correlation coefficient as well as the fitted regression model was obtained using. Analysis of Variance method. Key words: Allele, genotype, regression, correlation, F-ratio, analysis of variance. INTRODUCTION. Genetic recombination is an effective means of combining one individual ...

  14. Haplotype allelic classes for detecting ongoing positive selection

    Directory of Open Access Journals (Sweden)

    Lefebvre Jean-François

    2010-01-01

    Full Text Available Abstract Background Natural selection eliminates detrimental and favors advantageous phenotypes. This process leaves characteristic signatures in underlying genomic segments that can be recognized through deviations in allelic or haplotypic frequency spectra. To provide an identifiable signature of recent positive selection that can be detected by comparison with the background distribution, we introduced a new way of looking at genomic polymorphisms: haplotype allelic classes. Results The model combines segregating sites and haplotypic information in order to reveal useful data characteristics. We developed a summary statistic, Svd, to compare the distribution of the haplotypes carrying the selected allele with the distribution of the remaining ones. Coalescence simulations are used to study the distributions under standard population models assuming neutrality, demographic scenarios and selection models. To test, in practice, haplotype allelic class performance and the derived statistic in capturing deviation from neutrality due to positive selection, we analyzed haplotypic variation in detail in the locus of lactase persistence in the three HapMap Phase II populations. Conclusions We showed that the Svd statistic is less sensitive than other tests to confounding factors such as demography or recombination. Our approach succeeds in identifying candidate loci, such as the lactase-persistence locus, as targets of strong positive selection and provides a new tool complementary to other tests to study natural selection in genomic data.

  15. Distribution of forensic marker allelic frequencies in Pernambuco, Northestern Brazil.

    Science.gov (United States)

    Santos, S M; Souza, C A; Rabelo, K C N; Souza, P R E; Moura, R R; Oliveira, T C; Crovella, S

    2015-04-30

    Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the number of inhabitants. We examined the allele frequencies of 13 short tandem repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau of Investigation and commonly used in forensic genetics laboratories in Brazil, in a sample of 609 unrelated individuals from all geographic regions of Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant differences for any loci analyzed were observed compared with other publications in other various regions of Brazil. Most of the markers observed were in Hardy-Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles 35.1 and 39 (locus D21S11), also described in a single study of the Brazilian population, was observed. The other forensic parameters analyzed (matching probability, power of discrimination, polymorphic information content, paternity exclusion, complement factor I, observed heterozygosity, expected heterozygosity) indicated that the studied markers are very informative for human forensic identification purposes in the Pernambuco population.

  16. Molecular monitoring of resistant dhfr and dhps allelic haplotypes in ...

    African Journals Online (AJOL)

    Objective: The present study assesses the frequency of resistant dhfr and dhps alleles in Morogoro-Mvomero district in south eastern Tanzania and contrast their rate of change during 17 years of SP second line use against five years of SP first line use. Methodology: Cross sectional surveys of asymptomatic infections were ...

  17. Comparison of bovine lymphocyte antigen DRB3.2 allele ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... polymorphic bovine MHC class II gene which encodes the peptide-binding groove. Since different ... patibility Complex (MHC) of cattle is known as Bovine .... Table 1. Frequencies of BoLA-DRB3.2 alleles detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

  18. Allelic variations of functional markers for polyphenol oxidase (PPO)

    Indian Academy of Sciences (India)

    Allelic variations of functional markers for polyphenol oxidase (PPO) genes in Indian bread wheat (Triticum aestivum L.) cultivars. Rajender Singh, Umesh Goutam, R. K. Gupta, G. C. Pandey, Jag Shoran and Ratan Tiwari. J. Genet. 88, 325–329. Figure 1. Phenol colour reaction of kernels. Kernels without treatment by ...

  19. Allelic variation of HMW glutenin subunits of Ethiopian bread wheat ...

    African Journals Online (AJOL)

    There were highly significant differences between genotypes and banding patterns for the SDS-sedimentation test, mixograph development time, alveograph strength and loaf volume; but not for protein content. The frequency of subunits 5+10 among genotypes was 73%. The accumulation of high scoring alleles in our ...

  20. Allelic reůationships of Pea Nodulation Mutants

    Czech Academy of Sciences Publication Activity Database

    Novák, Karel

    2003-01-01

    Roč. 94, č. 2 (2003), s. 191-193 ISSN 0022-1503 R&D Projects: GA ČR GA521/00/0937 Institutional research plan: CEZ:AV0Z5020903 Keywords : allelic * relationships * pea Subject RIV: EE - Microbiology, Virology Impact factor: 1.707, year: 2003

  1. Distribution of HIV-1 resistance-conferring polymorphic alleles SDF ...

    Indian Academy of Sciences (India)

    ... number of mutant alleles (for the three loci together) carried by each individual varies from 0.475 (in Vizag Brahmins) to 0.959 (in Bohra Muslims). The estimated relative hazard values for the populations, computed from the three-locus genotype data, are comparable to those from Africa and Southeast Asia, where AIDS is ...

  2. Novel HLA Class I Alleles Associated with Indian Leprosy Patients

    Directory of Open Access Journals (Sweden)

    U. Shankarkumar

    2003-01-01

    A*0101, Cw*04011, and Cw*0602 leprosy patients was observed when compared to the controls. Further haplotype A*1102-B*4006-Cw*1502 was significantly increased among the lepromatous leprosy patients when compared to the controls. It seems that HLA class I alleles play vital roles in disease association/pathogenesis with leprosy among Indians.

  3. The 'rare allele phenomenon' in a ribosomal spacer

    NARCIS (Netherlands)

    Schilthuizen, M.; Hoekstra, R.F.; Gittenberger, E.

    2001-01-01

    We describe the increased frequency of a particular length variant of the internal transcribed spacer 1 (ITS-1) of the ribosomal DNA in a hybrid zone of the land snail Albinaria hippolyti. The phenomenon that normally rare alleles or other markers can increase in frequency in the centre of hybrid

  4. Allelic drop-out probabilities estimated by logistic regression

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Asplund, Maria

    2012-01-01

    We discuss the model for estimating drop-out probabilities presented by Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of the model has demonstrated that the model is not perfect. However, the model is very useful for advanced forensic genetic work, where allelic dro...

  5. Allele frequency analysis of Chinese chestnut ( Castanea mollissima ...

    African Journals Online (AJOL)

    The aim of this study was to establish a method for allele frequency detection in bulk samples. The abundance of polymerase chain reaction (PCR) products in bulk leaf samples was detected using fluorescent labeled Simple sequence repeat (SSR) primers and an Applied biosystems (AB) automatic DNA analyzer.

  6. weight glutenin subunits and waxy alleles on dough-mix

    Indian Academy of Sciences (India)

    weight glutenin subunits and waxy alleles on dough-mixing properties in common wheat. Zhiying Deng, Shuna Hu, Feifei Zheng, Junnan Chen, Xinye Zhang, Jiansheng Chen, Cailing Sun,. Yongxiang Zhang, Shouyi Wang and Jichun Tian. J. Genet. 92, 69–79. Table 1. The data of the mixing properties of the RIL population ...

  7. HLA-A alleles differentially associate with severity to Plasmodium ...

    African Journals Online (AJOL)

    Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A on malaria infection and/or disease is not fully understood. Recently, HLA-A ...

  8. Introgression of Crop Alleles into Wild or Weedy Populations

    NARCIS (Netherlands)

    Ellstrand, N.C.; Meir