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Sample records for alleles determine responsiveness

  1. 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.

  2. Determination of DQB1 alleles using PCR amplification and allele-specific primers.

    Science.gov (United States)

    Lepage, V; Ivanova, R; Loste, M N; Mallet, C; Douay, C; Naoumova, E; Charron, D

    1995-10-01

    Molecular genotyping of HLA class II genes is commonly carried out using polymerase chain reaction (PCR) in combination with sequence-specific oligotyping (PCR-SSO) or a combination of the PCR and restriction fragment length polymorphism methods (PCR-RFLP). However, the identification of the DQB1 type by PCR-SSO and PCR-RFLP is very time-consuming which is disadvantageous for the typing of cadaveric organ donors. We have developed a DQB1 typing method using PCR in combination with allele-specific amplification (PCR-ASA), which allows the identification of the 17 most frequent alleles in one step using seven amplification mixtures. PCR allele-specific amplification HLA-DQB1 typing is easy to perform, and the results are easy to interpret in routine clinical practice. The PCR-ASA method is therefore better suited to DQB1 typing for organ transplantation than other methods.

  3. Modification of an HLA-B PCR-SSOP typing system leading to improved allele determination.

    Science.gov (United States)

    Middleton, D; Williams, F; Cullen, C; Mallon, E

    1995-04-01

    Modifications have been introduced to a previously reported HLA-B PCR-SSOP typing system. This has enabled further definition of alleles, determination of the probe pattern of some alleles not previously examined and identification of patterns of possible new alleles. However there are still some alleles that cannot be differentiated and there are several alleles which when present as a homozygote have the same pattern as in combination with another allele. When the method was applied to the typing of 66 consecutive cadaveric donors there were three donors whose type differed from the serological type.

  4. A novel simple method for determining CYP2D6 gene copy number and identifying allele(s with duplication/multiplication.

    Directory of Open Access Journals (Sweden)

    Taimour Langaee

    Full Text Available Cytochrome P450 2D6 (CYP2D6 gene duplication and multiplication can result in ultrarapid drug metabolism and therapeutic failure or excessive response in patients. Long range polymerase chain reaction (PCR, restriction fragment length polymorphism (RFLP and sequencing are usually used for genotyping CYP2D6 duplication/multiplications and identification, but are labor intensive, time consuming, and costly.We developed a simple allele quantification-based Pyrosequencing genotyping method that facilitates CYP2D6 copy number variation (CNV genotyping while also identifying allele-specific CYP2D6 CNV in heterozygous samples. Most routine assays do not identify the allele containing a CNV. A total of 237 clinical and Coriell DNA samples with different known CYP2D6 gene copy numbers were genotyped for CYP2D6 *2, *3, *4, *6, *10, *17, *41 polymorphisms and CNV determination.The CYP2D6 gene allele quantification/identification were determined simultaneously with CYP2D6*2, *3, *4, *6, *10, *17, *41 genotyping. We determined the exact CYP2D6 gene copy number, identified which allele had the duplication or multiplication, and assigned the correct phenotype and activity score for all samples.Our method can efficiently identify the duplicated CYP2D6 allele in heterozygous samples, determine its copy number in a fraction of time compared to conventional methods and prevent incorrect ultrarapid phenotype calls. It also greatly reduces the cost, effort and time associated with CYP2D6 CNV genotyping.

  5. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    Science.gov (United States)

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

  6. Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.

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    Kwadwo A Kusi

    Full Text Available There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1. These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles and three (DiCo mix antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65-82% of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.

  7. Genetic tests for alleles of complementary-sex-determiner to support honeybee breeding programmes

    OpenAIRE

    Hyink, Otto; Laas, Frans; Dearden, Peter

    2013-01-01

    International audience The honeybee haplodiploid sex determination system depends on genetic variation at the complementary sex-determiner (csd) locus. In closed populations of honeybees, especially those undergoing selective breeding, the number of csd alleles can drop such that brood viability is affected. Here we present two polymerase chain reaction tests that allow the discrimination of csd alleles. Such tests should find utility in bee breeding programmes allowing the tracking and ma...

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

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    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.

  9. Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naive adults.

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    Edmond J Remarque

    Full Text Available Plasmodium falciparum: apical membrane antigen 1 (AMA1 is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 µg of a single allele AMA1 antigen (FVO formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naïve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i Antibody responses to various allelic variants, (ii Domain specificity, (iii Avidity, (iv IgG subclass levels, by ELISA and (v functionality of antibody responses by Growth Inhibition Assay (GIA. About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains.ClinicalTrials.gov NCT00730782.

  10. Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

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    Jill K Terra

    2011-12-01

    Full Text Available Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT, as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6 background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.

  11. 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.

  12. 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. PMID:27194288

  13. 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.

  14. The Plasmodium falciparum merozoite surface protein-1 19 KD antibody response in the Peruvian Amazon predominantly targets the non-allele specific, shared sites of this antigen

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    Silva Claudia

    2010-01-01

    Full Text Available Abstract Background Plasmodium falciparum re-emerged in Iquitos, Peru in 1994 and is now hypoendemic (P. falciparum infections can be followed using this population dynamic. Previous work demonstrated a strong association between this population's antibody response to PfMSP1-19KD and protection against febrile illness and parasitaemia. Therefore, some selection for PfMSP1-19KD allelic diversity would be expected if the protection is to allele-specific sites of PfMSP1-19KD. Here, the potential for allele-specific polymorphisms in this population is investigated, and the allele-specificity of antibody responses to PfMSP1-19KD are determined. Methods The 42KD region in PfMSP1 was genotyped from 160 individual infections collected between 2003 and 2007. Additionally, the polymorphic block 2 region of Pfmsp1 (Pfmsp1-B2 was genotyped in 781 infection-months to provide a baseline for population-level diversity. To test whether PfMSP1-19KD genetic diversity had any impact on antibody responses, ELISAs testing IgG antibody response were performed on individuals using all four allele-types of PfMSP1-19KD. An antibody depletion ELISA was used to test the ability of antibodies to cross-react between allele-types. Results Despite increased diversity in Pfmsp1-B2, limited diversity within Pfmsp1-42KD was observed. All 160 infections genotyped were Mad20-like at the Pfmsp1-33KD locus. In the Pfmsp1-19KD locus, 159 (99.4% were the Q-KSNG-F haplotype and 1 (0.6% was the E-KSNG-L haplotype. Antibody responses in 105 individuals showed that Q-KNG and Q-TSR alleles generated the strongest immune responses, while Q-KNG and E-KNG responses were more concordant with each other than with those from Q-TSR and E-TSR, and vice versa. The immuno-depletion ELISAs showed all samples responded to the antigenic sites shared amongst all allelic forms of PfMSP1-19KD. Conclusions A non-allele specific antibody response in PfMSP1-19KD may explain why other allelic forms have not

  15. A highly sensitive quantitative real-time pcr assay for determination of mutant jak2 exon 12 allele burden

    DEFF Research Database (Denmark)

    Kjær, L.; Riley, C.H.; Westman, M.;

    2012-01-01

    present a highly sensitive real-time quantitative PCR assay for determination of the mutant allele burden of JAK2 exon 12 mutations. In combination with high resolution melting analysis and sequencing the assay identified six patients carrying previously described JAK2 exon 12 mutations and one novel...... tool for quantitative monitoring of the mutant allele burden and accordingly also for determining the impact of treatment with interferon-α-2, shown to induce molecular remission in JAK2V617F-positive patients, which may be a future treatment option for JAK2 exon 12-positive patients as well. © 2012...

  16. Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays.

    Science.gov (United States)

    Smith, Andrew J P; Howard, Philip; Shah, Sonia; Eriksson, Per; Stender, Stefan; Giambartolomei, Claudia; Folkersen, Lasse; Tybjærg-Hansen, Anne; Kumari, Meena; Palmen, Jutta; Hingorani, Aroon D; Talmud, Philippa J; Humphries, Steve E

    2012-01-01

    Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAIRE, utilising large-scale genotyping technology (FAIRE-gen) to determine allelic effects on chromatin accessibility and regulatory potential. FAIRE-gen was explored using lymphoblastoid cells and the 50,000 SNP Illumina CVD BeadChip. The technique identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-α), rs7120118, coinciding with a previously GWAS-identified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016; p = 0.0006), and analysis of gene expression identified an allelic association with LXR-α expression in heart tissue. Using increasingly comprehensive genotyping chips and distinct tissues for examination, FAIRE-gen has the potential to aid the identification of many causal SNPs associated with disease from GWAS. PMID:22916038

  17. Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays.

    Directory of Open Access Journals (Sweden)

    Andrew J P Smith

    Full Text Available Following the widespread use of genome-wide association studies (GWAS, focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAIRE, utilising large-scale genotyping technology (FAIRE-gen to determine allelic effects on chromatin accessibility and regulatory potential. FAIRE-gen was explored using lymphoblastoid cells and the 50,000 SNP Illumina CVD BeadChip. The technique identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-α, rs7120118, coinciding with a previously GWAS-identified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016; p = 0.0006, and analysis of gene expression identified an allelic association with LXR-α expression in heart tissue. Using increasingly comprehensive genotyping chips and distinct tissues for examination, FAIRE-gen has the potential to aid the identification of many causal SNPs associated with disease from GWAS.

  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. Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles.

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    Eleonora Cocco

    Full Text Available Vitamin D response elements (VDREs have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects. Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients.

  20. 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.

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

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    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.

  2. Chromosomal instability determines taxane response

    DEFF Research Database (Denmark)

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

    2009-01-01

    -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...... 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...... resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents....

  3. Chromosomal instability determines taxane response.

    Science.gov (United States)

    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang; Howell, Michael; Ried, Thomas; Habermann, Jens K; Auer, Gert; Brenton, James D; Szallasi, Zoltan; Downward, Julian

    2009-05-26

    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 resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents. PMID:19458043

  4. Development of allele-specific multiplex PCR to determine the length of poly-T in intron 8 of CFTR

    OpenAIRE

    Neng Chen; Prada, Anne E.

    2014-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis has been implemented for Cystic Fibrosis (CF) carrier screening, and molecular diagnosis of CF and congenital bilateral absence of the vas deferens (CBAVD). Although poly-T allele analysis in intron 8 of CFTR is required when a patient is positive for R117H, it is not recommended for routine carrier screening. Therefore, commercial kits for CFTR mutation analysis were designed either to mask the poly-T allele re...

  5. Novel SLA-DR alleles of three Chinese pig strains and the related function in human T cell response.

    Science.gov (United States)

    Chen, Fuxiang; Xie, Jin; Zhou, Yun; Li, Ningli; Chou, Kuang-Yen

    2004-06-01

    To elucidate the structures of SLA-DR (swine leukocyte antigen DR) genes of three Chinese pig strains (Gz, Bm and Yn), the SLA-DRA and SLA-DRB cDNA were amplified by RT-PCR and subjected to determine the sequences. The whole structures of SLA-DRA alleles are identical among three strains, consisting of 759 nucleotides including an open reading frame (ORF), and are shared with those reported from NIH minipigs SLA-DRA(c) and SLA-DRA(d). The same length of the ORF-containing SLA-DRB genes of three Chinese pig strains was also identified. They are composed of 801 nucleotides encoding a xenogeneic antigen molecule of 266 amino acid residues. The nucleotide sequences of the SLA-DRB genes, however, are different when compared either among the three strains or with the published data of SLA-DRB sequences, which allowed our novel SLA-DRB alleles receiving their accession numbers AY102479, AY102480 and AY102481 from the GenBank. This study further reveals that the phylogenic homologies of MHC DR or DR-like genes in structures of nucleotides and deduced amino acids between Chinese pigs (SLA) and human (HLA-DRB1*0901) are better than those between pigs and mice (H-2(b)Ebeta). High similarities were also found for DRalpha-DRbeta heterodimers between Chinese pigs and human in terms of amino acids sequences critical for binding with human CD4 coreceptor molecule, which are better than those between SLA-DR and H-2 I-E molecules. A functional test indicated that, by cotransfection with Bm-DRA and Bm-DRB genes, the Bm-DR molecule-expressed L929 cells could stimulate human T cells quite well in a xenogeneic reaction in presence of human APCs.

  6. Novel SLA-DR Alleles of Three Chinese Pig Strains and the Related Function in Human T Cell Response

    Institute of Scientific and Technical Information of China (English)

    FuxiangChen; JinXie; YunZhou; NingliLi; Kuang-YenChou

    2004-01-01

    To elucidate the structures of SLA-DR (swine leukocyte antigen DR) genes of three Chinese pig strains (Gz, Bm and Yn), the SLA-DRA and SLA-DRB cDNA were amplified by RT-PCR and subjected to determine the sequences. The whole structures of SLA-DRA alleles are identical among three strains, consisting of 759 nucleotides including an open reading frame (ORF), and are shared with those reported from NIH minipigs SLA-DRAc and SLA-DRAd. The same length of the ORF-containing SLA-DRB genes of three Chinese pig strains was also identified. They are composed of 801 nucleotides encoding a xenogeneic antigen molecule of 266 amino acid residues. The nucleotide sequences of the SLA-DRB genes, however, are different when compared either among the three strains or with the published data of SLA-DRB sequences, which allowed our novel SLA-DRB alleles receiving their accession numbers AY102479, AY102480 and AY102481 from the GenBank. This study further reveals that the phylogenic homologies of MHC DR or DR-like genes in structures of nucleotides and deduced amino acids between Chinese pigs (SLA) and human (HLA-DRBI*0901) are better than those between pigs and mice (H-2b Eβ). High similarities were also found for DRα-DRβ heterodimers between Chinese pigs and human in terms of amino acids sequences critical for binding with human CD4 coreceptor molecule, which are better than those between SLA-DR and H-2 I-E molecules. A functional test indicated that, by cotransfection with Bm-DRA and Bm-DRB genes, the Bm-DR molecule-expressed L929 cells could stimulate human T cells quite well in a xenogeneic reaction in presence of human APCs.

  7. Novel SLA-DR Alleles of Three Chinese Pig Strains and the Related Function in Human T Cell Response

    Institute of Scientific and Technical Information of China (English)

    Fuxiang Chen; Jin Xie; Yun Zhou; Ningli Li; Kuang-Yen Chou

    2004-01-01

    To elucidate the structures of SLA-DR (swine leukocyte antigen DR) genes of three Chinese pig strains (Gz, Bm and Yn), the SLA-DRA and SLA-DRB cDNA were amplified by RT-PCR and subjected to determine the sequences. The whole structures of SLA-DRA alleles are identical among three strains, consisting of 759 nucleotides including an open reading frame (ORF), and are shared with those reported from NIH minipigs SLA-DRAc and SLA-DRAd. The same length of the ORF-containing SLA-DRB genes of three Chinese pig strains was also identified. They are composed of 801 nucleotides encoding a xenogeneic antigen molecule of 266 amino acid residues. The nucleotide sequences of the SLA-DRB genes, however, are different when compared either among the three strains or with the published data of SLA-DRB sequences, which allowed our novel SLA-DRB alleles receiving their accession numbers AY102479, AY102480 and AY102481 from the GenBank. This study further reveals that the phylogenic homologies of MHC DR or DR-like genes in structures of nucleotides and deduced amino acids between Chinese pigs (SLA) and human (HLA-DRB1*0901) are better than those between pigs and mice (H-2b Eβ). High similarities were also found for DRα-DRβ heterodimers between Chinese pigs and human in terms of amino acids sequences critical for binding with human CD4 coreceptor molecule, which are better than those between SLA-DR and H-2 I-E molecules. A functional test indicated that, by cotransfection with Bm-DRA and Bm-DRB genes, the Bm-DR molecule-expressed L929 cells could stimulate human T cells quite well in a xenogeneic reaction in presence of human APCs.

  8. Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele

    Science.gov (United States)

    Oni, Eileen N.; Halikere, Apoorva; Li, Guohui; Toro-Ramos, Alana J.; Swerdel, Mavis R.; Verpeut, Jessica L.; Moore, Jennifer C.; Bello, Nicholas T.; Bierut, Laura J.; Goate, Alison; Tischfield, Jay A.; Pang, Zhiping P.; Hart, Ronald P.

    2016-01-01

    Genetic variation in nicotinic receptor alpha 5 (CHRNA5) has been associated with increased risk of addiction-associated phenotypes in humans yet little is known the underlying neural basis. Induced pluripotent stem cells (iPSCs) were derived from donors homozygous for either the major (D398) or the minor (N398) allele of the nonsynonymous single nucleotide polymorphism (SNP), rs16969968, in CHRNA5. To understand the impact of these nicotinic receptor variants in humans, we differentiated these iPSCs to dopamine (DA) or glutamatergic neurons and then tested their functional properties and response to nicotine. Results show that N398 variant human DA neurons differentially express genes associated with ligand receptor interaction and synaptic function. While both variants exhibited physiological properties consistent with mature neuronal function, the N398 neuronal population responded more actively with an increased excitatory postsynaptic current response upon the application of nicotine in both DA and glutamatergic neurons. Glutamatergic N398 neurons responded to lower nicotine doses (0.1 μM) with greater frequency and amplitude but they also exhibited rapid desensitization, consistent with previous analyses of N398-associated nicotinic receptor function. This study offers a proof-of-principle for utilizing human neurons to study gene variants contribution to addiction. PMID:27698409

  9. Variation in ion leakage parameters of two wheat genotypes with different Rht-B1 alleles in response to drought

    Indian Academy of Sciences (India)

    Konstantina V Kocheva; Svetlana P Landjeva; Georgi I Georgiev

    2014-12-01

    The reaction to soil drying was evaluated in two Triticum aestivum near-isogenic lines carrying different alleles of the height-reducing gene Rht-B1 based on an improved method for assessment of electrolyte leakage. The two lines were previously shown to differ in their physiological responses to induced water deficit stress. Drought was imposed for 6 days on 10-day-old seedlings. Ion efflux from leaves was measured conductometrically in multiple time points during the 24 h incubation period, and the obtained biphasic kinetics was interpreted according to a previously developed theoretical model proposing different leakage rates through the apoplast and the symplast. Most of the model parameters were able to properly differentiate the two closely related genotypes. The mutant Rht-B1c displayed lower and slower electrolyte leakage in comparison with the wild-type Rht-B1a. It was speculated that the Rht genes expressing defective DELLA proteins might be involved in water stress response through modulation of cell wall stiffness, which influences its capacity for ions retention, and also by their contribution to ROS detoxification, thus indirectly stabilizing cellular membranes. The presented analytical approach relating processes of ion and water flow in and out of the cell could be used for characterization of membrane and cell wall properties of different genotypes under normal and stress conditions.

  10. Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays

    DEFF Research Database (Denmark)

    Smith, Frank Andrew; Howard, Philip; Shah, Sonia;

    2012-01-01

    Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory...... identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-α), rs7120118, coinciding with a previously GWAS-identified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic...

  11. 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.

  12. Development of allele-specific multiplex PCR to determine the length of poly-T in intron 8 of CFTR

    Directory of Open Access Journals (Sweden)

    Neng Chen

    2014-07-01

    Full Text Available Cystic fibrosis transmembrane conductance regulator (CFTR gene mutation analysis has been implemented for Cystic Fibrosis (CF carrier screening, and molecular diagnosis of CF and congenital bilateral absence of the vas deferens (CBAVD. Although poly-T allele analysis in intron 8 of CFTR is required when a patient is positive for R117H, it is not recommended for routine carrier screening. Therefore, commercial kits for CFTR mutation analysis were designed either to mask the poly-T allele results, unless a patient is R117H positive, or to have the poly-T analysis as a standalone reflex test using the same commercial platform. There are other standalone assays developed to detect poly-T alleles, such as heteroduplex analysis, High Resolution Melting (HRM curve analysis, allele-specific PCR (AS-PCR and Sanger sequencing. In this report, we developed a simple and easy-to-implement multiplex AS-PCR assay using unlabeled standard length primers, which can be used as a reflex or standalone test for CFTR poly-T track analysis. Out of 115 human gDNA samples tested, results from our new AS-PCR matched to the previous known poly-T results or results from Sanger sequencing.

  13. Role of swi7H4 mutant allele of DNA polymerase α in the DNA damage checkpoint response.

    Directory of Open Access Journals (Sweden)

    Saman Khan

    Full Text Available Besides being a mediator of initiation of DNA replication, DNA polymerase α plays a key role in chromosome maintenance. Swi7H4, a novel temperature sensitive mutant of DNA polymerase α was shown to be defective in transcriptional silencing at the mating type centromere and telomere loci. It is also required for the establishment of chromatin state that can recruit the components of the heterochromatin machinery at these regions. Recently the role of DNA polymerase α in the S-phase alkylation damage response in S. pombe has also been studied. Here we investigate whether defects generated by swi7H4, a mutant allele of DNA polymerase α can activate a checkpoint response. We show that swi7H4 exhibit conditional synthetic lethality with chk1 null mutant and the double mutant of swi7H4 with chk1 deletion aggravate the chromosome segregation defects. More importantly swi7H4 mutant cells delay the mitotic progression at non permissive temperature that is mediated by checkpoint protein kinase Chk1. In addition we show that, in the swi7H4 mutant background, cells accumulate DNA damage at non permissive temperature activating the checkpoint kinase protein Chk1. Further, we observed synthetic lethality between swi7H4 and a number of genes involved in DNA repair pathway at semi permissive temperature. We summarize that defects in swi7H4 mutant results in DNA damage that delay mitosis in a Chk1 dependent manner that also require the damage repair pathway for proper recovery.

  14. Merozoite surface protein 2 allelic variation influences the specific antibody response during acute malaria in individuals from a Brazilian endemic area

    OpenAIRE

    Selma Sallenave-Sales; Clarissa Perez Faria; Mariano Gustavo Zalis; Cláudio Tadeu Daniel-Ribeiro; Maria de Fátima Ferreira-da-Cruz

    2007-01-01

    The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2) on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil), by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG ant...

  15. The molecular determination of HLA-Cw alleles in the Mandenka (West Africa) reveals a close genetic relationship between Africans and Europeans.

    Science.gov (United States)

    Sanchez-Mazas, A; Steiner, Q G; Grundschober, C; Tiercy, J M

    2000-10-01

    HLA-Cw alleles were determined by high-resolution polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) oligotyping in a sample of 165 Mandenka, a population from Eastern Senegal previously analysed for A/B and DRB/DQB polymorphisms. A total of 18 Cw alleles were identified, with Cw*0401/5 and 1601 accounting for a combined frequency of 36%. A comparison of Cw allele frequencies among several populations of different origins, Mandenka, Swiss, English, Ashkenazi Jews from the UK and Japanese, reveals a high genetic heterogeneity among them, but also a much closer relationship between Mandenka, Europeans and Ashkenazi than between any of these populations and Japanese. Cw*0501, Cw*0701 and Cw*1601, among others, appear to be restricted to the European and African populations. Many B-Cw haplotypes exhibit a significant linkage disequilibrium in the Mandenka, among which B*3501-Cw*0401 and B*7801-Cw*1601, formed by the most frequent B and Cw alleles, and B*5201-Cw*1601, B*5702-Cw*18 and B*4410-Cw*0401, not yet observed in other populations. B*3501-Cw*0401 is found with similar frequencies in Europeans. The results possibly support a close historical relationship between Africans and Europeans as compared to East Asiatics. However, the HLA-Cw frequency distributions are characterised by an excess of heterozygotes, indicating that balancing selection may have played a role in the evolution of this polymorphism.

  16. Chromosomal instability determines taxane response

    OpenAIRE

    Swanton, Charles; Nicke, Barbara; Schuett, Marion; Eklund, Aron C.; Ng, Charlotte; Li, Qiyuan; Hardcastle, Thomas; Lee, Alvin; Roy, Rajat; East, Philip; Kschischo, Maik; Endesfelder, David; Wylie, Paul; Kim, Se Nyun; Chen, Jie-Guang

    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....

  17. Adaptation of CD8 T cell responses to changing HIV-1 sequences in a cohort of HIV-1 infected individuals not selected for a certain HLA allele.

    Directory of Open Access Journals (Sweden)

    Julia Roider

    Full Text Available HIV evades CD8 T cell mediated pressure by viral escape mutations in targeted CD8 T cell epitopes. A viral escape mutation can lead to a decline of the respective CD8 T cell response. Our question was what happened after the decline of a CD8 T cell response and - in the case of viral escape - if a new CD8 T cell response towards the mutated antigen could be generated in a population not selected for certain HLA alleles. We studied 19 antiretroviral-naïve HIV-1 infected individuals with different disease courses longitudinally. A median number of 12 (range 2-24 CD8 T cell responses towards Gag and Nef were detected per study subject. A total of 30 declining CD8 T cell responses were studied in detail and viral sequence analyses showed amino acid changes in 25 (83% of these. Peptide titration assays and definition of optimal CD8 T cell epitopes revealed 12 viral escape mutations with one de-novo response (8%. The de-novo response, however, showed less effector functions than the original CD8 T cell response. In addition we identified 4 shifts in immunodominance. For one further shift in immunodominance, the mutations occurred outside the optimal epitope and might represent processing changes. Interestingly, four adaptations to the virus (the de-novo response and 3 shifts in immunodominance occurred in the group of chronically infected progressors. None of the subjects with adaptation to the changing virus carried the HLA alleles B57, B*58:01 or B27. Our results show that CD8 T cell responses adapt to the mutations of HIV. However it was limited to only 20% (5 out of 25 of the epitopes with viral sequence changes in a cohort not expressing protective HLA alleles.

  18. Adaptation of CD8 T cell responses to changing HIV-1 sequences in a cohort of HIV-1 infected individuals not selected for a certain HLA allele.

    Science.gov (United States)

    Roider, Julia; Kalteis, Anna-Lena; Vollbrecht, Thomas; Gloning, Lisa; Stirner, Renate; Henrich, Nadja; Bogner, Johannes R; Draenert, Rika

    2013-01-01

    HIV evades CD8 T cell mediated pressure by viral escape mutations in targeted CD8 T cell epitopes. A viral escape mutation can lead to a decline of the respective CD8 T cell response. Our question was what happened after the decline of a CD8 T cell response and - in the case of viral escape - if a new CD8 T cell response towards the mutated antigen could be generated in a population not selected for certain HLA alleles. We studied 19 antiretroviral-naïve HIV-1 infected individuals with different disease courses longitudinally. A median number of 12 (range 2-24) CD8 T cell responses towards Gag and Nef were detected per study subject. A total of 30 declining CD8 T cell responses were studied in detail and viral sequence analyses showed amino acid changes in 25 (83%) of these. Peptide titration assays and definition of optimal CD8 T cell epitopes revealed 12 viral escape mutations with one de-novo response (8%). The de-novo response, however, showed less effector functions than the original CD8 T cell response. In addition we identified 4 shifts in immunodominance. For one further shift in immunodominance, the mutations occurred outside the optimal epitope and might represent processing changes. Interestingly, four adaptations to the virus (the de-novo response and 3 shifts in immunodominance) occurred in the group of chronically infected progressors. None of the subjects with adaptation to the changing virus carried the HLA alleles B57, B*58:01 or B27. Our results show that CD8 T cell responses adapt to the mutations of HIV. However it was limited to only 20% (5 out of 25) of the epitopes with viral sequence changes in a cohort not expressing protective HLA alleles.

  19. A Dominant Allele of Arabidopsis Pectin-Binding Wall-Associated Kinase Induces a Stress Response Suppressed by MPK6 but Not MPK3 Mutations

    Institute of Scientific and Technical Information of China (English)

    Bruce D.Kohorn; Susan L.Kohorn; Tanya Todorova; Gillian Baptiste; Kevin Stansky; Meghan McCullough

    2012-01-01

    The plant cell wall is composed of a matrix of cellulose fibers,flexible pectin polymers,and an array of assorted carbohydrates and proteins.The receptor-like Wall-Associated Kinases(WAKs)of Arabidopsis bind pectin in the wall,and are necessary both for cell expansion during development and for a response to pathogens and wounding.Mitogen Activated Protein Kinases(MPKs)form a major signaling link between cell surface receptors and both transcriptional and enzyme regulation in eukaryotes,and Arabidopsis MPK6 and MPK3 indeed have important roles in development and the response to stress and pathogens.A dominant allele of WAK2 requires kinase activity and activates a stress response that includes an increased ROS accumulation and the up-regulation of numerous genes involved in pathogen resistance,wounding,and cell wall biogenesis.This dominant allele requires a functional pectin binding and kinase domain,indicating that it is engaged in a WAK signaling pathway.A null mutant of the major plasma membrane ROS-producing enzyme complex,rbohd/f does not suppress the WAK2cTAP-induced phenotype.A mpk6,but not a mpk3,null allele is able to suppress the effects of this dominant WAK2 mutation,thus distinguishing MPK3 and MPK6,whose activity previously was thought to be redundant.Pectin activation of gene expression is abated in a wak2-null,but is tempered by the WAK-dominant allele that induces elevated basal stress-related transcript levels.The results suggest a mechanism in which changes to the cell wall can lead to a large change in cellular responses and help to explain how pathogens and wounding can have general effects on growth.

  20. Isolation of S-locus F-box alleles in Prunus avium and their application in a novel method to determine self-incompatibility genotype.

    Science.gov (United States)

    Vaughan, S P; Russell, K; Sargent, D J; Tobutt, K R

    2006-03-01

    This study characterises a series of 12 S-locus haplotype-specific F-box protein genes (SFB) in cherry (Prunus avium) that are likely candidates for the pollen component of gametophytic self-incompatibility in this species. Primers were designed to amplify 12 SFB alleles,including the introns present in the 50 untranslated region;sequences representing the S-alleles S1, S2, S3, S4, S40, S5,S6, S7, S10, S12, S13 and S16 were cloned and characterized. [The nucleotide sequences reported in this paper have been submitted to the EMBL/GenBank database under the following accession numbers: PaSFB1(AY805048), PaSFB2 (AY805049), PaSFB3 (AY805057),PaSFB4 (AY649872), PaSFB40 (AY649873), PaSFB5(AY805050), PaSFB6 (AY805051), PaSFB7 (AY805052),PaSFB10 (AY805053), PaSFB12 (AY805054), PaSFB13(AY805055), PaSFB16 (AY805056).] Though the coding regions of six of these alleles have been reported previously,the intron sequence has previously been reported only for S6. Analysis of the introns revealed sequence and length polymorphisms. A novel, PCR-based method to genotype cultivars and wild accessions was developed which combines fluorescently labelled primers amplifying the intron of SFB with similar primers for the first intron of S-RNase alleles. Intron length polymorphisms were then ascertained using a semi-automated sequencer. The convenience and reliability of this method for the determination of the self-incompatibility (SI) genotype was demonstrated both in sweet cherry cultivars representing alleles S1 to S16 and in individuals from a wild population encompassing S-alleles S17 to S22. This method will greatly expedite SI characterisation in sweet cherry and also facilitate large-scale studies of self-incompatibility in wild cherry and other Prunus populations.

  1. Functional screening of willow alleles in Arabidopsis combined with QTL mapping in willow (Salix) identifies SxMAX4 as a coppicing response gene.

    Science.gov (United States)

    Salmon, Jemma; Ward, Sally P; Hanley, Steven J; Leyser, Ottoline; Karp, Angela

    2014-05-01

    Willows (Salix spp.) are important biomass crops due to their ability to grow rapidly with low fertilizer inputs and ease of cultivation in short-rotation coppice cycles. They are relatively undomesticated and highly diverse, but functional testing to identify useful allelic variation is time-consuming in trees and transformation is not yet possible in willow. Arabidopsis is heralded as a model plant from which knowledge can be transferred to advance the improvement of less tractable species. Here, knowledge and methodologies from Arabidopsis were successfully used to identify a gene influencing stem number in coppiced willows, a complex trait of key biological and industrial relevance. The strigolactone-related More AXillary growth (MAX) genes were considered candidates due to their role in shoot branching. We previously demonstrated that willow and Arabidopsis show similar response to strigolactone and that transformation rescue of Arabidopsis max mutants with willow genes could be used to detect allelic differences. Here, this approach was used to screen 45 SxMAX1, SxMAX2, SxMAX3 and SxMAX4 alleles cloned from 15 parents of 11 mapping populations varying in shoot-branching traits. Single-nucleotide polymorphism (SNP) frequencies were locus dependent, ranging from 29.2 to 74.3 polymorphic sites per kb. SxMAX alleles were 98%-99% conserved at the amino acid level, but different protein products varying in their ability to rescue Arabidopsis max mutants were identified. One poor rescuing allele, SxMAX4D, segregated in a willow mapping population where its presence was associated with increased shoot resprouting after coppicing and colocated with a QTL for this trait.

  2. DETERMINANTS OF INTERNET CORPORATE SOCIAL RESPONSIBILITY COMMUNICATION

    OpenAIRE

    Laetitia Pozniak; Perrine Ferauge; Laurent Arnone; Angy Geerts

    2011-01-01

    The goal of this research is to identify determinants of internet Corporate Social Responsibility communication of 41 Belgian companies. Using a content analysis and scoring technique, this paper estimates the degree of website information disclosure of companies' involvement with corporate social responsibility. This score is then regressed via Ordinary Least Square (OLS) on variables presented in the literature as determinants of firm internet communication and led to the formulation of our...

  3. Merozoite surface protein 2 allelic variation influences the specific antibody response during acute malaria in individuals from a Brazilian endemic area

    Directory of Open Access Journals (Sweden)

    Selma Sallenave-Sales

    2007-06-01

    Full Text Available The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2 on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil, by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG antibody responses were predominantly directed to FC27 parasites and were correlated to the extension of polymorphism presented by each MSP-2 region. This finding demonstrated the impact of the genetic polymorphism on antibody response and therefore, its importance on malaria vaccine efficacy.

  4. Differences in the expressed HLA class I alleles effect the differential clustering of HIV type 1-specific T cell responses in infected Chinese and Caucasians

    Institute of Scientific and Technical Information of China (English)

    Yu,XG; Addo,MM; Perkins,BA; Wej,FL; Rathod,A; Geer,SC; Parta,M; Cohen,D; Stone,DR; Russell,CJ; Tanzi,G; Mei,S; Wureel,AG; Frahm,N; Lichterfeld,M; Heath,L; Mullins,JI; Marincola,F; Goulder,PJR; Brander,C; Allen,T; Cao,YZ; Walker,BD; Altfeld,M

    2005-01-01

    China is a region of the world with a rapidly spreading HIV-1 epidemic. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to support the design and testing of an effective HIV-1 vaccine for this population. HIV-1-specific T cell responses were characterized in 32 HIV-1-infected individuals of Chinese origin and compared to 34 infected caucasians using 410 overlapping peptides spanning the entire HIV-1 clade B consensus sequence in an IFN-gamma ELISpot assay. All HIV-1 proteins were targeted with similar frequency in both populations and all study subjects recognized at least one overlapping peptide. HIV-1-specific T cell responses clustered in seven different regions of the HIV-1 genome in the Chinese cohort and in nine different regions in the caucasian cohort. The dominant HLA class I alleles expressed in the two populations differed significantly, and differences in epitope clustering pattern were shown to be influenced by differences in class I alleles that restrict immunodominant epitopes. These studies demonstrate that the clustering of HIV-1-specific T cell responses is influenced by the genetic HLA class I background in the study populations. The design and testing of candidate vaccines to fight the rapidly growing HIV-1 epidemic must therefore take the HLA genetics of the population into account as specific regions of the virus can be expected to be differentially targeted in ethnically diverse populations.

  5. Association of BoLA DRB3 alleles with variability in immune response among the crossbred cattle vaccinated for foot-and-mouth disease (FMD).

    Science.gov (United States)

    Gowane, G R; Sharma, A K; Sankar, M; Narayanan, K; Das, Biswajit; Subramaniam, S; Pattnaik, B

    2013-08-01

    Polymorphism of bovine leukocyte antigen (BoLA) DRB3 gene is being intensively investigated for potential association with economically important diseases of cattle. Accordingly, we investigated the association of DRB3 Exon 2 polymorphism as evidenced by the variation in the binding pockets with variability in immune response to inactivated trivalent (O, A and Asia1) foot and mouth disease virus (FMDV) vaccine in a closed population of crossbred cattle. Antibody titer of ≥ 1.8 was set as the cut off value to distinguish the protected (≥ 1.8) and unprotected (Kabat index. Similarly, specific residues in pockets were crucial for immune response to FMD vaccine. There were specific substitutions in un-protected alleles such as absence of acidic amino acids substituted by basic amino acid at β71, presence of non-polar cysteine or basic histidine at β30 and presence of polar tyrosine at β37. From the observations, we hypothesize that the substitutions lead to unique conformational changes in the protein products of the studied alleles that would associate with the protective or unprotective antibody response to FMDV vaccine. The knowledge has potential implications in future selection programs if integrated with the complete BoLA haplotype details and production traits of the herd. PMID:23541924

  6. CYP2C19*2 and Other Allelic Variants Affecting Platelet Response to Clopidogrel Tested by Thrombelastography in Patients with Acute Coronary Syndrome

    Institute of Scientific and Technical Information of China (English)

    Jian Liu; Xiao-Yan Nie; Yong Zhang; Yun Lu; Lu-Wen Shi; Wei-Min Wang

    2015-01-01

    Background:To investigate the contributions ofCYP2C 19 polymorphisms to the various clopidogrel responses tested by thrombelastography (TEG) in Chinese patients with the acute coronary syndrome (ACS).Methods:Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy.CYP2C 19 loss of function (LOF) and gain of function (GOF) genotype,adenosine 5'-diphosphate (ADP)-channel platelet inhibition rate (PIR) tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients.Results:High on-treatment platelet reactivity (HTPR) prevalence defined by PIR <30% by TEG in ADP-channel was 32.76% (38/116).With respect to the normal wild type,CYP2C 19*2,and *3 LOF alleles,and * 17 GOF alleles,patients were classified into three metabolism phenotypes:41.38% were extensive metabolizers (EMs),56.90% were intermediate metabolizers (IMs),and 1.72% were poor metabolizers (PMs).Of the enrolled patients,31.47%,5.17%,and 0.43%,respectively,were carriers of *2,*3,and * 17 alleles.The HTPR incidence differed significantly according to CYP2C 19 genotypes,accounting for 18.75%,41.54%,and 100.00% in EMs,IMs,and PMs,respectively.Eighteen (17.24%) ischemic events occurred during the 3-month follow-up,and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group.Conclusions:Genetic CYP2C 19 polymorphisms are relative to the inferior,the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.

  7. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice.

    Science.gov (United States)

    Inoue, Masashi; Glendinning, John I; Theodorides, Maria L; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K; Bachmanov, Alexander A

    2007-12-19

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (D-tryptophan, D-phenylalanine, L-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (L-glutamine, L-threonine, L-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5'-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system. PMID:17911381

  8. Determinants of public T cell responses

    Institute of Scientific and Technical Information of China (English)

    Hanjie Li; Congting Ye; Guoli Ji; Jiahuai Han

    2012-01-01

    Historically,sharing T cell receptors (TCRs) between individuals has been speculated to be impossible,considering the dramatic discrepancy between the potential enormity of the TCR repertoire and the limited number of T cells generated in each individual.However,public T cell response,in which multiple individuals share identical TCRs in responding to a same antigenic epitope,has been extensively observed in a variety of immune responses across many species.Public T cell responses enable individuals within a population to generate similar antigen-specific TCRs against certain ubiquitous pathogens,leading to favorable biological outcomes.However,the relatively concentrated feature of TCR repertoire may limit T cell response in a population to some other pathogens.It could be a great benefit for human health if public T cell responses can be manipulated.Therefore,the mechanistic insight of public TCR generation is important to know.Recently,high-throughput DNA sequencing has revolutionized the study of immune receptor repertoires,which allows a much better understanding of the factors that determine the overlap of TCR repertoire among individuals.Here,we summarize the current knowledge on public T-cell response and discuss future challenges in this field.

  9. Pharmacogenomic determinants of response to cardiovascular drugs

    Directory of Open Access Journals (Sweden)

    Stankov Karmen M.

    2015-01-01

    Full Text Available Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Despite considerable advances in cardiovascular pharmacology, significant inter-individual variability in response to drugs affects both their efficacy and safety profile. Drug-gene associations have emerged as important factors determining a spectrum of response to therapy. Pharmacogenomic interactions in cardiovascular medicine are also involved in etiology of adverse effects that may be life-threatening, such as statininduced myopathy or a hemorrhage/thrombosis event during anticoagulant therapy. Introduction of genetic tests prior to the initiation of therapy and implementation of genetically-guided therapy represent a step forward to achieving a goal of individualized medicine in cardiology, already present in recommendations for warfarin and clopidogrel. However, further investigations addressing genomic predictors of variability in response to drugs are still needed and translating these findings into routine clinical practice remains a substantial challenge. [Projekat Ministarstva nauke Republike Srbije, br. III41012

  10. Determining fertility in a bovine subject comprises detecting in a sample from the bovine subject the presence or absence of genetic marker alleles associated with a trait indicative of fertility of the bovine subject and/or off-spring

    DEFF Research Database (Denmark)

    2009-01-01

    for determining fertility in a bovine subject; and selecting bovine subjects for breeding purposes (all claimed). DETAILED DESCRIPTION - Determining fertility in a bovine subject comprises detecting in a sample from the bovine subject the presence or absence of two or more genetic marker alleles......NOVELTY - Determining fertility in a bovine subject comprises detecting in a sample from the bovine subject the presence or absence of two or more genetic marker alleles that are associated with a trait indicative of fertility of the bovine subject and/or off-spring. USE - The methods are useful...... that are associated with a trait indicative of fertility of the bovine subject and/or off-spring, where the two or more genetic marker alleles are single nucleotide polymorphisms selected from Hapmap60827-rs29019866, ARS-BFGL-NGS-40979, Hapmap47854-BTA-119090, ARS-BFGL-NGS-114679, Hapmap43841-BTA-34601, Hapmap43407...

  11. HLA-A and HLA-B allele frequencies in a mestizo population from Guadalajara, Mexico, determined by sequence-based typing.

    Science.gov (United States)

    Leal, C A; Mendoza-Carrera, F; Rivas, F; Rodriguez-Reynoso, S; Portilla-de Buen, E

    2005-12-01

    HLA-A and HLA-B genes were typed by DNA sequencing in a mestizo population from Guadalajara, Jalisco, Mexico. Thirty-seven HLA-A and 51 HLA-B alleles were observed in 103 samples. The common typical Amerindian alleles (>5%) and haplotypes (>or=2.0%) found were A*02010101, *24020101, *310102, B*350101, and *4002, and A*310102-B*4002, A*240201-B*350101, and the typical European alleles were A*010101, *29010101, B*1402, B*180101, and A*020101-B*1402, A*020101-B*510101, and A*3002-B*180101. This reflects the blending of the two main parental populations of mestizos: Amerindian and Iberian. Mexicans were found to be relatively closer to the Portuguese than to Spaniards. This proximity may indicate a larger Portuguese influence in Mexicans than previously considered. Present data contribute to the understanding of the genetic structure in Mexico.

  12. 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

  13. 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...

  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. Influence of HLA-DRB1 and HLA-DQB1 alleles on IgG antibody response to the P. vivax MSP-1, MSP-3α and MSP-9 in individuals from Brazilian endemic area.

    Directory of Open Access Journals (Sweden)

    Josué C Lima-Junior

    Full Text Available BACKGROUND: The antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials. METHODS AND FINDINGS: In this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276 against P. vivax Merozoite Surface Protein-1 (MSP-1, MSP-3α and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. The proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%, PvMSP-3 (77% and PvMSP-9 (76%. Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1*01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein. CONCLUSIONS: HLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates.

  16. Initial invasion of gametophytic self-incompatibility alleles in the absence of tight linkage between pollen and pistil S alleles.

    Science.gov (United States)

    Sakai, Satoki; Wakoh, Haluka

    2014-08-01

    In homomorphic self-incompatibility (SI) systems of plants, the loci controlling the pollen and pistil types are tightly linked, and this prevents the generation of compatible combinations of alleles expressing pollen and pistil types, which would result in self-fertilization. We modeled the initial invasion of the first pollen and pistil alleles in gametophytic SI to determine whether these alleles can stably coexist in a population without tight linkage. We assume pollen and pistil loci each carry an incompatibility allele S and an allele without an incompatibility function N. We assume that pollen with an S allele are incompatible with pistils carrying S alleles, whereas other crosses are compatible. Ovules in pistils carrying an S allele suffer viability costs because recognition consumes resources. We found that the cost of carrying a pistil S allele allows pollen and pistil S alleles to coexist in a stable equilibrium if linkage is partial. This occurs because parents that carry pistil S alleles but are homozygous for pollen N alleles cannot avoid self-fertilization; however, they suffer viability costs. Hence, pollen N alleles are selected again. When pollen and pistil S alleles can coexist in a polymorphic equilibrium, selection will favor tighter linkage.

  17. RESPONSIBILITY, DETERMINANT FOR THE EFFICIENCY OF GOVERNANCE

    OpenAIRE

    Florina Popa

    2008-01-01

    Understanding the governance concept implies the identification of the leaders,rules and directions pursued by a country in terms of its economic, social and cultural policy.The article briefly refers to the concept of responsibility and its importance within democraticgovernance. It is one of the basic principles whose way of application influences the runningof institutions and the regulations of governance, either fostering or influencing theireffectiveness and efficiency. The paper presen...

  18. Genetic Determinants of Responses to Selenium Supplementation

    Science.gov (United States)

    In a cohort of healthy adults (106 M, 155 W) in eastern North Dakota, we determined the relationships of five biomarkers of selenium (Se) status (plasma Se, serum selenoprotein P [SePP], plasma glutathione peroxidase [GPX3] activity, buccal cell Se, urine Se) to genotype for four selenoproteins (cyt...

  19. Western-type diet modulates inflammatory responses and impairs functional outcome following permanent middle cerebral artery occlusion in aged mice expressing the human apolipoprotein E4 allele

    OpenAIRE

    Dhungana, Hiramani; Rolova, Taisia; Savchenko, Ekaterina; Wojciechowski, Sara; Savolainen, Kaisa; Ruotsalainen, Anna-Kaisa; Sullivan, Patrick M.; Koistinaho, Jari; Malm, Tarja

    2013-01-01

    Background Numerous clinical trials in stroke have failed, most probably partially due to preclinical studies using young, healthy male rodents with little relevance to the heterogenic conditions of human stroke. Co-morbid conditions such as atherosclerosis and infections coupled with advanced age are known to contribute to increased risk of cerebrovascular diseases. Clinical and preclinical studies have shown that the E4 allele of human apolipoprotein (ApoE4) is linked to poorer outcome in v...

  20. Determinant Factors of the Organizations’ Involvement in Social Responsibility Programs

    OpenAIRE

    Razvan Catalin DOBREA; Aurora BURCA

    2010-01-01

    The involvement in social responsibility programs became a current practice at the organizations’ level, determined by the necessity of an approach orientated on competition and performance. The social responsibility of actions diversity imposes an approach in stages that has to correlate the organization’s interests with those of the civil society. The present paper highlights the determinant factors ensemble of the implication in social responsibility actions as well as the main difficultie...

  1. What phylogeny and gene genealogy analyses reveal about homoplasy in citrus microsatellite alleles

    OpenAIRE

    Barkley, Noelle A.; Krueger, Robert R.; Federici, Claire T.; Roose, Mikeal L

    2009-01-01

    Sixty-five microsatellite alleles amplified from ancestral citrus accessions classified in three separate genera were evaluated for sequence polymorphism to establish the basis of inter- and intra-allelic genetic variation, evaluate the extent of size homoplasy, and determine an appropriate model (stepwise or infinite allele) for analysis of citrus microsatellite alleles. Sequences for each locus were aligned and subsequently used to determine relationships between alleles of different taxa v...

  2. Excess of transmission of the G allele of the -1438A/G polymorphism of the 5-HT2A receptor gene in patients with schizophrenia responsive to antipsychotics

    Directory of Open Access Journals (Sweden)

    Hamon Michel

    2008-05-01

    Full Text Available Abstract Background The -1438A/G polymorphism of the 5-HT2A gene has been found to be associated with clinical response to clozapine and other second generation antipsychotics. Testing the impact of this marker on response to first generation antipsychotics (which have a lower affinity for the 5-HT2A receptor provides the opportunity to help disentangling the two different roles that this polymorphism might have. A psychopharmacogenetic role should be detected only for antipsychotics with high affinity to the 5-HT2A receptor (therefore to second generation antipsychotics. An alternative role would imply tagging a subgroup of patients responsive to any antipsychotic, whatever their affinity, meaning that the association is more depending on non pharmacological charaterictics, such as clinical specificities. Methods A family-based sample of 100 Algerian patients with schizophrenia (according to DSM-IV criteria and their 200 biological parents was recruited, in order to avoid stratification biases. Patients were all treated, or have been treated, by conventional antipsychotics (mainly haloperidol for at least four weeks, at appropriate dosage. May and Dencker scale was used to distinguish responders and non responders. Results No allele of the -1438A/G polymorphism of the 5-HT2A gene was transmitted in excess (50 transmitted for 38 untransmitted in the whole sample of patients with schizophrenia (p = .90. In contrast, a significant excess of transmission of the G allele was observed (p = .02 in the subgroup of patients with good treatment response (17 transmitted for 6 untransmitted. Conclusion Using a TDT approach, we showed that the G allele of the -1438A/G polymorphism of the gene coding for the 5-HT2A receptor was associated to schizophrenia with good response to conventional antipsychotics, although this conclusion is based on 88 informative patients only. Because previous data showed the same result with atypical antipsychotics, it can be

  3. Federal tax compliance: implications for contractor responsibility determinations

    OpenAIRE

    Rendon, Juanita M.; Rendon, Rene G.

    2006-01-01

    The Federal Acquisition Regulation (FAR) states that no contract award shall be made unless the contracting officer makes an affirmative determination of the contractor's responsibility. Two aspects of determining responsibility include the contractor's financial resources and record of integrity and business ethics. Recent reports from the Governement Accountability Office (GAO) indicate that many federal contractors are not complying with federal tax compliance requirements and are abusin...

  4. Financial and Non Financial Determinants of Corporate Social Responsibility

    OpenAIRE

    Faris Nasif AL- Shubiri; Abedalfattah Zuhair Al-abedallat; Marwan Mohammad Abu Orabi

    2012-01-01

    Accounting, economic, social and political, and slack resources theories provide different perspectives to addressing corporate social responsibility in relation to disclosure, corporate financial performance e.t.c. This paper aims to identify the determinants financial and non financial of corporate social responsibility (CSR) in Jordan .The annual reports determine a sample of 60 industrial companies listed on the Amman Stock Exchange for a period from 2006 to 2010 in Jordan were used as a ...

  5. 40 CFR 1065.845 - Response factor determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Response factor determination. 1065.845 Section 1065.845 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response...

  6. Quantitative Sequencing for the Determination of Kdr-type Resistance Allele (V419L, L925I, I936F) Frequencies in Common Bed Bug (Hemiptera: Cimicidae) Populations Collected from Israel.

    Science.gov (United States)

    Palenchar, Daniel J; Gellatly, Kyle J; Yoon, Kyong Sup; Mumcuoglu, Kosta Y; Shalom, Uri; Clark, J Marshall

    2015-09-01

    Human bed bug infestations have dramatically increased worldwide since the mid-1990s. A similar phenomenon was also observed in Israel since 2005, when infestations were reported from all over the country. Two single nucleotide polymorphisms (V419L and L925I) in the bed bug voltage-sensitive sodium channel confer kdr-type resistance to pyrethroids. Using quantitative sequencing (QS), the resistance allele frequencies of Israeli bed bug populations from across the country were determined. Genomic DNA was extracted from samples of 12 populations of bed bugs collected from Israel and DNA fragments containing the V419L or L925I and I936F mutations sites were PCR amplified. The PCR products were analyzed by QS and the nucleotide signal ratios calculated and used to predict the resistance allele frequencies of the unknown populations. Results of the genetic analysis show that resistant nucleotide signals are highly correlated to resistance allele frequencies for both mutations. Ten of the 12 tested populations had 100% of the L925I mutation and 0% of the V419L mutation. One population was heterogeneous for the L925I mutation and had 0% of the V419L mutation and another population was heterogeneous for the V419L mutation and had 100% of the L925I mutation. I936F occurred only at low levels. These results indicate that bed bugs in Israel are genetically resistant to pyrethroids. Thus, pyrethroids should only be used for bed bug management with caution using effective application and careful monitoring procedures. Additionally, new and novel-acting insecticides and nonchemical means of controlling bed bugs should be explored. PMID:26336243

  7. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being the best. \\paragraph*{Conclusions:} Different allele coding methods lead to the same inference in the marker-based and equivalent models when a fixed...... 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...

  8. 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.

  9. High-speed droplet-allele-specific polymerase chain reaction for genotyping of single nucleotide polymorphisms.

    Science.gov (United States)

    Matsuda, Kazuyuki; Honda, Takayuki

    2015-01-01

    Single nucleotide alternations such as single nucleotide polymorphisms (SNPs) or single nucleotide mutations are useful genetic markers for molecular diagnosis, prognosis, drug response, and predisposition to diseases. Rapid identification of SNPs or mutations is clinically important, especially for determining drug responses and selection of molecular-targeted therapy. Here, we describe a rapid genotyping assay based on the allele-specific polymerase chain reaction (AS-PCR) by using our droplet-PCR machine (droplet-AS-PCR).

  10. The Length Distribution of Class I-Restricted T Cell Epitopes Is Determined by Both Peptide Supply and MHC Allele-Specific Binding Preference

    DEFF Research Database (Denmark)

    Trolle, Thomas; McMurtrey, Curtis P.; Sidney, John;

    2016-01-01

    HLA class I-binding predictions are widely used to identify candidate peptide targets of human CD8+ T cell responses. Many such approaches focus exclusively on a limited range of peptide lengths, typically 9 aa and sometimes 9-10 aa, despite multiple examples of dominant epitopes of other lengths...

  11. Calcium influx determines the muscular response to electrotransfer

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... reducing Ca(2+) influx. Larger Ca(2+) influx as induced by 8-HV pulses leads to muscle damage and muscle fiber regeneration through recruitment of satellite cells. The extent of Ca(2+) influx determines the muscular response to electrotransfer and, thus, the success of a given application. In the case...

  12. Determinants to optimize response to clopidogrel in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Betti Giusti

    2010-04-01

    Full Text Available Betti Giusti, Anna Maria Gori, Rossella Marcucci, Claudia Saracini, Anna Vestrini, Rosanna AbbateDepartment of Medical and Surgical Critical Care, University of Florence, SOD Atherothrombotic Diseases, AOU Careggi, Florence, ItalyAbstract: The inhibition of platelet function by antiplatelet therapy determines the improvement of the survival of patients with clinically evident cardiovascular disease. Clopidogrel in combination with aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. However, major adverse cardiovascular events including stent thrombosis occur in patients taking clopidogrel and aspirin. A growing body of evidence demonstrates that high post-treatment platelet reactivity on antiplatelet treatment is associated with increased risk of adverse clinical events. Clopidogrel requires conversion to active metabolite by cytochrome P450 isoenzymes. The active metabolite inhibits ADP-stimulated platelet activation by irreversibly binding to P2Y12 receptors. Recently, the loss-of-function CYP2C19*2 allele has been associated with decreased metabolization of clopidogrel, poor antiaggregant effect, and increased cardiovascular events. In high risk vascular patients, the CYP2C19*2 polymorphism is a strong predictor of adverse cardiovascular events and particularly of stent thrombosis. Prospective studies evaluating if an antiplatelet treatment tailored on individual characteristics of patients, CYP2C19*2 genotypes, platelet phenotype, drug–drug interaction, as well as traditional and procedural risk factors, are now urgently needed for the identification of therapeutic strategies providing the best benefit for the single subject.Keywords: antiplatelet therapy, clopidogrel, cytochrome P450 2C19 loss-of-function polymorphism, major adverse cardiovascular events, percutaneous coronary interventions

  13. Financial and Non Financial Determinants of Corporate Social Responsibility

    Directory of Open Access Journals (Sweden)

    Faris Nasif AL- Shubiri

    2012-12-01

    Full Text Available Accounting, economic, social and political, and slack resources theories provide different perspectives to addressing corporate social responsibility in relation to disclosure, corporate financial performance e.t.c. This paper aims to identify the determinants financial and non financial of corporate social responsibility (CSR in Jordan .The annual reports determine a sample of 60 industrial companies listed on the Amman Stock Exchange for a period from 2006 to 2010 in Jordan were used as a basis for the study. The results of the analysis imply that companies that are expected to be large in size firm, age of firm, maintaining growth and are highly leveraged are more likely to voluntary disclose social responsibility information. The result lends partial support to agency and political economy theories

  14. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice

    OpenAIRE

    Inoue, Masashi; Glendinning, John I.; Maria L Theodorides; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K.; Alexander A Bachmanov

    2007-01-01

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The res...

  15. 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.

  16. 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.

  17. HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia

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    Guseinova Dinara

    2010-10-01

    Full Text Available Abstract Juvenile idiopathic arthritis (JIA is a heterogeneous condition and therapeutic strategies vary in different JIA types. The routinely accepted practice to start with Sulphasalazine (SS as the first line treatment in patients with HLA B27 positive JIA proves to be ineffective in a large proportion of children. Objective to investigate HLA B27 positive JIA patients clinical characteristics, determined HLA B27 allele types and their connection with antirheumatic treatment in homogenous patient groups. Materials and methods 56 patients diagnosed with JIA and observed over the period 2006 to 2009 included in the study. HLAB27 allele types were determined using PCR method. Results In HLA B27 positive JIA patients mean disease onset was 12.34 ± 3.3 years. Most common (44% JIA type was enthesitis related arthritis. Positive response to the treatment with SS was found in 32% of patients, Methotrexate (MTX - in 43%, combined treatment - SS with MTX was effective in 12.5%. 12.5% of patients required combination MTX with Enbrel. Eight HLA B27 allele types were found in JIA patients in Latvia: *2702, *2703, *2704, *2705, *2710, *2715, *2717, *2728. The most common was *2705 - in 55% of cases. Among all the patients enthesitis related arthritis most commonly occurred in patients with HLAB*2705 allele (OR = 2.01, p Conclusions There are 8 different HLA B27 alleles in JIA patients in Latvia and the most common is *2705, but in order to assert them to be disease associated alleles, more extensive studies are needed, including control group of HLA B27 positive healthy individuals. Standard treatment approach with SS proves to be unsatisfactory in the majority of JIA patients. To improve children's quality of life achieving rapid disease control, the first line treatment in HLA B27 positive patients should be MTX. In order to start with the most appropriate drug it is necessary to determine HLAB 27 type at the onset of disease.

  18. Analysis of Natural Allelic Variation Controlling Arabiciopsis thaliana Seed Germinability in Response to Cold and Dark: Identification of Three Major Quantitative Trait Loci

    Institute of Scientific and Technical Information of China (English)

    Ping-Hong Meng; Audrey Macquet; Olivier Loudet; Annie Marion-Poll; Helen M.North

    2008-01-01

    Light and temperature are key external factors in the control of Arabidopsis thaliana seed germination and dormancy mechanisms. Perception and response to these stimuli have to ensure that seedling emergence and growth occur at the most advantageous time for correct establishment. Analysis of over 300 Arabidopsis accessions identified 14, from 12 different geographical locations, that were able to germinate to greater than 20% at 6℃ in the dark. This natural variation was exploited to identify genetic loci responsible for cold-tolerant, dark germination. A quantitative trait loci approach was used on recombinant inbred line progeny of a cross between Bay-0 and Shahdara. Six distinct quantitative trait loci were identified, three of which were major loci, each responsible for 17-25% of the phenotypic variability in this trait. Parental phenotypes indicated that the majority of the cold-tolerant, dark-germination characteristics are related to light responses. Validation of the three major loci using heterogeneous inbred families confirmed the feasibility of fine mapping and cloning the genes at the quantitative trait loci responsible for cold-tolerant, dark germination.

  19. Determinants of corporate social responsibility (CSR). Implementation in companies

    OpenAIRE

    Chodyński, Andrzej; Huszlak, Wojciech

    2014-01-01

    Praca recenzowana / peer-reviewed paper Growing number of businesses are incorporating social responsibility (CR) into their strategy. Businesses notice a number of benefits of CSR implementation. In the literature, there is lack of knowledge regarding the circumstances and conditions affecting CSR implementation. The aim of the present article is to attempt to determine the conditions affecting successful implementation of CSR in companies. The research method which we used is...

  20. A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele targets a conserved region of Gag HIV-1 clade CRF01_AE infected Thais.

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    Supranee Buranapraditkun

    Full Text Available BACKGROUND: CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, (277YSPVSILDI(285, YI9. Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response. CONCLUSIONS/SIGNIFICANCE: As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%, this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade.

  1. 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.

  2. Paralogous gene conversion, allelic divergence of attacin genes and its expression profile in response to BmNPV infection in silkworm Bombyx mori

    Directory of Open Access Journals (Sweden)

    G Lekha

    2015-08-01

    Full Text Available The genomic organization, structure and polymorphism of attacin gene within the mulberry silkworm Bombyx mori strains have been analyzed. Genomic contig (AADK01007556 of B. mori attacin gene contains locus with two transcribed basic attacin genes, which were designated as attacin I and attacin II. Survey of the naturally occurring genetic variation in different strains of silkworm B. mori at the promoter and coding regions of two attacin genes revealed high levels of silent nucleotide variations (1- 4 % per nucleotide heterozygosity without polymorphism at the amino acid level (nonSynonymous substitution. We also investigated variations in gene expression of attacin I and attacin II in silkworm B. mori infected with nucleopolyhedrovirus (BmNPV. Two B. mori strains, Sarupat, CSR-2 which were resistant and susceptible to BmNPV infection respectively were used in this study. Expression profiles of B. mori genes were analyzed using microarray technique and results revealed that the immune response genes including attacin were selectively up regulated in virus invaded midguts of both races. Microarray data and real-time qPCR results revealed that attacin I gene was significantly up-regulated in the midgut of Sarupat following BmNPV infection, indicating its specific role in the anti-viral response. Our results imply that these up-regulated attacin genes were not only involved in anti-bacterial mechanism, but are also involved in B. mori immune response against BmNPV infection.

  3. 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

  4. HLA-E(⁎)01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence.

    Science.gov (United States)

    Di Cristofaro, Julie; Pelardy, Mathieu; Loundou, Anderson; Basire, Agnès; Gomez, Carine; Chiaroni, Jacques; Thomas, Pascal; Reynaud-Gaubert, Martine; Picard, Christophe

    2016-01-01

    Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E(⁎)01:01 and HLA-E(⁎)01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E(⁎)01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E(⁎)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort. PMID:27493971

  5. HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

    Directory of Open Access Journals (Sweden)

    Julie Di Cristofaro

    2016-01-01

    Full Text Available Lung transplantation (LTx is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD. HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01. In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12, p=0.047. HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

  6. Technique for Determining Bridge Displacement Response Using MEMS Accelerometers.

    Science.gov (United States)

    Sekiya, Hidehiko; Kimura, Kentaro; Miki, Chitoshi

    2016-02-19

    In bridge maintenance, particularly with regard to fatigue damage in steel bridges, it is important to determine the displacement response of the entire bridge under a live load as well as that of each member. Knowing the displacement response enables the identification of dynamic deformations that can cause stresses and ultimately lead to damage and thus also allows the undertaking of appropriate countermeasures. In theory, the displacement response can be calculated from the double integration of the measured acceleration. However, data measured by an accelerometer include measurement errors caused by the limitations of the analog-to-digital conversion process and sensor noise. These errors distort the double integration results. Furthermore, as bridges in service are constantly vibrating because of passing vehicles, estimating the boundary conditions for the numerical integration is difficult. To address these problems, this paper proposes a method for determining the displacement of a bridge in service from its acceleration based on its free vibration. To verify the effectiveness of the proposed method, field measurements were conducted using nine different accelerometers. Based on the results of these measurements, the proposed method was found to be highly accurate in comparison with the reference displacement obtained using a contact displacement gauge.

  7. Technique for Determining Bridge Displacement Response Using MEMS Accelerometers

    Directory of Open Access Journals (Sweden)

    Hidehiko Sekiya

    2016-02-01

    Full Text Available In bridge maintenance, particularly with regard to fatigue damage in steel bridges, it is important to determine the displacement response of the entire bridge under a live load as well as that of each member. Knowing the displacement response enables the identification of dynamic deformations that can cause stresses and ultimately lead to damage and thus also allows the undertaking of appropriate countermeasures. In theory, the displacement response can be calculated from the double integration of the measured acceleration. However, data measured by an accelerometer include measurement errors caused by the limitations of the analog-to-digital conversion process and sensor noise. These errors distort the double integration results. Furthermore, as bridges in service are constantly vibrating because of passing vehicles, estimating the boundary conditions for the numerical integration is difficult. To address these problems, this paper proposes a method for determining the displacement of a bridge in service from its acceleration based on its free vibration. To verify the effectiveness of the proposed method, field measurements were conducted using nine different accelerometers. Based on the results of these measurements, the proposed method was found to be highly accurate in comparison with the reference displacement obtained using a contact displacement gauge.

  8. Transcriptome Analysis of Brassica rapa Near-Isogenic Lines Carrying Clubroot-Resistant and -Susceptible Alleles in Response to Plasmodiophora brassicae during Early Infection.

    Science.gov (United States)

    Chen, Jingjing; Pang, Wenxing; Chen, Bing; Zhang, Chunyu; Piao, Zhongyun

    2015-01-01

    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, 1875, and 2103 genes were found to be up- and down-regulated between CR BJN3-2 and BJN3-2, respectively, at 0, 12, 72, and 96 h 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. PMID:26779217

  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. Determinants of Corporate Social Responsibility in Japanese Companies

    Directory of Open Access Journals (Sweden)

    Magdalena Krukowska

    2014-12-01

    Full Text Available Purpose: The aim of this study was to analyze the factors that determine the Japanese approach to corporate social responsibility (CSR to facilitate future empirical research in the Polish conditions. Methodology: To conduct the research, the available literature concerning CSR, managerial behaviour and stakeholder relations in Japan was studied. The research was conducted onsite in Japan after consultation with local experts, both Japanese and foreigners, specialized in Japanese management and the economy. Findings: The Japanese approach to CSR is strongly determined by their religious, philosophical, cultural, historical, economic and legal factors. It is proof of the concept of CSR contextuality, which provokes questions about the nature of the business relations of Japanese companies with their foreign counterparts and their style of management while investing abroad. Research limitations: The methodology was only supposed to gain a general view of the factors infl uencing CSR in Japan. Studying more detailed issues with the use of empirical data was complicated because of the short time available for the research (6 weeks and the relatively low level of transparency of the Japanese companies. Value: The study helped in understanding managerial decisions and Japanese business behaviour in the context of corporate responsibility and the ethics of its everyday operations. It was the fi rst research thoroughly analyzing many of the determinants of CSR in Japan, which may be valuable for any counterparts cooperating with the Japanese companies and foreign researchers analyzing Japanese management systems.

  11. Four danger response programs determine glomerular and tubulointerstitial kidney pathology

    Science.gov (United States)

    Anders, Hans-Joachim

    2012-01-01

    Renal biopsies commonly display tissue remodeling with a combination of many different findings. In contrast to trauma, kidney remodeling largely results from intrinsic responses, but why? Distinct danger response programs were positively selected throughout evolution to survive traumatic injuries and to regenerate tissue defects. These are: (1) clotting to avoid major bleeding, (2) immunity to control infection, (3) epithelial repair and (4) mesenchymal repair. Collateral damages are acceptable for the sake of host survival but causes for kidney injury commonly affect the kidneys in a diffuse manner. This way, coagulation, inflammation, deregulated epithelial healing or fibrosis contribute to kidney remodeling. Here, I focus on how these ancient danger response programs determine renal pathology mainly because they develop in a deregulated manner, either as insufficient or overshooting processes that modulate each other. From a therapeutic point of view, immunopathology can be prevented by suppressing sterile renal inflammation, a useless atavism with devastating consequences. In addition, it appears as an important goal for the future to promote podocyte and tubular epithelial cell repair, potentially by stimulating the differentiation of their newly discovered intrarenal progenitor cells. By contrast, it is still unclear whether selectively targeting renal fibrogenesis can preserve or bring back lost renal parenchyma, which would be required to maintain or improve kidney function. Thus, renal pathology results from ancient danger responses that evolved because of their evolutional benefits upon trauma. Understanding these causalities may help to shape the search for novel treatments for kidney disease patients. PMID:22692229

  12. Distribution of HLA-DRB1 and HLA-DQB1 alleles in Lak population of Iran.

    Science.gov (United States)

    Varzi, Ali Mohammad; Shahsavar, Farhad; Tarrahi, Mohammad Javad

    2016-07-01

    Human leukocyte antigen (HLA) genes are the most polymorphic loci in the human genome and encode the highly polymorphic molecules critically involved in immune responses. Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine the HLA-DRB1 and HLA-DQB1 allele frequencies in 100 unrelated Lak individuals from Lorestan province of Iran. Finally, we compared the results with those previously described in four other Iranian populations. Commercial HLA-Type kits were used for determination of the HLA-DRB1 and HLA-DQB1 allele frequencies. Differences between populations in the distribution of HLA-DRB1 and HLA-DQB1 alleles were estimated by χ2 test with Yate's correction and Fisher's exact test. The most frequent HLA-DRB1 alleles were (*)1103=4 (23%), (*)1502 (9.5%), (*)0701 (9%), (*)0301 (8.5%), (*)1101 (7.5%) and (*)1501 (6%) while HLA-DQB1(*)0301 (40%), (*)0201 (15%), (*)0502 (10.5%), (*)0303 (10%), (*)0602=3 (9.5%), and (*)0501 (7.5%) were the most frequent alleles in Lak population. HLA-DRB1(*)0409, (*)0804, (*)1102, (*)1112, (*)1405, and HLA-DQB1(*)0503, (*)0604 were the least observed frequencies in Lak population. Our results based on HLA-DRB1 and HLA-DQB1 allele frequencies showed that the Lak population possesses the previously reported general features of the Lur and Kurd populations but still with unique, decreased or increased frequencies of several alleles. In other words, the Lak population is close to Lurs Khorramabadi and Kurd but far from Lurs Kohkiloyeh/Boyerahmad and Bakhtiari. PMID:27189628

  13. 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

    Background 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. Methods 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. Results 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). Conclusion 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. PMID:17716366

  14. Multilocus Inherited Neoplasia Alleles Syndrome

    DEFF Research Database (Denmark)

    Whitworth, James; Skytte, Anne-Bine; Sunde, Lone;

    2016-01-01

    as multilocus inherited neoplasia alleles syndrome [MINAS]) in patients with unusual inherited cancer syndrome phenotypes. To facilitate the clinical management of novel cases of MINAS, we have established a database to collect information on what is likely to be an increasingly recognized cohort...

  15. Genetic background determines response to hemostasis and thrombosis

    Directory of Open Access Journals (Sweden)

    Hill Annie E

    2006-10-01

    Full Text Available Abstract Background Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis. The objective of this study was to evaluate thrombosis and hemostasis in these two inbred strains and determine the phenotypic response of A/J chromosomes in the C57BL/6J background. Methods A/J and C57Bl/6J mice were evaluated for differences in thrombosis and hemostasis. A thrombus was induced in the carotid artery by application of the exposed carotid to ferric chloride and blood flow measured until the vessel occluded. Bleeding and rebleeding times, as surrogate markers for thrombosis and hemostasis, were determined after clipping the tail and placing in warm saline. Twenty-one chromosome substitution strains, A/J chromosomes in a C57BL/6J background, were screened for response to the tail bleeding assay. Results Thrombus occlusion time was markedly decreased in the A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two strains, but rebleeding time was markedly increased in the A/J mice compared to C57BL/6J mice. Coagulation times and tail morphology were similar, but tail collagen content was higher in A/J than C57BL/6J mice. Three chromosome substitution strains, B6-Chr5A/J, B6-Chr11A/J, and B6-Chr17A/J, were identified with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when these two chromosome substitution strains, B6-Chr5A/J and B6-Chr17A/J, were crossed, the A/J phenotype was restored in these doubly heterosomic progeny. Conclusion These results indicate that susceptibility to arterial

  16. 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.

  17. 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.

  18. 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

    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....... Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair. SIGNIFICANCE: Mutations in BRCA genes cause defects in DNA repair that predict sensitivity to DNA damaging agents, including platinum; however, some patients without BRCA mutations...

  19. Power of IRT in GWAS: successful QTL mapping of sum score phenotypes depends on interplay between risk allele frequency, variance explained by the risk allele, and test characteristics.

    Science.gov (United States)

    van den Berg, Stéphanie M; Service, Susan K

    2012-12-01

    As data from sequencing studies in humans accumulate, rare genetic variants influencing liability to disease and disorders are expected to be identified. Three simulation studies show that characteristics and properties of diagnostic instruments interact with risk allele frequency to affect the power to detect a quantitative trait locus (QTL) based on a test score derived from symptom counts or questionnaire items. Clinical tests, that is, tests that show a positively skewed phenotypic sum score distribution in the general population, are optimal to find rare risk alleles of large effect. Tests that show a negatively skewed sum score distribution are optimal to find rare protective alleles of large effect. For alleles of small effect, tests with normally distributed item parameters give best power for a wide range of allele frequencies. The item-response theory framework can help understand why an existing measurement instrument has more power to detect risk alleles with either low or high frequency, or both kinds.

  20. Invasive Allele Spread under Preemptive Competition

    OpenAIRE

    Yasi, J. A.; Korniss, G.; Caraco, T.

    2005-01-01

    We study a discrete spatial model for invasive allele spread in which two alleles compete preemptively, initially only the "residents" (weaker competitors) being present. We find that the spread of the advantageous mutation is well described by homogeneous nucleation; in particular, in large systems the time-dependent global density of the resident allele is well approximated by Avrami's law.

  1. 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. PMID:26918589

  2. Four danger response programs determine glomerular and tubulointerstitial kidney pathology

    OpenAIRE

    Anders, Hans-Joachim

    2012-01-01

    Renal biopsies commonly display tissue remodeling with a combination of many different findings. In contrast to trauma, kidney remodeling largely results from intrinsic responses, but why? Distinct danger response programs were positively selected throughout evolution to survive traumatic injuries and to regenerate tissue defects. These are: (1) clotting to avoid major bleeding, (2) immunity to control infection, (3) epithelial repair and (4) mesenchymal repair. Collateral damages are accepta...

  3. Allelic Interaction between CRELD1 and VEGFA in the Pathogenesis of Cardiac Atrioventricular Septal Defects

    Science.gov (United States)

    Redig, Jennifer K.; Fouad, Gameil T.; Babcock, Darcie; Reshey, Benjamin; Feingold, Eleanor; Reeves, Roger H.; Maslen, Cheryl L.

    2014-01-01

    Atrioventricular septal defects (AVSD) are highly heritable, clinically significant congenital heart malformations. Genetic and environmental modifiers of risk are thought to work in unknown combinations to cause AVSD. Approximately 5–10% of simplex AVSD cases carry a missense mutation in CRELD1. However, CRELD1 mutations are not fully penetrant and require interactions with other risk factors to result in AVSD. Vascular endothelial growth factor-A (VEGFA) is a well-characterized modulator of heart valve development. A functional VEGFA polymorphism, VEGFA c.–634C, which causes constitutively increased VEGFA expression, has been associated with cardiac septal defects suggesting it may be a genetic risk factor. To determine if there is an allelic association with AVSD we genotyped the VEGFA c.–634 SNP in a simplex AVSD study cohort. Over-representation of the c.–634C allele in the AVSD group suggested that this genotype may increase risk. Correlation of CRELD1 and VEGFA genotypes revealed that potentially pathogenic missense mutations in CRELD1 were always accompanied by the VEGFA c.–634C allele in individuals with AVSD suggesting a potentially pathogenic allelic interaction. We used a Creld1 knockout mouse model to determine the effect of deficiency of Creld1 combined with increased VEGFA on atrioventricular canal development. Morphogenic response to VEGFA was abnormal in Creld1-deficient embryonic hearts, indicating that interaction between CRELD1 and VEGFA has the potential to alter atrioventricular canal morphogenesis. This supports our hypothesis that an additive effect between missense mutations in CRELD1 and a functional SNP in VEGFA contributes to the pathogenesis of AVSD. PMID:25328912

  4. Allelic Interaction between CRELD1 and VEGFA in the Pathogenesis of Cardiac Atrioventricular Septal Defects

    Directory of Open Access Journals (Sweden)

    Jennifer K. Redig

    2014-03-01

    Full Text Available Atrioventricular septal defects (AVSD are highly heritable, clinically significant congenital heart malformations. Genetic and environmental modifiers of risk are thought to work in unknown combinations to cause AVSD. Approximately 5–10% of simplex AVSD cases carry a missense mutation in CRELD1. However, CRELD1 mutations are not fully penetrant and require interactions with other risk factors to result in AVSD. Vascular endothelial growth factor-A (VEGFA is a well-characterized modulator of heart valve development. A functional VEGFA polymorphism, VEGFA c.-634C, which causes constitutively increased VEGFA expression, has been associated with cardiac septal defects suggesting it may be a genetic risk factor. To determine if there is an allelic association with AVSD we genotyped the VEGFA c.-634 SNP in a simplex AVSD study cohort. Over-representation of the c.-634C allele in the AVSD group suggested that this genotype may increase risk. Correlation of CRELD1 and VEGFA genotypes revealed that potentially pathogenic missense mutations in CRELD1 were always accompanied by the VEGFA c.-634C allele in individuals with AVSD suggesting a potentially pathogenic allelic interaction. We used a Creld1 knockout mouse model to determine the effect of deficiency of Creld1 combined with increased VEGFA on atrioventricular canal development. Morphogenic response to VEGFA was abnormal in Creld1-deficient embryonic hearts, indicating that interaction between CRELD1 and VEGFA has the potential to alter atrioventricular canal morphogenesis. This supports our hypothesis that an additive effect between missense mutations in CRELD1 and a functional SNP in VEGFA contributes to the pathogenesis of AVSD.

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

    Directory of Open Access Journals (Sweden)

    Williamson Anna-Lise

    2003-01-01

    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

  6. Burn size determines the inflammatory and hypermetabolic response

    OpenAIRE

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

    2007-01-01

    Background 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. Methods Pediatric burned patients were divided into four burn ...

  7. SNP GENOTYPING BY TAQMAN ALLELE DISCRIMINATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    Lucian Negura

    2015-07-01

    Full Text Available Breast cancer is the most frequent neoplasm in women worldwide and the principal cause of deaths by cancer, the majority being by metastatic disease. About half of breast tumors are hormone dependent, and in post-menopause women the preferred first line treatment uses third generation aromatase inhibitors. Aromatase is encoded by CYP19 gene on 15q21.1, and there is strong evidence that mutations in this gene affect its expression, with directconsequences on cancer phenotype and response to treatment. Several single nucleotide polymorphisms have beenstudied on CYP19A1 transcription variant, notably rs727479, rs10046, rs4646 and rs700518. We implemented a Taqman-based allele discrimination assay for the rapid investigation of the 4 SNPs in CYP19A1. We genotyped 22 metastaticbreast cancer patients by the technique described.

  8. Determining medical fitness to drive: physicians' responsibilities in Canada.

    OpenAIRE

    Coopersmith, H G; Korner-Bitensky, N A; Mayo, N E

    1989-01-01

    Current legislation indicates that physicians in Canada have a legal responsibility to know which medical conditions may impede driving ability, to detect these conditions in their patients and to discuss with their patients the implications of these conditions. The requirements to report unfit drivers vary among the provinces, and the interpretations of the law vary among the courts; therefore, physicians' risks of liability are unclear. Physicians may be sued by their patients if they fail ...

  9. Moving beyond Technological Determinism and Autonomy to Face Our Responsibilities

    Science.gov (United States)

    Vanderburg, Willem H.

    2012-01-01

    This article shows that technological neutrality, determinism, and autonomy correspond to parts of a spectrum of possible historical relations between societies and their technologies. The spectrum of relations is based on the recognition that as we change technology, technology simultaneously changes us. This reinterpretation compels us to face…

  10. 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 Ole;

    2002-01-01

    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....

  11. 40 CFR Appendix E to Part 112 - Determination and Evaluation of Required Response Resources for Facility Response Plans

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Determination and Evaluation of Required Response Resources for Facility Response Plans E Appendix E to Part 112 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS OIL POLLUTION PREVENTION Pt. 112, App. E Appendix...

  12. Characterization of opsin gene alleles affecting color vision in a wild population of titi monkeys (Callicebus brunneus).

    Science.gov (United States)

    Bunce, John A; Isbell, Lynne A; Neitz, Maureen; Bonci, Daniela; Surridge, Alison K; Jacobs, Gerald H; Smith, David Glenn

    2011-02-01

    The color vision of most platyrrhine primates is determined by alleles at the polymorphic X-linked locus coding for the opsin responsible for the middle- to long-wavelength (M/L) cone photopigment. Females who are heterozygous at the locus have trichromatic vision, whereas homozygous females and all males are dichromatic. This study characterized the opsin alleles in a wild population of the socially monogamous platyrrhine monkey Callicebus brunneus (the brown titi monkey), a primate that an earlier study suggests may possess an unusual number of alleles at this locus and thus may be a subject of special interest in the study of primate color vision. Direct sequencing of regions of the M/L opsin gene using feces-, blood-, and saliva-derived DNA obtained from 14 individuals yielded evidence for the presence of three functionally distinct alleles, corresponding to the most common M/L photopigment variants inferred from a physiological study of cone spectral sensitivity in captive Callicebus. PMID:20938927

  13. Significance of TGFBR3 allelic loss in the deregulation of TGFβ signaling in primary human endometrial carcinomas.

    Science.gov (United States)

    Zakrzewski, Piotr K; Nowacka-Zawisza, Maria; Semczuk, Andrzej; Rechberger, Tomasz; Gałczyński, Krzysztof; Krajewska, Wanda M

    2016-02-01

    Downregulation of betaglycan (β-glycan) [transforming growth factor β receptor type III (TGFβR3)], which belongs to co-receptors of the TGFβ pathway, occurs in a broad spectrum of primary human malignancies. However, in the case of endometrial cancer (EC), the mechanisms responsible for genetic alterations are still unknown. Therefore, we investigated allelic imbalance at the TGFBR3 locus (1p33‑p32) in the context of β-glycan mRNA and protein expression, as a possible genetic event determining β-glycan deregulation in EC patients. Study of β-glycan allelic imbalance in 48 primary human ECs was performed with the use of three different microsatellite markers, spanned within or in direct proximity to the TGFBR3 locus. Real‑time PCR and western blotting were used for β-glycan mRNA and protein quantification methods, respectively. Altogether, 25 of 39 (64%) informative cases and 25 of 48 (52%) of all specimens showed allelic imbalance in at least one microsatellite marker, concomitantly with decrease at both the β-glycan transcript and protein levels. Interestingly, 54% (15/28), 36% (8/22) and 35% (7/20) of informative ECs displayed allelic loss in D1S188, D1S435 and D1S1588 microsatellite markers, respectively. It is worth pointing out that 5 out of 39 (13%) informative cases showed loss of heterozygosity (LOH) at two microsatellite markers. Microsatellite instability (MSI) was found in two markers, but to a very strictly limited extent. None of the clinicoprognostic features was found to be of significance. Our results suggest that LOH in the TGFBR3 locus may be one of the mechanisms responsible for loss of β-glycan expression. No correlation of LOH at the TGFBR3 locus with clinicopathological parameters suggests that allelic imbalance may be an early genetic event during neoplastic transformation of human endometrium. PMID:26548418

  14. 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...

  15. 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.

  16. 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.

  17. A common mutation associated with the Duarte galactosemia allele

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Dembure, P.P.; Langley, S.; Paulk, E.M.; Hjelm, L.N.; Fridovich-Keil, J. (Emory Univ. School of Medicine, Atlanta, GA (United States))

    1994-06-01

    The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalant mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have [approximately]75%, 50%, and 25% of normal GALT activity, respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here the authors systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, a transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. The authors conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. 36 refs., 3 figs., 2 tabs.

  18. Suitability of rapid energy magnitude determinations for emergency response purposes

    Science.gov (United States)

    Di Giacomo, Domenico; Parolai, Stefano; Bormann, Peter; Grosser, Helmut; Saul, Joachim; Wang, Rongjiang; Zschau, Jochen

    2010-01-01

    It is common practice in the seismological community to use, especially for large earthquakes, the moment magnitude Mw as a unique magnitude parameter to evaluate the earthquake's damage potential. However, as a static measure of earthquake size, Mw does not provide direct information about the released seismic wave energy and its high frequency content, which is the more interesting information both for engineering purposes and for a rapid assessment of the earthquake's shaking potential. Therefore, we recommend to provide to disaster management organizations besides Mw also sufficiently accurate energy magnitude determinations as soon as possible after large earthquakes. We developed and extensively tested a rapid method for calculating the energy magnitude Me within about 10-15 min after an earthquake's occurrence. The method is based on pre-calculated spectral amplitude decay functions obtained from numerical simulations of Green's functions. After empirical validation, the procedure has been applied offline to a large data set of 767 shallow earthquakes that have been grouped according to their type of mechanism (strike-slip, normal faulting, thrust faulting, etc.). The suitability of the proposed approach is discussed by comparing our rapid Me estimates with Mw published by GCMT as well as with Mw and Me reported by the USGS. Mw is on average slightly larger than our Me for all types of mechanisms. No clear dependence on source mechanism is observed for our Me estimates. In contrast, Me from the USGS is generally larger than Mw for strike-slip earthquakes and generally smaller for the other source types. For ~67 per cent of the event data set our Me differs events. A reason of that may be the overcorrection of the energy flux applied by the USGS for this type of earthquakes. We follow the original definition of magnitude scales, which does not apply a priori mechanism corrections to measured amplitudes, also since reliable fault-plane solutions are hardly

  19. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST)

    International Nuclear Information System (INIS)

    A method is described to discover if a gene carries one or more allelic mutations that confer risk for any specified common disease. The method does not depend upon genetic linkage of risk-conferring mutations to high frequency genetic markers such as single nucleotide polymorphisms. Instead, the sums of allelic mutation frequencies in case and control cohorts are determined and a statistical test is applied to discover if the difference in these sums is greater than would be expected by chance. A statistical model is presented that defines the ability of such tests to detect significant gene-disease relationships as a function of case and control cohort sizes and key confounding variables: zygosity and genicity, environmental risk factors, errors in diagnosis, limits to mutant detection, linkage of neutral and risk-conferring mutations, ethnic diversity in the general population and the expectation that among all exonic mutants in the human genome greater than 90% will be neutral with regard to any effect on disease risk. Means to test the null hypothesis for, and determine the statistical power of, each test are provided. For this 'cohort allelic sums test' or 'CAST', the statistical model and test are provided as an Excel (TM) program, CASTAT (C) at http://epidemiology.mit.edu. Based on genetics, technology and statistics, a strategy of enumerating the mutant alleles carried in the exons and splice sites of the estimated ∼25,000 human genes in case cohort samples of 10,000 persons for each of 100 common diseases is proposed and evaluated: A wide range of possible conditions of multi-allelic or mono-allelic and monogenic, multigenic or polygenic (including epistatic) risk are found to be detectable using the statistical criteria of 1 or 10 ''false positive'' gene associations per 25,000 gene-disease pair-wise trials and a statistical power of >0.8. Using estimates of the distribution of both neutral and gene-inactivating nondeleterious mutations in humans and

  20. Short mucin 6 alleles are associated with H pylori infection

    Institute of Scientific and Technical Information of China (English)

    Thai V Nguyen; Marcel JR Janssen; Paulien Gritters; René HM te Morsche; Joost PH Drenth; Henri van Asten; Robert JF Laheij; Jan BMJ Jansen

    2006-01-01

    AIM: To investigate the relationship between mucin 6(MUC6) VNTR length and H pylori infection.METHODS: Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (Pvu Ⅱ) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by 14C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (≤ 13.5 kbp)and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)].RESULTS: 160 patients were studied (mean age 43years, 36% were males, 58% H pylori positive). MUC6Pvu Ⅱ-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6genotype, 43% (24/56), 57% (25/58) and 76% (11/46)were infected with H pylori, respectively (P = 0.003).CONCLUSION: Short MUC6 alleles are associated with H pylori infection.

  1. 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.

  2. Allele-specific amplification in cancer revealed by SNP array analysis.

    Directory of Open Access Journals (Sweden)

    Thomas LaFramboise

    2005-11-01

    Full Text Available Amplification, deletion, and loss of heterozygosity of genomic DNA are hallmarks of cancer. In recent years a variety of studies have emerged measuring total chromosomal copy number at increasingly high resolution. Similarly, loss-of-heterozygosity events have been finely mapped using high-throughput genotyping technologies. We have developed a probe-level allele-specific quantitation procedure that extracts both copy number and allelotype information from single nucleotide polymorphism (SNP array data to arrive at allele-specific copy number across the genome. Our approach applies an expectation-maximization algorithm to a model derived from a novel classification of SNP array probes. This method is the first to our knowledge that is able to (a determine the generalized genotype of aberrant samples at each SNP site (e.g., CCCCT at an amplified site, and (b infer the copy number of each parental chromosome across the genome. With this method, we are able to determine not just where amplifications and deletions occur, but also the haplotype of the region being amplified or deleted. The merit of our model and general approach is demonstrated by very precise genotyping of normal samples, and our allele-specific copy number inferences are validated using PCR experiments. Applying our method to a collection of lung cancer samples, we are able to conclude that amplification is essentially monoallelic, as would be expected under the mechanisms currently believed responsible for gene amplification. This suggests that a specific parental chromosome may be targeted for amplification, whether because of germ line or somatic variation. An R software package containing the methods described in this paper is freely available at http://genome.dfci.harvard.edu/~tlaframb/PLASQ.

  3. 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),…

  4. 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 embedding...

  5. Detection of newly antibody-defined epitopes on HLA class I alleles reacting with antibodies induced during pregnancy.

    Science.gov (United States)

    Duquesnoy, R J; Hönger, G; Hösli, I; Marrari, M; Schaub, S

    2016-08-01

    The determination of HLA mismatch acceptability at the epitope level can be best performed with epitopes that have been verified experimentally with informative antibodies. The website-based International Registry of HLA Epitopes (http://www.epregistry.com.br) has a list of 81 antibody-verified HLA-ABC epitopes but more epitopes need to be added. Pregnancy offers an attractive model to study antibody responses to mismatched HLA epitopes which can be readily determined from the HLA types of child and mother. This report describes a HLAMatchmaker-based analysis of 16 postpregnancy sera tested in single HLA-ABC allele binding assays. Most sera reacted with alleles carrying epitopes that have been antibody-verified, and this study focused on the reactivity of additional alleles that share other epitopes corresponding to eplets and other amino acid residue configurations. This analysis led in the identification of 16 newly antibody-defined epitopes, seven are equivalent to eplets and nine correspond to combinations of eplets in combination with other nearby residue configurations. These epitopes will be added to the repertoire of antibody-verified epitopes in the HLA Epitope Registry. PMID:27312793

  6. Segregation of male-sterility alleles across a species boundary.

    Science.gov (United States)

    Weller, S G; Sakai, A K; Culley, T M; Duong, L; Danielson, R E

    2014-02-01

    Hybrid zones may serve as bridges permitting gene flow between species, including alleles influencing the evolution of breeding systems. Using greenhouse crosses, we assessed the likelihood that a hybrid zone could serve as a conduit for transfer of nuclear male-sterility alleles between a gynodioecious species and a hermaphroditic species with very rare females in some populations. Segregation patterns in progeny of crosses between rare females of hermaphroditic Schiedea menziesii and hermaphroditic plants of gynodioecious Schiedea salicaria heterozygous at the male-sterility locus, and between female S. salicaria and hermaphroditic plants from the hybrid zone, were used to determine whether male-sterility was controlled at the same locus in the parental species and the hybrid zone. Segregations of females and hermaphrodites in approximately equal ratios from many of the crosses indicate that the same nuclear male-sterility allele occurs in the parent species and the hybrid zone. These rare male-sterility alleles in S. menziesii may result from gene flow from S. salicaria through the hybrid zone, presumably facilitated by wind pollination in S. salicaria. Alternatively, rare male-sterility alleles might result from a reversal from gynodioecy to hermaphroditism in S. menziesii, or possibly de novo evolution of male sterility. Phylogenetic analysis indicates that some species of Schiedea have probably evolved separate sexes independently, but not in the lineage containing S. salicaria and S. menziesii. High levels of selfing and expression of strong inbreeding depression in S. menziesii, which together should favour females in populations, argue against a reversal from gynodioecy to hermaphroditism in S. menziesii.

  7. 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.

  8. Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D-negative pregnant women.

    Science.gov (United States)

    Stegmann, Tamara C; Veldhuisen, Barbera; Bijman, Renate; Thurik, Florentine F; Bossers, Bernadette; Cheroutre, Goedele; Jonkers, Remco; Ligthart, Peter; de Haas, Masja; Haer-Wigman, Lonneke; van der Schoot, C Ellen

    2016-05-01

    To guide anti-D prophylaxis, Dutch D- pregnant women are offered a quantitative fetal-RHD-genotyping assay to determine the RHD status of their fetus. This allowed us to determine the frequency of different maternal RHD variants in 37 782 serologically D- pregnant women. A variant allele is present in at least 0·96% of Dutch D- pregnant women The D- serology could be confirmed after further serological testing in only 54% of these women, which emphasizes the potential relevance of genotyping of blood donors. 43 different RHD variant alleles were detected, including 15 novel alleles (11 null-, 2 partial D- and 2 DEL-alleles). Of those novel null alleles, one allele contained a single missense mutation (RHD*443C>G) and one allele had a single amino acid deletion (RHD*424_426del). The D- phenotype was confirmed by transduction of human D- erythroblasts, consolidating that, for the first time, a single amino acid change or deletion causes the D- phenotype. Transduction also confirmed the phenotypes for the two new variant DEL-alleles (RHD*721A>C and RHD*884T>C) and the novel partial RHD*492C>A allele. Notably, in three additional cases the DEL phenotype was observed but sequencing of the coding sequence, flanking introns and promoter region revealed an apparently wild-type RHD allele without mutations. PMID:27018217

  9. Maximizing allele detection: Effects of analytical threshold and DNA levels on rates of allele and locus drop-out.

    Science.gov (United States)

    Rakay, Christine A; Bregu, Joli; Grgicak, Catherine M

    2012-12-01

    Interpretation of DNA evidence depends upon the ability of the analyst to accurately compare the DNA profile obtained from an item of evidence and the DNA profile of a standard. This interpretation becomes progressively more difficult as the number of 'drop-out' and 'drop-in' events increase. Analytical thresholds (AT) are typically selected to ensure the false detection of noise is minimized. However, there exists a tradeoff between the erroneous labeling of noise as alleles and the false non-detection of alleles (i.e. drop-out). In this study, the effect ATs had on both types of error was characterized. Various ATs were tested, where three relied upon the analysis of baseline signals obtained from 31 negative samples. The fourth AT was determined by utilizing the relationship between RFU signal and DNA input. The other ATs were the commonly employed 50, 150 and 200 RFU thresholds. Receiver Operating Characteristic (ROC) plots showed that although high ATs completely negated the false labeling of noise, DNA analyzed with ATs derived using analysis of the baseline signal exhibited the lowest rates of drop-out and the lowest total error rates. In another experiment, the effect small changes in ATs had on drop-out was examined. This study showed that as the AT increased from ∼10 to 60 RFU, the number of heterozygous loci exhibiting the loss of one allele increased. Between ATs of 60 and 150 RFU, the frequency of allelic drop-out remained constant at 0.27 (±0.02) and began to decrease when ATs of 150 RFU or greater were utilized. In contrast, the frequency of heterozygous loci exhibiting the loss of both alleles consistently increased with AT. In summary, for samples amplified with less than 0.5ng of DNA, ATs derived from baseline analysis of negatives were shown to decrease the frequency of drop-out by a factor of 100 without significantly increasing rates of erroneous noise detection.

  10. Detecting Determinism in Firing Activities of Retinal Ganglion Cells during Response to Complex Stimuli

    Institute of Scientific and Technical Information of China (English)

    CAI Chao-Feng; ZHANG Ying-Ying; LIU Xue; LIANG Pei-Ji; ZHANG Pu-Ming

    2008-01-01

    Complex stimuli are used to probe the response properties of the chicken's retinal ganglion cells (GCs). Thecorrelation dimension method and the nonlinear forecasting method are applied to detect the determinism in the firing activities of the retinal GCs during response to complex stimuli.The inter-spike interval (ISI) series and the first difference of the ISI (DISI) series are analysed.Two conclusions are drawn.Firstly,the first difference operation of the ISI series makes it comparatively easier for determinism detection in the firing activities of retinal GCs.Secondly,the nonlinear forecasting method is more efficient and reliable than the correlation dimension method for determinism detection.

  11. Neural heterogeneities determine response characteristics to second-, but not first-order stimulus features.

    Science.gov (United States)

    Metzen, Michael G; Chacron, Maurice J

    2015-02-18

    Neural heterogeneities are seen ubiquitously, but how they determine neural response properties remains unclear. Here we show that heterogeneities can either strongly, or not at all, influence neural responses to a given stimulus feature. Specifically, we recorded from peripheral electroreceptor neurons, which display strong heterogeneities in their resting discharge activity, in response to naturalistic stimuli consisting of a fast time-varying waveform (i.e., first-order) whose amplitude (i.e., second-order or envelope) varied slowly in the weakly electric fish Apteronotus leptorhynchus. Although electroreceptors displayed relatively homogeneous responses to first-order stimulus features, further analysis revealed two subpopulations with similar sensitivities that were excited or inhibited by increases in the envelope, respectively, for stimuli whose frequency content spanned the natural range. We further found that a linear-nonlinear cascade model incorporating the known linear response characteristics to first-order features and a static nonlinearity accurately reproduced experimentally observed responses to both first- and second-order features for all stimuli tested. Importantly, this model correctly predicted that the response magnitude is independent of either the stimulus waveform's or the envelope's frequency content. Further analysis of our model led to the surprising prediction that the mean discharge activity can be used to determine whether a given neuron is excited or inhibited by increases in the envelope. This prediction was validated by our experimental data. Thus, our results provide key insight as to how neural heterogeneities can determine response characteristics to some, but not other, behaviorally relevant stimulus features.

  12. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles.

    Science.gov (United States)

    Orozco-terWengel, Pablo; Kapun, Martin; Nolte, Viola; Kofler, Robert; Flatt, Thomas; Schlötterer, Christian

    2012-10-01

    The genomic basis of adaptation to novel environments is a fundamental problem in evolutionary biology that has gained additional importance in the light of the recent global change discussion. Here, we combined laboratory natural selection (experimental evolution) in Drosophila melanogaster with genome-wide next generation sequencing of DNA pools (Pool-Seq) to identify alleles that are favourable in a novel laboratory environment and traced their trajectories during the adaptive process. Already after 15 generations, we identified a pronounced genomic response to selection, with almost 5000 single nucleotide polymorphisms (SNP; genome-wide false discovery rates heterogeneous, with the alleles falling into two distinct classes: (i) alleles that continuously rise in frequency; and (ii) alleles that at first increase rapidly but whose frequencies then reach a plateau. Our data thus suggest that the genomic response to selection can involve a large number of selected SNPs that show unexpectedly complex evolutionary trajectories, possibly due to nonadditive effects.

  13. Addressing the Photometric Calibration Challenge: Explicit Determination of the Instrumental Response and Atmospheric Response Functions, and Tying it All Together.

    Science.gov (United States)

    Stubbs, C. W.; Tonry, J. L.

    2016-05-01

    Photometric calibration is currently the dominant source of systematic uncertainty in exploiting type Ia supernovae to determine the nature of the dark energy. We review our ongoing program to address this calibration challenge by performing measurements of both the instrumental response function and the optical transmission function of the atmosphere. A key aspect of this approach is to complement standard star observations by using NIST-calibrated photodiodes as a metrology foundation for optical flux measurements. We present our first attempt to assess photometric consistency between synthetic photometry and observations, by comparing predictions based on a NIST-diode-based determination of the PanSTARRS-1 instrumental response and empirical atmospheric transmission measurements, with fluxes we obtained from observing spectrophotometric standards.

  14. Addressing the Photometric Calibration Challenge: Explicit Determination of the Instrumental Response and Atmospheric Response Functions, and Tying it All Together

    CERN Document Server

    Stubbs, Christopher W

    2012-01-01

    Photometric calibration is currently the dominant source of systematic uncertainty in exploiting type Ia supernovae to determine the nature of the dark energy. We review our ongoing program to address this calibration challenge by performing measurements of both the instrumental response function and the optical transmission function of the atmosphere. A key aspect of this approach is to complement standard star observations by using NIST-calibrated photodiodes as a metrology foundation for optical flux measurements. We present our first attempt to assess photometric consistency between synthetic photometry and observations, by comparing predictions based on a NIST-diode-based determination of the PanSTARRS-1 instrumental response and empirical atmospheric transmission measurements, with fluxes we obtained from observing spectrophotometric standards.

  15. THE USE OF NEW REAGENT KITS FOR DETECTION AND DESCRIPTION OF ADDITIONAL ALLELES

    Directory of Open Access Journals (Sweden)

    M. A. Loginova

    2011-01-01

    Full Text Available During the screening typing of recruited volunteers with Volga Federal District for unrelated hematopoietic stem cell registry on the loci (HLA-A, B, DRB1, DRB345 in sample No 1758 identified a new allele at locus A. The use of basic kit AlleleSEQR HLA-A Sequencing in combination with HARP – A2F98A allowed to determine the genotype of this sample – А*30:01:01, a new allele А*25, В*13, 44, DRB1*03, 09, DRB3*02, DRB4*01. 

  16. Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture

    DEFF Research Database (Denmark)

    Enattah, Nabil Sabri; Jensen, Tine G K; Boyd, Mette;

    2008-01-01

    the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption...

  17. Effective marker alleles associated with type II resistance of wheat to Fusarium head blight infection in fields

    Science.gov (United States)

    Molecular markers associated with known quantitative trait loci (QTLs) for type 2 resistance to Fusarium head blight (FHB) in bi-parental mapping populations usually have more than two alleles in breeding populations. Therefore, understanding the association of each allele with FHB response is parti...

  18. Interleukin-6 Gene Promoter-572 C Allele May Play a Role in Rate of Disease Progression in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Judith M. Greer

    2012-10-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6. Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (−597 G>A and −174 G>C correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (−572 G>C in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different −597 or −174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position −572, although this was not significant after correction for multiple comparisons. Interestingly, however, the −572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.

  19. HLA-DRB1等位基因与吉林地区汉族乙肝疫苗免疫应答的关联研究%Association of HLA-DRB1 alleles with immune response to hepatitis B vaccine in Chinese Han people of Jilin region

    Institute of Scientific and Technical Information of China (English)

    张吉林; 李娜; 宋玉国; 毕胜利

    2011-01-01

    目的:探讨HLA-DRB1等位基因与吉林地区汉族乙肝疫苗免疫应答的关联性.方法:采用聚合酶链反应-序列特异性引物(PCR-SSP)分型技术,对84例乙肝疫苗无或低应答者HLA-DRB1等位基因进行检测,与78例乙肝疫苗中或强应答者人群进行对照.结果:①HLA-DRB1*14等位基因频率在无或低应答组为23.8%,中或强应答组为5.13%,两组之间比较有统计学差异(P<0.05);②HLA-DRB1*12、HLA-DRB1*15等位基因频率分别在无或低应答组为4.76%和7.14%,在中或强应答组为23.1%和24.4%,两组之间比较也存在统计学差异(P<0.05).③等位基因HLA-DRB1*07(2.38%和5.12%),HLA-DRB1*08(9.52%和8.97%),HLA-DRB1*09(7.14%和10.3%),HLA-DRB1*11(7.14%和7.69%),HLA-DRB1*13(4.76%和6.41%)及HLA-DRB1*16(4.76%和5.13%),在无或低应答组和在中或强应答组之间基因频率分布没有统计学差异(P>0.05).结论:吉林地区汉族乙肝疫苗接种后,①HLA-DRB1*14等位基因可能与无或低应答相关;②HLA-DRB1*12、15等位基因可能与中或强应答相关;③未检测到HLA-DRB1*07、08、09、11、13、16等位基因与免疫应答水平之间有明显的相关性.%Objective: To research the HLA-DRB1 alleles associated with immune response to hepatitis B vaccination in Chinese Han people of Jilin region.Methods: HLA-DRB1 alleles of 84 cases of non responders or hypo-responders to the Hepatitis B vaccination were detected by polymerase chain reaction sequence-specific primer (PCR-SSP), under the comparison with 78 cases of medium or hyper-responders.Results:①The allelic frequencies of HLA-DRB1 * 14 in non-responders or hypo-responders group was 23.8%, wheras in medium or hyper-responder group was 5.13 %, shown significant differences between the two groups ( P < 0.05); ②The allelic frequencies of HLA-DRB1 * 12 and HLA-DRB1 * 15 in non-responders or hypo-responders group was 4.76% and 7.14%, wheras in medium or hyper-responders group was 23.1% and 24.4

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

    OpenAIRE

    Romas Baronas; Juozas Kulys; Algirdas Lančinskas; Antanas Žilinskas

    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 n...

  1. Determining the direction of vestibular-evoked balance responses using stochastic vestibular stimulation

    OpenAIRE

    Mian, O. S.; Day, B. L.

    2009-01-01

    As a tool for investigating vestibulo-motor function, stochastic vestibular stimulation (SVS) has some advantages over galvanic vestibular stimulation. However, there is no technique currently available for extracting direction information from SVS-evoked motor responses. It is essential to be able to measure the direction of response if one wishes to investigate the operation of key spatial transformation processes in the brain. Here we describe and validate a technique for determining the d...

  2. DETERMINATION OF THE EMPATY LEVELS OF THE RESPONSIBLE PERSONS IN GROUPS AT NURSERIES AND CHILDREN'S HOME

    OpenAIRE

    BİBER, Kazım; Sezer, Türker

    2011-01-01

    ABSTRACT The purpose of this research is to determinate the empathy levels of the responsible persons in groups at nurseries and children's homes which are subject to social services and children society for the protection of children (SHÇEK) and to investigate them according to the some variables. The research was performed as a descriptive study and "Empathy Scale" was used to collect data about the empathy levels of the responsible persons in groups at nurseries and chil...

  3. Major histocompatibility complex class I chain related (MIC) A gene, TNFa microsatellite alleles and TNFB alleles in juvenile idiopathic arthritis patients from Latvia.

    Science.gov (United States)

    Nikitina Zake, Liene; Cimdina, Ija; Rumba, Ingrida; Dabadghao, Preethi; Sanjeevi, Carani B

    2002-05-01

    In order to analyze involvement of major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor a (TNFa) microsatellite polymorphisms as well as TNFB gene in juvenile idiopathic arthritis (JIA), we studied 128 patients divided into groups according to clinical features [monoarthritis (n = 14), oligoarthritis (n = 58), polyarthritis (n = 50), and systemic (n = 6)], and 114 age- and sex-matched healthy controls from Latvia. DNA samples were amplified with specific primers and used for genotyping of MICA and TNFa microsatellite. Typing for a biallelic NcoI polymerase chain reaction RFLP polymorphism located at the first intron of TNFB gene was done as follows: restriction digests generated fragments of 555bp and 185bp for TNFB*1 allele, and 740bp for TNFB*2 allele. The results were compared between cases and controls. We found significant increase of MICA allele A4 (p = 0.009; odds ratio [OR] = 2.3) and allele TNFa2 (p = 0.0001; OR = 4.4) in patients compared with controls. The frequency of allele TNFa9 was significantly decreased (p = 0.0001; OR = 0.1) in patients with JIA. No significant differences of TNFB allele frequency were found. Our data suggest that MICA and TNFa microsatellite polymorphisms may be used as markers for determination of susceptibility and protection from JIA.

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act c...

  5. Three allele combinations associated with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Kulakova Olga G

    2006-07-01

    Full Text Available Abstract Background Multiple sclerosis (MS is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. Methods 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. Results We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3, CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2 allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. Conclusion These results represent an independent validation of MS association with DRB1*15(2 and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles.

  6. Allelic discrimination in naturalized ovine from Pantanal Sul-Matogrossense by means of microsatellite markers

    Directory of Open Access Journals (Sweden)

    Crispim Bruno do Amaral

    2012-08-01

    Full Text Available The molecular biology techniques that are used in allelic discrimination for individual and sheep breeds characterization are important tools in breeding programs and conservation of genetic resources. The use of microsatellite markers allows allelic differentiation, which in turn allows us to infer the genetic variability of sample populations. The study aimed to test the sensitivity and efficiency of fluorescent capillary electrophoresis, using microsatellite primers, for allelic discrimination of the Crioulo breed from Pantanal sul-matogrossense, as well as verify the possibility of using the products of sequencing in genetic variability analysis. For this test, were used blood samples from Pantaneira breed sheep. The allelic discrimination of eight microsatellites was determined by capillary electrophoresis in automatic sequencer and the results analyses were performed on the programs CERVUS and Dendro-UPGMA. The results indicated the possibility of using this technique for the individual genotyping of all loci tested in electrophoretic analysis and its potential to allelic discrimination even in case of difference between two pairs of bases between the alleles. The resulting dendrogram based on the distance matrix by the UPGMA assembly method, indicated medium similarity coefficient of 0.72 in the group of animals. It was concluded that there is the viability and efficiency of the microsatellite molecular markers technique using capillary electrophoresis for allelic discrimination and the utility of results for studies of genetic variability, paternity diagnosis and characterization of the Crioulo sheep herd from Pantanal sul-matogrossense.

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

    International Nuclear Information System (INIS)

    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)

  8. 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

    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...... as induced by bed rest. Reduced paracrine glucagon stimulation may contribute to the impairment of beta-cell function in the carriers TCF7L2 rs7903146 T-allele associated with increased risk of type 2 diabetes....

  9. Determination of the Response Time of Photoanisotropy in Azobenzene Side-Chain Polyesters

    DEFF Research Database (Denmark)

    Bublitz, D.; Fleck, B.; Wenke, L.;

    2000-01-01

    We present a method which allows the determination of the response time to polarized light of an azobenzene side-chain polyester. This method is based on the measurement of intensities in dependence on the delay time between a pump and a probe pulse. The described method does not need a very...

  10. Using Exploratory Factor Analysis to Determine the Dimensionality of Discrete Responses

    NARCIS (Netherlands)

    Barendse, Mariska; Oort, Frans J.; Timmerman, Marieke

    2015-01-01

    Exploratory factor analysis (EFA) is commonly used to determine the dimensionality of continuous data. In a simulation study we investigate its usefulness with discrete data. We vary response scales (continuous, dichotomous, polytomous), factor loadings (medium, high), sample size (small, large), an

  11. Using exploratory factor analysis to determine the dimensionality of discrete responses

    NARCIS (Netherlands)

    M.T. Barendse; F.J. Oort; M.E Timmerman

    2014-01-01

    Exploratory factor analysis (EFA) is commonly used to determine the dimensionality of continuous data. In a simulation study we investigate its usefulness with discrete data. We vary response scales (continuous, dichotomous, polytomous), factor loadings (medium, high), sample size (small, large), an

  12. 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.

  13. 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

  14. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    Science.gov (United States)

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  15. Determining ecoregional numeric nutrient criteria by stressor-response models in Yungui ecoregion lakes, China.

    Science.gov (United States)

    Huo, Shouliang; Ma, Chunzi; Xi, Beidou; Tong, Zhonghua; He, Zhuoshi; Su, Jing; Wu, Fengchang

    2014-01-01

    The importance of developing numeric nutrient criteria has been recognized to protect the designated uses of water bodies from nutrient enrichment that is associated with broadly occurring levels of nitrogen/phosphorus pollution. The identification and estimation of stressor-response models in aquatic ecosystems has been shown to be useful in the determination of nutrient criteria. In this study, three methods based on stressor-response relationships were applied to determine nutrient criteria for Yungui ecoregion lakes with respect to total phosphorus (TP), total nitrogen (TN), and planktonic chlorophyll a (Chl a). Simple linear regression (SLR) models were established to provide an estimate of the relationship between a response variable and a stressor. Multiple linear regressions were used to simultaneously estimate the effect of TP and TN on Chl a. A morphoedaphic index (MEI) was applied to derive nutrient criteria using data from Yungui ecoregion lakes, which were considered as areas with less anthropogenic influences. Nutrient criteria, as determined by these three methods, showed broad agreement for all parameters. The ranges of numeric nutrient criteria for Yungui ecoregion lakes were determined as follows: TP 0.008-0.010 mg/L and TN 0.140-0.178 mg/L. The stressor-response analysis described will be of benefit to support countries in their numeric criteria development programs and to further the goal of reducing nitrogen/phosphorus pollution in China.

  16. Performance Determinants for Responsible Supply Chain Management in the European Emerging Countries

    Directory of Open Access Journals (Sweden)

    Camelia Chirilă

    2013-02-01

    Full Text Available Starting from the premise that there are numerous institutional and national factors influencing the performance of responsible supply chain management, the present article seeks to measure and quantify performance of the European emerging states by creating an index of performance of responsible supply chain management and to identify the factors that influence responsible supply chain management. The acquisition of this index was based on our own measurement methodology, starting from two classes of determinants for responsible supply chain management, with eight measuring variables, through the content analysis of various reports published by the World Economic Forum. The analysis of the correlation matrix established the intensity of the links between the proposed measuring variables. The application of the regression method on the multifactor econometric model has shown that responsible supply chain management is positively influenced by the GDP per capita, public services to improve business performance, infrastructure quality and performance of environmental actions. The results of the study have revealed that performance of responsible supply chain management depends rather on the national and local policies to stimulate social responsibility practices than on the level of economic development. Most of the time, organizations are concerned with the accountability of responsible supply chain management voluntarily, being aware of the long-term benefits to their business.

  17. Multiple origins of Plasmodium falciparum dihydropteroate synthetase mutant alleles associated with sulfadoxine resistance in India.

    Science.gov (United States)

    Lumb, Vanshika; Das, Manoj K; Singh, Neeru; Dev, Vas; Khan, Wajihullah; Sharma, Yagya D

    2011-06-01

    With the spread of chloroquine (CQ)-resistant malaria in India, sulfadoxine-pyrimethamine (SP) alone or in combination with artesunate is used as an alternative antimalarial drug. Due to continuous drug pressure, the Plasmodium falciparum parasite is exhibiting resistance to antifolates because of mutations in candidate genes dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps). Our earlier study on flanking microsatellite markers of dhfr mutant alleles from India had shown a single origin of the pyrimethamine resistance and some minor haplotypes which shared haplotypes with Southeast Asian (Thailand) strains. In the present study, we have analyzed 193 of these Indian P. falciparum isolates for 15 microsatellite loci around dhps to investigate the genetic lineages of the mutant dhps alleles in different parts of the country. Eighty-one of these samples had mutant dhps alleles, of which 62 were from Andaman and Nicobar Islands and the remaining 19 were from mainland India. Of 112 isolates with a wild-type dhps allele, 109 were from mainland India and only 3 were from Andaman and Nicobar Islands. Consistent with the model of selection, the mean expected heterozygosity (H(e)) around mutant dhps alleles (H(e) = 0.55; n = 81) associated with sulfadoxine resistance was lower (P ≤ 0.05) than the mean H(e) around the wild-type dhps allele (H(e) = 0.80; n = 112). There was more genetic diversity in flanking microsatellites of dhps than dhfr among these isolates, which confirms the assertion that dhps mutations are at a very early stage of fixation in the parasite population. Microsatellite haplotypes around various mutant dhps alleles suggest that the resistant dhps alleles have multiple independent origins in India, especially in Andaman and Nicobar Islands. Determining the genetic lineages of the resistant dhps alleles on Andaman and Nicobar Islands and mainland India is significant, given the role of Asia in the intercontinental spread of chloroquine

  18. Quantification of Allele Dosage in tetraploid Roses

    NARCIS (Netherlands)

    Vukosavljev, M.; Guardo, Di M.; Weg, van de W.E.; Arens, P.; Smulders, M.J.M.

    2012-01-01

    Many important crops (wheat, potato, strawberry, rose, etc.) are polyploid. This complicates genetic analyses, as the same locus can be present on multiple homologous or homoeologous chromosomes. SSR markers are suitable for mapping in segregating populations of polyploids as they are multi-allelic,

  19. 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 ...

  20. 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...

  1. 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-associated...... variant Udgivelsesdato: 2007-Mar...

  2. 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....

  3. Grid Inertial Response-Based Probabilistic Determination of Energy Storage System Capacity Under High Solar Penetration

    International Nuclear Information System (INIS)

    It is well-known that responsive battery energy storage systems (BESSs) are an effective means to improve the grid inertial response to various disturbances including the variability of the renewable generation. One of the major issues associated with its implementation is the difficulty in determining the required BESS capacity mainly due to the large amount of inherent uncertainties that cannot be accounted for deterministically. In this study, a probabilistic approach is proposed to properly size the BESS from the perspective of the system inertial response, as an application of probabilistic risk assessment (PRA). The proposed approach enables a risk-informed decision-making process regarding (1) the acceptable level of solar penetration in a given system and (2) the desired BESS capacity (and minimum cost) to achieve an acceptable grid inertial response with a certain confidence level

  4. HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides.

    Science.gov (United States)

    Kidnapillai, S; Sirisena, N D; Dissanayake, V H

    2016-06-01

    This preliminary study aims to describe the HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides (SA). An anonymised database of 373 Sri Lankan patients with SA referred for HLA-B27 testing was retrospectively analysed. Eighty five (22.8%) patients were positive for the HLA-B27 allele. A male preponderance was observed among the positives. The HLA-B27 allele frequency in this sample of patients with SA was relatively low compared to published studies in other populations. Further research is needed to identify the predominant subtypes of the allele to determine which subtypes are the most prevalent in a larger sample of Sri Lankan patients with SA, and to define their association with the specific types of SA. PMID:27423748

  5. Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lim, L.C.C.; Sham, P.; Castle, D. [Institute of Psychiatry, London (United Kingdom)] [and others

    1995-08-14

    We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significantly only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant. 58 refs., 1 fig., 3 tabs.

  6. Genetic heterogeneity within electrophoretic "alleles" of xanthine dehydrogenase in Drosophila pseudoobscura.

    Science.gov (United States)

    Singh, R S; Lewontin, R C; Felton, A A

    1976-11-01

    An experimental plan for an exhaustive determination of genic variation at structural gene loci is presented. In the initial steps of this program, 146 isochromosomal lines from 12 geographic populations of D. pseudoobscura were examined for allelic variation of xanthine dehydrogenase by the serial use of 4 different electrophoretic conditions and a head stability test. The 5 criteria revealed a total of 37 allelic classes out of the 146 genomes examined where only 6 had been previously revealed by the usual method of gel electrophoresis. This immense increase in genic variation also showed previously unsuspected population differences between the main part of the species distribution and the isolated population of Bogotá population. The average heterozygosity at the Xdh locus is at least 72% in natural populations. This result, together with the very large number of alleles segregating and the pattern of allelic frequencies, has implications for theories of genetic polymorphism which are discussed.

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

    Directory of Open Access Journals (Sweden)

    Romas Baronas

    2014-03-01

    Full Text Available 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.

  8. 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.

  9. Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Fu-Sheng Wang

    2003-01-01

    Chronic hepatitis B virus (HBV) infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic hepatitis, to acute hepatitis, chronic hepatitis, Liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the experimental factors. Among the human genetic factors, major candidate or identified genes involved in the process of HBV infection fall into the following categories: (1) genes that mediate the processes of viral entry into hepatocytes, induding genes involved in viral binding, fusion with cellular membrane and transportation in target cells; (2) genes that modulate or control the immune response to HBV infection; (3) genes that participate in the pathological alterations in liver tissue;(4) genes involved in the development of liver cirrhosis and hepatocellular carcinoma associated with chronic HBV infection, including genes related to mother-to-infant transmission of HBV infection; and (5) those that contribute to resistance to antiviral therapies. Most of the reports of human genes associated with HBV infection have currently focused on HLA associations. For example, some investigators reported the association of the HLA class Ⅱ alleles such as DRB1*1302 or HLA-DR13 or DQA1*0501-DQB1*0301-DQB1*1102 haplotypes with acute and/or chronic hepatitis B virus infection, respectively. Several pro-inflammatory cytokines such as Th1 cytokines (including IL-2 and IFN-γ)and TNF-α have been identified to participate the process of viral clearance and host immune response to HBV. In contrast, the Th2 cytokine IL-10 serves as a potent inhibitor of Th1 effector cells in HBV diseases. The MBP polymorphisms in its encoding region were found to be involved in chronic infection. Thus, reports from various laboratories have shown some inconsistencies with regard to the

  10. Allelic variations in Glu-1 and Glu-3 loci of historical and modern Iranian bread wheat (Triticum aestivum L.) cultivars

    Indian Academy of Sciences (India)

    Ali Izadi-Darbandi; Bahman Yazdi-Samadi; Ali-Akbar Su-Boushehri; Mohsen Mohammadi

    2010-08-01

    Proline and glutamine-rich wheat seed endosperm proteins are collectively referred to as prolamins. They are comprised of HMW-GSs, LMW-GSs and gliadins. HMW-GSs are major determinants of gluten elasticity and LMW-GSs considerably affect dough extensibility and maximum dough resistance. The inheritance of glutenin subunits follows Mendelian genetics with multiple alleles in each locus. Identification of the banding patterns of glutenin subunits could be used as an estimate for screening high quality wheat germplasm. Here, by means of a two-step 1D-SDS-PAGE procedure, we identified the allelic variations in high and low-molecular-weight glutenin subunits in 65 hexaploid wheat (Triticum aestivum L.) cultivars representing a historical trend in the cultivars introduced or released in Iran from the years 1940 to 1990. Distinct alleles 17 and 19 were detected for Glu-1 and Glu-3 loci, respectively. The allelic frequencies at the Glu-1 loci demonstrated unimodal distributions. At Glu-A1, Glu-B1 and Glu-D1, we found that the most frequent alleles were the null, 7 + 8, 2 + 12 alleles, respectively, in Iranian wheat cultivars. In contrast, Glu-3 loci showed bimodal or trimodal distributions. At Glu-A3, the most frequent alleles were c and e. At Glu-B3 the most frequent alleles were a, b and c. At Glu-D3 locus, the alleles b and a, were the most and the second most frequent alleles in Iranian wheat cultivars. This led to a significantly higher Nei coefficient of genetic variations in Glu-3 loci (0.756) as compared to Glu-1 loci (0.547). At Glu-3 loci, we observed relatively high quality alleles in Glu-A3 and Glu-D3 loci and low quality alleles at Glu-B3 locus.

  11. TREND AND DETERMINANTS OF CSR DISCLOSURE IN INDONESIA: A RESPONSE OF THE ACT NO. 40 (2007

    Directory of Open Access Journals (Sweden)

    Nur Cahyonowati

    2013-05-01

    Full Text Available This study aims to examine the trend of corporate social responsibility disclosure in Indonesia with regard to the Act No. 40 (2007. Mandatory corporate social responsibility has been debated among businessmen in Indonesia. This research proposes important suggestions to achieve effective implementation of the act. In addition,  this study aims to identify determinants of corporate social responsibility (CSR disclosure among companies listed on Indonesia Stock Exchange. This study uses content analysis on five year annual reports to measure the level of corporate social responsibility disclosure. To examine the trend of disclosure, the study requires complete annual reports during observed period. This study found the increase of trend in corporate social disclosure during observed period. However, the increase was not significant indicated by low response of companies to the act. The results of content analysis indicate that human resources or employee topic dominate CSR disclosure. Regarding to the quantity of disclosure, the study found that 55,9% of disclosures were written in paragraph which less than half of A4 size paper. The study also found that 71% of disclosures was in non-monetary term. The results of regression analysis indicate that firm size is a pivotal determinant of CSR but not for profitability and public ownership. However, these findings are lack of generalization due to small sample size.

  12. Allelic Diversity of MSP1 Gene in Plasmodium falciparum from Rural and Urban Areas of Gabon.

    Science.gov (United States)

    Mawili-Mboumba, Denise Patricia; Mbondoukwe, Noé; Adande, Elvire; Bouyou-Akotet, Marielle Karine

    2015-08-01

    The present study determined and compared the genetic diversity of Plasmodium falciparum strains infecting children living in 2 areas from Gabon with different malaria endemicity. Blood samples were collected from febrile children from 2008 to 2009 in 2 health centres from rural (Oyem) and urban (Owendo) areas. Genetic diversity was determined in P. falciparum isolates by analyzing the merozoite surface protein-1 (msp1) gene polymorphism using nested-PCR. Overall, 168 children with mild falciparum malaria were included. K1, Ro33, and Mad20 alleles were found in 110 (65.5%), 94 (55.9%), and 35 (20.8%) isolates, respectively, without difference according to the site (P>0.05). Allelic families' frequencies were comparable between children less than 5 years old from the 2 sites; while among the older children the proportions of Ro33 and Mad20 alleles were 1.7 to 2.0 fold higher at Oyem. Thirty-three different alleles were detected, 16 (48.5%) were common to both sites, and 10 out of the 17 specific alleles were found at Oyem. Furthermore, multiple infection carriers were frequent at Oyem (57.7% vs 42.2% at Owendo; P=0.04) where the complexity of infection was of 1.88 (±0.95) higher compared to that found at Owendo (1.55±0.75). Extended genetic diversity of P. falciparum strains infecting Gabonese symptomatic children and high multiplicity of infections were observed in rural area. Alleles common to the 2 sites were frequent; the site-specific alleles predominated in the rural area. Such distribution of the alleles should be taken into accounts when designing MSP1 or MSP2 malaria vaccine.

  13. The impact of library preparation protocols on the consistency of allele frequency estimates in Pool-Seq data.

    Science.gov (United States)

    Kofler, Robert; Nolte, Viola; Schlötterer, Christian

    2016-01-01

    Sequencing pools of individuals (Pool-Seq) is a cost-effective method to determine genome-wide allele frequency estimates. Given the importance of meta-analyses combining data sets, we determined the influence of different genomic library preparation protocols on the consistency of allele frequency estimates. We found that typically no more than 1% of the variation in allele frequency estimates could be attributed to differences in library preparation. Also read length had only a minor effect on the consistency of allele frequency estimates. By far, the most pronounced influence could be attributed to sequence coverage. Increasing the coverage from 30- to 50-fold improved the consistency of allele frequency estimates by at least 27%. We conclude that Pool-Seq data can be easily combined across different library preparation methods, but sufficient sequence coverage is key to reliable results.

  14. Mixed allele malaria vaccines: Host protection and within-host selection

    Science.gov (United States)

    Barclay, Victoria C.; Chan, Brian H.K.; Anders, Robin F.; Read, Andrew F.

    2008-01-01

    Malaria parasites are frequently polymorphic at the antigenic targets of many candidate vaccines, presumably as a consequence of selection pressure from protective immune responses. Conventional wisdom is therefore that vaccines directed against a single variant could select for non-target variants, rendering the vaccine useless. Many people have argued that a solution is to develop vaccines containing the products of more than one variant of the target. However, we are unaware of any evidence that multi-allele vaccines better protect hosts against parasites or morbidity. Moreover, selection of antigen-variants is not the only evolution that could occur in response to vaccination. Increased virulence could also be favored if more aggressive strains are less well controlled by vaccine-induced immunity. Virulence and antigenic identity have been confounded in all studies so far, and so we do not know formally from any animal or human studies whether vaccine failure has been due to evasion of protective responses by variants at target epitopes, or whether vaccines are just less good at protecting against more aggressive strains. Using the rodent malaria model Plasmodium chabaudi and recombinant apical membrane antigen-1 (AMA-1), we tested whether a bi-allelic vaccine afforded greater protection from parasite infection and morbidity than did vaccination with the component alleles alone. We also tested the effect of mono- and bi-allelic vaccination on within-host selection of mixed P. chabaudi infections, and whether parasite virulence mediates pathogen titres in immunized hosts. We found that vaccination with the bi-allelic AMA-1 formulation did not afford the host greater protection from parasite infection or morbidity than did mono-allelic AMA-1 immunization. Mono-allelic immunization increased the frequency of heterologous clones in mixed clone infections. There was no evidence that any type of immunization regime favored virulence. A single AMA-1 variant is a

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

    International Nuclear Information System (INIS)

    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

  16. Response Determination Of Propeller To Bird Strike Using High Speed Photography

    Science.gov (United States)

    Bertke, R. S.; Edinger, R. L.

    1984-11-01

    Static bench type impact tests of 4.0 and 1.5 pound artificial birds striking the leading edge of composite propeller blades are conducted to determine the damage response of the blades to bird strike. The artificial birds (cylindrical in shape) are launched at velo-cities up to 900 ft/sec (275 m/sec) to demonstrate that composite construction propeller blades will pass the Federal Aviation Administration (FAA) bird strike requirements. A high speed framing camera is used to determine the impact velocity of the birds, maximum tip deflections, bird/blade contact time, and the elapsed time required to achieve maximum deflection.

  17. Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size.

    Science.gov (United States)

    Garza, J C; Slatkin, M; Freimer, N B

    1995-07-01

    The distributions of allele sizes at eight simple-sequence repeat (SSR) or microsatellite loci in chimpanzees are found and compared with the distributions previously obtained from several human populations. At several loci, the differences in average allele size between chimpanzees and humans are sufficiently small that there might be a constraint on the evolution of average allele size. Furthermore, a model that allows for a bias in the mutation process shows that for some loci a weak bias can account for the observations. Several alleles at one of the loci (Mfd 59) were sequenced. Differences between alleles of different lengths were found to be more complex than previously assumed. An 8-base-pair deletion was present in the nonvariable region of the chimpanzee locus. This locus contains a previously unrecognized repeated region, which is imperfect in humans and perfect in chimpanzees. The apparently greater opportunity for mutation conferred by the two perfect repeat regions in chimpanzees is reflected in the higher variance in repeat number at Mfd 59 in chimpanzees than in humans. These data indicate that interspecific differences in allele length are not always attributable to simple changes in the number of repeats. PMID:7659015

  18. Cardiorespiratory responses to moderate exercise and determination of aerobic power in first year medical students

    OpenAIRE

    Subha Kavundapadi Chandrasekaran; Rajkumar Devaraj

    2016-01-01

    Background: Cardiovascular and metabolic disorder has become common in individuals leading a sedentary life. Exercise stress tests are carried out as part of the investigations for determining the individual fitness level. Aerobic power or VO2max which involves a full functional support from cardio respiratory and metabolic pathways is an appropriate test to study cardio pulmonary fitness. The main objective of the study is to find out the normal cardiopulmonary responses to exercise and thei...

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

    OpenAIRE

    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.

    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...

  20. Liquid-filled transient pressure measuring systems: A method for determining frequency response

    Science.gov (United States)

    Anderson, R. C.; Englund, D. R., Jr.

    1971-01-01

    An equation is given and experimentally verified for computing the resonant frequency of liquid-filled transient pressure measuring systems. Resonant frequencies of 100 to 1000 Hz are typical of those systems tested. The effect of noncondensable gas bubbles on system response is described. A method for determining transducer volumetric compliance is presented. An example system is described and analyzed to demonstrate the use of the theory.

  1. 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.

  2. 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.

  3. Estimation of allele frequencies for VNTR loci.

    OpenAIRE

    Devlin, B; Risch, N; Roeder, K

    1991-01-01

    VNTR loci provide valuable information for a number of fields of study involving human genetics, ranging from forensics (DNA fingerprinting and paternity testing) to linkage analysis and population genetics. Alleles of a VNTR locus are simply fragments obtained from a particular portion of the DNA molecule and are defined in terms of their length. The essential element of a VNTR fragment is the repeat, which is a short sequence of basepairs. The core of the fragment is composed of a variable ...

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

    Science.gov (United States)

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

    2010-02-19

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

  5. 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.

  6. A Novel Frequent BRCA1 Allele in Chinese Patients with Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    ZHOU Dongxian; XIONG Wen; XU Hongxan; SHAO Chaopeng

    2006-01-01

    The whole length of exon 11 of BRCA1 was sequenced (total 3427 bp) in 59 patients and 10 healthy female blood donors. To allow a rapid determination of the different BRCA1 alleles, a sequence-specific primer PCR method (PCR-SSP) was established and was applied to 57 additional female donors. Finally, the full-length coding region of BRCA1 was analyzed through reversed-transcriptase PCR (RT-PCR) and cDNA sequencing (total 5554 bp) in one donor with wild-type allele and 2 patients with one or two mutated alleles. By genomic DNA sequencing, 5 homozygous polymorphisms were observed in 18 patients: 2201C>T, 2430T>C, 2731C>T, 3232A>G and 3667A>G. All of them were previously observed in Caucasians, Malay and Chinese, but for the first time the mutations were found in one allele (GenBank AY304547). Twenty-six patients and 4donors were heterozygous at these 5 nucleotide positions. The remaining 15 patients and 6 donors showed a sequence identical with the standard BRCA1 gene. Combined the PCR-SSP results and in a summary, 6 of 67 (9.0 %) healthy individuals were homozygous for the mutated allele, whereas 18 of 59 (30.5 %) breast cancer patients were homozygous. A Chi-square test showed a significant correlation between homozygous mutated BRCA1 allele and breast cancer. The cDNA sequencing showed that 2 additional mutations, 4427T>C in exon 13 and 4956A>G in exon 16, were found. A new BRCA1 allele, which is BRCA1-2201T/2430C/2731T/3232G/3667G/4427C/4956G (GenBank AY751490), was found in Chinese. And the homozygote of this mutated allele may implicate a disease-association in Chinese.

  7. Detection of allelic variations of human gene expression by polymerase colonies

    Directory of Open Access Journals (Sweden)

    Mikkilineni Venugopal

    2004-02-01

    Full Text Available Abstract Background Quantification of variations of human gene expression is complicated by the small differences between different alleles. Recent work has shown that variations do exist in the relative allelic expression levels in certain genes of heterozygous individuals. Herein, we describe the application of an immobilized polymerase chain reaction technique as an alternative approach to measure relative allelic differential expression. Results Herein, we report a novel assay, based on immobilized polymerase colonies, that accurately quantifies the relative expression levels of two alleles in a given sample. Mechanistically, this was accomplished by PCR amplifying a gene in a cDNA library in a thin polyacrylamide gel. By immobilizing the PCR, it is ensured that each transcript gives rise to only a single immobilized PCR colony, or "polony". Once polony amplified, the two alleles of the gene were differentially labeled by performing in situ sequencing with fluorescently labeled nucleotides. For these sets of experiments, silent single nucleotide polymorphisms (SNPs were used to discriminate the two alleles. Finally, a simple count was then performed on the differentially labeled polonies in order to determine the relative expression levels of the two alleles. To validate this technique, the relative expression levels of PKD2 in a family of heterozygous patients bearing the 4208G/A SNP were examined and compared to the literature. Conclusions We were able to reproduce the results of allelic variation in gene expression using an accurate technology known as polymerase colonies. Therefore, we have demonstrated the utility of this method in human gene expression analysis.

  8. [Haemophilus influenzae b: a review on the determinants of pathogenicity and immune response to the infection].

    Science.gov (United States)

    Gómez de León, P; Cabrera-Contreras, R; Cravioto, A

    1991-01-01

    Haemophilus influenzae is still one of the main causes of diverse invasive diseases in children in México. Epidemiologic data indicate that these processes affect primarily the central nervous system and the respiratory tract. Several factors are involved in the expression of infectious disease by this organism, among them the pathogenic determinants of the parasite and those related with resistance in the host. Occurrence of disease is usually the result of the interaction between these determinants. Knowledge of these pathogenic determinants of the parasite and of factors involved in the immune response of the host have allowed an understanding of the infectious process and have directed research in a least three areas: 1) identification of bacterial membrane fractions related with diagnosis of the disease, 2) screening for immunogenic components in the bacterias as vaccine candidates to be used in the prevention of the disease and, 3) the planning of appropriate alternatives for specific antimicrobial therapy. PMID:1948428

  9. Determinants of Blood Pressure Response to Low Salt Intake in a Healthy Adult Population

    Science.gov (United States)

    Montasser, May E.; Douglas, Julie A.; Roy-Gagnon, Marie-Hèlène; Van Hout, Cristopher V.; Weir, Matthew R.; Vogel, Robert; Parsa, Afshin; Steinle, Nanette I.; Snitker, Soren; Brereton, Nga Hong; Chang, Yen-Pei C.; Shuldiner, Alan R.; Mitchell, Braxton D.

    2011-01-01

    Although the beneficial effects of lowering salt intake in hypertensives are widely appreciated, the impact of promoting dietary salt restriction for BP reduction at the population level remains controversial. We used 24-hr ambulatory blood pressure monitoring to characterize the determinants of systolic blood pressure (SBP) response to low salt intake in a large, relatively healthy Amish population. Subjects received a high and low sodium diet for 6 days each, separated by a 6–14 day washout period. Variance component analysis was used to assess the association of several variables with SBP response to low salt diet. Mean SBP was 0.7 ± 5.8 and 1.3 ± 6.1 mmHg lower on the low salt compared to the high salt diet during daytime (p=0.008) and nighttime (p<0.0001) respectively. SBP response to low salt diet was significantly associated with increasing age and pre-intervention SBP, in both daytime and nighttime, while the association with female gender and SBP response to cold pressor test (CPT) was significant only during nighttime. Our results suggest that salt reduction may have greater BP-lowering effects on females, older individuals, individuals with higher SBP, and individuals with higher SBP response to CPT. PMID:22051423

  10. Arthritogenic peptide binding to DRB1*01 alleles correlates with susceptibility to rheumatoid arthritis.

    Science.gov (United States)

    Roark, Christina L; Anderson, Kirsten M; Aubrey, Michael T; Rosloniec, Edward F; Freed, Brian M

    2016-08-01

    Genetic susceptibility to rheumatoid arthritis (RA) is often defined by the presence of a shared epitope (QKRAA, QRRAA, or RRRAA) at positions 70-74 in HLA-DRβ1. However, DRβ1*01:01 and 01:02 contain the same QRRAA epitope, but differ considerably in their susceptibility to RA. The purpose of this study was to determine if this difference could be explained by their ability to bind three arthritogenic peptides that we have previously shown to bind to the archetypal RA-susceptible allele, DRβ1*04:01, but not to the resistant DRβ1*08:01 allele. Binding of type II collagen(258-272), citrullinated and native vimentin(66-78), and citrullinated and native α-enolase(11-25) were measured on cell lines expressing either DRβ1*01:01, *01:02 or *01:03 in association with DRα1*01:01. DRβ1*01:01 and *01:02 both exhibited a 6.5-fold preference for citrullinated vimentin(66-78) compared to native vimentin. However, DRβ1*01:01 also exhibited a 1.7-fold preference for citrullinated α-enolase(11-25) and bound collagen(258-272), while DRβ1*01:02 bound neither of these peptides. Consistent with its known resistance to RA, DRβ1*01:03 preferentially bound native vimentin(66-78) and α-enolase(11-25) over the citrullinated forms of these peptides, and also failed to bind collagen(258-272). Site-directed mutagenesis was performed to determine which amino acid residues were responsible for the differences between these alleles. Mutating position 86 in DRβ1*01:01 from glycine to the valine residue found in DRβ1*01:02 eliminated binding of both citrullinated α-enolase(11-25) and collagen(258-272), thereby recapitulating the peptide-binding profile of DRβ1*01:02. The difference in susceptibility to rheumatoid arthritis between DRβ1*01:01 and *01:02 thus correlates with the effect of position 86 on the binding of these arthritogenic peptides. Consistent with their association with RA resistance, positions I67, D70 and E71 all contributed to the inability of DRβ1*01:03 to bind

  11. 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. PMID:27446145

  12. 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

  13. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles

    Science.gov (United States)

    Orozco-terWengel, Pablo; Kapun, Martin; Nolte, Viola; Kofler, Robert; Flatt, Thomas; Schlötterer, Christian

    2012-01-01

    The genomic basis of adaptation to novel environments is a fundamental problem in evolutionary biology that has gained additional importance in the light of the recent global change discussion. Here, we combined laboratory natural selection (experimental evolution) in Drosophila melanogaster with genome-wide next generation sequencing of DNA pools (Pool-Seq) to identify alleles that are favourable in a novel laboratory environment and traced their trajectories during the adaptive process. Already after 15 generations, we identified a pronounced genomic response to selection, with almost 5000 single nucleotide polymorphisms (SNP; genome-wide false discovery rates < 0.005%) deviating from neutral expectation. Importantly, the evolutionary trajectories of the selected alleles were heterogeneous, with the alleles falling into two distinct classes: (i) alleles that continuously rise in frequency; and (ii) alleles that at first increase rapidly but whose frequencies then reach a plateau. Our data thus suggest that the genomic response to selection can involve a large number of selected SNPs that show unexpectedly complex evolutionary trajectories, possibly due to nonadditive effects. PMID:22726122

  14. Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites.

    Science.gov (United States)

    Chebon, Lorna J; Ngalah, Bidii S; Ingasia, Luicer A; Juma, Dennis W; Muiruri, Peninah; Cheruiyot, Jelagat; Opot, Benjamin; Mbuba, Emmanuel; Imbuga, Mabel; Akala, Hoseah M; Bulimo, Wallace; Andagalu, Ben; Kamau, Edwin

    2016-01-01

    Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya. PMID:27611315

  15. 20 CFR 411.460 - Who is responsible for determining what information is contained in the IWP?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Who is responsible for determining what information is contained in the IWP? 411.460 Section 411.460 Employees' Benefits SOCIAL SECURITY... Who is responsible for determining what information is contained in the IWP? The beneficiary and...

  16. Four danger response programs determine glomerular and tubulointerstitial kidney pathology: clotting, inflammation, epithelial and mesenchymal healing.

    Science.gov (United States)

    Anders, Hans-Joachim

    2012-01-01

    Renal biopsies commonly display tissue remodeling with a combination of many different findings. In contrast to trauma, kidney remodeling largely results from intrinsic responses, but why? Distinct danger response programs were positively selected throughout evolution to survive traumatic injuries and to regenerate tissue defects. These are: (1) clotting to avoid major bleeding, (2) immunity to control infection, (3) epithelial repair and (4) mesenchymal repair. Collateral damages are acceptable for the sake of host survival but causes for kidney injury commonly affect the kidneys in a diffuse manner. This way, coagulation, inflammation, deregulated epithelial healing or fibrosis contribute to kidney remodeling. Here, I focus on how these ancient danger response programs determine renal pathology mainly because they develop in a deregulated manner, either as insufficient or overshooting processes that modulate each other. From a therapeutic point of view, immunopathology can be prevented by suppressing sterile renal inflammation, a useless atavism with devastating consequences. In addition, it appears as an important goal for the future to promote podocyte and tubular epithelial cell repair, potentially by stimulating the differentiation of their newly discovered intrarenal progenitor cells. By contrast, it is still unclear whether selectively targeting renal fibrogenesis can preserve or bring back lost renal parenchyma, which would be required to maintain or improve kidney function. Thus, renal pathology results from ancient danger responses that evolved because of their evolutional benefits upon trauma. Understanding these causalities may help to shape the search for novel treatments for kidney disease patients. PMID:22692229

  17. Dideoxy single allele-specific PCR - DSASP new method to discrimination allelic

    Directory of Open Access Journals (Sweden)

    Eleonidas Moura Lima

    2015-06-01

    Full Text Available Gastric cancer (GC is a multifactorial disease with a high mortality rate in Brazil and worldwide. This work aimed to evaluate single nucleotide polymorphisms (SNP rs1695, in the Glutathione S-Transferase Pi (GSTP1 gene in GC samples by comparative analysis Specific PCR - ASP and Dideoxy Single Allele-Specific PCR - DSASP methods. The DSASP is the proposed new method for allelic discrimination. This work analyzed 60 GC samples, 26 diffuse and 34 intestinal types. The SNP rs1695 of the GSTP1 gene was significantly associated with GC analyzed by DSASP method (χ2 = 9.7, P 0.05. These results suggest that the SNP rs1695 of the GSTP1 gene was a risk factor associated with gastric carcinogens is and the DSASP method was a new successfully low-cost strategy to study allelic discrimination.

  18. Borrowed alleles and convergence in serpentine adaptation.

    Science.gov (United States)

    Arnold, Brian J; Lahner, Brett; DaCosta, Jeffrey M; Weisman, Caroline M; Hollister, Jesse D; Salt, David E; Bomblies, Kirsten; Yant, Levi

    2016-07-19

    Serpentine barrens represent extreme hazards for plant colonists. These sites are characterized by high porosity leading to drought, lack of essential mineral nutrients, and phytotoxic levels of metals. Nevertheless, nature forged populations adapted to these challenges. Here, we use a population-based evolutionary genomic approach coupled with elemental profiling to assess how autotetraploid Arabidopsis arenosa adapted to a multichallenge serpentine habitat in the Austrian Alps. We first demonstrate that serpentine-adapted plants exhibit dramatically altered elemental accumulation levels in common conditions, and then resequence 24 autotetraploid individuals from three populations to perform a genome scan. We find evidence for highly localized selective sweeps that point to a polygenic, multitrait basis for serpentine adaptation. Comparing our results to a previous study of independent serpentine colonizations in the closely related diploid Arabidopsis lyrata in the United Kingdom and United States, we find the highest levels of differentiation in 11 of the same loci, providing candidate alleles for mediating convergent evolution. This overlap between independent colonizations in different species suggests that a limited number of evolutionary strategies are suited to overcome the multiple challenges of serpentine adaptation. Interestingly, we detect footprints of selection in A. arenosa in the context of substantial gene flow from nearby off-serpentine populations of A. arenosa, as well as from A. lyrata In several cases, quantitative tests of introgression indicate that some alleles exhibiting strong selective sweep signatures appear to have been introgressed from A. lyrata This finding suggests that migrant alleles may have facilitated adaptation of A. arenosa to this multihazard environment. PMID:27357660

  19. Determination of Energy and Angular Response of an Albedo Neutron Personal Dosemeter

    International Nuclear Information System (INIS)

    The result of the determination of energy and angular response for the albedo neutron personal dosemeter used by CPHR, is described. The dosemeters consist of two pairs of LiF detectors (6LiF+7LiF) separated by a piece of boron-loaded plastic. For the study, the dosemeters were irradiated in three mixed neutron-gamma fields (thermal neutrons, moderated 241Am-Be and 241Am-Be) and at two incidence angles of radiation (0 deg. and 60 deg. ). The variation of the sensibility at different neutron spectra and incidence angles of radiation was determined. The methodology of dose evaluation, applying the obtained coefficients, was established. (author)

  20. Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites

    Science.gov (United States)

    Chebon, Lorna J.; Ngalah, Bidii S.; Ingasia, Luicer A.; Juma, Dennis W.; Muiruri, Peninah; Cheruiyot, Jelagat; Opot, Benjamin; Mbuba, Emmanuel; Imbuga, Mabel; Akala, Hoseah M.; Bulimo, Wallace; Andagalu, Ben; Kamau, Edwin

    2016-01-01

    Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p resistance in Kenya. PMID:27611315

  1. Evidence that intragenic recombination contributes to allelic diversity of the S-RNase gene at the self-incompatibility (S) locus in Petunia inflata.

    Science.gov (United States)

    Wang, X; Hughes, A L; Tsukamoto, T; Ando, T; Kao, T

    2001-02-01

    For Solanaceae type self-incompatibility, discrimination between self and nonself pollen by the pistil is controlled by the highly polymorphic S-RNase gene. To date, the mechanism generating the allelic diversity of this gene is largely unknown. Natural populations offer a good opportunity to address this question because they likely contain different alleles that share recent common progenitors. We identified 19 S haplotypes from a natural population of Petunia inflata in Argentina, used reverse transcriptase-polymerase chain reaction to obtain cDNAs for 15 alleles of the S-RNase gene, and sequenced all the cDNAs. Phylogenetic studies revealed that five of these alleles and two previously identified alleles form a major clade, and that the 5' region of S(19) allele was derived from an ancestor allele closely related to S(2), whereas its 3' region was derived from an ancestor allele closely related to S(8). A similar evolutionary relationship was found among S(3), S(12), and S(15) alleles. These findings suggest that intragenic recombination contributed to the generation of the allelic diversity of the S-RNase gene. Two additional findings emerged from the sequence comparisons. First, the nucleotide sequence of the S(1) allele identified in this work is completely identical to that of the previously identified S(1) allele of a different origin. Second, in the two hypervariable regions HVa and HVb, thought to be involved in determining S allele specificity, S(6) and S(9) alleles differ only by four nucleotides, all in HVb, resulting in two amino acid differences. The implications of these findings are discussed. PMID:11161057

  2. 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.

  3. Allelic analysis of sheath blight resistance with association mapping in rice.

    Directory of Open Access Journals (Sweden)

    Limeng Jia

    Full Text Available Sheath blight (ShB caused by the soil-borne pathogen Rhizoctonia solani is one of the most devastating diseases in rice world-wide. Global attention has focused on examining individual mapping populations for quantitative trait loci (QTLs for ShB resistance, but to date no study has taken advantage of association mapping to examine hundreds of lines for potentially novel QTLs. Our objective was to identify ShB QTLs via association mapping in rice using 217 sub-core entries from the USDA rice core collection, which were phenotyped with a micro-chamber screening method and genotyped with 155 genome-wide markers. Structure analysis divided the mapping panel into five groups, and model comparison revealed that PCA5 with genomic control was the best model for association mapping of ShB. Ten marker loci on seven chromosomes were significantly associated with response to the ShB pathogen. Among multiple alleles in each identified loci, the allele contributing the greatest effect to ShB resistance was named the putative resistant allele. Among 217 entries, entry GSOR 310389 contained the most putative resistant alleles, eight out of ten. The number of putative resistant alleles presented in an entry was highly and significantly correlated with the decrease of ShB rating (r = -0.535 or the increase of ShB resistance. Majority of the resistant entries that contained a large number of the putative resistant alleles belonged to indica, which is consistent with a general observation that most ShB resistant accessions are of indica origin. These findings demonstrate the potential to improve breeding efficiency by using marker-assisted selection to pyramid putative resistant alleles from various loci in a cultivar for enhanced ShB resistance in rice.

  4. Results for the response function determination of the Compact Neutron Spectrometer

    CERN Document Server

    Gagnon-Moisan, F; Zimbal, A

    2012-01-01

    The Compact Neutron Spectrometer (CNS) is a Joint European Torus (JET) Enhancement Project, designed for fusion diagnostics in different plasma scenarios. The CNS is based on a liquid scintillator (BC501A) which allows good discrimination between neutron and gamma radiation. Neutron spectrometry with a BC501A spectrometer requires the use of a reliable, fully characterized detector. The determination of the response matrix was carried out at the Ion Accelerator Facility (PIAF) of the Physikalisch-Technische Bundesanstalt (PTB). This facility provides several monoenergetic beams (2.5, 8, 10, 12 and 14 MeV) and a 'white field'(Emax ~17 MeV), which allows for a full characterization of the spectrometer in the region of interest (from ~1.5 MeV to ~17 MeV. The energy of the incoming neutrons was determined by the time of flight method (TOF), with time resolution in the order of 1 ns. To check the response matrix, the measured pulse height spectra were unfolded with the code MAXED and the resulting energy distribut...

  5. Results for the response function determination of the Compact Neutron Spectrometer

    Science.gov (United States)

    Gagnon-Moisan, F.; Reginatto, M.; Zimbal, A.

    2012-03-01

    The Compact Neutron Spectrometer (CNS) is a Joint European Torus (JET) Enhancement Project, designed for fusion diagnostics in different plasma scenarios. The CNS is based on a liquid scintillator (BC501A) which allows good discrimination between neutron and gamma radiation. Neutron spectrometry with a BC501A spectrometer requires the use of a reliable, fully characterized detector. The determination of the response matrix was carried out at the Ion Accelerator Facility (PIAF) of the Physikalisch-Technische Bundesanstalt (PTB). This facility provides several monoenergetic beams (2.5, 8, 10, 12 and 14 MeV) and a white field (Emax ~ 17 MeV), which allows for a full characterization of the spectrometer in the region of interest (from ~ 1.5 MeV to ~ 17 MeV). The energy of the incoming neutrons was determined by the time of flight method (TOF), with time resolution in the order of 1 ns. To check the response matrix, the measured pulse height spectra were unfolded with the code MAXED and the resulting energy distributions were compared with those obtained from TOF. The CNS project required modification of the PTB BC501A spectrometer design, to replace an analog data acquisition system (NIM modules) with a digital system developed by the Ente per le Nuove tecnologie, l'Energia e l'Ambiente (ENEA). Results for the new digital system were evaluated using new software developed specifically for this project.

  6. Determination of the mechanical response of sintering compacts by cyclic loading dilatometry

    International Nuclear Information System (INIS)

    Determination of the mechanical response of a powder compact during densification is critical in analyzing defect formation and macroscopic dimensional changes, particularly in systems where constrained sintering is involved. Cyclic loading dilatometry is proposed as a novel approach in evaluating the mechanical response of the sintering compact, including sintering pressure, elastic modulus, and viscosity. The advantage of this technique is that only one experiment is needed to determine the equilibrium elastic and viscous properties of a sintering material at any temperatures for any given heating schedule, and no interrupted tests are necessary. This methodology is demonstrated for sintering compacts of Al2O3, Ce-TZP, and their composite mixture. The loading dilatometric data showed that the compact behaved elastically prior to the onset of sintering and during the very initial stages of sintering, which was followed by a transition leading to a viscous behavior for the latter part of the densification. Application of different load levels, ranging from 0.25 to 1 MPa, showed that the compact viscosity is essentially linear within the applied stress range at temperatures greater than 1,100 C

  7. 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.

  8. Vaginal Mucosal Homeostatic Response May Determine Pregnancy Outcome in Women With Bacterial Vaginosis: A Pilot Study.

    Science.gov (United States)

    Faure, Emmanuel; Faure, Karine; Figeac, Martin; Kipnis, Eric; Grandjean, Teddy; Dubucquoi, Sylvain; Villenet, Céline; Grandbastien, Bruno; Brabant, Gilles; Subtil, Damien; Dessein, Rodrigue

    2016-02-01

    Bacterial vaginosis (BV) is considered as a trigger for an inflammatory response that could promote adverse pregnancy outcome (APO). We hypothesized that BV-related inflammation could be counterbalanced by anti-inflammatory and mucosal homeostatic responses that could participate in pregnancy outcomes.A total of 402 vaginal self-samples from pregnant women in their first trimester were screened by Nugent score. In this population, we enrolled 23 pregnant women with BV but without APO, 5 pregnant women with BV and developing APO, 21 pregnant women with intermediate flora, and 28 random control samples from pregnant women without BV or APO.BV without APO in pregnant women was associated with 28-fold interleukin-8, 5-fold interleukin-10, and 40-fold interleukin-22 increases in expression compared to controls. BV associated with APO in pregnant women shared 4-fold increase in tumor necrosis factor, 100-fold decrease in interleukin-10, and no variation in interleukin-22 expressions compared to controls. Next-generation sequencing of vaginal microbiota revealed a shift from obligate anaerobic bacteria dominance in BV without APO pregnant women to Lactobacillus dominance microbiota in BV with APO.Our results show that the anti-inflammatory and mucosal homeostatic responses to BV may determine outcome of pregnancy in the setting of BV possibly through effects on the vaginal microbiota. PMID:26844497

  9. Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults

    Directory of Open Access Journals (Sweden)

    Daly Melissa

    2006-08-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 105 TCID50/g body weight and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion Neonatal RSV exposure results in long term

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

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    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.

  11. 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. PMID:24877238

  12. Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing® technology

    Directory of Open Access Journals (Sweden)

    Gallagher Margaret L

    2009-08-01

    Full Text Available Abstract Background Identification of CYP2A6 alleles associated with reduced enzyme activity is important in the study of inter-individual differences in drug metabolism. CYP2A6*12 is a hybrid allele that results from unequal crossover between CYP2A6 and CYP2A7 genes. The 5' regulatory region and exons 1–2 are derived from CYP2A7, and exons 3–9 are derived from CYP2A6. Conventional methods for detection of CYP2A6*12 consist of two-step PCR protocols that are laborious and unsuitable for high-throughput genotyping. We developed a rapid and accurate method to detect the CYP2A6*12 allele by Pyrosequencing technology. Methods A single set of PCR primers was designed to specifically amplify both the CYP2A6*1 wild-type allele and the CYP2A6*12 hybrid allele. An internal Pyrosequencing primer was used to generate allele-specific sequence information, which detected homozygous wild-type, heterozygous hybrid, and homozygous hybrid alleles. We first validated the assay on 104 DNA samples that were also genotyped by conventional two-step PCR and by cycle sequencing. CYP2A6*12 allele frequencies were then determined using the Pyrosequencing assay on 181 multi-ethnic DNA samples from subjects of African American, European Caucasian, Pacific Rim, and Hispanic descent. Finally, we streamlined the Pyrosequencing assay by integrating liquid handling robotics into the workflow. Results Pyrosequencing results demonstrated 100% concordance with conventional two-step PCR and cycle sequencing methods. Allele frequency data showed slightly higher prevalence of the CYP2A6*12 allele in European Caucasians and Hispanics. Conclusion This Pyrosequencing assay proved to be a simple, rapid, and accurate alternative to conventional methods, which can be easily adapted to the needs of higher-throughput studies.

  13. 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 in per...

  14. 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

  15. Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy

    International Nuclear Information System (INIS)

    Purpose: To quantify the dose-time fractionation factors in preoperative radiation therapy for microscopic pelvic deposits of rectal cancer. This provides a biologic basis for understanding and improving the results of adjuvant therapies for this disease. Methods: The reduction in incidence of pelvic relapses as a function of radiation dose and overall treatment time was determined from the literature. The displacement of dose-response curves to higher doses reflects the growth during radiation treatment of subclinical pelvic deposits which are beyond the future surgical margins. Results: Dose-response curves are steep if the effect of overall duration of radiation therapy is accounted for. The time-related displacement of these steep dose-response curves is consistent with a median doubling time for malignant clonogenic cells of about 4 or 5 days, much faster than the growth rate of the average primary tumor at diagnosis. This rapid growth is evident within the first few days of irradiation, implying that the natural growth rate of these microscopic deposits if fast, and/or that an acceleration of growth follows initiation of radiation injury with a very short lag time. Conclusion: Subclinical pelvic deposits of rectal cancer grow rapidly during preoperative radiation therapy with an adverse influence on the rate of pelvic tumor control from protracting the duration of adjuvant treatment. Low doses only offer clinically relevant reduction in risk of pelvic relapses if the overall radiation treatment time is short. For a given overall treatment duration there is a relatively steep dose-response curve, predicting that significant improvements in tumor control are possible

  16. 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.

  17. Recommendations of the DNA Commission of the International Society for Forensic Genetics (ISFG) on quality control of autosomal Short Tandem Repeat allele frequency databasing (STRidER).

    Science.gov (United States)

    Bodner, Martin; Bastisch, Ingo; Butler, John M; Fimmers, Rolf; Gill, Peter; Gusmão, Leonor; Morling, Niels; Phillips, Christopher; Prinz, Mechthild; Schneider, Peter M; Parson, Walther

    2016-09-01

    The statistical evaluation of autosomal Short Tandem Repeat (STR) genotypes is based on allele frequencies. These are empirically determined from sets of randomly selected human samples, compiled into STR databases that have been established in the course of population genetic studies. There is currently no agreed procedure of performing quality control of STR allele frequency databases, and the reliability and accuracy of the data are largely based on the responsibility of the individual contributing research groups. It has been demonstrated with databases of haploid markers (EMPOP for mitochondrial mtDNA, and YHRD for Y-chromosomal loci) that centralized quality control and data curation is essential to minimize error. The concepts employed for quality control involve software-aided likelihood-of-genotype, phylogenetic, and population genetic checks that allow the researchers to compare novel data to established datasets and, thus, maintain the high quality required in forensic genetics. Here, we present STRidER (http://strider.online), a publicly available, centrally curated online allele frequency database and quality control platform for autosomal STRs. STRidER expands on the previously established ENFSI DNA WG STRbASE and applies standard concepts established for haploid and autosomal markers as well as novel tools to reduce error and increase the quality of autosomal STR data. The platform constitutes a significant improvement and innovation for the scientific community, offering autosomal STR data quality control and reliable STR genotype estimates. PMID:27352221

  18. Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk.

    Science.gov (United States)

    Foo, Jia Nee; Smedby, Karin E; Akers, Nicholas K; Berglund, Mattias; Irwan, Ishak D; Jia, Xiaoming; Li, Yi; Conde, Lucia; Darabi, Hatef; Bracci, Paige M; Melbye, Mads; Adami, Hans-Olov; Glimelius, Bengt; Khor, Chiea Chuen; Hjalgrim, Henrik; Padyukov, Leonid; Humphreys, Keith; Enblad, Gunilla; Skibola, Christine F; de Bakker, Paul I W; Liu, Jianjun

    2013-07-11

    Non-Hodgkin lymphoma represents a diverse group of blood malignancies, of which follicular lymphoma (FL) is a common subtype. Previous genome-wide association studies (GWASs) have identified in the human leukocyte antigen (HLA) class II region multiple independent SNPs that are significantly associated with FL risk. To dissect these signals and determine whether coding variants in HLA genes are responsible for the associations, we conducted imputation, HLA typing, and sequencing in three independent populations for a total of 689 cases and 2,446 controls. We identified a hexa-allelic amino acid polymorphism at position 13 of the HLA-DR beta chain that showed the strongest association with FL within the major histocompatibility complex (MHC) region (multiallelic p = 2.3 × 10⁻¹⁵). Out of six possible amino acids that occurred at that position within the population, we classified two as high risk (Tyr and Phe), two as low risk (Ser and Arg), and two as moderate risk (His and Gly). There was a 4.2-fold difference in risk (95% confidence interval = 2.9-6.1) between subjects carrying two alleles encoding high-risk amino acids and those carrying two alleles encoding low-risk amino acids (p = 1.01 × 10⁻¹⁴). This coding variant might explain the complex SNP associations identified by GWASs and suggests a common HLA-DR antigen-driven mechanism for the pathogenesis of FL and rheumatoid arthritis.

  19. Munc18-1 haploinsufficiency results in enhanced anxiety-like behavior as determined by heart rate responses in mice.

    Science.gov (United States)

    Hager, Torben; Maroteaux, Grégoire; Pont, Paula du; Julsing, Joris; van Vliet, Rick; Stiedl, Oliver

    2014-03-01

    Heterozygous (HZ) missense mutations in the gene encoding syntaxin binding protein 1 (Stxbp1 or Munc18-1), a presynaptic protein essential for neurotransmitter release, causes early infantile epileptic encephalopathy, abnormal brain structure and mental retardation in humans. Here we investigated whether the mouse model mimics symptoms of the human phenotype. The effects of the deletion of munc18-1 were studied in HZ and wild-type (WT) mice based on heart rate (HR) and its variability (HRV) as independent measures to expand previous behavioral results of enhanced anxiety and impaired emotional learning suggesting mild cognitive impairments. HR responses were assessed during novelty exposure, during the expression and extinction of conditioned tone-dependent fear and during the diurnal phase. Novelty exposure yielded no differences in activity patterns between the two genotypes, while maximum HR differed significantly (WT: 770 bpm; HZ: 790 bpm). Retention tests after both auditory delay and trace fear conditioning showed a delayed extinction of the conditioned HR response in HZ mice compared to WT mice. Since the HR versus HRV correlation and HR dynamics assessed by nonlinear methods revealed similar function in HZ and WT mice, the higher HR responses of munc18-1 HZ mice to different emotional challenges cannot be attributed to differences in autonomic nervous system function. Thus, in contrast to the adverse consequences of deletion of a single allele of munc18-1 in humans, C57BL/6J mice show enhanced anxiety responses based on HR adjustments that extend previous results on the behavioral level without support of cognitive impairment, epileptic seizures and autonomic dysregulation.

  20. Accounting for genotype uncertainty in the estimation of allele frequencies in autopolyploids.

    Science.gov (United States)

    Blischak, Paul D; Kubatko, Laura S; Wolfe, Andrea D

    2016-05-01

    Despite the increasing opportunity to collect large-scale data sets for population genomic analyses, the use of high-throughput sequencing to study populations of polyploids has seen little application. This is due in large part to problems associated with determining allele copy number in the genotypes of polyploid individuals (allelic dosage uncertainty-ADU), which complicates the calculation of important quantities such as allele frequencies. Here, we describe a statistical model to estimate biallelic SNP frequencies in a population of autopolyploids using high-throughput sequencing data in the form of read counts. We bridge the gap from data collection (using restriction enzyme based techniques [e.g. GBS, RADseq]) to allele frequency estimation in a unified inferential framework using a hierarchical Bayesian model to sum over genotype uncertainty. Simulated data sets were generated under various conditions for tetraploid, hexaploid and octoploid populations to evaluate the model's performance and to help guide the collection of empirical data. We also provide an implementation of our model in the R package polyfreqs and demonstrate its use with two example analyses that investigate (i) levels of expected and observed heterozygosity and (ii) model adequacy. Our simulations show that the number of individuals sampled from a population has a greater impact on estimation error than sequencing coverage. The example analyses also show that our model and software can be used to make inferences beyond the estimation of allele frequencies for autopolyploids by providing assessments of model adequacy and estimates of heterozygosity.

  1. Allele-specific copy number profiling by next-generation DNA sequencing.

    Science.gov (United States)

    Chen, Hao; Bell, John M; Zavala, Nicolas A; Ji, Hanlee P; Zhang, Nancy R

    2015-02-27

    The progression and clonal development of tumors often involve amplifications and deletions of genomic DNA. Estimation of allele-specific copy number, which quantifies the number of copies of each allele at each variant loci rather than the total number of chromosome copies, is an important step in the characterization of tumor genomes and the inference of their clonal history. We describe a new method, falcon, for finding somatic allele-specific copy number changes by next generation sequencing of tumors with matched normals. falcon is based on a change-point model on a bivariate mixed Binomial process, which explicitly models the copy numbers of the two chromosome haplotypes and corrects for local allele-specific coverage biases. By using the Binomial distribution rather than a normal approximation, falcon more effectively pools evidence from sites with low coverage. A modified Bayesian information criterion is used to guide model selection for determining the number of copy number events. Falcon is evaluated on in silico spike-in data and applied to the analysis of a pre-malignant colon tumor sample and late-stage colorectal adenocarcinoma from the same individual. The allele-specific copy number estimates obtained by falcon allows us to draw detailed conclusions regarding the clonal history of the individual's colon cancer. PMID:25477383

  2. GENETIC STRUCTURE AND ALLEL DIVERSITY OF THREE BALINESE GENERATIONS BASED ON FIVE AUTOSOMAL MICROSATELLITE DNA LOCI

    Directory of Open Access Journals (Sweden)

    Ayu Saka Laksmita

    2015-09-01

    Full Text Available This research was aimed to find out the genetic structures of three generations of Balinese population, in order to determine the best loci used for paternity testing among this population, and observed the mutation rate of these loci. The DNA samples were taken from the epithelium cell of 25 families which were collected from the children, father, mother, grandfather and grandmother of the children, from both mother and father sides (family with three generations. The DNA was extracted in Phenol-Chloroform method with modifications. DNA amplification was conducted in PCR method using pairs of primer 5, namely: FGA, D18S51, D2S1338, TPOX, and D16S539, and its products were electrophoresed and visualized in 10% of PAGE, stained in silver nitrate. The genetic structures of the three family generations showed 30 variants with different frequencies in each locus. The highest heterozygosity value was detected in FGA (8 alleles, then followed by D18S51 (7 alleles, TPOX (6 alleles, D16S539 (5 alleles, and the lowest was in D2S1338 (4 alleles. The highest value of heterozigosity and Power of Discrimination were found in FGA, followed by TPOX, D18S51, D2S1338, and the lowest was in D16S539. Therefore, it can be concluded that out of five loci tested, 4 of them can be recommended to be used for paternity testing of Balinese population, except D16S539

  3. SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes.

    Science.gov (United States)

    Krueger, Felix; Andrews, Simon R

    2016-01-01

    Sequencing reads overlapping polymorphic sites in diploid mammalian genomes may be assigned to one allele or the other. This holds the potential to detect gene expression, chromatin modifications, DNA methylation or nuclear interactions in an allele-specific fashion. SNPsplit is an allele-specific alignment sorter designed to read files in SAM/BAM format and determine the allelic origin of reads or read-pairs that cover known single nucleotide polymorphic (SNP) positions. For this to work libraries must have been aligned to a genome in which all known SNP positions were masked with the ambiguity base 'N' and aligned using a suitable mapping program such as Bowtie2, TopHat, STAR, HISAT2, HiCUP or Bismark. SNPsplit also provides an automated solution to generate N-masked reference genomes for hybrid mouse strains based on the variant call information provided by the Mouse Genomes Project. The unique ability of SNPsplit to work with various different kinds of sequencing data including RNA-Seq, ChIP-Seq, Bisulfite-Seq or Hi-C opens new avenues for the integrative exploration of allele-specific data. PMID:27429743

  4. 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

  5. Substrate specificity of allelic variants of the TAP peptide transporter.

    Science.gov (United States)

    Heemels, M T; Ploegh, H L

    1994-12-01

    The transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum (ER). An important determinant for the specificity of translocation is the identity of the C-terminal residue of the peptide substrate. In the rat, a suitable C terminus is necessary but not always sufficient for a peptide to be selected for translocation. Here we show that sequence constraints within a peptide of optimal length (9 residues) may interfere with transport; that the transporter selectively translocates shorter derivatives of a 16-mer peptide rather than the 16-mer itself; and that the transporter cimb allele, which is most selective in the C termini it will tolerate, is more relaxed in peptide length preference than is the clma variant.

  6. Substrate specificity of allelic variants of the TAP peptide transporter.

    Science.gov (United States)

    Heemels, M T; Ploegh, H L

    1994-12-01

    The transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum (ER). An important determinant for the specificity of translocation is the identity of the C-terminal residue of the peptide substrate. In the rat, a suitable C terminus is necessary but not always sufficient for a peptide to be selected for translocation. Here we show that sequence constraints within a peptide of optimal length (9 residues) may interfere with transport; that the transporter selectively translocates shorter derivatives of a 16-mer peptide rather than the 16-mer itself; and that the transporter cimb allele, which is most selective in the C termini it will tolerate, is more relaxed in peptide length preference than is the clma variant. PMID:7895166

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

    International Nuclear Information System (INIS)

    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.)

  8. Elevational differences in developmental plasticity determine phenological responses of grasshoppers to recent climate warming.

    Science.gov (United States)

    Buckley, Lauren B; Nufio, César R; Kirk, Evan M; Kingsolver, Joel G

    2015-06-22

    Annual species may increase reproduction by increasing adult body size through extended development, but risk being unable to complete development in seasonally limited environments. Synthetic reviews indicate that most, but not all, species have responded to recent climate warming by advancing the seasonal timing of adult emergence or reproduction. Here, we show that 50 years of climate change have delayed development in high-elevation, season-limited grasshopper populations, but advanced development in populations at lower elevations. Developmental delays are most pronounced for early-season species, which might benefit most from delaying development when released from seasonal time constraints. Rearing experiments confirm that population, elevation and temperature interact to determine development time. Population differences in developmental plasticity may account for variability in phenological shifts among adults. An integrated consideration of the full life cycle that considers local adaptation and plasticity may be essential for understanding and predicting responses to climate change.

  9. Elevational differences in developmental plasticity determine phenological responses of grasshoppers to recent climate warming

    Science.gov (United States)

    Buckley, Lauren B.; Nufio, César R.; Kirk, Evan M.; Kingsolver, Joel G.

    2015-01-01

    Annual species may increase reproduction by increasing adult body size through extended development, but risk being unable to complete development in seasonally limited environments. Synthetic reviews indicate that most, but not all, species have responded to recent climate warming by advancing the seasonal timing of adult emergence or reproduction. Here, we show that 50 years of climate change have delayed development in high-elevation, season-limited grasshopper populations, but advanced development in populations at lower elevations. Developmental delays are most pronounced for early-season species, which might benefit most from delaying development when released from seasonal time constraints. Rearing experiments confirm that population, elevation and temperature interact to determine development time. Population differences in developmental plasticity may account for variability in phenological shifts among adults. An integrated consideration of the full life cycle that considers local adaptation and plasticity may be essential for understanding and predicting responses to climate change. PMID:26041342

  10. Expression of the PlA2 allele of glycoprotein IIIa and its impact on platelet function

    Directory of Open Access Journals (Sweden)

    Christopher N Floyd

    2015-11-01

    Full Text Available Background The platelet fibrinogen receptor represents the final common pathway of platelet activation, and is formed from two glycoprotein (GP subunits (GPIIb/IIIa. Carriage of the mutant PlA2 allele of GPIIIa has been shown to confer an increased risk of cardiovascular events, but published studies have disagreed as to the mechanism for this association. Objectives To assess whether carriage of the PlA2 allele conforms to Mendelian patterns of expression and to identify whether carriage of the mutant allele modulates platelet function. Methods Expression of the PlA2 allele was assessed in both healthy subjects (n = 25 and patients with known coronary artery disease (n = 90 through the development and validation of a liquid chromatography, tandem mass spectrometry (LC-MS/MS assay. Platelet function was assessed in the patient cohort in response to multiple agonists, and these data were analysed in the context of the proteomic data. Results Expression of the wild-type PlA1 allele and mutant PlA2 alleles was readily quantifiable and conformed to Mendelian patterns in both healthy and patient cohorts. Patients who were homozygous for the mutant PlA2 allele had an increased aggregatory response to adenosine diphosphate, collagen, adrenaline, ristocetin, thrombin receptor-activating peptide 6 and U46619, when assessed using agonist-concentration response curves. Conclusions These findings support the hypothesis that carriage of the mutant PlA2 allele mediates an increased risk of cardiovascular events through the modulation of platelet reactivity.

  11. Correlation of MRI-determined small bowel Crohn's disease categories with medical response and surgical pathology

    Institute of Scientific and Technical Information of China (English)

    Ian Craig Lawrance; Christopher J Welman; Peter Shipman; Kevin Murray

    2009-01-01

    AIM: To determine whether magnetic resonance imaging (MRI) can be used to categorize small bowel Crohn's disease (SB CD) into groups that correlate with response to medical therapy and surgical pathology. METHODS: Data was collected from all patients with MRI evidence of SB CD without significant colonic disease over a 32-mo period. Two radiologists,blinded to clinical findings, evaluated each MRI and grouped them based on bowel wall thickness and wall enhancement. These categories were: (1) "fibrosis",(2) "mild segmental hyper-enhancement and mild wall thickening", (3) "mild segmental hyper-enhancement and marked wall thickening", (4) "marked segmental transmural hyper-enhancement". Patient response to additional medical therapy post-MRI was prospectively determined at 8-wk. Non-responders underwent endoscopy and were offered therapeutic endoscopy or surgery. Surgical pathology was assessed against the MRI category.RESULTS: Fifty-five patients were included. Females and category "2" patients were more likely, and patients with luminal narrowing and hold-up less likely,to respond to medical therapy ( P < 0.05). Seventeen patients underwent surgery. The surgical pathological findings of fibrosis and the severity of inflammation correlated with the MRI category in all cases. CONCLUSION: Our findings suggest that SB CD can be grouped by the MRI findings and that these groups are associated with patients more likely to respond to continued medical therapy. The MRI categories also correlated with the presence and level of intestinal inflammation and fibrosis on surgical pathology, and may be of prognostic use in the management of CD patients.

  12. 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

    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...

  13. Response surface optimization of microwave-assisted extraction for HPLC-fluorescence determination of puerarin and daidz

    Institute of Scientific and Technical Information of China (English)

    Ying-Kun Liu; E Yan; Han-Ying Zhan; Zhi-Qi Zhang

    2011-01-01

    Microwave-assisted extraction was optimized with response surface methodology for HPLC-fluorescence determination of puerarin and daidzein in Radix Puerariae thomsonii.The optimized extraction procedure was achieved by soaking the sample with 70% methanol

  14. Tertiary lymphoid organ development coincides with determinant spreading of the myelin-specific T cell response.

    Science.gov (United States)

    Kuerten, Stefanie; Schickel, Achim; Kerkloh, Christian; Recks, Mascha S; Addicks, Klaus; Ruddle, Nancy H; Lehmann, Paul V

    2012-12-01

    While the role of T cells has been studied extensively in multiple sclerosis (MS), the pathogenic contribution of B cells has only recently attracted major attention, when it was shown that B cell aggregates can develop in the meninges of a subset of MS patients and were suggested to be correlates of late-stage and more aggressive disease in this patient population. However, whether these aggregates actually exist has subsequently been questioned and their functional significance has remained unclear. Here, we studied myelin basic protein (MBP)-proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE), which is one of the few animal models for MS that is dependent on B cells. We provide evidence that B cell aggregation is reflective of lymphoid neogenesis in the central nervous system (CNS) in MBP-PLP-elicited EAE. B cell aggregation was present already few days after disease onset. With disease progression CNS B cell aggregates increasingly displayed the phenotype of tertiary lymphoid organs (TLOs). Our results further imply that these TLOs were not merely epiphenomena of the disease, but functionally active, supporting intrathecal determinant spreading of the myelin-specific T cell response. Our data suggest that the CNS is not a passive "immune-privileged" target organ, but rather a compartment, in which highly active immune responses can perpetuate and amplify the autoimmune pathology and thereby autonomously contribute to disease progression.

  15. 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

  16. 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.

  17. Relative Responses of Noble Gases Using a Pulsed Discharge Helium Photoionization Detector:Theoretical Calculation and Experimental Determination

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hai-tao; WU Di; ZHANG Li-xing

    2008-01-01

    The relative response factors(RRFs) for noble gas(Ng) were determined on a pulsed discharge helium photoionization detector,Using ab initio method,the atomic orbitals of noble gas were calculated and used to determine the number of ionizable electrons on the basis of the continuous emission of He2,The molar responses of noble gases is well correlated with the number of ionizable electrons.

  18. Identification, isolation, characterization and response factor determination of process-related impurity in meprobamate drug substance.

    Science.gov (United States)

    Karthikeyan, K; Arularasu, G T; Murali, V; Pillai, K Chandrasekara

    2011-01-01

    This paper describes identification and characterization of a process-related impurity of meprobamate drug substance observed in HPLC-UV method. Forced degradation studies were carried out under acidic, basic, oxidation, light and thermal conditions to assess the nature of the impurity. The pure impurity was obtained by preparative LC isolation and analyzed by NMR and mass. Structural elucidation by spectral data and formation of this impurity were discussed in detail. The structure of the process-related impurity was established as carbamic acid-2-carbamoyloxymethyl-2-methyl-pent-3-enyl ester (olefin). Also, the relative response factor, linearity, detection limit (DL), quantitation limit (QL) and recovery were determined for meprobamate and the impurity. Good linearity was obtained for the impurity over the concentration range of 0.03-0.20% (w/w) with the coefficient of determination (r(2)) of 0.999. The DL and QL of olefin impurity were 0.0003 and 0.001% (w/w), respectively. The isolated impurity was co-injected with meprobamate sample to confirm the retention time in HPLC. PMID:20727702

  19. 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. PMID:25321095

  20. The cysteine-rich region of T1R3 determines responses to intensely sweet proteins.

    Science.gov (United States)

    Jiang, Peihua; Ji, Qingzhou; Liu, Zhan; Snyder, Lenore A; Benard, Lumie M J; Margolskee, Robert F; Max, Marianna

    2004-10-22

    A wide variety of chemically diverse compounds taste sweet, including natural sugars such as glucose, fructose, sucrose, and sugar alcohols, small molecule artificial sweeteners such as saccharin and acesulfame K, and proteins such as monellin and thaumatin. Brazzein, like monellin and thaumatin, is a naturally occurring plant protein that humans, apes, and Old World monkeys perceive as tasting sweet but that is not perceived as sweet by other species including New World monkeys, mouse, and rat. It has been shown that heterologous expression of T1R2 plus T1R3 together yields a receptor responsive to many of the above-mentioned sweet tasting ligands. We have determined that the molecular basis for species-specific sensitivity to brazzein sweetness depends on a site within the cysteine-rich region of human T1R3. Other mutations in this region of T1R3 affected receptor activity toward monellin, and in some cases, overall efficacy to multiple sweet compounds, implicating this region as a previously unrecognized important determinant of sweet receptor function. PMID:15299024

  1. Nomenclature for human CYP2D6 alleles.

    Science.gov (United States)

    Daly, A K; Brockmöller, J; Broly, F; Eichelbaum, M; Evans, W E; Gonzalez, F J; Huang, J D; Idle, J R; Ingelman-Sundberg, M; Ishizaki, T; Jacqz-Aigrain, E; Meyer, U A; Nebert, D W; Steen, V M; Wolf, C R; Zanger, U M

    1996-06-01

    To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that alleles be designated by CYP2D6 followed by an asterisk and a combination of roman letters and arabic numerals distinct for each allele with the number specifying the key mutation and, where appropriate, a letter specifying additional mutations. Criteria for classification as a separate allele and protein nomenclature are also presented. PMID:8807658

  2. Determinants of motion response anisotropies in human early visual cortex: the role of configuration and eccentricity.

    Science.gov (United States)

    Maloney, Ryan T; Watson, Tamara L; Clifford, Colin W G

    2014-10-15

    Anisotropies in the cortical representation of various stimulus parameters can reveal the fundamental mechanisms by which sensory properties are analysed and coded by the brain. One example is the preference for motion radial to the point of fixation (i.e. centripetal or centrifugal) exhibited in mammalian visual cortex. In two experiments, this study used functional magnetic resonance imaging (fMRI) to explore the determinants of these radial biases for motion in functionally-defined areas of human early visual cortex, and in particular their dependence upon eccentricity which has been indicated in recent reports. In one experiment, the cortical response to wide-field random dot kinematograms forming 16 different complex motion patterns (including centrifugal, centripetal, rotational and spiral motion) was measured. The response was analysed according to preferred eccentricity within four different eccentricity ranges. Response anisotropies were characterised by enhanced activity for centripetal or centrifugal patterns that changed systematically with eccentricity in visual areas V1-V3 and hV4 (but not V3A/B or V5/MT+). Responses evolved from a preference for centrifugal over centripetal patterns close to the fovea, to a preference for centripetal over centrifugal at the most peripheral region stimulated, in agreement with previous work. These effects were strongest in V2 and V3. In a second experiment, the stimuli were restricted to within narrow annuli either close to the fovea (0.75-1.88°) or further in the periphery (4.82-6.28°), in a way that preserved the local motion information available in the first experiment. In this configuration a preference for radial motion (centripetal or centrifugal) persisted but the dependence upon eccentricity disappeared. Again this was clearest in V2 and V3. A novel interpretation of the dependence upon eccentricity of motion anisotropies in early visual cortex is offered that takes into account the spatiotemporal

  3. SEQUENCE OF THE STRUCTURAL GENE FOR GRANULE-BOUND STARCH SYNTHASE OF POTATO (SOLANUM-TUBEROSUM L) AND EVIDENCE FOR A SINGLE POINT DELETION IN THE AMF ALLELE

    NARCIS (Netherlands)

    van der Leij, Feike R.; VISSER, RGF; Ponstein, Anne S.; Jacobsen, Evert; Feenstra, Willem

    1991-01-01

    The genomic sequence of the potato gene for starch granule-bound starch synthase (GBSS; "waxy protein") has been determined for the wild-type allele of a monoploid genotype from which an amylose-free (amf) mutant was derived, and for the mutant part of the amf allele. Comparison of the wild-type seq

  4. Identification of Multiple Alleles at the Wx Locus and Development of Single Segment Substitution Lines for the Alleles in Rice

    Institute of Scientific and Technical Information of China (English)

    ZENG Rui-zhen; ZHANG Ze-min; HE Feng-hua; XI Zhang-ying; Akshay TALUKDAR; SHI Jun-qiong; QIN Li-jun; HUANG Chao-feng; ZHANG Gui-quan

    2006-01-01

    The microsatellite markers 484/485 and 484/W2R were used to identify the multiple alleles at the Wx locus in rice germplasm. Fifteen alleles were identified in 278 accessions by using microsatellite class and G-T polymorphism. Among these alleles, (CT)12-G, (CT)15-G, (CT)16-G, (CT)17-G, (CT)18-G and (CT)21-G have not been reported. Seventy-two single-segment substitution lines (SSSLs) carrying different alleles at the Wx locus were developed by using Huajingxian 74 with the (CT)11-G allele as a recipient and 20 accessions containing 12 different alleles at the Wx locus as donors. The estimated length of the substituted segments ranged from 2.2 to 77.3 cM with an average of 17.4 cM.

  5. 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...

  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. 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.

  8. The HLA class II Allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Jianmin Xue

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients.HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7% compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55. The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004. IPF patients with DRB1*1501 (n = 91 tended to have decreased diffusing capacities for carbon monoxide (DL(CO compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036.DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for

  9. Genetic determinants of response and adverse effects following vitamin K antagonist oral anticoagulants

    Directory of Open Access Journals (Sweden)

    Parameshwar S.

    2016-06-01

    Full Text Available Background: Vitamin K antagonist anticoagulants (warfarin/acenocoumarol are commonly used anticoagulants that require careful clinical management to balance the risks of over anticoagulation and bleeding with those of under anticoagulation and clotting. Genetic variants of the enzyme that metabolizes vitamin K antagonist anticoagulant, cytochrome P-450 2C9 (CYP2C9, and of a key pharmacologic target of vitamin K antagonists anticoagulant, vitamin K epoxide reductase (VKORC1, contribute to differences in patients responses to various anticoagulant doses. Methods: In thirty patients on oral vitamin K antagonist anticoagulant therapy, presented with either clotting manifestations (valve thrombosis, pulmonary embolism and DVT or prolonged INR/bleeding manifestations, we assessed CYP2C9 genotypes, VKORC1 haplotypes, clinical characteristics, response to therapy (as determined by the international normalized ratio [INR], and bleeding events. Results: Of the thirty patients, thirteen patients INR was high and four patients presented with major bleeding and four with minor bleeding manifestations. Out of thirteen patients with high INR, ten patients showed CYP2C9 polymorphism ( 1/ 3 and 2/ 3 of poor metabolizer genotype. Most of the high INR patients were recently started on oral vitamin K antagonist anticoagulant. Most patients presented with clotting manifestations with below therapeutic INR are noncompliant with anticoagulants. Conclusions: The results of this study suggest that the CYP2C9 polymorphisms are associated with an increased risk of over anticoagulation and of bleeding events among patients on vitamin K antagonists' anticoagulant setting. Screening for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance techniques to reduce the risk of adverse drug reactions in patients receiving vitamin K antagonist anticoagulants. However the cost-effectiveness of genotyping of patients must be considered. [Int J Res Med Sci

  10. Characterization of new allele influencing flowering time in bread wheat introgressed from Triticum militinae.

    Science.gov (United States)

    Ivaničová, Zuzana; Jakobson, Irena; Reis, Diana; Šafář, Jan; Milec, Zbyněk; Abrouk, Michael; Doležel, Jaroslav; Järve, Kadri; Valárik, Miroslav

    2016-09-25

    Flowering time variation was identified within a mapping population of doubled haploid lines developed from a cross between the introgressive line 8.1 and spring bread wheat cv. Tähti. The line 8.1 carried introgressions from tetraploid Triticum militinae in the cv. Tähti genetic background on chromosomes 1A, 2A, 4A, 5A, 7A, 1B and 5B. The most significant QTL for the flowering time variation was identified within the introgressed region on chromosome 5A and its largest effect was associated with the VRN-A1 locus, accounting for up to 70% of phenotypic variance. The allele of T. militinae origin was designated as VRN-A1f-like. The effect of the VRN-A1f-like allele was verified in two other mapping populations. QTL analysis identified that in cv. Tähti and cv. Mooni genetic background, VRN-A1f-like allele incurred a delay of 1.9-18.6 days in flowering time, depending on growing conditions. Sequence comparison of the VRN-A1f-like and VRN-A1a alleles from the parental lines of the mapping populations revealed major mutations in the promoter region as well as in the first intron, including insertion of a MITE element and a large deletion. The sequence variation allowed construction of specific diagnostic PCR markers for VRN-A1f-like allele determination. Identification and quantification of the effect of the VRN-A1f-like allele offers a useful tool for wheat breeding and for studying fine-scale regulation of flowering pathways in wheat. PMID:26899284

  11. RANTES In1.1C allele polymorphisms in 13 Chinese ethnic populations

    Institute of Scientific and Technical Information of China (English)

    QIAN Yuan; SUN Hao; CHU Jia-you

    2009-01-01

    Background The In1.1C single nucleotide polymorphism (SNP) allele results in reduced RANTES transcription, which is associated with increased frequency of HIV-1 infection, and rapid progression to AIDS among HIV-1-infected individuals. This study aimed to study the mutant frequency and polymorphism of RANTES in Chinese populations.Methods The genotypes of RANTES In1.1C were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with the digestion of restriction endonuclease Mbo Ⅱ.Results Of the 617 individuals, 290 (47%) were carriers of the RANTES In1.1C allele, 52 of whom were homozygotes,whereas 238 were heterozygotes. The frequency of the RANTES In1.1C allele in those tested individuals was 0.2840.The frequencies of Inl.lC allele vaded from 0.07-0.27 in most of the populations in South-west China except for the two Lisu populations, while the frequencies of In1.1C spans from 0.35 to 0.45 in North-west China. The prevalence of the allele varied substantially between the South-west groups and North-west groups (X2=7.838, P=0.006).Conclusions The prevalence of the RANTES In1.1C allele varies substantially between the South-west groups and North-west groups. There is no significant difference between the groups with different languages, which suggests that language relationship is not consistent with the genetic relationship. These results have important implications for the design, assessment, and implementation of HIV-1 vaccines.

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

    Directory of Open Access Journals (Sweden)

    Brian B Tuch

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

  13. Allelic differences in a vacuolar invertase affect Arabidopsis growth at early plant development.

    Science.gov (United States)

    Leskow, Carla Coluccio; Kamenetzky, Laura; Dominguez, Pia Guadalupe; Díaz Zirpolo, José Antonio; Obata, Toshihiro; Costa, Hernán; Martí, Marcelo; Taboga, Oscar; Keurentjes, Joost; Sulpice, Ronan; Ishihara, Hirofumi; Stitt, Mark; Fernie, Alisdair Robert; Carrari, Fernando

    2016-07-01

    Improving carbon fixation in order to enhance crop yield is a major goal in plant sciences. By quantitative trait locus (QTL) mapping, it has been demonstrated that a vacuolar invertase (vac-Inv) plays a key role in determining the radical length in Arabidopsis. In this model, variation in vac-Inv activity was detected in a near isogenic line (NIL) population derived from a cross between two divergent accessions: Landsberg erecta (Ler) and Cape Verde Island (CVI), with the CVI allele conferring both higher Inv activity and longer radicles. The aim of the current work is to understand the mechanism(s) underlying this QTL by analyzing structural and functional differences of vac-Inv from both accessions. Relative transcript abundance analyzed by quantitative real-time PCR (qRT-PCR) showed similar expression patterns in both accessions; however, DNA sequence analyses revealed several polymorphisms that lead to changes in the corresponding protein sequence. Moreover, activity assays revealed higher vac-Inv activity in genotypes carrying the CVI allele than in those carrying the Ler allele. Analyses of purified recombinant proteins showed a similar K m for both alleles and a slightly higher V max for that of Ler. Treatment of plant extracts with foaming to release possible interacting Inv inhibitory protein(s) led to a large increase in activity for the Ler allele, but no changes for genotypes carrying the CVI allele. qRT-PCR analyses of two vac-Inv inhibitors in seedlings from parental and NIL genotypes revealed different expression patterns. Taken together, these results demonstrate that the vac-Inv QTL affects root biomass accumulation and also carbon partitioning through a differential regulation of vac-Inv inhibitors at the mRNA level. PMID:27194734

  14. HIV-1 disease-influencing effects associated with ZNRD1, HCP5 and HLA-C alleles are attributable mainly to either HLA-A10 or HLA-B*57 alleles.

    Directory of Open Access Journals (Sweden)

    Gabriel Catano

    specifically demonstrate that the influence of ZNRD1 alleles on disease progression rates are attributable to HLA-A10, help clarify the relationship between the HCP5, HLA-C and HLA-B*57 alleles, and reaffirm a critical role of HLA-B*57 alleles in HIV disease. Furthermore, as the protective B*57-containing genotypes convey striking salutary effects independent of their strong impact on viral control, it is conceivable that T cell-based therapeutic vaccine strategies aimed at reducing viral loads may be inadequate for limiting AIDS progression, raising the potential need for complementary strategies that target viral load-independent determinants of pathogenesis.

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

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    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/.

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

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    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

  17. Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.

    Directory of Open Access Journals (Sweden)

    Jaan-Olle Andressoo

    2006-10-01

    Full Text Available Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals.

  18. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

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

    2013-01-01

    -out of true alleles is possible. As part of the validation of the IrisPlex assay in our ISO17025 accredited, forensic genetic laboratory, we estimated the probability of drop-out of specific SNP alleles using 29 and 30 PCR cycles and 25, 50 and 100 Single Base Extension (SBE) cycles. We observed no drop...

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

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    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.

  20. Defining genes using "blueprint" versus "instruction" metaphors: effects for genetic determinism, response efficacy, and perceived control.

    Science.gov (United States)

    Parrott, Roxanne; Smith, Rachel A

    2014-01-01

    Evidence supports mixed attributions aligned with personal and/or clinical control and gene expression for health in this era of genomic science and health care. We consider variance in these attributions and possible relationships to individual mind sets associated with essentialist beliefs that genes determine health versus threat beliefs that genes increase susceptibility for disease and severity linked to gene-environment interactions. Further, we contribute to theory and empirical research to evaluate the use of metaphors to define genes. Participants (N = 324) read a message that varied the introduction by providing a definition of genes that used either an "instruction" metaphor or a "blueprint" metaphor. The "instruction" metaphor compared to the "blueprint" metaphor promoted stronger threat perceptions, which aligned with both belief in the response efficacy of genetic research for health and perceived behavioral control linked to genes and health. The "blueprint" metaphor compared to the "instruction" metaphor promoted stronger essentialist beliefs, which aligned with more intense positive regard for the efficacy of genetic research and human health. Implications for health communicators include societal effects aligned with stigma and discrimination that such findings portend.

  1. Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans.

    Science.gov (United States)

    Sinoway, L I; Rea, R F; Mosher, T J; Smith, M B; Mark, A L

    1992-06-01

    We examined the effects of exercise conditioning on muscle sympathetic nerve activity (MSNA) during handgrip and posthandgrip circulatory arrest (PHG-CA). Two conditioning stimuli were studied: forearm dominance and bodybuilding. Static handgrip at 30% maximal voluntary contraction followed by PHG-CA led to a rise in MSNA smaller in dominant than in nondominant forearms (99% vs. 222%; P less than 0.02) and in body builders than in normal volunteers (28% vs. 244%; P less than 0.01). Separate 31P NMR experiments showed no effect of dominance on forearm pH but a pH in bodybuilders higher (6.88) than in normal volunteers (6.79; P less than 0.02) during PHG-CA. Our second goal was to determine if factors besides attenuated [H+] contribute to this conditioning effect. If differences in MSNA during exercise were noted at the same pH, then other mechanisms must contribute to the training effect. We measured MSNA during ischemic fatiguing handgrip. No dominance or bodybuilding effect on pH was noted. However, we noted increases in MSNA smaller in dominant than nondominant forearms (212% vs. 322%; P less than 0.02) and in bodybuilders than in normal volunteers (161% vs. 334%; P less than 0.01). In summary, MSNA responses were less during exercise of conditioned limbs. Factors aside from a lessening of muscle acidosis contribute to this effect.

  2. The Met-allele of the BDNF Val66Met polymorphism enhances task switching in elderly.

    Science.gov (United States)

    Gajewski, Patrick D; Hengstler, Jan G; Golka, Klaus; Falkenstein, Michael; Beste, Christian

    2011-12-01

    In this study we examined the relevance of the functional brain-derived neurotrophic factor (BDNF) Val66Met polymorphism as a modulator of task-switching performance in healthy elderly by using behavioral and event-related potential (ERP) measures. Task switching was examined in a cue-based and a memory-based paradigm. Val/Val carriers were generally slower, showed enhanced reaction time variability and higher error rates, particularly during memory-based task switching than the Met-allele individuals. On a neurophysiological level these dissociative effects were reflected by variations in the N2 and P3 ERP components. The task switch-related N2 was increased while the P3 was decreased in Met-allele carriers, while the Val/Val genotype group revealed the opposite pattern of results. In cue-based task-switching no behavioral and ERP differences were seen between the genotypes. These data suggest that superior memory-based task-switching performance in elderly Met-allele carriers may emerge due to more efficient response selection processes. The results implicate that under special circumstances the Met-allele renders cognitive processes more efficient than the Val/Val genotype in healthy elderly, corroborating recent findings in young subjects.

  3. Naturally occurring ERAP1 haplotypes encode functionally distinct alleles with fine substrate specificity.

    Science.gov (United States)

    Reeves, Emma; Edwards, Christopher J; Elliott, Tim; James, Edward

    2013-07-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims peptides for MHC class I presentation, influencing the degree and specificity of CD8(+) T cell responses. Single-nucleotide polymorphisms within the exons encoding ERAP1 are associated with autoimmune diseases and cervical carcinoma, but it is not known whether they act independently or as disease-associated haplotypes. We sequenced ERAP1 from 20 individuals and show that single-nucleotide polymorphisms occur as distinct haplotypes in the human population and that these haplotypes encode functionally distinct ERAP1 alleles. Using a wide range of substrates, we are able to demonstrate that for any given substrate distinct ERAP1 alleles can be "normal," "hypofunctional," or "hyperfunctional" and that each allele has a trend bias toward one of these three activities. Thus, the repertoire of peptides presented at the cell surface for recognition by CTL is likely to depend on the precise combination of both MHC class I and ERAP1 alleles expressed within an individual, and has important implications for predisposition to disease. PMID:23733883

  4. 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; Hanski, Ilkka

    2016-03-01

    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.

  5. Cognitive and Neural Determinants of Response Strategy in the Dual-Solution Plus-Maze Task

    Science.gov (United States)

    De Leonibus, Elvira; Costantini, Vivian J. A.; Massaro, Antonio; Mandolesi, Georgia; Vanni, Valentina; Luvisetto, Siro; Pavone, Flaminia; Oliverio, Alberto; Mele, Andrea

    2011-01-01

    Response strategy in the dual-solution plus maze is regarded as a form of stimulus-response learning. In this study, by using an outcome devaluation procedure, we show that it can be based on both action-outcome and stimulus-response habit learning, depending on the amount of training that the animals receive. Furthermore, we show that…

  6. 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...

  7. Initial size structure of natural phytoplankton communities determines the response to Daphnia diel vertical migration

    Directory of Open Access Journals (Sweden)

    Maarten Boersma

    2012-01-01

    Full Text Available Diel vertical migration (DVM is a common behavior of many pelagic herbivorous zooplankton species in response to predation pressure. It is characterized by a twice daily habitat shift of the zooplankton species: staying in the epilimnion only during night time and migrating down in the crack of dawn in deeper water layers, staying there during the day time. This causes a discontinuous grazing regime and previous studies have shown that the direction and strength of phytoplankton community responses to zooplankton DVM most probably depends on the size of phytoplankton species. To examine the influence of zooplankton DVM on different sized phytoplankton communities, we designed an experiment where we manipulated the size distribution of a natural phytoplankton community a priori in field mesocosms. We investigated the influence of DVM of the cladoceran Daphnia hyalina on two different phytoplankton communities, by the use of deep (10 m field enclosures. Epilimnetic lake water, containing a summer phytoplankton community, was filtered with two different mesh sizes (11 mm and 64 mm. The 11 mm phytoplankton community (“small” contained mainly small algal species, while the 64 mm community (“large” had a wider range of phytoplankton sizes. To simulate zooplankton DVM, D. hyalina were placed in mesh cages that were lowered or raised (“migration” as dictated by the study design; a “no migration” (representing absence of DVM treatment was also tested. Phytoplankton abundance was measured using chlorophyll-a and biovolume; size distribution of the algae and nutrient availability was also determined in each treatment. The results indicated that DVM had contrasting effects on the two evaluated phytoplankton communities. Comparison of “migration” and “no migration” zooplankton treatments showed that nutrient availability and total phytoplankton biovolume was higher in (1 “no migration” treatments with phytoplankton communities

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

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    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.

  9. Decomposing the electromagnetic response of magnetic dipoles to determine the geometric parameters of a dipole conductor

    Science.gov (United States)

    Desmarais, Jacques K.; Smith, Richard S.

    2016-03-01

    A novel automatic data interpretation algorithm is presented for modelling airborne electromagnetic (AEM) data acquired over resistive environments, using a single-component (vertical) transmitter, where the position and orientation of a dipole conductor is allowed to vary in three dimensions. The algorithm assumes that the magnetic fields produced from compact vortex currents are expressed as a linear combinations of the fields arising from dipoles in the subsurface oriented parallel to the [1, 0, 0], [0, 1, 0], and [0, 0, 1], unit vectors. In this manner, AEM responses can be represented as 12 terms. The relative size of each term in the decomposition can be used to determine geometrical information about the orientation of the subsurface conductivity structure. The geometrical parameters of the dipole (location, depth, dip, strike) are estimated using a combination of a look-up table and a matrix inverted in a least-squares sense. Tests on 703 synthetic models show that the algorithm is capable of extracting most of the correct geometrical parameters of a dipole conductor when three-component receiver data is included in the interpretation procedure. The algorithm is unstable when the target is perfectly horizontal, as the strike is undefined. Ambiguities may occur in predicting the orientation of the dipole conductor if y-component data is excluded from the analysis. Application of our approach to an anomaly on line 15 of the Reid Mahaffy test site yields geometrical parameters in reasonable agreement with previous authors. However, our algorithm provides additional information on the strike and offset from the traverse line of the conductor. Disparities in the values of predicted dip and depth are within the range of numerical precision. The index of fit was better when strike and offset were included in the interpretation procedure. Tests on the data from line 15701 of the Chibougamau MEGATEM survey shows that the algorithm is applicable to situations where

  10. Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

    Science.gov (United States)

    Fatouros, Ioannis G.; Chatzinikolaou, Athanasios; Tournis, Symeon; Nikolaidis, Michalis G.; Jamurtas, Athanasios Z.; Douroudos, Ioannis I.; Papassotiriou, Ioannis; Thomakos, Petros M.; Taxildaris, Kyriakos; Mastorakos, George; Mitrakou, Asimina

    2009-01-01

    OBJECTIVE To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period. RESULTS Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 ± 8.8 vs. 295.6 ± 10.7 and 281.6 ± 9.8 kcal, P < 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P < 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P < 0.001) in all groups at 12 h in an intensity-dependent manner (P < 0.05). REE reached baseline after 48 h in the low- and moderate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P < 0.001) and remained elevated (P < 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 h and remained elevated for 24 h only in the high-intensity group (P < 0.001). CONCLUSIONS Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals. PMID:19729520

  11. Heme oxygenase-1 determines the differential response of breast cancer and normal cells to piperlongumine.

    Science.gov (United States)

    Lee, Ha-Na; Jin, Hyeon-Ok; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, BoRa; Kim, Wonki; Hong, Sung-Eun; Lee, Yun-Han; Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun; Park, In-Chul; Surh, Young-Joon; Lee, Jin Kyung

    2015-04-01

    Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic α,β-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine. PMID:25813625

  12. Determinants of erythropoietin release in response to short-term hypobaric hypoxia

    Science.gov (United States)

    Ge, Ri-Li; Witkowski, S.; Zhang, Y.; Alfrey, C.; Sivieri, M.; Karlsen, T.; Resaland, G. K.; Harber, M.; Stray-Gundersen, J.; Levine, B. D.

    2002-01-01

    We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.

  13. Endogenous LXA4 circuits are determinants of pathological angiogenesis in response to chronic injury.

    Science.gov (United States)

    Leedom, Alexander J; Sullivan, Aaron B; Dong, Baiyan; Lau, Denise; Gronert, Karsten

    2010-01-01

    Inflammation and angiogenesis are intimately linked, and their dysregulation leads to pathological angiogenesis in human diseases. 15-lipoxygenase (15-LOX) and lipoxin A(4) receptors (ALX) constitute a LXA(4) circuit that is a key feature of inflammatory resolution. LXA(4) analogs have been shown to regulate vascular endothelial growth factor (VEGF)-A-induced angiogenic response in vitro. 15-LOX and ALX are highly expressed in the avascular and immune-privileged cornea. However, the role of this endogenous LXA(4) circuit in pathological neovascularization has not been determined. We report that suture-induced chronic injury in the cornea triggered polymorphonuclear leukocytes (PMN) infiltration, pathological neovascularization, and up-regulation of mediators of inflammatory angiogenesis, namely VEGF-A and the VEGF-3 receptor (FLT4). Up-regulation of the VEGF circuit and neovascularization correlated with selective changes in both 15-LOX (Alox15) and ALX (Fpr-rs2) expression and a temporally defined increase in basal 15-LOX activity. More importantly, genetic deletion of 15-LOX or 5-LOX, key and obligatory enzymes in the formation of LXA(4), respectively, led to exacerbated inflammatory neovascularization coincident with increased VEGF-A and FLT4 expression. Direct topical treatment with LXA(4), but not its metabolic precursor 15-hydroxyeicosatetraenoic acid, reduced expression of VEGF-A and FLT4 and inflammatory angiogenesis and rescued 15-LOX knockout mice from exacerbated angiogenesis. In summary, our findings and the prominent expression of 15-LOX and ALX in epithelial cells and macrophages place the LXA(4) circuit as an endogenous regulator of pathological angiogenesis.

  14. Assignment of SNP allelic configuration in polyploids using competitive allele-specific PCR: application to citrus triploid progeny

    Science.gov (United States)

    Cuenca, José; Aleza, Pablo; Navarro, Luis; Ollitrault, Patrick

    2013-01-01

    Background Polyploidy is a major component of eukaryote evolution. Estimation of allele copy numbers for molecular markers has long been considered a challenge for polyploid species, while this process is essential for most genetic research. With the increasing availability and whole-genome coverage of single nucleotide polymorphism (SNP) markers, it is essential to implement a versatile SNP genotyping method to assign allelic configuration efficiently in polyploids. Scope This work evaluates the usefulness of the KASPar method, based on competitive allele-specific PCR, for the assignment of SNP allelic configuration. Citrus was chosen as a model because of its economic importance, the ongoing worldwide polyploidy manipulation projects for cultivar and rootstock breeding, and the increasing availability of SNP markers. Conclusions Fifteen SNP markers were successfully designed that produced clear allele signals that were in agreement with previous genotyping results at the diploid level. The analysis of DNA mixes between two haploid lines (Clementine and pummelo) at 13 different ratios revealed a very high correlation (average = 0·9796; s.d. = 0·0094) between the allele ratio and two parameters [θ angle = tan−1 (y/x) and y′ = y/(x + y)] derived from the two normalized allele signals (x and y) provided by KASPar. Separated cluster analysis and analysis of variance (ANOVA) from mixed DNA simulating triploid and tetraploid hybrids provided 99·71 % correct allelic configuration. Moreover, triploid populations arising from 2n gametes and interploid crosses were easily genotyped and provided useful genetic information. This work demonstrates that the KASPar SNP genotyping technique is an efficient way to assign heterozygous allelic configurations within polyploid populations. This method is accurate, simple and cost-effective. Moreover, it may be useful for quantitative studies, such as relative allele-specific expression analysis and bulk segregant analysis

  15. 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

  16. 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.

  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. Prevalence of human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti children with juvenile rheumatoid arthritis.

    Science.gov (United States)

    Alsaeid, Khaled; Haider, M Z; Kamal, H; Srivastva, B S; Ayoub, E M

    2002-02-01

    The prevalence of human leukocyte antigen (HLA) DR alleles has been determined in 69 Kuwaiti Arab children with juvenile rheumatoid arthritis (JRA) and compared to that in 212 ethnically matched normal healthy controls using a PCR-sequence specific primers (PCR-SSP) method. A very high incidence of DR3 was detected in JRA patients compared to the controls (P JRA patients was accounted for mainly by an excess of DRB1*0307 (P JRA were analysed separately; 73% compared to 58% for the whole JRA patient group. The frequency of DR1 was also higher in the JRA group compared to controls (P = 0.019, RR = 3.585). Although the incidence of some alleles was higher in the control group (DR13 and DR7), none reached a statistically significant level. All the patients with iridocyclitis had either a DR1 or DR3 allele, except for one child. The frequency of DRB1*03 was found to be much higher in the polyarticular subtype of Kuwaiti JRA cases compared to the oligoarticular subgroup and the controls. Also, a non-significant increase in the frequency of the DRB1*04, *11 and *15 alleles was detected in the polyarticular subtype of the Kuwaiti JRA cases compared to the controls.

  19. Short aggrecan gene repetitive alleles associated with lumbar degenerative disc disease in Turkish patients.

    Science.gov (United States)

    Eser, O; Eser, B; Cosar, M; Erdogan, M O; Aslan, A; Yıldız, H; Solak, M; Haktanır, A

    2011-01-01

    We investigated a possible association between aggrecan gene polymorphism and lumbar degenerative disc disease in Turkish patients. One hundred 20-30-year-old patients with or without low back pain were selected for the study. Lumbar magnetic resonance imaging was performed on all patients. The patient group had low back pain clinically and degenerative disc disease radiographically. The control group included patients with and without low back pain: all were negative radiographically for degenerative disc disease. Genomic DNA was extracted from all participants. A PCR assay were used to evaluate variable number of tandem repeat polymorphism of aggrecan gene alleles to determine if there was any correlation with degenerative disc disease. Significant associations were found between short repeated alleles of the aggrecan gene and severe disc degeneration. A significant association was also found between short repeated alleles of the aggrecan gene and multilevel disc herniation as well as extrusion and sequestration types of disc herniation. In Turkish population, short repeated alleles of the aggrecan gene are associated with increased disc degeneration and disc herniation. PMID:21948754

  20. Common alleles contribute to schizophrenia in CNV carriers

    Science.gov (United States)

    Tansey, K E; Rees, E; Linden, D E; Ripke, S; Chambert, K D; Moran, J L; McCarroll, S A; Holmans, P; Kirov, G; Walters, J; Owen, M J; O'Donovan, M C

    2016-01-01

    The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10−17) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely. PMID:26390827

  1. 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

  2. THE INFLUENCE OF APOLIPOPROTEIN B AND E GENE POLYMORPHISMS ON THE RESPONSE TO SIMVASTATIN THERAPY IN PATIENTS WITH HYPERLIPIDEMIA

    Institute of Scientific and Technical Information of China (English)

    叶平; 尚延忠; 丁小平

    2003-01-01

    Objective.To investigate the effect of apolipoprotein B(apoB)and E(apoE)genetic variations on lipid profile at baseline(before treatment),and also on the subsequent response to simvastatin therapy.Methods. Eighty-eight patients with hyperlipidemia were treated with simvastatin 5mg daily. The plasma levels of total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C),triglyceride(TG)and apo B were measured pretreatment and at the end of the 4th,8th and 12th post-treatment week.Polymorphisms of apoB at XbaI locus and apoE were determined by restriction fragment length polymorphism(RFLP).Results. In all patients,relative frequencies of X-allele and X+ allele were 0.943 and 0.057 for apoB gene respectively. For apoE gene the relative frequency of ε 2 allele was determined as 0.182,ε3 as 0.580 and ε4 as 0.238.The reduction in TC level was more prominent in patients carrying X- allele than in those with X+ allele following treatment(-23.9% vs. -13.6%,P< 0.05).Compared with patients carrying ε3 or ε4 allele,those with ε 2 allele showed a significantly higher percentage in reduction of apoB level after treatment(P< 0.05). Conclusion. The relative frequency of apoB X+ allele is high in patients with hyperlipidemia,in whom the TC-lowering efficacy is decreased following treatment of simvastatin. The relative frequencies of ε 2 and ε 4 are also high in hyperlipidemic patients,and the ε2 allele is associated with reduction in apoB level during lipid-regulating therapy.

  3. Performance Determinants for Responsible Supply Chain Management in the European Emerging Countries

    OpenAIRE

    Camelia Chirilă; Andreea Gangone; Mihaela Asandei; Mariana Cristina Ganescu

    2013-01-01

    Starting from the premise that there are numerous institutional and national factors influencing the performance of responsible supply chain management, the present article seeks to measure and quantify performance of the European emerging states by creating an index of performance of responsible supply chain management and to identify the factors that influence responsible supply chain management. The acquisition of this index was based on our own measurement methodology, starting from two c...

  4. Exploring models for the roles of health systems’ responsiveness and social determinants in explaining universal health coverage and health outcomes

    OpenAIRE

    Valentine, Nicole Britt; Bonsel, Gouke J.

    2016-01-01

    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 moni...

  5. Determinants of Erythrocyte Omega‐3 Fatty Acid Content in Response to Fish Oil Supplementation: A Dose–Response Randomized Controlled Trial

    OpenAIRE

    Flock, Michael R.; Skulas‐Ray, Ann C.; William S. Harris; Etherton, Terry D.; Fleming, Jennifer A.; Kris‐Etherton, Penny M.

    2013-01-01

    Background The erythrocyte membrane content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which constitutes the omega‐3 index (O3I), predicts cardiovascular disease mortality. The amount of EPA+DHA needed to achieve a target O3I is poorly defined, as are the determinants of the O3I response to a change in EPA+DHA intake. The objective of this study was to develop a predictive model of the O3I response to EPA+DHA supplementation in healthy adults, specifically identifying fact...

  6. Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.

    Science.gov (United States)

    Weber, H; Richter, J; Straube, B; Lueken, U; Domschke, K; Schartner, C; Klauke, B; Baumann, C; Pané-Farré, C; Jacob, C P; Scholz, C-J; Zwanzger, P; Lang, T; Fehm, L; Jansen, A; Konrad, C; Fydrich, T; Wittmann, A; Pfleiderer, B; Ströhle, A; Gerlach, A L; Alpers, G W; Arolt, V; Pauli, P; Wittchen, H-U; Kent, L; Hamm, A; Kircher, T; Deckert, J; Reif, A

    2016-06-01

    Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.

  7. Initial community and environment determine the response of bacterial communities to dispersant and oil contamination.

    Science.gov (United States)

    Ortmann, Alice C; Lu, YueHan

    2015-01-15

    Bioremediation of seawater by natural bacterial communities is one potential response to coastal oil spills, but the success of the approach may vary, depending on geographical location, oil composition and the timing of spill. The short term response of coastal bacteria to dispersant, oil and dispersed oil was characterized using 16S rRNA gene tags in two mesocosm experiments conducted two months apart. Despite differences in the amount of oil-derived alkanes across the treatments and experiments, increases in the contributions of hydrocarbon degrading taxa and decreases in common estuarine bacteria were observed in response to dispersant and/or oil. Between the two experiments, the direction and rates of changes in particulate alkane concentrations differed, as did the magnitude of the bacterial response to oil and/or dispersant. Together, our data underscore large variability in bacterial responses to hydrocarbon pollutants, implying that bioremediation success varies with starting biological and environmental conditions. PMID:25487088

  8. 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.

  9. Determination and Analysis of the Putative AcaCD-Responsive Promoters of Salmonella Genomic Island 1

    Science.gov (United States)

    Olasz, Ferenc; Kiss, János

    2016-01-01

    The integrative genomic island SGI1 and its variants confer multidrug resistance in numerous Salmonella enterica serovariants and several Proteus mirabilis and Acinetobacter strains. SGI1 is mobilized by the IncA/C family plasmids. The island exploits not only the conjugation apparatus of the plasmid, but also utilizes the plasmid-encoded master regulator AcaCD to induce the excision and formation of its transfer-competent form, which is a key step in the horizontal transfer of SGI1. Triggering of SGI1 excision occurs via the AcaCD-dependent activation of xis gene expression. AcaCD binds in Pxis to an unusually long recognition sequence. Beside the Pxis promoter, upstream regions of four additional SGI1 genes, S004, S005, S012 and S018, also contain putative AcaCD-binding sites. Furthermore, SGI1 also encodes an AcaCD-related activator, FlhDCSGI1, which has no known function. Here, we have analysed the functionality of the putative AcaCD-dependent promoter regions and proved their activation by either AcaCD or FlhDCSGI1. Moreover, we provide evidence that both activators act on the same binding site in Pxis and that FlhDCSGI1 is able to complement the acaCD deletion of the IncA/C family plasmid R16a. We determined the transcription start sites for the AcaCD-responsive promoters and showed that orf S004 is expressed probably from a different start codon than predicted earlier. Additionally, expression of S003 from promoter PS004 was ruled out. Pxis and the four SGI1 promoters examined here also lack obvious -35 promoter box and their promoter profile is consistent with the class II-type activation pathway. Although the role of the four additionally analysed AcaCD/FlhDCSGI1-controlled genes in transfer and/or maintenance of SGI1 is not yet clear, the conservation of the whole region suggests the existence of some selection for their functionality. PMID:27727307

  10. Caregiving responsibilities and burden among older people by HIV status and other determinants in Uganda.

    Science.gov (United States)

    Mugisha, Joseph; Scholten, Francien; Owilla, Sebastian; Naidoo, Nirmala; Seeley, Janet; Chatterji, Somnath; Kowal, Paul; Boerma, Ties

    2013-01-01

    Older caregivers have major caregiving responsibilities in countries severely affected by the HIV epidemic, but little is known about their own health and well-being. We conducted this study to assess the association of caregiving responsibilities and self-perceived burden with caregivers' health, HIV status, background characteristics and care-receiving among older people in South Western Uganda. Men and women aged 50 years and older were recruited from existing cohort studies and clinic registers and interviewed at home. Health was measured through a composite score of health in eight domains, anthropometry and handgrip strength. Summary measures of caregiving responsibilities and self-reported burden were used to analyse the main associations. There were 510 participants, including 198 living with HIV. Four fifths of women and 66% of men were caregivers. Older respondents with no care responsibility had poorer scores on all health indicators (self-reported health score, body mass index and grip strength). Having a caregiving responsibility was not associated with poorer health status or quality of life. Notably, HIV-infected people, whether on antiretroviral treatment (ART) or not, had similar caregiving responsibilities and health status as others. The self-reported burden associated with caregiving was significantly associated with a poorer health score. One third of female caregivers were the single adult in the household with larger caregiving responsibilities. Many of these women are in the poorest wealth quartile of the households in the study and are therefore more likely to need assistance. Physical and financial supports were received by 70% and 63%, respectively. Those with larger caregiving responsibilities more frequently received support. Caregiving responsibilities were associated with better health status, greater satisfaction and quality of life. Older HIV-infected people, whether on ART or not, had similar caregiving responsibilities and self

  11. HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia

    OpenAIRE

    Guseinova Dinara; Lazareva Arina; Sochnevs Arturs; Zavadska Dace; Eglite Jelena; Stanevicha Valda; Shantere Ruta; Gardovska Dace

    2010-01-01

    Abstract Juvenile idiopathic arthritis (JIA) is a heterogeneous condition and therapeutic strategies vary in different JIA types. The routinely accepted practice to start with Sulphasalazine (SS) as the first line treatment in patients with HLA B27 positive JIA proves to be ineffective in a large proportion of children. Objective to investigate HLA B27 positive JIA patients clinical characteristics, determined HLA B27 allele types and their connection with antirheumatic treatment in homogenou...

  12. Pre-Service Teachers: Does Cultural Responsiveness Affect Anticipated Self-Determination to Teach in Specific Settings?

    Science.gov (United States)

    Cox, Michelle L.

    2010-01-01

    Motivation to teach is essential to educating all children in the public schools. This study examined the anticipated self-determination of pre-service teachers to teach in classroom settings that varied in the ethnic and racial composition of the students in the classes. Additionally the cultural responsiveness of participants was measured to…

  13. Apolipoprotein E-epsilon 4 allele and familial risk in Alzheimer's disease.

    Science.gov (United States)

    Li, G; Silverman, J M; Altstiel, L D; Haroutunian, V; Perl, D P; Purohit, D; Birstein, S; Lantz, M; Mohs, R C; Davis, K L

    1996-01-01

    Recent studies have found an association between presence of apolipoprotein E (APOE) epsilon 4 allele and Alzheimer's disease (AD). The present study compared the cumulative risk of primary progressive dementia (PPD) in relatives of AD probands carrying at least one copy of the epsilon 4 allele with the relatives of AD probands not carrying epsilon 4 and with relatives of non-demented controls. Our aim was to determine whether the familial aggregation of PPD in relatives of AD probands is primarily due to those carrying epsilon 4. Seventy-seven neuropathologically diagnosed AD patients were obtained as probands through our Alzheimer's Disease Research Center Brain Bank. AD probands were genotyped for APOE. As a comparison group, 198 non-demented probands were also included. Through family informants, demographic and diagnostic data were collected on 382 first-degree relatives (age > or = 45 years) of AD probands and 848 relatives of the controls. We found that the cumulative risk of PPD in both relatives of AD probands with and without the epsilon 4 allele was significantly higher than that in the relatives of non-demented controls. However, the increased risk in the relatives of AD probands with the epsilon 4 allele was marginally, but not significantly, lower than the risk in the relatives of probands without epsilon 4. A greater likelihood of death by heart diseases over developing PPD in relatives of AD probands with epsilon 4 (3.1-fold increase) was found compared to relatives of probands without epsilon 4 (1.7-fold increase), especially prior to age 70, although the difference was not statistically significant. The increased familial risk for PPD in the relatives of AD probands with the APOE-epsilon 4 allele relative to controls suggests that familial factors in addition to APOE-epsilon 4 are risk factors for AD. Differential censorship from increased mortality of heart diseases may have prevented a higher incidence of PPD among the relatives of probands with

  14. Distribution of CYP2D6 Alleles and Phenotypes in the Brazilian Population

    Science.gov (United States)

    Sortica, Vinicius A.; Suarez-Kurtz, Guilherme; de Moraes, Maria Elizabete; Pena, Sergio D. J.; dos Santos, Ândrea K. Ribeiro; Romano-Silva, Marco A.; Hutz, Mara H.

    2014-01-01

    Abstract The CYP2D6 enzyme is one of the most important members of the cytochrome P450 superfamily. This enzyme metabolizes approximately 25% of currently prescribed medications. The CYP2D6 gene presents a high allele heterogeneity that determines great inter-individual variation. The aim of this study was to evaluate the variability of CYP2D6 alleles, genotypes and predicted phenotypes in Brazilians. Eleven single nucleotide polymorphisms and CYP2D6 duplications/multiplications were genotyped by TaqMan assays in 1020 individuals from North, Northeast, South, and Southeast Brazil. Eighteen CYP2D6 alleles were identified in the Brazilian population. The CYP2D6*1 and CYP2D6*2 alleles were the most frequent and widely distributed in different geographical regions of Brazil. The highest number of CYPD6 alleles observed was six and the frequency of individuals with more than two copies ranged from 6.3% (in Southern Brazil) to 10.2% (Northern Brazil). The analysis of molecular variance showed that CYP2D6 is homogeneously distributed across different Brazilian regions and most of the differences can be attributed to inter-individual differences. The most frequent predicted metabolic status was EM (83.5%). Overall 2.5% and 3.7% of Brazilians were PMs and UMs respectively. Genomic ancestry proportions differ only in the prevalence of intermediate metabolizers. The IM predicted phenotype is associated with a higher proportion of African ancestry and a lower proportion of European ancestry in Brazilians. PM and UM classes did not vary among regions and/or ancestry proportions therefore unique CYP2D6 testing guidelines for Brazilians are possible and could potentially avoid ineffective or adverse events outcomes due to drug prescriptions. PMID:25329392

  15. Distribution of CYP2D6 alleles and phenotypes in the Brazilian population.

    Directory of Open Access Journals (Sweden)

    Deise C Friedrich

    Full Text Available The CYP2D6 enzyme is one of the most important members of the cytochrome P450 superfamily. This enzyme metabolizes approximately 25% of currently prescribed medications. The CYP2D6 gene presents a high allele heterogeneity that determines great inter-individual variation. The aim of this study was to evaluate the variability of CYP2D6 alleles, genotypes and predicted phenotypes in Brazilians. Eleven single nucleotide polymorphisms and CYP2D6 duplications/multiplications were genotyped by TaqMan assays in 1020 individuals from North, Northeast, South, and Southeast Brazil. Eighteen CYP2D6 alleles were identified in the Brazilian population. The CYP2D6*1 and CYP2D6*2 alleles were the most frequent and widely distributed in different geographical regions of Brazil. The highest number of CYPD6 alleles observed was six and the frequency of individuals with more than two copies ranged from 6.3% (in Southern Brazil to 10.2% (Northern Brazil. The analysis of molecular variance showed that CYP2D6 is homogeneously distributed across different Brazilian regions and most of the differences can be attributed to inter-individual differences. The most frequent predicted metabolic status was EM (83.5%. Overall 2.5% and 3.7% of Brazilians were PMs and UMs respectively. Genomic ancestry proportions differ only in the prevalence of intermediate metabolizers. The IM predicted phenotype is associated with a higher proportion of African ancestry and a lower proportion of European ancestry in Brazilians. PM and UM classes did not vary among regions and/or ancestry proportions therefore unique CYP2D6 testing guidelines for Brazilians are possible and could potentially avoid ineffective or adverse events outcomes due to drug prescriptions.

  16. Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

    Science.gov (United States)

    Friedenberg, Steven G; Buhrman, Greg; Chdid, Lhoucine; Olby, Natasha J; Olivry, Thierry; Guillaumin, Julien; O'Toole, Theresa; Goggs, Robert; Kennedy, Lorna J; Rose, Robert B; Meurs, Kathryn M

    2016-03-01

    Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.

  17. Frequency of CCR5Δ32 allele in healthy Bosniak population.

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    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. 

  18. 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

  19. Allelic exclusion of immunoglobulin genes: models and mechanisms.

    Science.gov (United States)

    Vettermann, Christian; Schlissel, Mark S

    2010-09-01

    The allelic exclusion of immunoglobulin (Ig) genes is one of the most evolutionarily conserved features of the adaptive immune system and underlies the monospecificity of B cells. While much has been learned about how Ig allelic exclusion is established during B-cell development, the relevance of monospecificity to B-cell function remains enigmatic. Here, we review the theoretical models that have been proposed to explain the establishment of Ig allelic exclusion and focus on the molecular mechanisms utilized by developing B cells to ensure the monoallelic expression of Ig kappa and Ig lambda light chain genes. We also discuss the physiological consequences of Ig allelic exclusion and speculate on the importance of monospecificity of B cells for immune recognition.

  20. A loss-of-function allele of OsHMA3 associated with high cadmium accumulation in shoots and grain of Japonica rice cultivars.

    Science.gov (United States)

    Yan, Jiali; Wang, Peitong; Wang, Peng; Yang, Meng; Lian, Xingming; Tang, Zhong; Huang, Chao-Feng; Salt, David E; Zhao, Fang Jie

    2016-09-01

    Excessive cadmium (Cd) accumulation in rice poses a risk to food safety. OsHMA3 plays an important role in restricting Cd translocation from roots to shoots. A non-functional allele of OsHMA3 has been reported in some Indica rice cultivars with high Cd accumulation, but it is not known if OsHMA3 allelic variation is associated with Cd accumulation in Japonica cultivars. In this study, we identified a Japonica cultivar with consistently high Cd accumulation in shoots and grain in both field and greenhouse experiments. The cultivar possesses an OsHMA3 allele with a predicted amino acid mutation at the 380(th) position from Ser to Arg. The haplotype had no Cd transport activity when the gene was expressed in yeast, and the allele did not complement a known nonfunctional allele of OsHMA3 in F1 test. The allele is present only in temperate Japonica cultivars among diversity panels of 1483 rice cultivars. Different cultivars possessing this allele showed greatly increased root-to-shoot Cd translocation and a shift in root Cd speciation from Cd-S to Cd-O bonding determined by synchrotron X-ray absorption spectroscopy. Our study has identified a new loss-of-function allele of OsHMA3 in Japonica rice cultivars leading to high Cd accumulation in shoots and grain. PMID:27038090

  1. Identification of incompatibility alleles in the tetraploid species sour cherry.

    Science.gov (United States)

    Tobutt, K R; Bosković, R; Cerović, R; Sonneveld, T; Ruzić, D

    2004-03-01

    The incompatibility genetics of sour cherry ( Prunus cerasus), an allotetraploid species thought to be derived from sweet cherry (diploid) and ground cherry (tetraploid), were investigated by test crossing and by analysis of stylar ribonucleases which are known to be the products of incompatibility alleles in sweet cherry. Stylar extracts of 36 accessions of sour cherry were separated electrophoretically and stained for ribonuclease activity. The zymograms of most accessions showed three bands, some two or four. Of the ten bands seen, six co-migrated with bands that in sweet cherry are attributed to the incompatibility alleles S(1), S(3), S(4), S(6, ) S(9) and S(13). 'Cacanski Rubin', 'Erdi Botermo B', 'Koros' and 'Ujfehertoi Furtos', which showed bands apparently corresponding to S(1) and S(4), were test pollinated with the sweet cherry 'Merton Late' ( S(1) S(4)). Monitoring pollen tube growth, and, in one case, fruit set, showed that these crosses were incompatible and that the four sour cherries indeed have the alleles S(1) and S(4). Likewise, test pollination of 'Marasca Piemonte', 'Marasca Savena' and 'Morello, Dutch' with 'Noble' ( S(6) S(13)) showed that these three sour cherries have the alleles S(6) and S(13). S(13) was very frequent in sour cherry cultivars, but is rare in sweet cherry cultivars, whereas with S(3) the situation is reversed. It was suggested that the other four bands are derived from ground cherry and one of these, provisionally attributed to S(B), occurred frequently in a small set of ground cherry accessions surveyed. Analysing some progenies from sour by sweet crosses by S allele-specific PCR and monitoring the success of some sweet by sour crosses were informative. They indicated mostly disomic inheritance, with sweet cherry S alleles belonging to one locus and, presumably, the ground cherry alleles to the other, and helped clarify the genomic arrangement of the alleles and the interactions in heteroallelic pollen. PMID:14689184

  2. ALLELIC POLYMORPHISM OF IFNγ GENE IN PATIENTS WITH PULMONARY TUBERCULOSIS

    OpenAIRE

    E. L. Nikulina; I. O. Naslednikova; Urazova, O. I.; O. V. Voronkova; V. V. Novitsky; E. V. Nekrasov; O. V. Filiniuk; E. G. Churina; K. O. Mikheyeva; R. R. Hasanova; V. A. Serebryakova; N. A. Sukhalentseva

    2014-01-01

    In present work, some immunogenetic aspects of pulmonary tuberculosis were studied, using modern techniques from molecular genetics and immunology. It is shown that carriage of Т allele and homozygous TT genotype in +874А/Т IFNγ gene polymorphism comprise a immunogenetic factor which correlated with a protective effect, regarding a susceptibility to pulmonary tuberculosis. Predisposition for tuberculosis infection is associated with A allele of this gene, as well as with АА and АТ genotypes o...

  3. Determination of the response distributions of cantilever beam under sinusoidal base excitation

    International Nuclear Information System (INIS)

    As a kind of base excitation, shaking table is often used to test the dynamic characteristics of structures. However, the prediction of response to base excitation hasn't been solved effectively, which limits the further research on the test and analysis method with respect to base movement. This article is based on a cantilever beam and focuses on its response prediction under sinusoidal base excitation. By moment and force equilibrium equations, an analytical model is built for this cantilever beam, and then a method to predict dynamic response at base excitation is proposed. Finally, the method is used to solve the vibration response distributions of the cantilever beam at base excitation. Correctness of this method is also proved by comparing the result with experimental data

  4. Reactor Room Experimental SF6 Tests to Determine Probable Stack Activity Response to Radioactive Releases

    International Nuclear Information System (INIS)

    This study was performed to obtain information that could be useful for obtaining an early estimate of the probable total stack activity monitor response in the event of an accidental release of radioactive activity in the process room

  5. Determinants of Managerial Values on Corporate Social Responsibility: Evidence from China

    OpenAIRE

    Zu, Liangrong; Song, Lina

    2008-01-01

    This paper empirically investigates how Chinese executives and managers perceive and interpret corporate social responsibility (CSR), to what extent firms' productive characteristics influence managers' attitudes towards their CSR rating, and whether their values in favour of CSR are positively correlated to firms' economic performance. Although a large proportion of respondents express a favourable view of CSR and a willingness to participate in socially responsible activities, we find that ...

  6. Apolipoprotein E Alleles, Dyslipidemia,and Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To describe the association between apolipoprotein E alleles, dyslipidemia, and coronary heart disease (CHD). Methods Using polymerase chain reaction (PCR) the restriction fragment length polymorphism (RFLP), we studied the apolipoprotein E genotypes in 142 patients with coronary artery disease (CAD) and 131 age-matched healthy subjects, as well as the association between apolipoprotein, plasma lipids, and CHD. Results Compared with the E3 allele, the E4 allele was associated with elevated total cholesterol (TC) values (average increase about 0.32-0.58 mmol/L), low-density lipoprotein cholesterol (LDL-C) values, and apolipoprotein B (APOB). The E2 allele has opposite effects (average decrease about 0.34-0.61 mmol/L at TC). Both in cases and controls, the allelic frequency of E3/3 was highest, reaching 67.8% of whole volume, hemozygote of apo E3 was moderate, and homozygote E4/4 was low, E2/2 and E4/2 were rare. The frequencies of E3/4 and E4/4 were significantly higher in patients with CAD compared with controls (P<0.001).Conclusion Apolipoprotein E alleles are important genetic markers for dyslipidemia and CHD.The carrier of E4 gene was the risk factor of CHD.

  7. 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.

  8. Contribution of non-reference alleles in mtDNA of Alzheimer's disease patients.

    Science.gov (United States)

    Casoli, Tiziana; Di Stefano, Giuseppina; Spazzafumo, Liana; Balietti, Marta; Giorgetti, Belinda; Giuli, Cinzia; Postacchini, Demetrio; Fattoretti, Patrizia; Conti, Fiorenzo

    2014-04-01

    Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChip v2.0 array. Our analysis identified 270 significantly different nps which, with one exception, showed an increased contribution of non-reference alleles in AD patients. Principal component analysis (PCA) and cluster analysis showed that five of these nps could discriminate AD from control subjects with 80% of cases correctly classified. Our data support the hypothesis of mtDNA alterations as an important factor in the etiology of AD. PMID:25590040

  9. Extremely high frequency of autoimmune-predisposing alleles in medieval specimens

    Institute of Scientific and Technical Information of China (English)

    WITAS H.W.; J(E)DRYCHOWSKA-DA(N)SKA K.; ZAWICKI P.

    2007-01-01

    The precise etiology and reasons for the increase in incidence of autoimmune disorders still remain unclear, and although both genetic and environmental factors have been proven to shape individual predisposition, it is not known which of the factors, if not both, is responsible for the boom observed during the last decades. In order to establish whether a higher frequency of autoimmune-predisposing alleles may explain this increase we took advantage of ancient DNA methodology to establish the genetic predisposition, conferred by cytotoxic T lymphocyte associated antigen-4 (CTLA4) +49A/G and human leukocyte antigens (HLA)DQB157, in population inhabiting Poland in the Middle Ages. After successful typing of 42 individuals from a 12th~14th's century archeological burial site, we found that frequencies of the predisposing alleles in the medieval population were higher than they are at present, suggesting thus that the recently observed incidence increase results most probably from factors of other than genetic nature.

  10. Genotype and allele frequencies of heme oxygenase-1 promoter region in a Greek cohort

    Institute of Scientific and Technical Information of China (English)

    Eleni P. Katana; Lemonia G. Skoura; Zacharias G Scouras; Michail A. Daniilidis

    2011-01-01

    Background Heme oxygenase-1 (HO-1) is an enzyme,which catabolizes heme into carbon monoxide,biliverdin and free iron.The induction of this enzyme is an important cytoprotective mechanism,which occurs as an adaptive and beneficial response to a wide variety of oxidant stimuli.HO-1 inducibility is mainly modulated by a (GT)n polymorphism in the promoter region,and has been shown that short (S) repeats are associated with greater up-regulation of HO-1,compared with long (L) repeats.Methods In the present study,250 healthy Greek individuals have been screened in order to estimate the frequencies of (GT)n alleles in the HO-1 gene.Results Nineteen different alleles,ranging from 17 to 39 repeats,with (GT)23 and (GT)30 being the most common ones,were identified.Conclusion The possible role of this polymorphism in disease states is discussed.

  11. 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.

  12. Association of HLA-DRB1 Alleles in Juvenile-onset Systemic Lupus Erythematosus (SLE in Iranian Children

    Directory of Open Access Journals (Sweden)

    Shirin Farivar

    2015-04-01

    Full Text Available Introduction Systemic Lupus Erythematosus (SLE is a complex autoimmune and inflammatory disease. Many studies show HLA alleles can be associated with SLE. The aim of this study was to determine the association of HLA-DRB1 alleles with juvenile- onset in Iranian children. Materials and Methods At a case – control study, 31 children with systemic lupus erythematosus (case group who referred to Mofid Children’s Hospital, Shahid Behehsti University of Medical Sciences, Tehran, and 56 healthy children (control group were participant.  Genomic  DNA  was  extracted  and  HLA  typing  was performed by Polymerase Chain Reaction (PCR with Sequence - Specific Primers (SSP technique. Results HLA- DRB1*01, HLA- DRB1*04, HLA- DRB1*11 and HLA- DRB1*13 were detected to as most frequent alleles associated with SLE in Iranian children. The frequency of HLA DRB1*08 was not significantly different in both groups (P>0.05(.  HLA- DRB1*07 had a higher rate of repetition in the control group than patients with SLE. Conclusion There was a significant difference in the frequency of some alleles between patients and controls group, which could be related to susceptibility to SLE. These differences between frequencies of some alleles in both groups may help to determine the onset of lupus in children.

  13. 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

  14. A statistical approach to determining responses to individual peptides from pooled-peptide ELISpot data.

    Science.gov (United States)

    Ström, Peter; Støer, Nathalie; Borthwick, Nicola; Dong, Tao; Hanke, Tomáš; Reilly, Marie

    2016-08-01

    To investigate in detail the effect of infection or vaccination on the human immune system, ELISpot assays are used to simultaneously test the immune response to a large number of peptides of interest. Scientists commonly use "peptide pools", where, instead of an individual peptide, a test well contains a group of peptides. Since the response from a well may be due to any or many of the peptides in the pool, pooled assays usually need to be followed by confirmatory assays of a number of individual peptides. We present a statistical method that enables estimation of individual peptide responses from pool responses using the Expectation Maximization (EM) algorithm for "incomplete data". We demonstrate the accuracy and precision of these estimates in simulation studies of ELISpot plates with 90 pools of 6 or 7 peptides arranged in three dimensions and three Mock wells for the estimation of background. In analysis of real pooled data from 6 subjects in a HIV-1 vaccine trial, where 199 peptides were arranged in 80 pools if size 9 or 10, our estimates were in very good agreement with the results from individual-peptide confirmatory assays. Compared to the classical approach, we could identify almost all the same peptides with high or moderate response, with less than half the number of confirmatory tests. Our method facilitates efficient use of the information available in pooled ELISpot data to avoid or reduce the need for confirmatory testing. We provide an easy-to-use free online application for implementing the method, where on uploading two spreadsheets with the pool design and pool responses, the user obtains the estimates of the individual peptide responses. PMID:27196788

  15. 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

  16. Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA

    OpenAIRE

    Wong, Kwong-Kwok; Tsang, Yvonne T.M.; Shen, Jianhe; Cheng, Rita S.; Chang, Yi-Mieng; Man, Tsz-Kwong; Lau, Ching C.

    2004-01-01

    Besides their use in mRNA expression profiling, oligonucleotide microarrays have also been applied to single-nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) or allelic imbalance studies. In this report, we evaluate the reliability of using whole genome amplified DNA for analysis with an oligonucleotide microarray containing 11 560 SNPs to detect allelic imbalance and chromosomal copy number abnormalities. Whole genome SNP analyses were performed with DNA extracted from osteosar...

  17. 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. PMID:27164216

  18. 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...... by changing the excitation or fluorescence wave-lengths of the testing equipment....

  19. 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

  20. Criteria for determining whether mismatch responses exist in animal models: Focus on rodents.

    Science.gov (United States)

    Harms, Lauren; Michie, Patricia T; Näätänen, Risto

    2016-04-01

    The mismatch negativity (MMN) component of the auditory event-related potential, elicited in response to unexpected stimuli in the auditory environment, has great value for cognitive neuroscience research. It is changed in several neuropsychiatric disorders such as schizophrenia. The ability to measure and manipulate MMN-like responses in animal models, particularly rodents, would provide an enormous opportunity to learn more about the neurobiology underlying MMN. However, the MMN in humans is a very specific phenomenon: how do we decide which features we should focus on emulating in an animal model to achieve the highest level of translational validity? Here we discuss some of the key features of MMN in humans and summarise the success with which they have been translated into rodent models. Many studies from several different labs have successfully shown that the rat brain is capable of generating deviance detection responses that satisfy of the criteria for the human MMN. PMID:26196895

  1. 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.

  2. Impriniting of human H19: Allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Shields, T.; Crenshaw, T.; Hao, Y.; Moulton, T.; Tycko, B. (Columbia Univ., New York (United States))

    1993-07-01

    Genomic imprinting and monoallelic gene expression appear to play a role in human genetic disease and tumorigenesis. The human H19 gene, at chromosome 11p15, has previously been shown to be monoallelically expressed. Since CpG methylation has been implicated in imprinting, the authors analyzed methylation of H19 DNA. In fetal and adult organs the transcriptionally silent H19 allele was extensively hypermethylated through the entire gene and its promoter, and, consistent with a functional role for DNA methylation, expression of an H19 promoter-reporter construct was inhibited by in vitro methylation. Gynogenetic ovarian teratomas were found to contain only hypomethylated H19 DNA, suggesting that the expressed H19 allele might be maternal. This was confirmed by analysis of 11p15 polymorphisms in a patient with Wilms tumor. The tumor had lost the maternal 11p15, and H19 expression in the normal kidney was exclusively from this allele. Imprinting of human H19 appears to be susceptible to tissue-specific modulation in somatic development; in one individual, cerebellar cells were found to express only the otherwise silent allele. Implications of these findings for the role of DNA methylation in imprinting and for H19 as a candidate imprinted tumor-suppressor gene are discussed. 57 refs., 7 figs.

  3. Allele-Specific Reduction of the Mutant Huntingtin Allele Using Transcription Activator-Like Effectors in Human Huntington's Disease Fibroblasts.

    Science.gov (United States)

    Fink, Kyle D; Deng, Peter; Gutierrez, Josh; Anderson, Joseph S; Torrest, Audrey; Komarla, Anvita; Kalomoiris, Stefanos; Cary, Whitney; Anderson, Johnathon D; Gruenloh, William; Duffy, Alexandra; Tempkin, Teresa; Annett, Geralyn; Wheelock, Vicki; Segal, David J; Nolta, Jan A

    2016-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of CAG repeats. Although pathogenesis has been attributed to this polyglutamine expansion, the underlying mechanisms through which the huntingtin protein functions have yet to be elucidated. It has been suggested that postnatal reduction of mutant huntingtin through protein interference or conditional gene knockout could prove to be an effective therapy for patients suffering from HD. For allele-specific targeting, transcription activator-like effectors (TALE) were designed to target single-nucleotide polymorphisms (SNP) in the mutant allele and packaged into a vector backbone containing KRAB to promote transcriptional repression of the disease-associated allele. Additional TALEs were packaged into a vector backbone containing heterodimeric FokI and were designed to be used as nucleases (TALEN) to cause a CAG-collapse in the mutant allele. Human HD fibroblasts were treated with each TALE-SNP or TALEN. Allele-expression was measured using a SNP-genotyping assay and mutant protein aggregation was quantified with Western blots for anti-ubiquitin. The TALE-SNP and TALEN significantly reduced mutant allele expression (p TALE proteins, and provides a foundation for targeted treatment for individuals suffering from Huntington's or other genetically linked diseases. PMID:26850319

  4. Gender differences in stress response: Role of developmental and biological determinants

    Directory of Open Access Journals (Sweden)

    Rohit Verma

    2011-01-01

    Full Text Available Stress response is associated with manifestations of various psychosomatic and psychiatric disorders. Hence, it is important to understand the underlying mechanisms that influence this association. Moreover, men and women tend to react differently with stress-both psychologically and biologically. These differences also need to be studied in order to have a better understanding in the gender difference observed for many disorders, which are likely to be contributed by the gender difference in stress reactivity and responses. Such an understanding would have a significant impact on our understanding about how adult health is set during early life and how adult disease could be prevented in men and women.

  5. 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

  6. Noninvasive fetal genotyping of paternally inherited alleles

    NARCIS (Netherlands)

    Scheffer, P.G.

    2012-01-01

    The results presented in this thesis indicate that cell-free fetal DNA is a reliably analyte for prenatal genetic diagnosis in everyday clinical practice. Already, invasive procedures solely to determine the fetal sex or red cell antigen status belong to the past. Large-scale nation-wide prenatal sc

  7. 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.

  8. Inheritance of microsatellite alleles in pedigrees of Latvian barley varieties and related European ancestors.

    Science.gov (United States)

    Sjakste, T G; Rashal, I; Röder, M S

    2003-02-01

    Genetic diversity and inheritance of 65 microsatellite (SSR) loci were studied in a set of 37 barley varieties involved in the pedigrees of seven Latvian barley varieties: Abava, Agra, Balga, Imula, Linga, Priekulu 1 and Stendes. Cluster analysis divided all the varieties into two large groups according to their geographic distribution. Moravian, Swedish and Danish varieties clustered separately from varieties from Norway and Finland. The pattern of subgroups of both European and Latvian varieties was in accordance with their pedigree information. Graphical genotypes of microsatellite alleles of all seven barley chromosomes were determined for all the 37 varieties studied. Parental inheritance and transmission of microsatellite alleles through the generations of the pedigrees were analysed. The results confirmed the importance and informative value of microsatellite markers for genetic studies in barley and their utility for barley breeding and other applications in fundamental and applied barley genetics. PMID:12589555

  9. NF1 Is a Tumor Suppressor in Neuroblastoma that Determines Retinoic Acid Response and Disease Outcome

    NARCIS (Netherlands)

    M. Hölzel; S. Huang; J. Koster; I. Ora; A. Lakeman; H. Caron; W. Nijkamp; J. Xie; T. Callens; S. Asgharzadeh; R.C. Seeger; L. Messiaen; R. Versteeg; R. Bernards

    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 large-s

  10. 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 func...

  11. 42 CFR 402.212 - Response to notice of proposed determination to exclude.

    Science.gov (United States)

    2010-10-01

    ... to the initiating agency a written response stating whether the proposed exclusion is warranted, and... appropriate. (b) The person is also afforded an opportunity to make an oral presentation to the initiating... request, the initiating agency initiates communication with the person to establish a mutually agreed...

  12. Determining polarizable force fields with electrostatic potentials from quantum mechanical linear response theory.

    Science.gov (United States)

    Wang, Hao; Yang, Weitao

    2016-06-14

    We developed a new method to calculate the atomic polarizabilities by fitting to the electrostatic potentials (ESPs) obtained from quantum mechanical (QM) calculations within the linear response theory. This parallels the conventional approach of fitting atomic charges based on electrostatic potentials from the electron density. Our ESP fitting is combined with the induced dipole model under the perturbation of uniform external electric fields of all orientations. QM calculations for the linear response to the external electric fields are used as input, fully consistent with the induced dipole model, which itself is a linear response model. The orientation of the uniform external electric fields is integrated in all directions. The integration of orientation and QM linear response calculations together makes the fitting results independent of the orientations and magnitudes of the uniform external electric fields applied. Another advantage of our method is that QM calculation is only needed once, in contrast to the conventional approach, where many QM calculations are needed for many different applied electric fields. The molecular polarizabilities obtained from our method show comparable accuracy with those from fitting directly to the experimental or theoretical molecular polarizabilities. Since ESP is directly fitted, atomic polarizabilities obtained from our method are expected to reproduce the electrostatic interactions better. Our method was used to calculate both transferable atomic polarizabilities for polarizable molecular mechanics' force fields and nontransferable molecule-specific atomic polarizabilities. PMID:27305996

  13. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes.

    Science.gov (United States)

    Fang, Jing; Liu, Xiaona; Bolanos, Lyndsey; Barker, Brenden; Rigolino, Carmela; Cortelezzi, Agostino; Oliva, Esther N; Cuzzola, Maria; Grimes, H Leighton; Fontanillo, Celia; Komurov, Kakajan; MacBeth, Kyle; Starczynowski, Daniel T

    2016-07-01

    Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. We identified GPR68, which encodes a G-protein-coupled receptor that has been implicated in calcium metabolism, as the top candidate gene for modulating sensitivity to LEN. LEN induced GPR68 expression via IKAROS family zinc finger 1 (IKZF1), resulting in increased cytosolic calcium levels and activation of a calcium-dependent calpain, CAPN1, which were requisite steps for induction of apoptosis in MDS cells and in acute myeloid leukemia (AML) cells. In contrast, deletion of GPR68 or inhibition of calcium and calpain activation suppressed LEN-induced cytotoxicity. Moreover, expression of calpastatin (CAST), an endogenous CAPN1 inhibitor that is encoded by a gene (CAST) deleted in del(5q) MDS, correlated with LEN responsiveness in patients with del(5q) MDS. Depletion of CAST restored responsiveness of LEN-resistant non-del(5q) MDS cells and AML cells, providing an explanation for the superior responses of patients with del(5q) MDS to LEN treatment. Our study describes a cellular mechanism by which LEN, acting through CRBN and IKZF1, has cytotoxic effects in MDS and AML that depend on a calcium- and calpain-dependent pathway.

  14. Distribution of photoperiod-insensitive alleles Ppd-B1a and Ppd-D1a and their effect on heading time in Japanese wheat cultivars.

    Science.gov (United States)

    Seki, Masako; Chono, Makiko; Matsunaka, Hitoshi; Fujita, Masaya; Oda, Shunsuke; Kubo, Katashi; Kiribuchi-Otobe, Chikako; Kojima, Hisayo; Nishida, Hidetaka; Kato, Kenji

    2011-12-01

    The genotypes of photoperiod response genes Ppd-B1 and Ppd-D1 in Japanese wheat cultivars were determined by a PCR-based method, and heading times were compared among genotypes. Most of the Japanese wheat cultivars, except those from the Hokkaido region, carried the photoperiod-insensitive allele Ppd-D1a, and heading was accelerated 10.3 days compared with the Ppd-D1b genotype. Early cultivars with Ppd-D1a may have been selected to avoid damage from preharvest rain. In the Hokkaido region, Ppd-D1a frequency was lower and heading date was late regardless of Ppd-D1 genotype, suggesting another genetic mechanism for late heading in Hokkaido cultivars. In this study, only 11 cultivars proved to carry Ppd-B1a, and all of them carried another photoperiod-insensitive allele, Ppd-D1a. The Ppd-B1a/Ppd-D1a genotype headed 6.7 days earlier than the Ppd-B1b/Ppd-D1a genotype, indicating a significant effect of Ppd-B1a in the genetic background with Ppd-D1a. Early-maturity breeding in Japan is believed to be accelerated by the introduction of the Ppd-B1a allele into medium-heading cultivars carrying Ppd-D1a. Pedigree analysis showed that Ppd-B1a in three extra-early commercial cultivars was inherited from 'Shiroboro 21' by early-heading Chugoku lines bred at the Chugoku Agriculture Experimental Station.

  15. 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)

    Pazhani, Gururaja Perumal; Abiodun, Iwalokun Bamidele; Afolabi, Oluwadun; Kolawole, Olukoya Daniel; Mukhopadhyay, Asish K.; Ramamurthy, Thanadarayan

    2016-01-01

    Background and Objectives 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. Results 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. Conclusion 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. PMID:27479360

  16. Matrix method of determining the longitudinal-stability coefficients and frequency response of an aircraft from transient flight data

    Science.gov (United States)

    Donegan, James J; Pearson, Henry A

    1952-01-01

    A matrix method is presented for determining the longitudinal-stability coefficients and frequency response of an aircraft from arbitrary maneuvers. The method is devised so that it can be applied to time-history measurements of combinations of such simple quantities as angle of attack, pitching velocity, load factor, elevator angle, and hinge moment to obtain the over-all coefficients. Although the method has been devised primarily for the evaluation of stability coefficients which are of primary interest in most aircraft loads and stability studies, it can be used also, with a simple additional computation, to determine the frequency-response characteristics. The entire procedure can be applied or extended to other problems which can be expressed by linear differential equations.

  17. Determination of heavy metals contamination using a silicon sensor with extended responsive to the UV

    Science.gov (United States)

    Aceves-Mijares, M.; Ramírez, J. M.; Pedraza, J.; Román-López, S.; Chávez, C.

    2013-03-01

    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.

  18. Determination of heavy metals contamination using a silicon sensor with extended responsive to the UV

    International Nuclear Information System (INIS)

    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.

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

    OpenAIRE

    Jeff Niederdeppe; Sungjong Roh; 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 individua...

  20. Principal component analysis of Birkeland currents determined by the Active Magnetosphere and Planetary Electrodynamics Response Experiment

    CERN Document Server

    Milan, S E; Korth, H; Anderson, B J

    2016-01-01

    Principal component analysis is performed on Birkeland or field-aligned current (FAC) measurements from the Active Magnetosphere and Planetary Electrodynamics Response Experiment. Principal component analysis (PCA) identifies the patterns in the FACs that respond coherently to different aspects of geomagnetic activity. The regions 1 and 2 current system is shown to be the most reproducible feature of the currents, followed by cusp currents associated with magnetic tension forces on newly reconnected field lines. The cusp currents are strongly modulated by season, indicating that their strength is regulated by the ionospheric conductance at the foot of the field lines. PCA does not identify a pattern that is clearly characteristic of a substorm current wedge. Rather, a superposed epoch analysis of the currents associated with substorms demonstrates that there is not a single mode of response, but a complicated and subtle mixture of different patterns.

  1. Mammalian Host-Versus-Phage immune response determines phage fate in vivo.

    Science.gov (United States)

    Hodyra-Stefaniak, Katarzyna; Miernikiewicz, Paulina; Drapała, Jarosław; Drab, Marek; Jończyk-Matysiak, Ewa; Lecion, Dorota; Kaźmierczak, Zuzanna; Beta, Weronika; Majewska, Joanna; Harhala, Marek; Bubak, Barbara; Kłopot, Anna; Górski, Andrzej; Dąbrowska, Krystyna

    2015-01-01

    Emerging bacterial antibiotic resistance draws attention to bacteriophages as a therapeutic alternative to treat bacterial infection. Examples of phage that combat bacteria abound. However, despite careful testing of antibacterial activity in vitro, failures nevertheless commonly occur. We investigated immunological response of phage antibacterial potency in vivo. Anti-phage activity of phagocytes, antibodies, and serum complement were identified by direct testing and by high-resolution fluorescent microscopy. We accommodated the experimental data into a mathematical model. We propose a universal schema of innate and adaptive immunity impact on phage pharmacokinetics, based on the results of our numerical simulations. We found that the mammalian-host response to infecting bacteria causes the concomitant removal of phage from the system. We propose the notion that this effect as an indirect pathway of phage inhibition by bacteria with significant relevance for the clinical outcome of phage therapy. PMID:26440922

  2. Principle Component Analysis of Birkeland Currents Determined by the Active Magnetosphere and Planetary Electrodynamics Response Experiment

    Science.gov (United States)

    Milan, S. E.; Carter, J. A.; Korth, H.; Anderson, B. J.

    2015-12-01

    Principle Component Analysis is performed on northern and southern hemisphere Birkeland or field-aligned current (FAC) measurements from the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE). PCA identifies the patterns in the FACs that respond coherently to different aspects of geomagnetic activity. The region 1 and 2 current system is shown to be the most reproducible feature of the currents, followed by cusp currents associated with magnetic tension forces on newly-reconnected field lines. The cusp currents are strongly modulated by season, indicating that their strength is regulated by the ionospheric conductance at the foot of the field lines. PCA does not identify a pattern that is clearly characteristic of a substorm current wedge. Rather, a superposed epoch analysis of the currents associated with substorms demonstrates that there is not a single mode of response, but a complicated and subtle mixture of different patterns. Other interhemispheric differences are discussed.

  3. Principal component analysis of Birkeland currents determined by the Active Magnetosphere and Planetary Electrodynamics Response Experiment

    Science.gov (United States)

    Milan, S. E.; Carter, J. A.; Korth, H.; Anderson, B. J.

    2015-12-01

    Principal component analysis is performed on Birkeland or field-aligned current (FAC) measurements from the Active Magnetosphere and Planetary Electrodynamics Response Experiment. Principal component analysis (PCA) identifies the patterns in the FACs that respond coherently to different aspects of geomagnetic activity. The regions 1 and 2 current system is shown to be the most reproducible feature of the currents, followed by cusp currents associated with magnetic tension forces on newly reconnected field lines. The cusp currents are strongly modulated by season, indicating that their strength is regulated by the ionospheric conductance at the foot of the field lines. PCA does not identify a pattern that is clearly characteristic of a substorm current wedge. Rather, a superposed epoch analysis of the currents associated with substorms demonstrates that there is not a single mode of response, but a complicated and subtle mixture of different patterns.

  4. 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

    Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy...... 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...... 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....

  5. Placental Responses to Changes in the Maternal Environment Determine Fetal Growth

    OpenAIRE

    Dimasuay, Kris Genelyn; Boeuf, Philippe; Powell, Theresa L.; Jansson, Thomas

    2016-01-01

    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 hormo...

  6. Source of Biomass Cooking Fuel Determines Pulmonary Response to Household Air Pollution

    OpenAIRE

    Thomas E Sussan; Ingole, Vijendra; Kim, Jung-Hyun; McCormick, Sarah; Negherbon, Jesse; FALLICA, JONATHAN; Akulian, Jason; Yarmus, Lonny; Feller-Kopman, David; Wills-Karp, Marsha; Maureen R. Horton; Breysse, Patrick N; Agrawal, Anurag; Juvekar, Sanjay; Salvi, Sundeep

    2014-01-01

    Approximately 3 billion people—half the worldwide population—are exposed to extremely high concentrations of household air pollution due to the burning of biomass fuels on inefficient cookstoves, accounting for 4 million annual deaths globally. Yet, our understanding of the pulmonary responses to household air pollution exposure and the underlying molecular and cellular events is limited. The two most prevalent biomass fuels in India are wood and cow dung, and typical 24-hour mean particulate...

  7. Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

    OpenAIRE

    Fatouros, Ioannis G.; Chatzinikolaou, Athanasios; Tournis, Symeon; Michalis G. Nikolaidis; Jamurtas, Athanasios Z.; Douroudos, Ioannis I.; Papassotiriou, Ioannis; Thomakos, Petros M.; Taxildaris, Kyriakos; Mastorakos, George; Mitrakou, Asimina

    2009-01-01

    OBJECTIVE To evaluate the time course of leptin, adiponectin, and resting energy expenditure (REE) responses in overweight elderly males after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS Forty inactive men (65–82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, ...

  8. DETERMINANTS OF SOCIAL RESPONSIBILITY EXPENDITURES OF SMALL AND MEDIUM ENTERPRISES FROM BIHOR COUNTY

    OpenAIRE

    Saveanu Tomina Gabriela

    2015-01-01

    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 scientif...

  9. Mammalian Host-Versus-Phage immune response determines phage fate in vivo

    OpenAIRE

    Katarzyna Hodyra-Stefaniak; Paulina Miernikiewicz; Jarosław Drapała; Marek Drab; Ewa Jończyk-Matysiak; Dorota Lecion; Zuzanna Kaźmierczak; Weronika Beta; Joanna Majewska; Marek Harhala; Barbara Bubak; Anna Kłopot; Andrzej Górski; Krystyna Dąbrowska

    2015-01-01

    Emerging bacterial antibiotic resistance draws attention to bacteriophages as a therapeutic alternative to treat bacterial infection. Examples of phage that combat bacteria abound. However, despite careful testing of antibacterial activity in vitro, failures nevertheless commonly occur. We investigated immunological response of phage antibacterial potency in vivo. Anti-phage activity of phagocytes, antibodies, and serum complement were identified by direct testing and by high-resolution fluor...

  10. Initial size structure of natural phytoplankton communities determines the response to Daphnia diel vertical migration

    OpenAIRE

    Maarten Boersma; Florian Haupt; Maria Stockenreiter; Herwig Stibor

    2012-01-01

    Diel vertical migration (DVM) is a common behavior of many pelagic herbivorous zooplankton species in response to predation pressure. It is characterized by a twice daily habitat shift of the zooplankton species: staying in the epilimnion only during night time and migrating down in the crack of dawn in deeper water layers, staying there during the day time. This causes a discontinuous grazing regime and previous studies have shown that the direction and strength of phytoplankton community re...

  11. Mechanisms Determining the Winter Atmospheric Response to the Atlantic Overturning Circulation

    OpenAIRE

    Gastineau, Guillaume; L’Hévéder, B.; Codron, Francis; Frankignoul, Claude

    2016-01-01

    International audience In climate models, an intensification of the Atlantic meridional overturning circulation (AMOC) precedes a warming in the North Atlantic subpolar basin by a few years. In the IPSL-CM5A-LR model, this warming may explain the atmospheric response to the AMOC observed in winter, which resembles a negative phase of the North Atlantic Oscillation (NAO). To firmly establish the causality links between the ocean and the atmosphere and illustrate the underlying mechanisms in...

  12. A randomised controlled trial to determine the effect on response of including a lottery incentive in health surveys [ISRCTN32203485

    Directory of Open Access Journals (Sweden)

    Bridge P

    2004-11-01

    Full Text Available Abstract Background Postal questionnaires are an economical and simple method of data collection for research purposes but are subject to non-response bias. Several studies have explored the effect of monetary and non-monetary incentives on response. Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates. However, large surveys rarely have the resources to reward individual participants. Three previous papers report on the effectiveness of lottery incentives with contradictory results. This study aimed to determine the effect of including a lottery-style incentive on response rates to a postal health survey. Methods Randomised controlled trial. Setting: North and West Birmingham. 8,645 patients aged 18 or over randomly selected from registers of eight general practices (family physician practices. Intervention: Inclusion of a flyer and letter with a health questionnaire informing patients that returned questionnaires would be entered into a lottery-style draw for £100 of gift vouchers. Control: Health questionnaire accompanied only by standard letter of explanation. Main outcome measures: Response rate and completion rate to questionnaire. Results 5,209 individuals responded with identical rates in both groups (62.1%. Practice, patient age, sex and Townsend score (a postcode based deprivation measure were identified as predictive of response, with higher response related to older age, being female and living in an area with a lower Townsend score (less deprived. Conclusion This RCT, using a large community based sample, found that the offer of entry into a lottery style draw for £100 of High Street vouchers has no effect on response rates to a postal health questionnaire.

  13. Identification and characterization of variant alleles at CODIS STR loci.

    Science.gov (United States)

    Allor, Catherine; Einum, David D; Scarpetta, Marco

    2005-09-01

    Short tandem repeat (STR) profiles from 32,671 individuals generated by the ABI Profiler Plus and Cofiler systems were screened for variant alleles not represented within manufacturer-provided allelic ladders. A total of 85 distinct variants were identified at 12 of the 13 CODIS loci, most of which involve a truncated tetranucleotide repeat unit. Twelve novel alleles, identified at D3S1358, FGA, D18S51, D5S818, D7S820 and TPOX, were confirmed by nucleotide sequence analysis and include both insertions and deletions involving the repeat units themselves as well as DNA flanking the repeat regions. Population genetic data were collected for all variants and frequencies range from 0.0003 (many single observations) to 0.0042 (D7S820 '10.3' in North American Hispanics). In total, the variant alleles identified in this study are carried by 1.6% of the estimated 1 million individuals tested annually in the U.S. for the purposes of parentage resolution. A paternity case involving a recombination event of paternal origin is presented and demonstrates how variant alleles can significantly strengthen the genetic evidence in troublesome cases. In such instances, increased costs and turnaround time associated with additional testing may be eliminated.

  14. A Platform for Interrogating Cancer-Associated p53 Alleles

    Science.gov (United States)

    D’Brot, Alejandro; Kurtz, Paula; Regan, Erin; Jakubowski, Brandon; Abrams, John M

    2016-01-01

    p53 is the most frequently mutated gene in human cancer. Compelling evidence argues that full transformation involves loss of growth suppression encoded by wild-type p53 together with poorly understood oncogenic activity encoded by missense mutations. Furthermore, distinguishing disease alleles from natural polymorphisms is an important clinical challenge. To interrogate the genetic activity of human p53 variants, we leveraged the Drosophila model as an in vivo platform. We engineered strains that replace the fly p53 gene with human alleles, producing a collection of stocks that are, in effect, ‘humanized’ for p53 variants. Like the fly counterpart, human p53 transcriptionally activated a biosensor and induced apoptosis after DNA damage. However, all humanized strains representing common alleles found in cancer patients failed to complement in these assays. Surprisingly, stimulus-dependent activation of hp53 occurred without stabilization, demonstrating that these two processes can be uncoupled. Like its fly counterpart, hp53 formed prominent nuclear foci in germline cells but cancer-associated p53 variants did not. Moreover, these same mutant alleles disrupted hp53 foci and inhibited biosensor activity, suggesting that these properties are functionally linked. Together these findings establish a functional platform for interrogating human p53 alleles and suggest that simple phenotypes could be used to stratify disease variants. PMID:26996664

  15. Genetically determined variation in stress responsiveness in rainbow trout: behavior and neurobiology.

    Science.gov (United States)

    Schjolden, Joachim; Winberg, Svante

    2007-01-01

    It is becoming increasingly recognized that the diversity in stressors, their intensity, predictability and the context in which they are experienced, will result in behavioral and physiological responses just as diverse. In addition, stress responses are characterized by individual variations where the physiological and behavioral reactions are associated in such a manner that distinct stress coping styles encompassing suites of correlated traits can be identified. These are often referred to as proactive and reactive stress coping styles. Proactive coping is characterized by more aggression, higher general activity and higher sympathetic activation, whereas reactive coping is characterized by immobility, lack of initiative and a higher parasympathetic/hypothalamic activation. Stable coping styles appear to coexist within populations, and these strategies appear to be largely innate. Moreover, the physiological and behavioral traits of coping styles appear to be heritable. These stress coping styles have proven to play a major role in competitive ability and subsequent social position in different species of vertebrates. However, there are also studies showing that social position can affect parameters encompassing the stress coping style of individuals. In this regard it is important, but not always easy, to distinguish between causes and effects of behavioral and physiological responses to stressors. The question raised is to what extent and rigidness stress coping styles are guided by genetic factors. PMID:17914254

  16. SLAMF1 regulation of chemotaxis and autophagy determines CLL patient response

    Science.gov (United States)

    Bologna, Cinzia; Buonincontri, Roberta; Serra, Sara; Vaisitti, Tiziana; Audrito, Valentina; Brusa, Davide; Pagnani, Andrea; Coscia, Marta; D’Arena, Giovanni; Mereu, Elisabetta; Piva, Roberto; Furman, Richard R.; Rossi, Davide; Gaidano, Gianluca; Terhorst, Cox; Deaglio, Silvia

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is a variable disease; therefore, markers to identify aggressive forms are essential for patient management. Here, we have shown that expression of the costimulatory molecule and microbial sensor SLAMF1 (also known as CD150) is lost in a subset of patients with an aggressive CLL that associates with a shorter time to first treatment and reduced overall survival. SLAMF1 silencing in CLL-like Mec-1 cells, which constitutively express SLAMF1, modulated pathways related to cell migration, cytoskeletal organization, and intracellular vesicle formation and recirculation. SLAMF1 deficiency associated with increased expression of CXCR4, CD38, and CD44, thereby positively affecting chemotactic responses to CXCL12. SLAMF1 ligation with an agonistic monoclonal antibody increased ROS accumulation and induced phosphorylation of p38, JNK1/2, and BCL2, thereby promoting the autophagic flux. Beclin1 dissociated from BCL2 in response to SLAMF1 ligation, resulting in formation of the autophagy macrocomplex, which contains SLAMF1, beclin1, and the enzyme VPS34. Accordingly, SLAMF1-silenced cells or SLAMF1lo primary CLL cells were resistant to autophagy-activating therapeutic agents, such as fludarabine and the BCL2 homology domain 3 mimetic ABT-737. Together, these results indicate that loss of SLAMF1 expression in CLL modulates genetic pathways that regulate chemotaxis and autophagy and that potentially affect drug responses, and suggest that these effects underlie unfavorable clinical outcome experienced by SLAMF1lo patients. PMID:26619119

  17. 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...

  18. Engaging Environmental Turbulence : Organizational Determinants for Repetitive, Quick and Adequate Responses

    NARCIS (Netherlands)

    E.J. Waard (Erik)

    2010-01-01

    textabstractIn the academic debate on dealing with environmental turbulence survival or organizational success is being presented as a result of activating dynamic capabilities to repetitively create temporary advantages. A practical question left open in this debate is which organizational determin

  19. SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Felix Krueger

    2016-06-01

    Full Text Available Sequencing reads overlapping polymorphic sites in diploid mammalian genomes may be assigned to one allele or the other. This holds the potential to detect gene expression, chromatin modifications, DNA methylation or nuclear interactions in an allele-specific fashion. SNPsplit is an allele-specific alignment sorter designed to read files in SAM/BAM format and determine the allelic origin of reads or read-pairs that cover known single nucleotide polymorphic (SNP positions. For this to work libraries must have been aligned to a genome in which all known SNP positions were masked with the ambiguity base ’N’ and aligned using a suitable mapping program such as Bowtie2, TopHat, STAR, HISAT2, HiCUP or Bismark. SNPsplit also provides an automated solution to generate N-masked reference genomes for hybrid mouse strains based on the variant call information provided by the Mouse Genomes Project. The unique ability of SNPsplit to work with various different kinds of sequencing data including RNA-Seq, ChIP-Seq, Bisulfite-Seq or Hi-C opens new avenues for the integrative exploration of allele-specific data.

  20. SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes [version 2; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Felix Krueger

    2016-07-01

    Full Text Available Sequencing reads overlapping polymorphic sites in diploid mammalian genomes may be assigned to one allele or the other. This holds the potential to detect gene expression, chromatin modifications, DNA methylation or nuclear interactions in an allele-specific fashion. SNPsplit is an allele-specific alignment sorter designed to read files in SAM/BAM format and determine the allelic origin of reads or read-pairs that cover known single nucleotide polymorphic (SNP positions. For this to work libraries must have been aligned to a genome in which all known SNP positions were masked with the ambiguity base 'N' and aligned using a suitable mapping program such as Bowtie2, TopHat, STAR, HISAT2, HiCUP or Bismark. SNPsplit also provides an automated solution to generate N-masked reference genomes for hybrid mouse strains based on the variant call information provided by the Mouse Genomes Project. The unique ability of SNPsplit to work with various different kinds of sequencing data including RNA-Seq, ChIP-Seq, Bisulfite-Seq or Hi-C opens new avenues for the integrative exploration of allele-specific data.

  1. Association of polymorphic alleles of CTLA4 with inflammatory bowel disease in the Japanese

    Institute of Scientific and Technical Information of China (English)

    Haruhisa Machida; Ikuo Murata; Shigeru Kohno; Kazuhiro Tsukamoto; Chun-Yang Wen; Yukiko Narumi; Saburou Shikuwa; Hajime Isomoto; Fuminao Takeshima; Yohei Mizuta; Norio Niikawa

    2005-01-01

    AIM: To examine an association between the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis (UC) and Crohn's disease (CD) in the Japanese.METHODS: We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms (SNPs)in CTLA4, such as C-318T in the promoter region, A+49G in exon 1 and G+6230A in the 3' untranslated region (3'-UTR) by a PCR-restriction fragment length polymorphism method, and to an (AT)n repeat polymorphism in 3'-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using χ2 and Fisher exact tests.RESULTS: The frequency of "A/A" genotype at the G+6230A SNP site was statistically lower in UC patients than in controls (3.7% vs 11.0%, P= 0.047, odds ratio (OR) = 0.311). Moreover, the frequency of"G/G" genotype at the A+49G SNP site was significantly higher in CD patients with fistula (48.6%) than those without it (26.2%)(P = 0.0388, OR=2.67).CONCLUSION: The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.

  2. Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma

    OpenAIRE

    Hong, Jun Young; Chung, Yutein; Steenrod, Jessica; Chen, Qiang; Lei, Jing; Comstock, Adam T.; Goldsmith, Adam M.; Bentley, J. Kelley; Sajjan, Uma S.; Hershenson, Marc B.

    2014-01-01

    Background The mechanisms by which viruses cause asthma exacerbations are not precisely known. Previously, we showed that, in ovalbumin (OVA)-sensitized and -challenged mice with allergic airway inflammation, rhinovirus (RV) infection increases type 2 cytokine production from alternatively-activated (M2) airway macrophages, enhancing eosinophilic inflammation and airways hyperresponsiveness. In this paper, we tested the hypothesis that IL-4 signaling determines the state of macrophage activat...

  3. Direct assessment of P-glycoprotein efflux to determine tumor response to chemotherapy

    OpenAIRE

    Patwardhan, Gauri; Gupta, Vineet; Huang, Juowen; Gu, Xin; Liu, Yong-Yu

    2010-01-01

    Multidrug resistance is a major impediment to the success of cancer chemotherapy. The overproduced P-glycoprotein that extrudes anticancer drugs from cells, is the most common mechanism detected in multidrug-resistant cancers. Direct measurement of cellular efflux of tumors in vivo, rather than estimation of MDR1 mRNA and P-glycoprotein levels in samples stored or embedded, can functionally characterize the mechanism of drug resistance and determine the choice of anticancer drugs for cancer p...

  4. 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 ...

  5. 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.

  6. Analysis of vibration waveforms of electromechanical response to determine piezoelectric and electrostrictive coefficients.

    Science.gov (United States)

    Izumi, Tatsuya; Hagiwara, Manabu; Hoshina, Takuya; Takeda, Hiroaki; Tsurumi, Takaaki

    2012-08-01

    We developed a possible method to determine both coefficients of piezoelectricity (d) and electrostriction (M) at the same time by a waveform analysis of current and vibration velocity in the resonance state. The waveforms of the current and vibration velocity were theoretically described using the equations of motion and piezoelectric constitutive equations, considering the dissipation effect. The dissipation factor of the d coefficient and M coefficient is dielectric loss tangent tan δ. The waveforms measured in all of the ceramics, such as Pb(Zr,Ti)O(3) (PZT), Pb(Mg,Nb)O(3) (PMN), and 0.8Pb(Mg(1/3)Nb2/3)O(3)-0.2PbTiO(3) (PMN-PT), were well fitted with the calculated waveform. This fitting produced both the d and M coefficients, which agreed with those determined via the conventional methods. Moreover, the respective contributions of both piezoelectricity and electrostriction to the d value determined in the resonance-antiresonance method were clarified. PMID:22899111

  7. Determination of the onset of beta-methyl-digoxin action by potentiation of the adenosine response in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Fukuda,Tamotsu

    1985-06-01

    Full Text Available The onset of beta-methyl-digoxin action was investigated by the potentiation of the adenosine response in guinea pigs and rats, and compared with that of digoxin and dipyridamole. A number of i.v. infusions of adenosine were given to determine the mean control adenosine response and its 95% confidence limits. After oral administration of the drugs, successive infusions of adenosine were continued until a drug-induced potentiation of the adenosine response was observed. The time of appearance of the potentiated adenosine response was marked as the onset of action of the drugs. The onset of action in guinea pigs was 9 to 12 min for 0.2 to 0.4 mg/kg of beta-methyl-digoxin, 90 to 100 min for 0.2 mg/kg of digoxin and 25 min for 5 mg/kg of dipyridamole. The maximal potentiation was 48.8 to 53.8% at 18 to 21 min for beta-methyl-digoxin, 74.5% at 130 min for digoxin and 74.8% at 80 min for dipyridamole. Adenosine infused i.v. into rats produced heart block, as in guinea pigs. However, in rats, the adenosine response was not potentiated by beta-methyl-digoxin and digoxin. Dipyridamole at a dose as high as 200 mg/kg produced 25.8% potentiation at 36 min after oral administration to rats.

  8. 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...

  9. Food availability determines the response to pond desiccation in anuran tadpoles.

    Science.gov (United States)

    Enriquez-Urzelai, Urtzi; San Sebastián, Olatz; Garriga, Núria; Llorente, Gustavo A

    2013-09-01

    Food availability and pond desiccation are two of the most studied factors that condition amphibian metamorphosis. It is well known that, when food is abundant, organisms undergo metamorphosis early and when they are relatively large. The capability of anurans to accelerate their developmental rate in response to desiccation is also common knowledge. These two variables must act together in nature, since we know that, as a pond dries, the per capita resources decrease. We conduct an experiment to evaluate the effects of desiccation and food availability separately and in combination in tadpoles of the painted frog (Discoglossus pictus). We demonstrate that food deprivation leads to slow growth rates, which delay metamorphosis and produce smaller size and weight. The capability to accelerate metamorphosis when facing a drying pond is also confirmed, but, nevertheless, with factor interaction (when the pool is drying and resources are scarce) the capacity to respond to desiccation is lost. In addition, slow drying rates are shown to be stressful situations, but not enough to provoke a shortening of the larval period; in fact, the larval period becomes longer. We also demonstrate that the interaction of these factors changes the allometric relationship of different parts of the hind limb, which has implications for the biomechanics of jumping. Due to low mortality rates and an adequate response to both environmental factors, we expect D. pictus to have a great invasive potential in its new Mediterranean distribution area, where lots of temporary and ephemeral ponds are present. PMID:23344427

  10. Genetic Diversity Based on Allozyme Alleles of Chinese Cultivated Rice

    Institute of Scientific and Technical Information of China (English)

    TANG Sheng-xiang; WEI Xing-hua; JIANG Yun-zhu; D S Brar; G S Khush

    2007-01-01

    Genetic diversity was analyzed with 6 632 core rice cultivars selected from 60 282 Chinese rice accessions on the basis of 12 allozyme loci, Pgil, Pgi2, Ampl, Amp2, Amp3, Amp4, Sdh1, Adh1, Est1, Est2, Est5 and Est9, by starch gel electrophoresis. Among the materials examined, 52 alleles at 12 polymorphic loci were identified, which occupied 96.3% of 54 alleles found in cultivated germplasm of O.sativa L. The number of alleles per locus ranged from 2 to 7 with an average of 4.33. The gene diversity (He) each locus varied considerably from 0.017 for Amp4 to 0.583 for Est2 with an average gene diversity (Ht) 0.271, and Shannon-Wiener index from 0.055 to 0.946 with an average of 0.468. The degree of polymorphism (DP) was in a range from 0.9 to 46.9% with an average of 21.4%. It was found that the genetic diversity in japonica (Keng) subspecies was lower in terms of allele's number, Ht and S-W index, being 91.8, 66.2 and 75.7% of indica (Hsien) one, respectively. Significant genetic differentiation between indica and japonica rice has been appeared in the loci Pgil, Amp2, Pgi2, and Est2, with higher average coefficient of genetic differentiation (Gst) 0.635, 0.626, 0.322 and 0.282, respectively. Except less allele number per locus (3.33) for modern cultivars, being 76.9% of landraces, the Ht and S-W index showed in similar between the modern cultivars and the landraces detected. In terms of allozyme, the rice cultivars in the Southwest Plateau and Central China have richer genetic diversity. The present study reveals again that Chinese cultivated rice germplasm has rich genetic diversity, showed by the allozyme allele variation.

  11. Allele-specific DNA methylation reinforces PEAR1 enhancer activity.

    Science.gov (United States)

    Izzi, Benedetta; Pistoni, Mariaelena; Cludts, Katrien; Akkor, Pinar; Lambrechts, Diether; Verfaillie, Catherine; Verhamme, Peter; Freson, Kathleen; Hoylaerts, Marc F

    2016-08-18

    Genetic variation in the PEAR1 locus is linked to platelet reactivity and cardiovascular disease. The major G allele of rs12041331, an intronic cytosine guanine dinucleotide-single-nucleotide polymorphism (CpG-SNP), is associated with higher PEAR1 expression in platelets and endothelial cells than the minor A allele. The molecular mechanism underlying this difference remains elusive. We have characterized the histone modification profiles of the intronic region surrounding rs12041331 and identified H3K4Me1 enhancer-specific enrichment for the region that covers the CpG-SNP. Interestingly, methylation studies revealed that the CpG site is fully methylated in leukocytes of GG carriers. Nuclear protein extracts from megakaryocytes, endothelial cells, vs control HEK-293 cells show a 3-fold higher affinity for the methylated G allele compared with nonmethylated G or A alleles in a gel electrophoretic mobility shift assay. To understand the positive relationship between methylation and gene expression, we studied DNA methylation at 4 different loci of PEAR1 during in vitro megakaryopoiesis. During differentiation, the CpG-SNP remained fully methylated, while we observed rapid methylation increases at the CpG-island overlapping the first 5'-untranslated region exon, paralleling the increased PEAR1 expression. In the same region, A-allele carriers of rs12041331 showed significantly lower DNA methylation at CGI1 compared with GG homozygote. This CpG-island contains binding sites for the methylation-sensitive transcription factor CTCF, whose binding is known to play a role in enhancer activation and/or repression. In conclusion, we report the molecular characterization of the first platelet function-related CpG-SNP, a genetic predisposition that reinforces PEAR1 enhancer activity through allele-specific DNA methylation. PMID:27313330

  12. The inheritance of resistance alleles in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sreeram V Ramagopalan

    2007-09-01

    Full Text Available Multiple sclerosis (MS is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. HLA-DRB1*15 and HLA-DRB1*17-bearing haplotypes and interactions at the HLA-DRB1 locus increase risk of MS but it has taken large samples to identify resistance HLA-DRB1 alleles. In this investigation of 7,093 individuals from 1,432 MS families, we have assessed the validity, mode of inheritance, associated genotypes, and the interactions of HLA-DRB1 resistance alleles. HLA-DRB1*14-, HLA-DRB1*11-, HLA-DRB1*01-, and HLA-DRB1*10-bearing haplotypes are protective overall but they appear to operate by different mechanisms. The first type of resistance allele is characterised by HLA-DRB1*14 and HLA-DRB1*11. Each shows a multiplicative mode of inheritance indicating a broadly acting suppression of risk, but a different degree of protection. In contrast, a second type is exemplified by HLA-DRB1*10 and HLA-DRB1*01. These alleles are significantly protective when they interact specifically in trans with HLA-DRB1*15-bearing haplotypes. HLA-DRB1*01 and HLA-DRB1*10 do not interact with HLA-DRB1*17, implying that several mechanisms may be operative in major histocompatibility complex-associated MS susceptibility, perhaps analogous to the resistance alleles. There are major practical implications for risk and for the exploration of mechanisms in animal models. Restriction of antigen presentation by HLA-DRB1*15 seems an improbably simple mechanism of major histocompatibility complex-associated susceptibility.

  13. 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.

  14. 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.

  15. Discrimination of HLA null and low expression alleles by cytokine-induced secretion of recombinant soluble HLA.

    Science.gov (United States)

    Hinrichs, Jan; Figueiredo, Constança; Hirv, Kaimo; Mytilineos, Joannis; Blasczyk, Rainer; Horn, Peter A; Eiz-Vesper, Britta

    2009-04-01

    The disruption of disulfide bridges can decrease or abolish the cell surface expression of HLA class I molecules. Such disulfide bridges are formed by cysteine residues between amino acid (aa) positions 101/164 (alpha(2) domain) and 203/259 (alpha(3) domain). Sequence alterations in codons 101, 164, 203 and 259 have been observed in eleven HLA-A molecules. All of these variants except of A*3014L and A*3211Q have been reported to result in null expression alleles. In the case of HLA-A*3014L, a transversion at nucleotide position 563 replaces cysteine by serine at position 164 of the mature polypeptide. HLA-A*3014L is not detectable by standard microlymphocytotoxicity assay. To verify low or non-expression of this allele, we cloned soluble HLA-A*3014L and the reference allele HLA-A*3001 into a eukaryotic expression vector and transfected K562, C1R and HEK293 cells. Expression of soluble HLA-A*3014L and HLA-A*3001 was measured in the supernatants of transfected and untransfected cells incubated with or without IFN-gamma and/or TNF-alpha using a W6/32 and anti-beta(2)-microglobulin-based sandwich ELISA. Expression of mRNA transcripts of both alleles was determined by real-time RT-PCR. HLA-A*3014L was not detected in the supernatant of unstimulated transfectants. Stimulation with IFN-gamma and/or TNF-alpha led to an increase of HLA-A*3014L secretion to a detectable level and increased HLA-A*3001 expression up to 8-fold, but did not show any difference in the increase of mRNA levels between HLA-A*3014L and A*3001. Because of this lack of any difference in the mRNA transcription, the protein expression defect is most likely caused by the missing disulfide bond formation in the alpha2 domain. Thus, exposing the cells to cytokine stress allows to distinguish between low- and non-expressed alleles and to classify alleles with a questionable expression pattern (Q alleles). Classifying HLA alleles in expressed and non-expressed variants is essential for matching assessments

  16. Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans

    Directory of Open Access Journals (Sweden)

    Chandak Giriraj R

    2006-10-01

    Full Text Available Abstract Background The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. Methods We genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. Results The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001, whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015. Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003. This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07. Conclusion This is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated

  17. Allele-specific gene silencing in two mouse models of autosomal dominant skeletal myopathy.

    Directory of Open Access Journals (Sweden)

    Ryan E Loy

    Full Text Available We explored the potential of mutant allele-specific gene silencing (ASGS in providing therapeutic benefit in two established mouse models of the autosomal dominantly-inherited muscle disorders, Malignant Hyperthermia (MH and Central Core Disease (CCD. Candidate ASGS siRNAs were designed and validated for efficacy and specificity on ryanodine receptor (RyR1 cDNA mini-constructs expressed in HEK293 cells using RT-PCR- and confocal microscopy-based assays. In vivo delivery of the most efficacious identified siRNAs into flexor digitorum brevis (FDB muscles was achieved by injection/electroporation of footpads of 4-6 month old heterozygous Ryr1(Y524S/+ (YS/+ and Ryr1(I4895T/+ (IT/+ knock-in mice, established mouse models of MH with cores and CCD, respectively. Treatment of IT/+ mice resulted in a modest rescue of deficits in the maximum rate (∼38% rescue and magnitude (∼78% of ligand-induced Ca(2+ release that occurred in the absence of a change in the magnitude of electrically-evoked Ca(2+ release. Compared to the difference between the caffeine sensitivity of Ca(2+ release in FDB fibers from YS/+ and WT mice treated with SCR siRNA (EC(50: 1.1 mM versus 4.4 mM, respectively, caffeine sensitivity was normalized in FDB fibers from YS/+ mice following 2 (EC(50: 2.8 mM and 4 week (EC(50: 6.6 mM treatment with YS allele-specific siRNA. Moreover, the temperature-dependent increase in resting Ca(2+ observed in FDB fibers from YS/+ mice was normalized to WT levels after 2 weeks of treatment with YS allele-specific siRNA. As determined by quantitative real time PCR, the degree of functional rescue in YS/+ and IT/+ mice correlated well with the relative increase in fractional WT allele expression.

  18. 3-D Confocal microscopy track analysis: a promising tool for determining CR-39 response function

    Energy Technology Data Exchange (ETDEWEB)

    Vaginay, F. E-mail: francois.vaginay@univ-fcomte.fr; Fromm, M.; Pusset, D.; Meesen, G.; Chambaudet, A.; Poffijn, A

    2001-06-01

    A new method based on the use of the confocal microscope is described in order to evaluate the CR-39 response function for Li-7 ions with an incident energy of 10.77 MeV. This method uses the formulations developed by Fromm et al. and considers two etching velocities: V{sub B} represents the bulk etch rate and remains constant, and V{sub T} the track etch rate, which varies along the particle's path. The confocal microscope seems to bring big improvements for track analysis. The first results of V{sub T} versus the particle range are presented and compared with the curves obtained by the sequential etching method. The obtained V{sub T} are plotted and compared to LET, REL{sub 350} and the cumulative radial dose.

  19. Three-state interactions determine the second-order nonlinear optical response

    CERN Document Server

    Perez-Moreno, Javier

    2016-01-01

    Using the sum-rules, the sum-over-states expression for the diagonal term of first hyperpolarizability can be expressed as the sum of three-state interaction terms. We study the behavior of a generic three-state term to show that is possible to tune the contribution of resonant terms by tuning the spectrum of the molecule. When extrapolated to the off-resonance regime, the three-state interaction terms are shown to behave in a similar manner as the three-level model used to derive the fundamental limits. We finally show that most results derived using the three-level ansatz are general, and apply to molecules where more than three levels contribute to the second-order nonlinear response or/and far from optimization.

  20. In situ protocol for the determination of dose-response effect of low-fluoride dentifrices on enamel remineralization

    Directory of Open Access Journals (Sweden)

    Rebeca Lima AFONSO

    2013-12-01

    Full Text Available No in situ protocol has assessed the dose-response effects of fluoride dentifrices involving low-fluoride formulations. Objective: To assess the ability of an in situ remineralization model in determining dose-response effects of dentifrices containing low fluoride concentrations ([F] on bovine enamel. Material and Methods: Volunteers wore palatal appliances containing demineralized enamel blocks and brushed their teeth and devices with the dentifrices supplied (double-blind, crossover protocol separately for 3 and 7 days. Surface hardness (SH, integrated subsurface hardness (ΔKHN and [F] in enamel were determined. Data were analyzed by ANOVA, Tukey's test and Pearson's correlation (p<0.05. Results: Dose-response relationships were verified between [F] in dentifrices and SH, ΔKHN and enamel [F]. Higher correlation coefficients between enamel [F] and SH and ΔKHN were obtained for the 3-day period. Significant differences in SH and ΔKHN were observed among all groups for the 3-day period, but not between 0-275, 275-550, and 550-1,100 µg F/g dentifrices for the 7-day period, nor between 3- and 7-day periods for the 1,100 µg F/g groups. Conclusions: Considering that the peak remineralization capacity of the conventional dentifrice (1,100 µg F/g was achieved in 3 days, this experimental period could be used in future studies assessing new dentifrice formulations, especially at low-fluoride concentrations.

  1. Population studies of the human V kappa A18 gene polymorphism in Caucasians, blacks and Eskimos. New functional alleles and evidence for evolutionary selection of a more restricted antibody repertoire

    DEFF Research Database (Denmark)

    Juul, L; Hougs, L; Andersen, V;

    1997-01-01

    and sequenced four apparently functional alleles and determined the gene frequencies in three well-defined populations: Danish Caucasians, eastern Greenland Eskimos and Mozambican blacks. The A18b allele that was recently described in Native American Navajos by Atkinson et al. was found in all three populations...

  2. A generalized model for determining the thermal response to a nuclear waste repository

    International Nuclear Information System (INIS)

    A generalized integral method for determining unsteady, one-dimensional heat conduction in multi-layer systems with arbitrary thermophysical properties has been developed. Temperature distributions within each sublayer are represented with approximating polynomials, and the source of heat can exist at any location in the system. The recurrence relations between coefficients of temperature profiles are generalized so that any number of sublayers can be handled. Although the model is a general one, it has been applied to temperature independent thermal properties in this study to illustrate the efficiency of the computations. The model is exercised for the stratigraphy of the proposed National High Level Nuclear Waste Repository at Yucca Mountain, Nevada. Results indicate that the model provides a powerful tool for both bounding the coupled thermal and hydrologic performance of the repository and assessing thermal uncertainties over both short and long time scales of repository operations

  3. 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

  4. Allele-specific expression of the low density lipoprotein receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Minnich, A.; Lussier-Cacan, S.; Roy, M. [Clincial Research Institute of Montreal, Quebec (Canada)

    1994-09-01

    Approximately 60% of familial hypercholesterolemia (FH) in French Canadians is due to a > 10 kb deletion of the promoter region of the gene encoding the low density lipoprotein (LDL) receptor (LDL-R), allowing determination of the influence of a single LDL-R allele on phenotypic expression of FH. Normal allele haplotypes of approximately 250 heterozygotes were determined with 7 RFLPs. In vitro maximal LDL-R activity of blood lymphocytes from a subset of approximately 150 heterozygotes, measured by immunocytofluorometry, was significantly higher (20 to 30%) in subjects with LDL-R normal allele haplotype G (n=11), and O (n=7) compared to the most frequent haplotype F (n=43), while no differences were observed among F, E (n=11), and the 2 other most prevalent haplotypes (n=43). LDL-R mRNA in these lymphocytes was significantly elevated 2.3-, 1.7-, and 1.8- fold, in G, O, and E, respectively, compared to F, while no significant differences were apparent between F and the other two most frequent haplotyes. Large interindividual variability in lymphocyte LDL-R mRNA levels and activity was observed even among subjects with the same LDL-R normal allele haplotype. However, maximally induced lymphocyte LDL-R mRNA levels correlated poorly with levels measured in freshly isolated cells (n=14). Relative to haplotype F (n=47 women (W), 39 men (M)), mean plasma LDL cholesterol levels adjusted for age and apolipoprotein E genotype were 5-10% lower in men and women with haplotypes G (n=16 W, 12 M) and O (n=8 W, 6 M), and 20% lower in 7 W with haplotype E. These results suggest that (1) normal LDL-R allele haplotype G and O may contain sequence variations which confer relatively high gene expression and (2) environmental and genetic influences other than the LDL-R gene contribute substantially to variability in LDL-R expression and plasma LDL cholesterol levels in French Canadian FH heterozygotes.

  5. Original encounter with antigen determines antigen-presenting cell imprinting of the quality of the immune response in mice.

    Directory of Open Access Journals (Sweden)

    Valérie Abadie

    Full Text Available BACKGROUND: Obtaining a certain multi-functionality of cellular immunity for the control of infectious diseases is a burning question in immunology and in vaccine design. Early events, including antigen shuttling to secondary lymphoid organs and recruitment of innate immune cells for adaptive immune response, determine host responsiveness to antigens. However, the sequence of these events and their impact on the quality of the immune response remain to be elucidated. Here, we chose to study Modified Vaccinia virus Ankara (MVA which is now replacing live Smallpox vaccines and is proposed as an attenuated vector for vaccination strategies against infectious diseases. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed in vivo mechanisms triggered following intradermal (i.d. and intramuscular (i.m. Modified Vaccinia virus Ankara (MVA administration. We demonstrated significant differences in the antigen shuttling to lymphoid organs by macrophages (MPhis, myeloid dendritic cells (DCs, and neutrophils (PMNs. MVA i.d. administration resulted in better antigen distribution and more sustained antigen-presenting cells (APCs recruitment into draining lymph nodes than with i.m. administration. These APCs, which comprise both DCs and MPhis, were differentially involved in T cell priming and shaped remarkably the quality of cytokine-producing virus-specific T cells according to the entry route of MVA. CONCLUSIONS/SIGNIFICANCE: This study improves our understanding of the mechanisms of antigen delivery and their consequences on the quality of immune responses and provides new insights for vaccine development.

  6. Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival.

    Science.gov (United States)

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

    2016-05-27

    A delay in the completion of metaphase induces a stress response that inhibits further cell proliferation or induces apoptosis. This response is thought to protect against genomic instability and is important for the effects of anti-mitotic cancer drugs. Here, we show that mitotic arrest induces a caspase-dependent DNA damage response (DDR) at telomeres in non-apoptotic cells. This pathway is under the control of Mcl-1 and other Bcl-2 family proteins and requires caspase-9, caspase-3/7 and the endonuclease CAD/DFF40. The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a DDR that involves DNA-dependent protein kinase (DNA-PK). Suppression of mitotic telomere damage by enhanced expression of TRF2, or the inhibition of either caspase-3/7 or DNA-PK during mitotic arrest, promotes subsequent cell survival. Thus, we demonstrate that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis.

  7. Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival.

    Science.gov (United States)

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

    2016-01-01

    A delay in the completion of metaphase induces a stress response that inhibits further cell proliferation or induces apoptosis. This response is thought to protect against genomic instability and is important for the effects of anti-mitotic cancer drugs. Here, we show that mitotic arrest induces a caspase-dependent DNA damage response (DDR) at telomeres in non-apoptotic cells. This pathway is under the control of Mcl-1 and other Bcl-2 family proteins and requires caspase-9, caspase-3/7 and the endonuclease CAD/DFF40. The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a DDR that involves DNA-dependent protein kinase (DNA-PK). Suppression of mitotic telomere damage by enhanced expression of TRF2, or the inhibition of either caspase-3/7 or DNA-PK during mitotic arrest, promotes subsequent cell survival. Thus, we demonstrate that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. PMID:27230693

  8. 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.

  9. Determining the precise cerebral response to acupuncture: an improved FMRI study.

    Directory of Open Access Journals (Sweden)

    Hua Liu

    Full Text Available BACKGROUND: In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects' psychological attitude to acupuncture and their physical state are the three most confounding factors. OBJECTIVE: To obtain more precise and accurate cerebral fMRI mapping of acupuncture. DESIGN AND SETTING: A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China. PARTICIPANTS: Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D. INTERVENTIONS: Group A received real acupuncture (RA and treatment instruction (TI; Group B received RA and non-treatment instruction (NI; Group C received sham acupuncture (SA and TI; Group D received SA and NI. RESULTS: Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas. CONCLUSIONS: The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results.

  10. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    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 TCD50 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

  11. 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.

  12. Fabrication of multi-parametric platforms based on nanocone arrays for determination of cellular response

    Directory of Open Access Journals (Sweden)

    Lindarti Purwaningsih

    2011-09-01

    Full Text Available Cellular response to both surface topography and surface chemistry has been studied for several years. However, most of the studies focus on only one of the two parameters and do not consider their possible synergistic effects. Here, we report on a fabrication method for nanostructured surfaces composed of highly ordered arrays of silica nanocones with gold tips. By using a combination of block copolymer nanolithography, electroless deposition, and reactive ion etching several parameters such as structure height and structure distance could easily be adjusted to the desired values. The gold tips allow for easy functionalization of the substrates through a thiol linker system. Improved neural cell adhesion can be obtained and is dependent on the nature of the nanocone surface, thus illustrating the influence of different surface topographies on the nanometer length scale, on a complex cellular behavior such as cell adhesion. Substrate and surface functionality are shown to last over several days, leading to the conclusion that the features of our substrates can also be used for longer term experiments. Finally, initial neural cell adhesion is found to be more prominent on substrates with short intercone distances, which is an important finding for research dealing with the reactions of neuron-like tissue in the immediate moments after direct contact with an implanted surface.

  13. Distribution of two western clapper rail races as determined by responses to taped calls

    Science.gov (United States)

    Tomlinson, R.E.; Todd, R.L.

    1973-01-01

    During 1969 and 1970, surveys of the endangered Yuma Clapper Rail were conducted using taped calls to elicit responses from the birds. During the two summers, more than 158 Yuma clappers were located in cattailtule marshes along the Colorado River south of Needles, California, to the International Boundary, a distance of about 240 miles. Clappers (probably of the same race) were also found in estuarian marshes of the Colorado River Delta of Mexico; in the Salton Sea; in two freshwater marsh areas near Phoenix, Arizona; and in two freshwater marshes adjacent to the lower Gila River near Tacna, Arizona.....Populations of Sonora Clapper Rails were discovered as permanent residents in five separate mangrove swamps along the west coast of Mexico in the vicinity of Kino Bay, Sonora. These observations were farther north than any heretofore reported for the race R. l. rhizophorae, and the swamps also represent the extreme northward limit of mangroves in Sonora.....During the winter, Yuma clappers did not respond to taped calls north of the International Boundary, whereas clappers along the coast of Sonora readily answered the calls during the same period of time. We conclude that most Yuma Clapper Rails migrate from their summer habitat along the Colorado River in September and do not return to the breeding areas until late April.

  14. Selective pressure for allelic diversity in SeM of Streptococcus equi does not affect immunoreactive proteins SzPSe or Se18.9.

    Science.gov (United States)

    Ijaz, Muhammad; Velineni, Sridhar; Timoney, John F

    2011-07-01

    Streptococcus equi, a clone or biovar of an ancestral Streptococcus zooepidemicus of Lancefield group C causes equine strangles, a highly contagious tonsillitis and lymphadenitis of the head and neck. At least 74 alleles based on N-terminal amino acid sequence of the anti-phagocytic SeM have been observed among isolates of S. equi from N. America, Europe and Japan. A d(N)/d(S) ratio of 5.93 for the 5' region of sem is indicative of positive selective pressure. The aim of this study was to determine whether variations in SeM were accompanied by variations in the surface exposed SzPSe and secreted Se18.9, both of which bind to equine tonsillar epithelium and, along with SeM, elicit strong nasopharyngeal IgA responses during convalescence. Sequences of genes for these proteins from 25 S. equi expressing 19 different SeM alleles isolated over 40 years in different countries were compared. No variation was observed in szpse, except for an Australian isolate with a deletion of a single repeat in the 3' end of the gene. Interestingly, only two SNP loci were detected in se18.9 compared to 93 and 55 in sem and szpse, respectively. The high frequency of nucleotide substitutions in szpse may be related to its mosaic structure since this gene in S. zooepidemicus exists in a variety of combinations of sequence segments and has a central hypervariable region that includes exogenous DNA sequence based on an atypical G-C percentage. In summary, the results of this study document very different responses of streptococcal genes for 3 immunoreactive proteins to selection pressure of the nasopharyngeal mucosal immune response.

  15. Impact of autoimmune risk alleles on the immune system

    OpenAIRE

    Ray, John P.; Hacohen, Nir

    2015-01-01

    Genetic analyses of autoimmune diseases have revealed hundreds of disease-associated DNA variants, but the identity and function of the causal variants are understudied and warrant deeper mechanistic studies. Here, we highlight methods for deciphering how alleles that are associated with autoimmune disease alter the human immune system, and suggest strategies for future autoimmune genetic research.

  16. Disease-Causing Allele-Specific Silencing by RNA Interference

    Directory of Open Access Journals (Sweden)

    Hirohiko Hohjoh

    2013-04-01

    Full Text Available Small double-stranded RNAs (dsRNAs of approximately 21-nucleotides in size, referred to as small interfering RNA (siRNA duplexes, can induce sequence-specific posttranscriptional gene silencing, or RNA interference (RNAi. Since chemically synthesized siRNA duplexes were found to induce RNAi in mammalian cells, RNAi has become a powerful reverse genetic tool for suppressing the expression of a gene of interest in mammals, including human, and its application has been expanding to various fields. Recent studies further suggest that synthetic siRNA duplexes have the potential for specifically inhibiting the expression of an allele of interest without suppressing the expression of other alleles, i.e., siRNA duplexes likely confer allele-specific silencing. Such gene silencing by RNAi is an advanced technique with very promising applications. In this review, I would like to discuss the potential utility of allele-specific silencing by RNAi as a therapeutic method for dominantly inherited diseases, and describe possible improvements in siRNA duplexes for enhancing their efficacy.

  17. 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

    2015-01-01

    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. PMID:25966202

  18. Estimating the age of alleles by use of intraallelic variability

    Energy Technology Data Exchange (ETDEWEB)

    Slatkin, M.; Rannala, B. [Univ of California, Berkeley, CA (United States)

    1997-02-01

    A method is presented for estimating the age of an allele by use of its frequency and the extent of variation among different copies. The method uses the joint distribution of the number of copies in a population sample and the coalescence times of the intraallelic gene genealogy conditioned on the number of copies. The linear birth-death process is used to approximate the dynamics of a rare allele in a finite population. A maximum-likelihood estimate of the age of the allele is obtained by Monte Carlo integration over the coalescence times. The method is applied to two alleles at the cystic fibrosis (CFTR) locus, {Delta}F508 and G542X, for which intraallelic variability at three intronic microsatellite loci has been examined. Our results indicate that G542X is somewhat older than {Delta}F508. Although absolute estimates depend on the mutation rates at the microsatellite loci, our results support the hypothesis that {Delta}F508 arose <500 generations ({approx}10,000 years) ago. 32 refs., 4 figs.

  19. Energy response characteristics of several neutron measuring devices determined by using the scattered neutron calibration fields of KAERI

    International Nuclear Information System (INIS)

    The energy response characteristics of several neutron measuring devices used popularly for radiation protection purpose were determined under the simulated neutron calibration fields which was produced by using the radionuclide neutron sources and the shadow objects to scatter and to moderate the fast neutrons emitted from the source. The simulated neutron calibration fields for the calibration of personal dosemeters and survey meters were constructed in the Radiation Calibration Laboratory (RCL) of Korea Atomic Energy Research Institute (KAERI). The radionuclide sources of 252Cf and 241AmBe were used for producing the neutron calibration fields with little different from the method recommended by ISO. The calibration points of interest were behind the shadow objects and the concrete wall in the irradiation room. In order to characterize the neutron calibration fields at the point of test, the spectral neutron fluence rate was determined by means of the Bonner Multi-sphere Spectrometry System (BMSS) and the measured spectra unfolded using the BUNKI code. The dosimetric quantities were derived from the unfolded spectra and used as the reference value to determine the response of each detector. Five kinds of the active detector (three for detector with heavy moderator, one for detector having two spherical tubes with different size, and a TEPC, Tissue Equivalent Proportional Counter) and a TLD as the passive detector were used in this study. The spectral mean energy at the reference calibration points ranged from 0.1 MeV to 3.44 MeV and the dose rate from 0.12 mSv/hr to 4.62 mSv/hr. This paper shows that the big difference, more than four times in case of TLD, in the response of detector with the neutron field spectra should be corrected when the detector is used for monitoring and the dosimetric data of KAERI 's scattered neutron calibration fields. (author)

  20. HPLC method for the simultaneous determination of Levocetirizine, Ambroxol and Montelukast in human Plasma employing response Surface Methodology

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    Ramalingam Suresh

    2012-09-01

    Full Text Available Multiple response simultaneous optimizations employing the Derringer’s desirability function for the development of reversed-phase HPLC methods for the simultaneous determination of Ambroxol(AMB and Montelukast(MLS with Levocetirizine (LCT and Probenecid(PRO as Internal standard in human plasma samples is described. The ranges of the independent variables used for the optimization were MeCN: 30-40%, buffer conc.: 10-20 mM and flow rate: 0.8-1.2 ml/min. The influence of these independent variables on the output responses: capacity factor of the first peak (k1, resolutions (Rs2,3, and Retention time (tR4 were evaluated. Using this strategy, mathematical model were defined and response surface were derived for the separation. The coefficient of determination R2 was more than 0.8972 for all the models. The three responses were simultaneously optimized by using Derringer’s desirability functions. Optimum conditions chosen for assay were MeCN, MeOH, 20.00 mM K2HPO4 (pH 7.0 ± 0.5 solution (32.7:30: 37.3 v/v/v and flow rate 0.85 ml/min. The eluate was monitored using an UV detector set at 230 nm. Peak area ratio of the analyte and internal standard was used for the quantification of plasma samples. Total chromatographic analysis time per sample was approximately 8.665 min. The validation of the proposed analytical method was conducted in accordance to the recommendations of the guidelines ‘‘Bioanalytical method validation’’ [FDA-CDER, 2001]. The method was found to be simple, sensitive and hence it could be applied in bioavailability studies.

  1. Bioturbation determines the response of benthic ammonia-oxidizing microorganisms to ocean acidification.

    Science.gov (United States)

    Laverock, B; Kitidis, V; Tait, K; Gilbert, J A; Osborn, A M; Widdicombe, S

    2013-01-01

    Ocean acidification (OA), caused by the dissolution of increasing concentrations of atmospheric carbon dioxide (CO2) in seawater, is projected to cause significant changes to marine ecology and biogeochemistry. Potential impacts on the microbially driven cycling of nitrogen are of particular concern. Specifically, under seawater pH levels approximating future OA scenarios, rates of ammonia oxidation (the rate-limiting first step of the nitrification pathway) have been shown to dramatically decrease in seawater, but not in underlying sediments. However, no prior study has considered the interactive effects of microbial ammonia oxidation and macrofaunal bioturbation activity, which can enhance nitrogen transformation rates. Using experimental mesocosms, we investigated the responses to OA of ammonia oxidizing microorganisms inhabiting surface sediments and sediments within burrow walls of the mud shrimp Upogebia deltaura. Seawater was acidified to one of four target pH values (pHT 7.90, 7.70, 7.35 and 6.80) in comparison with a control (pHT 8.10). At pHT 8.10, ammonia oxidation rates in burrow wall sediments were, on average, fivefold greater than in surface sediments. However, at all acidified pH values (pH ≤ 7.90), ammonia oxidation rates in burrow sediments were significantly inhibited (by 79-97%; p < 0.01), whereas rates in surface sediments were unaffected. Both bacterial and archaeal abundances increased significantly as pHT declined; by contrast, relative abundances of bacterial and archaeal ammonia oxidation (amoA) genes did not vary. This research suggests that OA could cause substantial reductions in total benthic ammonia oxidation rates in coastal bioturbated sediments, leading to corresponding changes in coupled nitrogen cycling between the benthic and pelagic realms.

  2. Uncontrollable and unpredictable stress interacts with subclinical depression and anxiety scores in determining anxiety response.

    Science.gov (United States)

    Havranek, Michael M; Bolliger, Bianca; Roos, Sophie; Pryce, Christopher R; Quednow, Boris B; Seifritz, Erich

    2016-01-01

    According to learned helplessness theory, uncontrollable stress is assumed to be a critical etiological factor in the pathogenesis of depression. In contrast, unpredictability of stressors is assumed to facilitate the development of sustained anxiety. Despite the frequent co-morbidity of depression and anxiety disorders, these two factors have rarely been studied simultaneously in humans. Therefore, we investigated whether there are interaction effects of uncontrollability and unpredictability on anxiety response in healthy participants. Seventy-nine healthy participants performed a visual dot probe task with emotional faces, while receiving mild electrical shocks in four different conditions (2 × 2 factorial design). In (un)controllable conditions, participants were (not) able to attenuate shock intensity. In (un)predictable conditions, participants were (not) able to anticipate shock occurrence. Before the experiment, participants' subclinical depression and anxiety scores were measured using the Beck Depression and Anxiety Inventories (BDI/BAI). During the experiment, continuous skin conductance and self-reported state anxiety were assessed and attentional biases towards angry faces were calculated. As expected, participants showed greater anxiety in uncontrollable compared to controllable and in unpredictable compared to predictable conditions. Additionally, anxiety decreased within the test sessions in participants with low BDI/BAI scores but not in participants with higher BDI/BAI scores. Most importantly, controllability and predictability interacted with each other and with BDI/BAI scores with regard to anxiety. Our results provide evidence that uncontrollability and unpredictability of stressors not only have separate but also interaction effects on several anxiety measures in susceptible individuals and may provide insights into the psychological mechanisms underlying a depressive/anxiety co-morbidity.

  3. 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.

  4. Determination of the critical residues responsible for cardiac myosin binding protein C's interactions.

    Science.gov (United States)

    Bhuiyan, Md Shenuarin; Gulick, James; Osinska, Hanna; Gupta, Manish; Robbins, Jeffrey

    2012-12-01

    Despite early demonstrations of myosin binding protein C's (MyBP-C) interaction with actin, different investigators have reached different conclusions regarding the relevant and necessary domains mediating this binding. Establishing the detailed structure-function relationships is needed to fully understand cMyBP-C's ability to impact on myofilament contraction as mutations in different domains are causative for familial hypertrophic cardiomyopathy. We defined cMyBP-C's N-terminal structural domains that are necessary or sufficient to mediate interactions with actin and/or the head region of the myosin heavy chain (S2-MyHC). Using a combination of genetics and functional assays, we defined the actin binding site(s) present in cMyBP-C. We confirmed that cMyBP-C's C1 and m domains productively interact with actin, while S2-MyHC interactions are restricted to the m domain. Using residue-specific mutagenesis, we identified the critical actin binding residues and distinguished them from the residues that were critical for S2-MyHC binding. To validate the structural and functional significance of these residues, we silenced the endogenous cMyBP-C in neonatal rat cardiomyocytes (NRC) using cMyBP-C siRNA, and replaced the endogenous cMyBP-C with normal or actin binding-ablated cMyBP-C. Replacement with actin binding-ablated cMyBP-C showed that the mutated protein did not incorporate into the sarcomere normally. Residues responsible for actin and S2-MyHC binding are partially present in overlapping domains but are unique. Expression of an actin binding-deficient cMyBP-C resulted in abnormal cytosolic distribution of the protein, indicating that interaction with actin is essential for the formation and/or maintenance of normal cMyBP-C sarcomeric distribution.

  5. Test and rules for computer programs used in gamma spectrometry for the determination of the efficiency response

    International Nuclear Information System (INIS)

    Several computer programs used in gamma spectrometry for the calcul of the efficiency responses, operational in different programmable analysis systems, were tested with a test called Lot no.2. One of them APOCODE, was elaborated by CEA, the others were provided by system suppliers. This test includes three ranges of energy and efficiency points with which it is possible: to know the methods used for the efficiency determination, to estimate the results, to precise the limits of the methods. With this test, the portability of the logiciel APOCOPE, was proved

  6. Cloning and characterization of genomic DNA sequences of four self-incompatibility alleles in sweet cherry ( Prunus avium L.).

    Science.gov (United States)

    Wünsch, A; Hormaza, J I

    2004-01-01

    Gametophytic self-incompatibility (GSI) in sweet cherry is determined by a locus S with multiple alleles. In the style, the S-locus codifies for an allele-specific ribonuclease ( S-RNase) that is involved in the rejection of pollen that carries the same S allele. In this work we report the cloning and genomic DNA sequence analysis including the 5' flanking regions of four S-RNases of sweet cherry ( Prunus avium L., Rosaceae). DNA from the cultivars Ferrovia, Pico Colorado, Taleguera Brillante and Vittoria was amplified through PCR using primers designed in the conserved sequences of sweet cherry S-RNases. Two alleles were amplified for each cultivar and three of them correspond to three new S-alleles named S23, S24 and S25 present in 'Pico Colorado', 'Vittoria' and 'Taleguera Brillante' respectively. To confirm the identity of the amplified fragments, the genomic DNA of these three putative S-RNases and the allele S12 amplified in the cultivar Ferrovia were cloned and sequenced. The nucleotide and deduced amino-acid sequences obtained contained the structural features of rosaceous S-RNases. The isolation of the 5'-flanking sequences of these four S-RNases revealed a conserved putative TATA box and high similarity among them downstream from that sequence. However, similarity was low compared with the 5'-flanking regions of S-RNases from the Maloideae. S6- and S24-RNase sequences are highly similar, and most amino-acid substitutions among these two RNases occur outside the rosaceous hypervariable region (RHV), but within another highly variable region. The confirmation of the different specificity of these two S-RNases would help elucidate which regions of the S-RNase sequences play a role in S-pollen specific recognition.

  7. Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI frequently occur together in tumor cells.

    Directory of Open Access Journals (Sweden)

    Junichi Soh

    Full Text Available BACKGROUND: Activating mutations in one allele of an oncogene (heterozygous mutations are widely believed to be sufficient for tumorigenesis. However, mutant allele specific imbalance (MASI has been observed in tumors and cell lines harboring mutations of oncogenes. METHODOLOGY/PRINCIPAL FINDINGS: We determined 1 mutational status, 2 copy number gains (CNGs and 3 relative ratio between mutant and wild type alleles of KRAS, BRAF, PIK3CA and EGFR genes by direct sequencing and quantitative PCR assay in over 400 human tumors, cell lines, and xenografts of lung, colorectal, and pancreatic cancers. Examination of a public database indicated that homozygous mutations of five oncogenes were frequent (20% in 833 cell lines of 12 tumor types. Our data indicated two major forms of MASI: 1 MASI with CNG, either complete or partial; and 2 MASI without CNG (uniparental disomy; UPD, due to complete loss of wild type allele. MASI was a frequent event in mutant EGFR (75% and was due mainly to CNGs, while MASI, also frequent in mutant KRAS (58%, was mainly due to UPD. Mutant: wild type allelic ratios at the genomic level were precisely maintained after transcription. KRAS mutations or CNGs were significantly associated with increased ras GTPase activity, as measured by ELISA, and the two molecular changes were synergistic. Of 237 lung adenocarcinoma tumors, the small number with both KRAS mutation and CNG were associated with shortened survival. CONCLUSIONS: MASI is frequently present in mutant EGFR and KRAS tumor cells, and is associated with increased mutant allele transcription and gene activity. The frequent finding of mutations, CNGs and MASI occurring together in tumor cells indicates that these three genetic alterations, acting together, may have a greater role in the development or maintenance of the malignant phenotype than any individual alteration.

  8. Normal ATXN3 allele but not CHIP polymorphisms modulates age at onset in Machado-Joseph Disease

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    Marcondes C. França Jr

    2012-11-01

    Full Text Available Background: Age at onset (AO in Machado-Joseph disease (MJD is closely associated with the length of the CAG repeat at the mutant ATXN3 allele, but there are other intervening factors. Experimental evidence indicates that the normal ATXN3 allele and the C-terminal heat shock protein 70 (Hsp70-interacting protein (CHIP may be genetic modifiers of AO in MJD. Methods: To investigate this hypothesis, we determined the length of normal and expanded CAG repeats at the ATXN3 gene in 210 unrelated patients with MJD. In addition, we genotyped five single nucleotide polymorphisms (SNPs within the CHIP gene. We first compared the frequencies of the different genotypes in two subgroups of patients who were highly discordant for AO after correction for the length of the expanded CAG allele. The possible modifier effect of each gene was then evaluated in a stepwise multiple linear regression model. Results: AO was associated with the length of the expanded CAG allele (r2 = 0.596, p<0.001. Frequencies of the normal CAG repeats at the ATXN3 gene and of CHIP polymorphisms did not differ significantly between groups with highly discordant ages at onset. However, addition of the normal allele improved the model fit for prediction of AO (r2 = 0.604, p=0.014. Indeed, we found that the normal CAG allele at ATXN3 had a positive independent effect on AO. Conclusion: The normal CAG repeat at the ATXN3 gene has a small but significant influence on AO of MJD.

  9. Sex Determination in Papaya

    Science.gov (United States)

    Sex determination is an intriguing system in trioecious papaya. Over the past seven decades various hypotheses, based on the knowledge and information available at the time, have been proposed to explain the genetics of the papaya's sex determination. These include a single gene with three alleles...

  10. Polyphosphate kinase 2: a novel determinant of stress responses and pathogenesis in Campylobacter jejuni.

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    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.

  11. The NQO1 allelic frequency in hindu population of central India varies from that of other Asian populations

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    Parihar Sher

    2010-01-01

    Full Text Available Context: The enzymes encoded by the polymorphic genes NAD (P H: quinone oxidoreductase 1 (NQO1 play an important role in the activation and inactivation of xenobiotics. This enzyme has been associated with xenobiotic related diseases, such as cancer, therapeutic failure and abnormal effects of drugs. Aim: The aim of the present study was to determine the allelic and genotypic frequencies of NQO Hinf I polymorphisms in a Hindu population of Central India. Settings and Design: Polymorphisms of NQO1 were determined in 311 unrelated Hindu individuals. Materials and Methods: Polymerase chain reaction- Restriction Fragment Length Polymorphism (PCR-RFLP analysis in peripheral blood DNA for NQO1 Hinf I polymorphism was used in 311 unrelated Hindu individuals. Statistical Analysis: Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi-square goodness of fit test. Results: The observed allelic frequency was 81% for C (wild and 19% for T (mutant in the total sample. Conclusions: The allelic frequency of "C" was higher than in other Asians (57%, but similar to Caucasians (81%. The genotype distributions for Hinf I polymorphisms were in Hardy-Weinberg equilibrium.

  12. DNA TYPING SYSTEM FOR HLA-A2 ALLELES BY POLYMERASE CHAIN REACTION WITH SEQUENCE-SPECIFIC PRIMERS

    Institute of Scientific and Technical Information of China (English)

    张庆瑞; 翟宁; 耿龙; 宋芳吉

    2001-01-01

    Objectivs. To establish a PCR-SSP method for discriminating as many HLA-A+02 alleles, which could easilybe introduced into a routine laboratory. Methods. In this study we typed HLA-A+02 polymorphisms by a sequence-specific primer (SSP) method,which involved round 1 and round 2 PCR reactions to detect 17 HLA-A+02 alleles (they are HLA-A+0201- 0217 alleles) covering exon 2 and exon 3. Results. We have fmmd that DNA sample concentration and purity were the most important variables in determin-ing the quality of the results. For identiffing correct band size, the size marker used was important. We noticed that different PCR machines pedormed differently. By this method, we detected 20 HLA-A+02 positive genomic DNA samples and found 4 kinds of HLA-A +02 alleles. They were HLA-A +0201, 0203, 0206 and 0210. Condusion. The HLA-A +02 PCR-SSP method was proven to be a reliable and easily applicable typing method. Our results suggest that the SSP described here provides an optimal HLA-A +02 typing technique that may be useful in selecting donor-recipient pairs in bone marrow transplantation between unrelated individuals.

  13. High frequency of the apolipoprotein E *4 allele in African pygmies and most of the African populations in sub-Saharan Africa.

    Science.gov (United States)

    Zekraoui, L; Lagarde, J P; Raisonnier, A; Gérard, N; Aouizérate, A; Lucotte, G

    1997-08-01

    Apolipoprotein E genotypes (alleles *2, *3, and *4) have been determined in 70 Aka Pygmies and 470 unrelated African sub-Saharan subjects. Allele frequencies for Pygmies are 5.7% for APOE*2, 53.6% for APOE*3, and 40.7% for APOE*4, and the global proportions for sub-Saharan subjects are 11.6% for APOE*2, 70.6% for APOE*3, and 17.8% for APOE*4. The frequencies in some ethnic groups are statistically different from the overall mean in the Afar and the Isa, the Ewe (Togo), the Malinke (Guinea), and the Mossi; three ethnic groups have a higher allele frequency of APOE*4 (Fon, 29.4%; Zairians, 33.3%; Tutsi, 38.5%). The APOE*4 allele is considered the ancestral form because of its high frequency in African Pygmies and other aboriginal populations.

  14. Association of HLA-B Alleles With Human Immunodeficiency Virus Type 1 Infection in the Yi Ethnic Group in Sichuan Province

    Institute of Scientific and Technical Information of China (English)

    MING-YAN XU; YI-MING SHAO; KUN-XUE HONG; XIAO-LING DENG; JUN LI; HONG PENG; YU-HUA RUAN; GUAN-MING QIN; HUI XING; XIAO-HU XU

    2004-01-01

    Objective To determine the distribution of HLA-B alleles in the Chinese Yi ethnic group and its association with HIV infection. Methods One hundred and six unrelated healthy HIV negative and 73 HIV positive Chinese Yi ethnic individuals were typed by PCR-SSP. Results The frequency of alleles B*07, B*35, and B*46 were increased in HIV-1-positive subjects, whereas the alleles B*55, B*44 and B*78 were absent in the HIV-infected persons studied. The B*46 allele was present in a significantly higher gene frequency among HIV-1-positive individuals (P=0.02, OR=3.32, 95% CI=1.13-9.78) compared with control subjects. Conclusion HLA-B*46 may be associated with its susceptibility to HIV-1 infections.

  15. Analysis of HIV-1 Vpr determinants responsible for cell growth arrest in Saccharomyces cerevisiae

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    Yao Xiao-Jian

    2004-08-01

    Full Text Available Abstract Background The HIV-1 genome encodes a well-conserved accessory gene product, Vpr, that serves multiple functions in the retroviral life cycle, including the enhancement of viral replication in nondividing macrophages, the induction of G2 cell-cycle arrest, and the modulation of HIV-1-induced apoptosis. We previously reported the genetic selection of a panel of di-tryptophan (W-containing peptides capable of interacting with HIV-1 Vpr and inhibiting its cytostatic activity in Saccharomyces cerevisiae (Yao, X.-J., J. Lemay, N. Rougeau, M. Clément, S. Kurtz, P. Belhumeur, and E. A. Cohen, J. Biol. Chem. v. 277, p. 48816–48826, 2002. In this study, we performed a mutagenic analysis of Vpr to identify sequence and/or structural determinants implicated in the interaction with di-W-containing peptides and assessed the effect of mutations on Vpr-induced cytostatic activity in S. cerevisiae. Results Our data clearly shows that integrity of N-terminal α-helix I (17–33 and α-helix III (53–83 is crucial for Vpr interaction with di-W-containing peptides as well as for the protein-induced cytostatic effect in budding yeast. Interestingly, several Vpr mutants, mainly in the N- and C-terminal domains, which were previously reported to be defective for cell-cycle arrest or apoptosis in human cells, still displayed a cytostatic activity in S. cerevisiae and remained sensitive to the inhibitory effect of di-W-containing peptides. Conclusions Vpr-induced growth arrest in budding yeast can be effectively inhibited by GST-fused di-W peptide through a specific interaction of di-W peptide with Vpr functional domain, which includes α-helix I (17–33 and α-helix III (53–83. Furthermore, the mechanism(s underlying Vpr-induced cytostatic effect in budding yeast are likely to be distinct from those implicated in cell-cycle alteration and apoptosis in human cells.

  16. Allelic divergence and cultivar-specific SSR alleles revealed by capillary electrophoresis using fluorescence-labeled SSR markers in sugarcane

    Science.gov (United States)

    Though sugarcane cultivars (Saccharum spp. hybrids) are complex aneu-polyploid hybrids, genetic evaluation and tracking of clone- or cultivar-specific alleles become possible due to capillary electrophoregrams (CE) using fluorescence-labeled SSR primer pairs. Twenty-four sugarcane cultivars, 12 each...

  17. No severe bottleneck during human evolution: evidence from two apolipoprotein C-II deficiency alleles.

    OpenAIRE

    Xiong, W J; Li, W. H.; Posner, I; Yamamura, T.; Yamamoto, A.; Gotto, A M; Chan, L

    1991-01-01

    The DNA sequences of a Japanese and a Venezuelan apolipoprotein (apo) C-II deficiency allele, of a normal Japanese apo C-II gene, and of a chimpanzee apo C-II gene were amplified by PCR, and their nucleotide sequences were determined on multiple clones of the PCR products. The normal Japanese sequence is identical to--and the chimpanzee sequence differs by only three nucleotides from--a previously published normal Caucasian sequence. In contrast, the two human mutant sequences each differ fro...

  18. Association between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis.

    Science.gov (United States)

    Das, Rituparna; Loughran, Kerry; Murchison, Charles; Qian, Feng; Leng, Lin; Song, Yan; Montgomery, Ruth R; Loeb, Mark; Bucala, Richard

    2016-02-01

    Infection with mosquito-borne West Nile virus (WNV) is usually asymptomatic but can lead to severe WNV encephalitis. The innate cytokine, macrophage migration inhibitory factor (MIF), is elevated in patients with WNV encephalitis and promotes viral neuroinvasion and mortality in animal models. In a case-control study, we examined functional polymorphisms in the MIF locus in a cohort of 454 North American patients with neuroinvasive WNV disease and found patients homozygous for high-expression MIF alleles to be >20-fold (p=0.008) more likely to have WNV encephalitis. These data indicate that MIF is an important determinant of severity of WNV neuropathogenesis and may be a therapeutic target.

  19. HLA-G allele and haplotype frequencies in a healthy population of Iran.

    Science.gov (United States)

    Kuroshli, Zahra; Gourabi, Hamid; Bazrgar, Masoud; Sanati, Mohammad Hossein; Bahraminejad, Elmira; Anisi, Khadije

    2014-06-01

    The human leukocyte antigen (HLA)-G molecule is expressed in cytotrophoblast cells, adult thymic epithelial cells, erythroblasts, pancreatic islets and mesenchymal stem cells. Although, HLA-G expression in allotransplanted patients is correlated with a better allograft acceptance, it is associated with an advanced grade of the tumor in cancer. In addition to the role on the immune system, HLA-G is also involved in successful pregnancy through the embryo implantation, fetal survival and the initial steps of hematopoiesis and angiogenesis. The aim of this study was determination of HLA-G allele frequencies in a healthy population of Iran. In this research, we selected 100 samples from healthy Iranian individuals and henceforth, we used polymerase chain reaction (PCR) followed by sequencing technique for exon 2, 3, 4 and intron 2 of the gene for evaluating the HLA-G alleles frequencies. Investigation of intronic (intron 2) variation is the novelty of our study. The obtained results indicated thirteen alleles of HLA-G in Iranian individuals including G*01:01:01:01, G*01:06, G*01:01:01:06, G*01:01:02, G*01:01:03, G*01:01:05, G*01:01:06, G*01:01:07, G*01:01:08, G*01:03, G*01:04:01, G*01:04:03, and G*01:04:04. According to this study, the most prevalent alleles in the Iranian population were G*01:01:01:01 (52.5%), G*01:01:02 (16%) and G*01:04:03 (14.5%) and also the lowest alleles regarding the frequency were G*01:01:01:06 (0.5%) and G*01:03 (0.5%). The results of G*01:01:01:01 and G*01:04:01 frequencies showed some similarities with the polish population. Our results were similar to the north Indian population for the frequencies of G*01:06 and G*01:01:02. PMID:24659125

  20. Determination of Optimal Parameters for Diffusion Bonding of Semi-Solid Casting Aluminium Alloy by Response Surface Methodology

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    Kaewploy Somsak

    2015-01-01

    Full Text Available Liquid state welding techniques available are prone to gas porosity problems. To avoid this solid state bonding is usually an alternative of preference. Among solid state bonding techniques, diffusion bonding is often employed in aluminium alloy automotive parts welding in order to enhance their mechanical properties. However, there has been no standard procedure nor has there been any definitive criterion for judicious welding parameters setting. It is thus a matter of importance to find the set of optimal parameters for effective diffusion bonding. This work proposes the use of response surface methodology in determining such a set of optimal parameters. Response surface methodology is more efficient in dealing with complex process compared with other techniques available. There are two variations of response surface methodology. The one adopted in this work is the central composite design approach. This is because when the initial upper and lower bounds of the desired parameters are exceeded the central composite design approach is still capable of yielding the optimal values of the parameters that appear to be out of the initially preset range. Results from the experiments show that the pressing pressure and the holding time affect the tensile strength of jointing. The data obtained from the experiment fits well to a quadratic equation with high coefficient of determination (R2 = 94.21%. It is found that the optimal parameters in the process of jointing semi-solid casting aluminium alloy by using diffusion bonding are the pressing pressure of 2.06 MPa and 214 minutes of the holding time in order to achieve the highest tensile strength of 142.65 MPa

  1. Temperature response of mesophyll conductance. Implications for the determination of Rubisco enzyme kinetics and for limitations to photosynthesis in vivo.

    Science.gov (United States)

    Bernacchi, Carl J; Portis, Archie R; Nakano, Hiromi; von Caemmerer, Susanne; Long, Stephen P

    2002-12-01

    CO(2) transfer conductance from the intercellular airspaces of the leaf into the chloroplast, defined as mesophyll conductance (g(m)), is finite. Therefore, it will limit photosynthesis when CO(2) is not saturating, as in C3 leaves in the present atmosphere. Little is known about the processes that determine the magnitude of g(m). The process dominating g(m) is uncertain, though carbonic anhydrase, aquaporins, and the diffusivity of CO(2) in water have all been suggested. The response of g(m) to temperature (10 degrees C-40 degrees C) in mature leaves of tobacco (Nicotiana tabacum L. cv W38) was determined using measurements of leaf carbon dioxide and water vapor exchange, coupled with modulated chlorophyll fluorescence. These measurements revealed a temperature coefficient (Q(10)) of approximately 2.2 for g(m), suggesting control by a protein-facilitated process because the Q(10) for diffusion of CO(2) in water is about 1.25. Further, g(m) values are maximal at 35 degrees C to 37.5 degrees C, again suggesting a protein-facilitated process, but with a lower energy of deactivation than Rubisco. Using the temperature response of g(m) to calculate CO(2) at Rubisco, the kinetic parameters of Rubisco were calculated in vivo from 10 degrees C to 40 degrees C. Using these parameters, we determined the limitation imposed on photosynthesis by g(m). Despite an exponential rise with temperature, g(m) does not keep pace with increased capacity for CO(2) uptake at the site of Rubisco. The fraction of the total limitations to CO(2) uptake within the leaf attributable to g(m) rose from 0.10 at 10 degrees C to 0.22 at 40 degrees C. This shows that transfer of CO(2) from the intercellular air space to Rubisco is a very substantial limitation on photosynthesis, especially at high temperature. PMID:12481082

  2. Regulation of T cell response to leishmania antigens by determinants of histocompatibility leukocyte class I and II molecules

    Directory of Open Access Journals (Sweden)

    Bacellar O.

    1998-01-01

    Full Text Available It has been shown that HLA class I molecules play a significant role in the regulation of the proliferation of T cells activated by mitogens and antigens. We evaluated the ability of mAb to a framework determinant of HLA class I molecules to regulate T cell proliferation and interferon gamma (IFN-g production against leishmania, PPD, C. albicans and tetanus toxoid antigens in patients with tegumentary leishmaniasis and healthy subjects. The anti-major histocompatibility complex (MHC mAb (W6/32 suppressed lymphocyte proliferation by 90% in cultures stimulated with aCD3, but the suppression was variable in cultures stimulated with leishmania antigen. This suppression ranged from 30-67% and was observed only in 5 of 11 patients. IFN-g production against leishmania antigen was also suppressed by anti-HLA class I mAb. In 3 patients IFN-g levels were suppressed by more than 60%, while in the other 2 cultures IFN-g levels were 36 and 10% lower than controls. The suppression by HLA class I mAb to the proliferative response in leishmaniasis patients and in healthy controls varied with the antigens and the patients or donors tested. To determine whether the suppression is directed at antigen presenting cells (APCs or at the responding T cells, experiments with antigen-primed non-adherent cells, separately incubated with W6/32, were performed. Suppression of proliferation was only observed when the W6/32 mAb was added in the presence of T cells. These data provide evidence that a mAb directed at HLA class I framework determinants can suppress proliferation and cytokine secretion in response to several antigens.

  3. Role of CO2 responsiveness and breathing efficiency in determining exercise capacity of patients with chronic airway obstruction.

    Science.gov (United States)

    Chonan, T; Hida, W; Kikuchi, Y; Shindoh, C; Takishima, T

    1988-12-01

    We examined the role of CO2 responsiveness and breathing efficiency in limiting exercise capacity in 15 patients with chronic airway obstruction (FEV1 = 0.88 +/- 0.25 L, mean +/- SD). Responses of minute ventilation and P0.1 (mouth pressure 0.1 s after the onset of occluded inspiration) to hypercapnia (delta VE/delta PCO2, delta P0.1/delta PCO2) were measured by rebreathing, and the ratio of the two (delta VE/delta P0.1) was defined as an index of breathing efficiency during hyperventilation. Exercise capacity was measured as symptom-limited, maximal oxygen consumption (VO2max/BW) in an incremental treadmill test and also as the 12-min walking distance (TMD). All patients discontinued the treadmill test because of dyspnea, and the exercise capacity correlated with the degree of airway obstruction, although there was a wide variability among patients with comparable FEV1. There were no significant correlations between the responses to CO2 and exercise capacity. However, there was a significant correlation between delta VE/delta P0.1 and VO2max/BW (r = 0.87, p less than 0.001) or TMD (r = 0.78, p less than 0.001), and these correlations remained significant even when the relational effects of FEV1 were taken out. These results support the hypothesis that airway obstruction and breathing efficiency are important, but that CO2 responsiveness is not a major factor in determining the exercise capacity of patients with chronic airway obstruction.

  4. Response Surface Optimization of a Rapid Ultrasound-Assisted Extraction Method for Simultaneous Determination of Tetracycline Antibiotics in Manure

    Directory of Open Access Journals (Sweden)

    Lanqing Li

    2015-01-01

    Full Text Available A rapid and cleanup-free ultrasound-assisted extraction method is proposed for the simultaneous extraction of oxytetracycline, tetracycline, chlortetracycline, and doxycycline in manure. The analytes were determined using high-performance liquid chromatography with ultraviolet detector. The influence of several variables on the efficiency of the extraction procedure was investigated by single-factor experiments. The temperature, pH, and amount of extraction solution were selected for optimization experiment using response surface methodology. The calibration curves showed good linearity (R2>0.99 for all analytes in the range of 0.1–20 μg/mL. The four antibiotics were successfully extracted from manure with recoveries ranging from 81.89 to 92.42% and good reproducibility (RSD, <4.06% under optimal conditions, which include 50 mL of McIlvaine buffer extraction solution (pH 7.15 mixed with 1 g of manure sample, extraction temperature of 40°C, extraction time of 10 min, and three extraction cycles. Method quantification limits of 1.75–2.32 mg/kg were obtained for the studied compounds. The proposed procedure demonstrated clear reductions in extraction time and elimination of cleanup steps. Finally, the applicability to tetracyclines antibiotics determination in real samples was evaluated through the successful determination of four target analytes in swine, cow manure, and mixture of animal manure with inorganic fertilizer.

  5. A stilbene synthase allele from a Chinese wild grapevine confers resistance to powdery mildew by recruiting salicylic acid signalling for efficient defence

    Science.gov (United States)

    Jiao, Yuntong; Xu, Weirong; Duan, Dong; Wang, Yuejin; Nick, Peter

    2016-01-01

    Stilbenes are central phytoalexins in Vitis, and induction of the key enzyme stilbene synthase (STS) is pivotal for disease resistance. Here, we address the potential for breeding resistance using an STS allele isolated from Chinese wild grapevine Vitis pseudoreticulata (VpSTS) by comparison with its homologue from Vitis vinifera cv. ‘Carigane’ (VvSTS). Although the coding regions of both alleles are very similar (>99% identity on the amino acid level), the promoter regions are significantly different. By expression in Arabidopsis as a heterologous system, we show that the allele from the wild Chinese grapevine can confer accumulation of stilbenes and resistance against the powdery mildew Golovinomyces cichoracearum, whereas the allele from the vinifera cultivar cannot. To dissect the upstream signalling driving the activation of this promoter, we used a dual-luciferase reporter system in a grapevine cell culture. We show elevated responsiveness of the promoter from the wild grape to salicylic acid (SA) and to the pathogen-associated molecular pattern (PAMP) flg22, equal induction of both alleles by jasmonic acid (JA), and a lack of response to the cell death-inducing elicitor Harpin. This elevated SA response of the VpSTS promoter depends on calcium influx, oxidative burst by RboH, mitogen-activated protein kinase (MAPK) signalling, and JA synthesis. We integrate the data in the context of a model where the resistance of V. pseudoreticulata is linked to a more efficient recruitment of SA signalling for phytoalexin synthesis. PMID:27702992

  6. Habitat temperature and precipitation of Arabidopsis thaliana ecotypes determine the response of foliar vasculature, photosynthesis, and transpiration to growth temperature

    Directory of Open Access Journals (Sweden)

    William Walter Adams III

    2016-07-01

    Full Text Available Acclimatory adjustments of foliar vascular architecture, photosynthetic capacity, and transpiration rate in Arabidopsis thaliana ecotypes (Italian, Polish [Col-0], Swedish were characterized in the context of habitat of origin. Temperatures of the habitat of origin decreased linearly with increasing habitat latitude, but habitat precipitation was greatest in Italy, lowest in Poland, and intermediate in Sweden. Plants of the three ecotypes raised under three different growth temperature regimes (low, moderate, and high exhibited highest photosynthetic capacities, greatest leaf thickness, highest chlorophyll a/b ratio and levels of β-carotene, and greatest levels of wall ingrowths in phloem transfer cells, and, in the Col-0 and Swedish ecotypes, of phloem per minor vein in plants grown at the low temperature. In contrast, vein density and minor vein tracheary to sieve element ratio increased with increasing growth temperature – most strongly in Col-0 and least strongly in the Italian ecotype – and transpirational water loss correlated with vein density and number of tracheary elements per minor vein. Plotting of these vascular features as functions of climatic conditions in the habitat of origin suggested that temperatures during the evolutionary history of the ecotypes determined acclimatory responses of the foliar phloem and photosynthesis to temperature in this winter annual that upregulates photosynthesis in response to lower temperature, whereas the precipitation experienced during the evolutionary history of the ecotypes determined adjustment of foliar vein density, xylem, and transpiration to temperature. In particular, whereas photosynthetic capacity, leaf thickness, and foliar minor vein phloem features increased linearly with increasing latitude and decreasing temperature of the habitats of origin in response to experimental growth at low temperature, transpiration rate, foliar vein density, and minor vein tracheary element numbers

  7. Habitat Temperature and Precipitation of Arabidopsis thaliana Ecotypes Determine the Response of Foliar Vasculature, Photosynthesis, and Transpiration to Growth Temperature

    Science.gov (United States)

    Adams, William W.; Stewart, Jared J.; Cohu, Christopher M.; Muller, Onno; Demmig-Adams, Barbara

    2016-01-01

    Acclimatory adjustments of foliar vascular architecture, photosynthetic capacity, and transpiration rate in Arabidopsis thaliana ecotypes (Italian, Polish [Col-0], Swedish) were characterized in the context of habitat of origin. Temperatures of the habitat of origin decreased linearly with increasing habitat latitude, but habitat precipitation was greatest in Italy, lowest in Poland, and intermediate in Sweden. Plants of the three ecotypes raised under three different growth temperature regimes (low, moderate, and high) exhibited highest photosynthetic capacities, greatest leaf thickness, highest chlorophyll a/b ratio and levels of β-carotene, and greatest levels of wall ingrowths in phloem transfer cells, and, in the Col-0 and Swedish ecotypes, of phloem per minor vein in plants grown at the low temperature. In contrast, vein density and minor vein tracheary to sieve element ratio increased with increasing growth temperature – most strongly in Col-0 and least strongly in the Italian ecotype – and transpirational water loss correlated with vein density and number of tracheary elements per minor vein. Plotting of these vascular features as functions of climatic conditions in the habitat of origin suggested that temperatures during the evolutionary history of the ecotypes determined acclimatory responses of the foliar phloem and photosynthesis to temperature in this winter annual that upregulates photosynthesis in response to lower temperature, whereas the precipitation experienced during the evolutionary history of the ecotypes determined adjustment of foliar vein density, xylem, and transpiration to temperature. In particular, whereas photosynthetic capacity, leaf thickness, and foliar minor vein phloem features increased linearly with increasing latitude and decreasing temperature of the habitats of origin in response to experimental growth at low temperature, transpiration rate, foliar vein density, and minor vein tracheary element numbers and cross

  8. Habitat Temperature and Precipitation of Arabidopsis thaliana Ecotypes Determine the Response of Foliar Vasculature, Photosynthesis, and Transpiration to Growth Temperature.

    Science.gov (United States)

    Adams, William W; Stewart, Jared J; Cohu, Christopher M; Muller, Onno; Demmig-Adams, Barbara

    2016-01-01

    Acclimatory adjustments of foliar vascular architecture, photosynthetic capacity, and transpiration rate in Arabidopsis thaliana ecotypes (Italian, Polish [Col-0], Swedish) were characterized in the context of habitat of origin. Temperatures of the habitat of origin decreased linearly with increasing habitat latitude, but habitat precipitation was greatest in Italy, lowest in Poland, and intermediate in Sweden. Plants of the three ecotypes raised under three different growth temperature regimes (low, moderate, and high) exhibited highest photosynthetic capacities, greatest leaf thickness, highest chlorophyll a/b ratio and levels of β-carotene, and greatest levels of wall ingrowths in phloem transfer cells, and, in the Col-0 and Swedish ecotypes, of phloem per minor vein in plants grown at the low temperature. In contrast, vein density and minor vein tracheary to sieve element ratio increased with increasing growth temperature - most strongly in Col-0 and least strongly in the Italian ecotype - and transpirational water loss correlated with vein density and number of tracheary elements per minor vein. Plotting of these vascular features as functions of climatic conditions in the habitat of origin suggested that temperatures during the evolutionary history of the ecotypes determined acclimatory responses of the foliar phloem and photosynthesis to temperature in this winter annual that upregulates photosynthesis in response to lower temperature, whereas the precipitation experienced during the evolutionary history of the ecotypes determined adjustment of foliar vein density, xylem, and transpiration to temperature. In particular, whereas photosynthetic capacity, leaf thickness, and foliar minor vein phloem features increased linearly with increasing latitude and decreasing temperature of the habitats of origin in response to experimental growth at low temperature, transpiration rate, foliar vein density, and minor vein tracheary element numbers and cross

  9. Allele-selective inhibition of trinucleotide repeat genes

    OpenAIRE

    Matsui, Masayuki; Corey, David R.

    2012-01-01

    Expanded trinucleotide repeats cause Huntington’s disease (HD) and many other neurodegenerative disorders. There are no cures for these devastating illnesses and treatments are urgently needed. Each trinucleotide repeat disorder is the result of the mutation of just one gene, and agents that block expression of the mutant gene offer a promising option for treatment. Therapies that block expression of both mutant and wild-type alleles can have adverse effects, challenging researchers to develo...

  10. Allele-Specific DNA Methylation Detection by Pyrosequencing®

    DEFF Research Database (Denmark)

    Sommer Kristensen, Lasse; Johansen, Jens Vilstrup; Grønbæk, Kirsten

    2015-01-01

    DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

  11. Multiplex allele-specific target amplification based on PCR suppression

    OpenAIRE

    Broude, Natalia E.; Zhang, Lingang; Woodward, Karen; Englert, David; Cantor, Charles R.

    2001-01-01

    We have developed a strategy for multiplex PCR based on PCR suppression. PCR suppression allows DNA target amplification with only one sequence-specific primer per target and a second primer that is common for all targets. Therefore, an n-plex PCR would require only n + 1 primers. We have demonstrated uniform, efficient amplification of targeted sequences in 14-plex PCR. The high specificity of suppression PCR also provides multiplexed amplification with allele specifi...

  12. Effect of wheat puroindoline alleles on functional properties of starch

    OpenAIRE

    Brites, Carla Moita; Santos, Carla Alexandra Lourenço; Bagulho, Ana Sofia; Beirão-da-Costa, Maria Luisa

    2008-01-01

    Puroindoline a and b (Pina, Pinb) form the molecular basis of bread wheat grain hardness. Varieties with a softer endosperm and a wild genotype, in which both Pina and Pinb were present, seemed to produce less damaged starch Xour than hard varieties, where Pin mutations occurred and changed the starch rheological properties. The functional property of starch samples extracted from wheat varieties with diVerent Pin alleles was evaluated. Starch morphology was characteri...

  13. Generating Novel Allelic Variation Through Activator Insertional Mutagenesis in Maize

    OpenAIRE

    Bai, Ling; Singh, Manjit; Pitt, Lauren; Sweeney, Meredith; Brutnell, Thomas P.

    2007-01-01

    The maize transposable element Activator (Ac) has been exploited as an insertional mutagen to disrupt, clone, and characterize genes in a number of plant species. To develop an Ac-based mutagenesis platform for maize, a large-scale mutagenesis was conducted targeting the pink scutellum1 locus. We selected 1092 Ac transposition events from a closely linked donor Ac, resulting in the recovery of 17 novel ps1 alleles. Multiple phenotypic classes were identified corresponding to Ac insertions in ...

  14. Gene identification and allele-specific marker development for two allelic low phytic acid mutations in rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Phytic acid (PA, myo-inositol 1,2,3,4,5,6-hexakisphosphate) is an important anti-nutritional component in cereal and legume grains. PA forms of phosphorus (P) and its salts with micronutrient cations, such as iron and zinc, are indigestible in humans and non-ruminant animals, and hence could affect food/feed nutritional value and cause P pollution of ground water from animal waste. We previously developed a set of low phytic acid (LPA) rice mutants with the aim to increase their nutritional quality. Among them, one line, i.e., Os-lpa -XQZ-1 (hereafter lpa 1-2), was identified to have a mutation allelic to the KBNT lpa 1-1 mutation (hereafter lpa 1-1), which was already delimited to a 47-kb region on chromosome 2. In this study, we searched the candidate gene for these two allelic LPA mutations using T-DNA insertion mutants, mutation detection by CEL I facilitated mismatch cleavage, and gene sequencing. The TIGR locus LOCOs02g57400 was revealed as the candidate gene hosting these two mutations. Sequence analysis showed that the lpa 1-1 is a single base pair substitution mutation, while lpa 1-2 involves a 1,475-bp fragment deletion. A CAPS marker (LPA1CAPS) was developed for distinguishing the lpa 1-1 allele from lpa 1-2 and WT alleles, and InDel marker (LPA1InDel) was developed for differentiating the lpa 1-2 allele from lpa 1-1 and WT ones. Analysis of two populations derived from the two mutants with wild-type varieties confirmed the complete co-segregation of these two markers and LPA phenotype. The LOCOs02g57400 is predicted to encode, through alternative splicing, four possible proteins that are homologous to the 2-phosphoglycerate kinase reported in hyperthermophilic and thermophilic bacteria. The identification of the LPA gene and development of allele-specific markers are of importance not only for breeding LPA varieties, but also for advancing genetics and genomics of phytic acid biosynthesis in rice and other plant species. (author)

  15. DNA TYPING SYSTEM FOR HLA-A2 ALLELES BY POLYMERASE CHAIN REACTION WITH SEQUENCE-SPECIFIC PRIMERS

    Institute of Scientific and Technical Information of China (English)

    张庆瑞; 翟宁; 耿龙; 宋芳吉

    2001-01-01

    Objective. To establish a PCR-SSP method for discriminating as many HLA-A* 02 alleles, which could easily be introduced into a rourine laboratory.``Methods. In this study we typed HLA-A*02 polymorphisms by a sequence-specific primer (SSP) method,which involved round 1 and round 2 PCR reactions to detect 17 HLA-A*02 alleles (they are HLA-A*0201- 0217alleles) covering exon 2 and exon 3.``Results. We have found that DNA sample concentration and purity were the most important variables in determining the quality of the results. For identifying correct band size, the size marker used was important. We noticed that different PCR machines performed differently. By this method, we detected 20 HLA-A* 02 positive genomic DNA samples and found 4 kinds of HLA-A*02 alleles. They were HLA-A*0201, 0203, 0206 and 0210.``Conclusior. The HLA-A* 02 PCR-SSP method was proven to be a reliable and easily applicable typing method. Our results suggest that the SSP described here provides an optimal HLA-A* 02 typing technique that may be useful in selecting donor-recipient pairs in bone marrow transplantation between unrelated individuals.

  16. Distribution of photoperiod-insensitive allele Ppd-A1a and its effect on heading time in Japanese wheat cultivars.

    Science.gov (United States)

    Seki, Masako; Chono, Makiko; Nishimura, Tsutomu; Sato, Mikako; Yoshimura, Yasuhiro; Matsunaka, Hitoshi; Fujita, Masaya; Oda, Shunsuke; Kubo, Katashi; Kiribuchi-Otobe, Chikako; Kojima, Hisayo; Nishida, Hidetaka; Kato, Kenji

    2013-09-01

    The Ppd-A1 genotype of 240 Japanese wheat cultivars and 40 foreign cultivars was determined using a PCR-based method. Among Japanese cultivars, only 12 cultivars, all of which were Hokkaido winter wheat, carried the Ppd-A1a allele, while this allele was not found in Hokkaido spring wheat cultivars or Tohoku-Kyushu cultivars. Cultivars with a photoperiod-insensitive allele headed 6.9-9.8 days earlier in Kanto and 2.5 days earlier in Hokkaido than photoperiod-sensitive cultivars. The lower effect of photoperiod-insensitive alleles observed in Hokkaido could be due to the longer day-length at the spike formation stage compared with that in Kanto. Pedigree analysis showed that 'Purple Straw' and 'Tohoku 118' were donors of Ppd-A1a and Ppd-D1a in Hokkaido wheat cultivars, respectively. Wheat cultivars recently developed in Hokkaido carry photoperiod-insensitive alleles at a high frequency. For efficient utilization of Ppd-1 alleles in the Hokkaido wheat-breeding program, the effect of Ppd-1 on growth pattern and grain yield should be investigated. Ppd-A1a may be useful as a unique gene source for fine tuning the heading time in the Tohoku-Kyushu region since the effect of Ppd-A1a on photoperiod insensitivity appears to differ from the effect of Ppd-B1a and Ppd-D1a.

  17. Cytotoxic T lymphocyte responses by chimeric thymocytes. Self-recognition is determined early in T cell development

    Energy Technology Data Exchange (ETDEWEB)

    Kruisbeek, A.M.; Hodes, R.J.; Singer, A.

    1981-01-01

    In this study the cytotoxic T lymphocyte (CTL) recognition pattern of thymocytes from recently reconstituted parent leads to F1 and F1 leads to parent radiation bone marrow chimeras was investigated. Chimeric thymocytes were entirely of donor origin approximately 4 weeks after irradiation and reconstitution but were not capable of autonomously generating either alloreactive or trinitrophenyl (TNP)-modified-self-reactive CTL responses. These experiments demonstrte that even at the earliest time CTL effectors of donor origin from the thymuses of chimeras can be studied, their self-receptor repertoire has already been restricted to recognition of host MHC determinants. These results support the cocept that the host environment influences the self-recognition capacity of T cells at the pre- or intrathymic stage of differentation.

  18. Cellular release of and response to ATP as key determinants of the set-point of signal transduction pathways.

    Science.gov (United States)

    Ostrom, R S; Gregorian, C; Insel, P A

    2000-04-21

    The determinants of "basal" activity of signaling pathways regulating cellular responses are poorly defined. One possibility is that cells release factors to establish the set-point of such pathways. Here we show that treatment of Madin-Darby canine kidney cells with the nucleotidase apyrase decreases basal arachidonic acid release and cAMP production 30-40% and that inhibitors of P2Y receptor action also affect basal and forskolin-stimulated cAMP accumulation. Changing medium prominently increases extracellular levels of ATP in Madin-Darby canine kidney, COS-7, and HEK-293 cells. Mechanical stimulation of ATP release likely occurs in virtually every experimental protocol with cultured cells, implicating such release and P2Y receptor activation as critical in establishing the set-point for signal transduction pathways. PMID:10766795

  19. Determination of optimum pH and temperature for pasteurization of citrus juices by response surface methodology.

    Science.gov (United States)

    Ulgen, N; Ozilgen, M

    1993-01-01

    Optimization of microbial death, enzyme inactivation and vitamin C retention during pasteurization of pH-adjusted orange juice is discussed free of equipment-dependent parameters such as the heating lag. The pH-temperature optimum was determined by response surface methodology in the range of 65 degrees C-75 degrees C and pH 2.5-4.0. The results implied that there was no pectinesterase activity below pH 3.5. Leuconostoc mesenteroides had its maximum and minimum thermal resistance at pH 3.5 and pH 2.7, respectively. For an ideal theoretical process requiring four log cycles of microbial reduction the optimum pasteurization conditions were 12 min at 75 degrees C and pH 2.7.

  20. Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Michael Watson

    Full Text Available DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG and CHH (H representing A, C or T. Each of these patterns has traditionally been associated with distinct DNA methylation pathways with CHH methylation being controlled by the RNA dependent DNA methylation (RdDM pathway employing small RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2, and maintenance DNA METHYLTRANSFERASE1 (MET1 being responsible for faithful propagation of CG methylation. Here we report an unusual 'dense methylation' pattern under the control of MET1, with methylation in all three sequence contexts. We identified epi-alleles of dense methylation at a non coding RNA locus (At4g15242 in Arabidopsis ecotypes, with distinct dense methylation and expression characteristics, which are stably maintained and transmitted in genetic crosses and which can be heritably altered by depletion of MET1. This suggests that, in addition to its classical CG maintenance function, at certain loci MET1 plays a role in creating transcriptional diversity based on the generation of independent epi-alleles. Database inspection identified several other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes contain distinct epi-alleles of these loci with expression patterns that inversely correlate with methylation density, predominantly within the transcribed region. In Arabidopsis, dense methylation appears to be an exception as it is only found at a small number of loci. Its presence does, however, highlight the potential for MET1 as a contributor to epigenetic diversity, and it will be interesting to investigate the representation of dense methylation in other plant species.

  1. Using RNA-seq to determine the transcriptional landscape and the hypoxic response of the pathogenic yeast Candida parapsilosis

    LENUS (Irish Health Repository)

    Guida, Alessandro

    2011-12-22

    Abstract Background Candida parapsilosis is one of the most common causes of Candida infection worldwide. However, the genome sequence annotation was made without experimental validation and little is known about the transcriptional landscape. The transcriptional response of C. parapsilosis to hypoxic (low oxygen) conditions, such as those encountered in the host, is also relatively unexplored. Results We used next generation sequencing (RNA-seq) to determine the transcriptional profile of C. parapsilosis growing in several conditions including different media, temperatures and oxygen concentrations. We identified 395 novel protein-coding sequences that had not previously been annotated. We removed > 300 unsupported gene models, and corrected approximately 900. We mapped the 5\\' and 3\\' UTR for thousands of genes. We also identified 422 introns, including two introns in the 3\\' UTR of one gene. This is the first report of 3\\' UTR introns in the Saccharomycotina. Comparing the introns in coding sequences with other species shows that small numbers have been gained and lost throughout evolution. Our analysis also identified a number of novel transcriptional active regions (nTARs). We used both RNA-seq and microarray analysis to determine the transcriptional profile of cells grown in normoxic and hypoxic conditions in rich media, and we showed that there was a high correlation between the approaches. We also generated a knockout of the UPC2 transcriptional regulator, and we found that similar to C. albicans, Upc2 is required for conferring resistance to azole drugs, and for regulation of expression of the ergosterol pathway in hypoxia. Conclusion We provide the first detailed annotation of the C. parapsilosis genome, based on gene predictions and transcriptional analysis. We identified a number of novel ORFs and other transcribed regions, and detected transcripts from approximately 90% of the annotated protein coding genes. We found that the transcription factor

  2. Regional lung response to bronchodilator reversibility testing determined by electrical impedance tomography in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Vogt, Barbara; Zhao, Zhanqi; Zabel, Peter; Weiler, Norbert; Frerichs, Inéz

    2016-07-01

    Patients with obstructive lung diseases commonly undergo bronchodilator reversibility testing during examination of their pulmonary function by spirometry. A positive response is defined by an increase in forced expiratory volume in 1 s (FEV1). FEV1 is a rather nonspecific criterion not allowing the regional effects of bronchodilator to be assessed. We employed the imaging technique of electrical impedance tomography (EIT) to visualize the spatial and temporal ventilation distribution in 35 patients with chronic obstructive pulmonary disease at baseline and 5, 10, and 20 min after bronchodilator inhalation. EIT scanning was performed during tidal breathing and forced full expiration maneuver in parallel with spirometry. Ventilation distribution was determined by EIT by calculating the image pixel values of FEV1, forced vital capacity (FVC), tidal volume, peak flow, and mean forced expiratory flow between 25 and 75% of FVC. The global inhomogeneity indexes of each measure and histograms of pixel FEV1/FVC values were then determined to assess the bronchodilator effect on spatial ventilation distribution. Temporal ventilation distribution was analyzed from pixel values of times needed to exhale 75 and 90% of pixel FVC. Based on spirometric FEV1, significant bronchodilator response was found in 17 patients. These patients exhibited higher postbronchodilator values of all regional EIT-derived lung function measures in contrast to nonresponders. Ventilation distribution was inhomogeneous in both groups. Significant improvements were noted for spatial distribution of pixel FEV1 and tidal volume and temporal distribution in responders. By providing regional data, EIT might increase the diagnostic and prognostic information derived from reversibility testing. PMID:27190067

  3. Differences in Acinetobacter baumannii strains and host innate immune response determine morbidity and mortality in experimental pneumonia.

    Directory of Open Access Journals (Sweden)

    Anna de Breij

    Full Text Available Despite many reports documenting its epidemicity, little is known on the interaction of Acinetobacter baumannii with its host. To deepen our insight into this relationship, we studied persistence of and host response to different A. baumannii strains including representatives of the European (EU clones I-III in a mouse pneumonia model. Neutropenic mice were inoculated intratracheally with five A. baumannii strains and an A. junii strain and at several days morbidity, mortality, bacterial counts, airway inflammation, and chemo- and cytokine production in lungs and blood were determined. A. baumannii RUH875 and RUH134 (EU clone I and II, respectively and sporadic strain LUH8326 resulted in high morbidity/mortality, whereas A. baumannii LUH5875 (EU clone III, which is less widespread than clone I and II caused less symptoms. A. baumannii type strain RUH3023(T and A. junii LUH5851 did not cause disease. All strains, except A. baumannii RUH3023(T and A. junii LUH5851, survived and multiplied in the lungs for several days. Morbidity and mortality were associated with the severity of lung pathology and a specific immune response characterized by low levels of anti-inflammatory (IL-10 and specific pro-inflammatory (IL-12p40 and IL-23 cytokines at the first day of infection. Altogether, a striking difference in behaviour among the A. baumannii strains was observed with the clone I and II strains being most virulent, whereas the A. baumannii type strain, which is frequently used in virulence studies appeared harmless.

  4. Experience and BCC subtypes as determinants of MAL-PDT response: preliminary results of a national Brazilian project.

    Science.gov (United States)

    Ramirez, Dora P; Kurachi, Cristina; Inada, Natalia M; Moriyama, Lilian T; Salvio, Ana G; Vollet Filho, José D; Pires, Layla; Buzzá, Hilde H; de Andrade, Cintia Teles; Greco, Clovis; Bagnato, Vanderlei S

    2014-03-01

    Non-melanoma skin cancer is the most prevalent cancer type in Brazil and worldwide. Photodynamic therapy (PDT) is a noninvasive technique with excellent cosmetic outcome and good curative results, when used for the initial stages of skin cancer. A Brazilian program was established to determine the efficacy of methyl aminolevulinate (MAL)-PDT, using Brazilian device and drug. The equipment is a dual device that combines the photodiagnosis, based on widefield fluorescence, and the treatment at 630nm. A protocol was defined for the treatment of basal cell carcinoma with 20% MAL cream application. The program also involves the training of the medical teams at different Brazilian regions, and with distinct facilities and previous PDT education. In this report we present the partial results of 27 centers with 366 treated BCC lesions in 294 patients. A complete response (CR) was observed in 76.5% (280/366). The better response was observed for superficial BCC, with CR 160 lesions (80.4%), when compared with nodular or pigmented BCC. Experienced centers presented CR of 85.8% and 90.6% for superficial and nodular BCC respectively. A high influence of the previous doctor experience on the CR values was observed, especially due to a better tumor selection.

  5. Electric response of a magnetic colloid to periodic external excitation for different nanoparticles concentrations: Determination of the particles' effective charge

    Science.gov (United States)

    Batalioto, F.; Barbero, G.; Sehnem, A. L.; Figueiredo Neto, A. M.

    2016-08-01

    The effective electric charge of a nanoparticle in an ionic magnetic colloidal system (an ionic ferrofluid) is determined by using the impedance spectroscopy technique. The electric response of the samples to a harmonic external electric field excitation is described by means of the Poisson-Nernst-Planck model. The model proposed for the theoretical interpretation of the impedance spectroscopy data considers that the magnetic particles are electrically charged with H+ and have in their vicinity Cl- counterions, resulting in an effective charge Qeff. In the presence of an harmonic, in time, external field (frequency bigger than 10 4 Hz ) particles are assumed to be at rest, due to inertial reason. In this framework, the response of the cell is due to the H+ and Cl- present in the solution. From the spectra of the real and imaginary components of the electric impedance of the cell, by means of a best fit procedure to our model, we derive the effective electric charge of the magnetic particles and the bulk density of ions. From an independent measurement of the ζ-potential of the suspension, it is possible to calculate the hydrodynamic radius of the particle, in good agreement with that independently measured.

  6. Avian responses to an extreme ice storm are determined by a combination of functional traits, behavioural adaptations and habitat modifications

    Science.gov (United States)

    Zhang, Qiang; Hong, Yongmi; Zou, Fasheng; Zhang, Min; Lee, Tien Ming; Song, Xiangjin; Rao, Jiteng

    2016-01-01

    The extent to which species’ traits, behavior and habitat synergistically determine their response to extreme weather events (EWE) remains poorly understood. By quantifying bird and vegetation assemblages before and after the 2008 ice storm in China, combined with interspecific interactions and foraging behaviours, we disentangled whether storm influences avian reassembly directly via functional traits (i.e. behavioral adaptations), or indirectly via habitat variations. We found that overall species richness decreased, with 20 species detected exclusively before the storm, and eight species detected exclusively after. These shifts in bird relative abundance were linked to habitat preferences, dietary guild and flocking behaviours. For instance, forest specialists at higher trophic levels (e.g. understory-insectivores, woodpeckers and kingfishers) were especially vulnerable, whereas open-habitat generalists (e.g. bulbuls) were set to benefit from potential habitat homogenization. Alongside population fluctuations, we found that community reassembly can be rapidly adjusted via foraging plasticity (i.e. increased flocking propensity and reduced perching height). And changes in preferred habitat corresponded to a variation in bird assemblages and traits, as represented by intact canopy cover and high density of large trees. Accurate predictions of community responses to EWE are crucial to understanding ecosystem disturbances, thus linking species-oriented traits to a coherent analytical framework. PMID:26929387

  7. Response of Spring Diatoms to CO2 Availability in the Western North Pacific as Determined by Next-Generation Sequencing.

    Science.gov (United States)

    Endo, Hisashi; Sugie, Koji; Yoshimura, Takeshi; Suzuki, Koji

    2016-01-01

    Next-generation sequencing (NGS) technologies have enabled us to determine phytoplankton community compositions at high resolution. However, few studies have adopted this approach to assess the responses of natural phytoplankton communities to environmental change. Here, we report the impact of different CO2 levels on spring diatoms in the Oyashio region of the western North Pacific as estimated by NGS of the diatom-specific rbcL gene (DNA), which encodes the large subunit of RubisCO. We also examined the abundance and composition of rbcL transcripts (cDNA) in diatoms to assess their physiological responses to changing CO2 levels. A short-term (3-day) incubation experiment was carried out on-deck using surface Oyashio waters under different pCO2 levels (180, 350, 750, and 1000 μatm) in May 2011. During the incubation, the transcript abundance of the diatom-specific rbcL gene decreased with an increase in seawater pCO2 levels. These results suggest that CO2 fixation capacity of diatoms decreased rapidly under elevated CO2 levels. In the high CO2 treatments (750 and 1000 μatm), diversity of diatom-specific rbcL gene and its transcripts decreased relative to the control treatment (350 μatm), as well as contributions of Chaetocerataceae, Thalassiosiraceae, and Fragilariaceae to the total population, but the contributions of Bacillariaceae increased. In the low CO2 treatment, contributions of Bacillariaceae also increased together with other eukaryotes. These suggest that changes in CO2 levels can alter the community composition of spring diatoms in the Oyashio region. Overall, the NGS technology provided us a deeper understanding of the response of diatoms to changes in CO2 levels in terms of their community composition, diversity, and photosynthetic physiology.

  8. Association of HY-restricting HLA class II alleles with pregnancy outcome in patients with recurrent miscarriage subsequent to a firstborn boy

    DEFF Research Database (Denmark)

    Nielsen, Henriette Svarre; Steffensen, Rudi; Varming, Kim;

    2009-01-01

    Healthy females, pregnant with a boy, generate immune responses against male-specific minor histocompatibility (HY) antigens. The clinical importance of these responses is evident in stem cell transplantation. Birth of a boy prior to a series of miscarriages reduces the chance of a subsequent live...... birth. This study explores the putative impact of known HY-presenting HLA alleles on future pregnancy outcome in women with at least three consecutive miscarriages following a birth [secondary recurrent miscarriage (SRM)]. HLA-A, -B, -DRB1, DRB3-5 and DQB1 genotyping was performed in 358 SRM patients...... and in 203 of their children born prior to the miscarriages. The subsequent live birth in women with boys prior to the miscarriages compared with girls is lower in women with HY-restricting HLA class II alleles [odds ratio (OR): 0.17 (0.1-0.4), P = 0.0001]. One HY-restricting HLA class II allele in...

  9. Responsibilities

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    ONE day in 1993, a woman named Xing Jun came to the Organization Department of Tianjin’s Municipal Party Committee. She approached the door to the director’s office, opened it, and walked straight into the responsibility for training, examining, recommending and appointing cadres at all levels of the municipal government. Because the office has so much influence over the fate of many cadres, the director’s position commands much respect and awe. However, people see no

  10. Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment

    Directory of Open Access Journals (Sweden)

    Boscarino JA

    2012-03-01

    Full Text Available Joseph A Boscarino1,2, Porat M Erlich1,3, Stuart N Hoffman4, Xiaopeng Zhang51Center for Health Research, Geisinger Clinic, Danville, PA, 2Department of Psychiatry, 3Department of Medicine, Temple University School of Medicine, Philadelphia, PA, 4Department of Neurology, 5Department of Anesthesiology, Geisinger Clinic, Danville, PA, USAObjective: The study aim was to assess the cumulative burden of polymorphisms located within four genetic loci previously associated with posttraumatic stress disorder (PTSD among outpatients at risk for PTSD.Methods: Diagnostic interviews were completed and DNA samples collected among 412 pain patients to determine if FKBP5 (rs9470080, COMT (rs4680, CHRNA5 (rs16969968, and CRHR1 (rs110402 single nucleotide polymorphisms were cumulatively associated with increased risk for PTSD.Results: In bivariate analyses, it was found that a count of specific PTSD risk alleles located within FKBP5, COMT, CHRNA5, and CRHR1 genetic loci (allele range = 0–6, mean count = 2.92, standard deviation = 1.36 was associated with lifetime (t [409] = 3.430, P = 0.001 and early onset PTSD (t [409] = 4.239, P = 0.000028. In logistic regression, controlling for demographic factors, personality traits, and trauma exposures, this risk allele count remained associated with both lifetime (odds ratio = 1.49, P = 0.00158 and early onset PTSD (odds ratio = 2.36, P = 0.000093. Interaction effects were also detected, whereby individuals with higher risk allele counts and higher trauma exposures had an increased risk of lifetime PTSD (allele count × high trauma, P = 0.026 and early onset PTSD (allele count × high trauma, P = 0.016 in these logistic regressions. Those with no or few risk alleles appeared resilient to PTSD, regardless of exposure history.Conclusion: A cumulative risk allele count involving four single nucleotide polymorphisms located within the FKBP5, COMT, CHRNA5, and CRHR1 genes are associated with PTSD. Level of trauma exposure

  11. Allele-Specific Transcriptome and Methylome Analysis Reveals Stable Inheritance and Cis-Regulation of DNA Methylation in Nasonia.

    Science.gov (United States)

    Wang, Xu; Werren, John H; Clark, Andrew G

    2016-07-01

    Gene expression divergence between closely related species could be attributed to both cis- and trans- DNA sequence changes during evolution, but it is unclear how the evolutionary dynamics of epigenetic marks are regulated. In eutherian mammals, biparental DNA methylation marks are erased and reset during gametogenesis, resulting in paternal or maternal imprints, which lead to genomic imprinting. Whether DNA methylation reprogramming exists in insects is not known. Wasps of the genus Nasonia are non-social parasitoids that are emerging as a model for studies of epigenetic processes in insects. In this study, we quantified allele-specific expression and methylation genome-wide in Nasonia vitripennis and Nasonia giraulti and their reciprocal F1 hybrids. No parent-of-origin effect in allelic expression was found for >8,000 covered genes, suggesting a lack of genomic imprinting in adult Nasonia. As we expected, both significant cis- and trans- effects are responsible for the expression divergence between N. vitripennis and N. giraulti. Surprisingly, all 178 differentially methylated genes are also differentially methylated between the two alleles in F1 hybrid offspring, recapitulating the parental methylation status with nearly 100% fidelity, indicating the presence of strong cis-elements driving the target of gene body methylation. In addition, we discovered that total and allele-specific expression are positively correlated with allele-specific methylation in a subset of the differentially methylated genes. The 100% cis-regulation in F1 hybrids suggests the methylation machinery is conserved and DNA methylation is targeted by cis features in Nasonia. The lack of genomic imprinting and parent-of-origin differentially methylated regions in Nasonia, together with the stable inheritance of methylation status between generations, suggests either a cis-regulatory motif for methylation at the DNA level or highly stable inheritance of an epigenetic signal in Nasonia. PMID

  12. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations

    Science.gov (United States)

    Pedro, Liliana; Van Voorhis, Wesley C.; Quinn, Ronald J.

    2016-05-01

    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase (PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each.

  13. Multiple responses optimization in the development of a headspace gas chromatography method for the determination of residual solvents in pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Carla M. Teglia

    2015-10-01

    Full Text Available An efficient generic static headspace gas chromatography (HSGC method was developed, optimized and validated for the routine determination of several residual solvents (RS in drug substance, using a strategy with two sets of calibration. Dimethylsulfoxide (DMSO was selected as the sample diluent and internal standards were used to minimize signal variations due to the preparative step. A gas chromatograph from Agilent Model 6890 equipped with flame ionization detector (FID and a DB-624 (30 m×0.53 mm i.d., 3.00 µm film thickness column was used. The inlet split ratio was 5:1. The influencing factors in the chromatographic separation of the analytes were determined through a fractional factorial experimental design. Significant variables: the initial temperature (IT, the final temperature (FT of the oven and the carrier gas flow rate (F were optimized using a central composite design. Response transformation and desirability function were applied to find out the optimal combination of the chromatographic variables to achieve an adequate resolution of the analytes and short analysis time. These conditions were 30 °C for IT, 158 °C for FT and 1.90 mL/min for F. The method was proven to be accurate, linear in a wide range and very sensitive for the analyzed solvents through a comprehensive validation according to the ICH guidelines.

  14. Optimization of Electrospray Ionization by Statistical Design of Experiments and Response Surface Methodology: Protein-Ligand Equilibrium Dissociation Constant Determinations

    Science.gov (United States)

    Pedro, Liliana; Van Voorhis, Wesley C.; Quinn, Ronald J.

    2016-09-01

    Electrospray ionization mass spectrometry (ESI-MS) binding studies between proteins and ligands under native conditions require that instrumental ESI source conditions are optimized if relative solution-phase equilibrium concentrations between the protein-ligand complex and free protein are to be retained. Instrumental ESI source conditions that simultaneously maximize the relative ionization efficiency of the protein-ligand complex over free protein and minimize the protein-ligand complex dissociation during the ESI process and the transfer from atmospheric pressure to vacuum are generally specific for each protein-ligand system and should be established when an accurate equilibrium dissociation constant (KD) is to be determined via titration. In this paper, a straightforward and systematic approach for ESI source optimization is presented. The method uses statistical design of experiments (DOE) in conjunction with response surface methodology (RSM) and is demonstrated for the complexes between Plasmodium vivax guanylate kinase ( PvGK) and two ligands: 5'-guanosine monophosphate (GMP) and 5'-guanosine diphosphate (GDP). It was verified that even though the ligands are structurally similar, the most appropriate ESI conditions for KD determination by titration are different for each.

  15. A framework for parametric modeling of ankle ligaments to determine the in situ response under gross foot motion.

    Science.gov (United States)

    Nie, Bingbing; Panzer, Matthew Brian; Mane, Adwait; Mait, Alexander Ritz; Donlon, John-Paul; Forman, Jason Lee; Kent, Richard Wesley

    2016-09-01

    Ligament sprains account for a majority of injuries to the foot and ankle complex, but ligament properties have not been understood well due to the difficulties in replicating the complex geometry, in situ stress state, and non-uniformity of the strain. For a full investigation of the injury mechanism, it is essential to build up a foot and ankle model validated at the level of bony kinematics and ligament properties. This study developed a framework to parameterize the ligament response for determining the in situ stress state and heterogeneous force-elongation characteristics using a finite element ankle model. Nine major ankle ligaments and the interosseous membrane were modeled as discrete elements corresponding functionally to the ligamentous microstructure of collagen fibers and having parameterized toe region and stiffness at the fiber level. The range of the design variables in the ligament model was determined from existing experimental data. Sensitivity of the bony kinematics to each variable was investigated by design of experiment. The results highlighted the critical role of the length of the toe region of the ligamentous fibers on the bony kinematics with the cumulative influence of more than 95%, while the fiber stiffness was statistically insignificant with an influence of less than 1% under the given variable range and loading conditions. With the flexibility of variable adjustment and high computational efficiency, the presented ankle model was generic in nature so as to maximize its applicability to capture the individual ligament behaviors in future studies. PMID:26712301

  16. Multiple responses optimization in the development of a headspace gas chromatography method for the determination of residual solvents in pharmaceuticals

    Institute of Scientific and Technical Information of China (English)

    Carla M. Teglia; Milagros Montemurro; María M. De Zan; María S. Cámara

    2015-01-01

    An efficient generic static headspace gas chromatography (HSGC) method was developed, optimized and validated for the routine determination of several residual solvents (RS) in drug substance, using a strategy with two sets of calibration. Dimethylsulfoxide (DMSO) was selected as the sample diluent and internal standards were used to minimize signal variations due to the preparative step. A gas chroma-tograph from Agilent Model 6890 equipped with flame ionization detector (FID) and a DB-624 (30 m × 0.53 mm i.d., 3.00μm film thickness) column was used. The inlet split ratio was 5:1. The influ-encing factors in the chromatographic separation of the analytes were determined through a fractional factorial experimental design. Significant variables: the initial temperature (IT), the final temperature (FT) of the oven and the carrier gas flow rate (F) were optimized using a central composite design. Response transformation and desirability function were applied to find out the optimal combination of the chromatographic variables to achieve an adequate resolution of the analytes and short analysis time. These conditions were 30 °C for IT, 158 °C for FT and 1.90 mL/min for F. The method was proven to be accurate, linear in a wide range and very sensitive for the analyzed solvents through a comprehensive validation according to the ICH guidelines.

  17. TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis.

    Science.gov (United States)

    Liu, Jing; Dong, Zheng; Zhu, Qi; He, Dongyi; Ma, Yanyun; Du, Aiping; He, Fan; Zhao, Dongbao; Xu, Xia; Zhang, Hui; Jin, Li; Wang, Jiucun

    2016-08-31

    While previous studies have researched in association analyses between TNFα promoter polymorphisms and responses to TNF blockers in spondyloarthritis patients, their results were conflicting. Therefore, we aimed to determine whether TNFα promoter polymorphisms could predict response to TNF blockers and find the source of heterogeneity. Data were extracted and analyzed from published articles and combined with our unpublished data. We found that the greatest potential sources of heterogeneity in the results were gender ratio, disease type, continents, and TNF blockers. Then Stratification analysis showed that the TNFα -308 G allele and the -238 G allele predicted a good response to TNF blockers (OR = 2.64 [1.48-4.73]; 2.52 [1.46-4.37]). However, G alleles of TNFα -308 and -238 could predict the response to etanercept (OR = 4.02 [2.24-7.23]; 5.17 [2.29-11.67]) much more powerfully than the response to infiliximab/adalimumab (OR = 1.68 [1.02-2.78]; 1.28 [0.57-2.86]). TNFα -857 could not predict the response in either subgroup. Cumulative meta-analysis performed in ankylosing spondylitis patients presented the odds ratio decreased with stricter response criteria. In conclusion, TNFα -308 A/G and -238 A/G are more powerful to predict the response to Etanercept and it is dependent on the criteria of response.

  18. H pylori iceA alleles are disease-specific virulence factors

    Institute of Scientific and Technical Information of China (English)

    Vildan Caner; Mustafa Yilmaz; Nadir Yonetci; Sevil Zencir; Nedim Karagenc; Ilknur Kaleli; Huseyin Bagci

    2007-01-01

    AIM: To characterize and compare genotype profiles of H pylori strains isolated from patients with chronic gastritis and duodenal ulcer in western part of Turkey.METHODS: A total of 46 patients [30 chronic gastritis (CG) and 16 duodenal ulcer (DU)] who had undergone endoscopy because of dyspeptic complaints were studied. The antral biopsy specimens were evaluated for the presence of H pylori by rapid urease test and culture,and the genotype profiles were determined by real-time PCR.RESULTS: The cagA gene was observed in 43 (93.5%)isolates. The vacA s1m2 genotype was the predominant subtype, found in 63.3% and 68.7% of isolates in patients with CG and DU, respectively. Twenty (66.6%)isolates from patients with CG were iceA2 positive while the iceA1 was predominant in those with DU (68.8%).In terms of the association of the iceA alleles to other genes, both alleles were significantly associated with the cagA vacA s1m2 genotype.CONCLUSION: The prevalent circulating genotypes in CG and DU were cagA vacA s1m2 iceA2 and cagA vacA s1m2 iceA1 genotype, respectively. It was found that cagA vacA s1m2 genotype seems to be common virulence factors in both CG and DU while iceA alleles show specificity for gastroduodenal pathologies in this study.

  19. Cellular adhesion gene SELP is associated with rheumatoid arthritis and displays differential allelic expression.

    Directory of Open Access Journals (Sweden)

    Jana Burkhardt

    Full Text Available In rheumatoid arthritis (RA, a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1 were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies = 407. Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal = 0.003. This allele was also expressed preferentially (p<10-6 with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1 = 0.004; p2 = 0.0177. Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA.

  20. Inheritance and interactions of incompatibility alleles in the tetraploid sour cherry.

    Science.gov (United States)

    Bosković, R I; Wolfram, B; Tobutt, K R; Cerović, R; Sonneveld, T

    2006-01-01

    Three progenies of sour cherry (Prunus cerasus) were analysed to correlate self-(in)compatibility status with S-RNase phenotype in this allotetraploid hybrid of sweet and ground cherry. Self-(in)compatibility was assessed in the field and by monitoring pollen tube growth after selfing. The S-RNase phenotypes were determined by isoelectric focusing of stylar proteins and staining for RNase activity and, for the parents, confirmed by PCR. Seedling phenotypes were generally consistent with disomic segregation of S-RNase alleles. The genetic arrangements of the parents were deduced to be 'Köröser' (self-incompatible) S1S4.S(B) S(D), 'Schattenmorelle' (self-compatible) S6S13.S(B)S(B), and clone 43.87 (self-compatible) S4S13.S(B)S(B), where "." separates the two homologous genomes. The presence of S4 and S6 alleles at the same locus led to self-incompatibility, whereas S13 and S(B) at homologous loci led to self-compatibility. The failure of certain heteroallelic genotypes in the three crosses or in the self-incompatible seedlings indicates that S4 and S6 are dominant to S(B). However, the success of S13S(B) pollen on styles expressing corresponding S-RNases indicates competitive interaction or lack of pollen-S components. In general, the universal compatibility of S13S(B) pollen may explain the frequent occurrence of S13 and S(B) together in sour cherry cultivars. Alleles S(B) and S(D), that are presumed to derive from ground cherry, and S13, presumably from sweet cherry, were sequenced. Our findings contribute to an understanding of inheritance of self-(in)compatibility, facilitate screening of progenies for self-compatibility and provide a basis for studying molecular interactions in heteroallelic pollen. PMID:16307228

  1. A high-throughput method for genotyping S-RNase alleles in apple

    DEFF Research Database (Denmark)

    Larsen, Bjarne; Ørgaard, Marian; Toldam-Andersen, Torben Bo;

    2016-01-01

    We present a new efficient screening tool for detection of S-alleles in apple. The protocol using general and multiplexed primers for PCR reaction and fragment detection on an automatized capillary DNA sequencer exposed a higher number of alleles than any previous studies. Analysis of alleles...

  2. Two major er1 alleles confer powdery mildew resistance in three pea cultivars bred in Yunnan Province, China

    Directory of Open Access Journals (Sweden)

    Suli Sun

    2016-10-01

    Full Text Available Powdery mildew, caused by Erysiphe pisi D.C., is an important disease of pea (Pisum sativum L.. The use of cultivars carrying powdery mildew resistance alleles at the er1 locus is the most effective and economical means of controlling this disease. The objectives of this study were to screen Chinese elite pea cultivars for resistance to E. pisi and to identify the responsible gene at the er1 locus. Among the 37 pea cultivars tested, three (Yunwan 8, Yunwan 21, and Yunwan 23 were immune to E. pisi infection in phenotypic evaluations. The full-length cDNA sequences of the er1 candidate gene, PsMLO1, from the three resistant cultivars and control plants were analyzed. Comparison of the cDNA sequences of 10 clones revealed differences among the powdery mildew-resistant cultivars, susceptible controls, and wild-type cultivar Sprinter. The observed resistance in Yunwan 8 plants resulted from a point mutation (C → G at position 680 of PsMLO1 that introduced a stop codon, leading to premature termination of protein synthesis. The responsible resistance allele was identified as er1–1. Powdery mildew resistance in Yunwan 21 and Yunwan 23 plants was caused by identical insertions or deletions in PsMLO1. Three distinct PsMLO1 transcripts were observed in Yunwan 21 and Yunwan 23 plants. These transcripts were characterized by a 129-bp deletion and 155- and 220-bp insertions, respectively. The responsible resistance allele was identified as er1–2. We have characterized two important er1 alleles in three E. pisi-resistant pea cultivars bred in Yunnan Province, China. These cultivars represent important genetic resources for the breeding of powdery mildew-resistant pea cultivars.

  3. Determining Possible Professionals and Respective Roles and Responsibilities for a Model Comprehensive Elder Abuse Intervention: A Delphi Consensus Survey.

    Directory of Open Access Journals (Sweden)

    Janice Du Mont

    Full Text Available We have undertaken a multi-phase, multi-method program of research to develop, implement, and evaluate a comprehensive hospital-based nurse examiner elder abuse intervention that addresses the complex functional, social, forensic, and medical needs of older women and men. In this study, we determined the importance of possible participating professionals and respective roles and responsibilities within the intervention.Using a modified Delphi methodology, recommended professionals and their associated roles and responsibilities were generated from a systematic scoping review of relevant scholarly and grey literatures. These items were reviewed, new items added for review, and rated/re-rated for their importance to the intervention on a 5-point Likert scale by an expert panel during a one day in-person meeting. Items that did not achieve consensus were subsequently re-rated in an online survey.Those items that achieved a mean Likert rating of 4+ (rated important to very important, and an interquartile range<1 in the first or second round, and/or for which 80% of ratings were 4+ in the second round were retained for the model elder abuse intervention.Twenty-two of 31 recommended professionals and 192 of 229 recommended roles and responsibilities rated were retained for our model elder abuse intervention. Retained professionals were: public guardian and trustee (mean rating = 4.88, geriatrician (4.87, police officer (4.87, GEM (geriatric emergency management nurse (4.80, GEM social worker (4.78, community health worker (4.76, social worker/counsellor (4.74, family physician in community (4.71, paramedic (4.65, financial worker (4.59, lawyer (4.59, pharmacist (4.59, emergency physician (4.57, geriatric psychiatrist (4.33, occupational therapist (4.29, family physician in hospital (4.28, Crown prosecutor (4.24, neuropsychologist (4.24, bioethicist (4.18, caregiver advocate (4.18, victim support worker (4.18, and respite care worker (4.12.A large and

  4. Allele walking: a new and highly accurate approach to HLA-DRB1 typing. Application to DRB1*04 alleles.

    Science.gov (United States)

    Nieto, A; Tobes, R; Martín, J; Pareja, E

    1997-02-01

    We have developed a typing method, which can be used even in small laboratories, to produce a highly accurate and reliable allele assignment in any homozygous or heterozygous situation. We have called the method allele walking (AW) and it consists of sequential rounds of PCR-RFLP. After digestion, electrophoresis separates alleles positive for the mutation from the negative alleles; the cleaved fragment is then recovered from the gel and analyzed for mutations at another codon. In this way, AW is able to positively ascertain which mutations are in the same chromosome (cis-linkage) and assigns alleles independently from each other. Artificial sites are created in the PCR step in order to positively detect substitutions not naturally recognized by any of the existing or convenient enzymes. We report the application of AW for typing the 22 DRB1*04 alleles. The first PCR-RFLP round groups DRB1*04 alleles. Subsequently, the mutations at codons 86, 74, 71, 57 and 37 can be analyzed for the unambiguous assignment of the majority of the alleles. Additional polymorphisms at different codons can be assayed to resolve any undetermined alleles. The viability of all the restriction sites used as well as the feasibility of AW were successfully tested. PMID:9062970

  5. Allele-specific marker development and selection efficiencies for both flavonoid 3'-hydroxylase and flavonoid 3',5'-hydroxylase genes in soybean subgenus soja.

    Science.gov (United States)

    Guo, Yong; Qiu, Li-Juan

    2013-06-01

    Color is one of the phenotypic markers mostly used to study soybean (Glycine max L. Merr.) genetic, molecular and biochemical processes. Two P450-dependent mono-oxygenases, flavonoid 3'-hydroxylase (F3'H; EC1.14.3.21) and flavonoid 3',5'-hydroxylase (F3'5'H, EC1.14.13.88), both catalyzing the hydroxylation of the B-ring in flavonoids, play an important role in coloration. Previous studies showed that the T locus was a gene encoding F3'H and the W1 locus co-segregated with a gene encoding F3'5'H in soybean. These two genetic loci have identified to control seed coat, flower and pubescence colors. However, the allelic distributions of both F3'H and F3'5'H genes in soybean were unknown. In this study, three novel alleles were identified (two of four alleles for GmF3'H and one of three alleles for GmF3'5'H). A set of gene-tagged markers was developed and verified based on the sequence diversity of all seven alleles. Furthermore, the markers were used to analyze soybean accessions including 170 cultivated soybeans (G. max) from a mini core collection and 102 wild soybeans (G. soja). For both F3'H and F3'5'H, the marker selection efficiencies for pubescence color and flower color were determined. The results showed that one GmF3'H allele explained 92.2 % of the variation in tawny and two gmf3'h alleles explained 63.8 % of the variation in gray pubescence colors. In addition, two GmF3'5'H alleles and one gmF3'5'h allele explained 94.0 % of the variation in purple and 75.3 % in white flowers, respectively. By the combination of the two loci, seed coat color was determined. In total, 90.9 % of accessions possessing both the gmf3'h-b and gmf3'5'h alleles had yellow seed coats. Therefore, seed coat colors are controlled by more than two loci.

  6. TrueAllele casework on Virginia DNA mixture evidence: computer and manual interpretation in 72 reported criminal cases.

    Directory of Open Access Journals (Sweden)

    Mark W Perlin

    Full Text Available Mixtures are a commonly encountered form of biological evidence that contain DNA from two or more contributors. Laboratory analysis of mixtures produces data signals that usually cannot be separated into distinct contributor genotypes. Computer modeling can resolve the genotypes up to probability, reflecting the uncertainty inherent in the data. Human analysts address the problem by simplifying the quantitative data in a threshold process that discards considerable identification information. Elevated stochastic threshold levels potentially discard more information. This study examines three different mixture interpretation methods. In 72 criminal cases, 111 genotype comparisons were made between 92 mixture items and relevant reference samples. TrueAllele computer modeling was done on all the evidence samples, and documented in DNA match reports that were provided as evidence for each case. Threshold-based Combined Probability of Inclusion (CPI and stochastically modified CPI (mCPI analyses were performed as well. TrueAllele's identification information in 101 positive matches was used to assess the reliability of its modeling approach. Comparison was made with 81 CPI and 53 mCPI DNA match statistics that were manually derived from the same data. There were statistically significant differences between the DNA interpretation methods. TrueAllele gave an average match statistic of 113 billion, CPI averaged 6.68 million, and mCPI averaged 140. The computer was highly specific, with a false positive rate under 0.005%. The modeling approach was precise, having a factor of two within-group standard deviation. TrueAllele accuracy was indicated by having uniformly distributed match statistics over the data set. The computer could make genotype comparisons that were impossible or impractical using manual methods. TrueAllele computer interpretation of DNA mixture evidence is sensitive, specific, precise, accurate and more informative than manual

  7. HLA-DRB, DQA and DQB allele frequencies in Iranian patients with chronic hepatitis B by PCR-SSP

    Directory of Open Access Journals (Sweden)

    Baniaghil S

    2007-05-01

    Full Text Available Background: The outcome of acute hepatitis B infection may be influenced by host genetic factors like human leukocyte antigen (HLA. To investigate the association between the HLA-DRB, DQA1 and DQB1 alleles and chronic hepatitis B infection, 50 patients with chronic hepatitis B (based on 6 months positive of HBsAg and HBc antibody and HBeAg and antibody by serological test, were selected from Turkman population in north east of Iran .Allele frequency in patients were compared with a 65 aged and sex match control group from healthy blood donor of that ethnic population. Methods: HLA DRB, DQA1 and DQB1 alleles were determined using polymerase chain reaction based on sequence specific primer (PCR-SSP method. Allele frequencies in patients and control subjects were compared by Epi-info statistical soft-wear. Results: There was a significant increase and positive association in HLA-DRB1*0301, DQA1*0501 and DQB1*0604 allele frequency in patients group while the frequency of HLA-DRB1*1301, 1501 and DQB1*0401 and DQA1*0401, 0102 were lower in patients than control group and shows negative association. Conclusion: In Iranian Torkman population, HLA DRB1*0301, DQA1*0501 and DQB1*0604 have an important role in susceptibility to chronic hepatitis B infection and HLA DRB1*1301, 1501, DQB1*0401 are associated with protection to chronic hepatitis B infection. Larger case control studies may be helpful to confirm our investigation.

  8. TrueAllele casework on Virginia DNA mixture evidence: computer and manual interpretation in 72 reported criminal cases.

    Science.gov (United States)

    Perlin, Mark W; Dormer, Kiersten; Hornyak, Jennifer; Schiermeier-Wood, Lisa; Greenspoon, Susan

    2014-01-01

    Mixtures are a commonly encountered form of biological evidence that contain DNA from two or more contributors. Laboratory analysis of mixtures produces data signals that usually cannot be separated into distinct contributor genotypes. Computer modeling can resolve the genotypes up to probability, reflecting the uncertainty inherent in the data. Human analysts address the problem by simplifying the quantitative data in a threshold process that discards considerable identification information. Elevated stochastic threshold levels potentially discard more information. This study examines three different mixture interpretation methods. In 72 criminal cases, 111 genotype comparisons were made between 92 mixture items and relevant reference samples. TrueAllele computer modeling was done on all the evidence samples, and documented in DNA match reports that were provided as evidence for each case. Threshold-based Combined Probability of Inclusion (CPI) and stochastically modified CPI (mCPI) analyses were performed as well. TrueAllele's identification information in 101 positive matches was used to assess the reliability of its modeling approach. Comparison was made with 81 CPI and 53 mCPI DNA match statistics that were manually derived from the same data. There were statistically significant differences between the DNA interpretation methods. TrueAllele gave an average match statistic of 113 billion, CPI averaged 6.68 million, and mCPI averaged 140. The computer was highly specific, with a false positive rate under 0.005%. The modeling approach was precise, having a factor of two within-group standard deviation. TrueAllele accuracy was indicated by having uniformly distributed match statistics over the data set. The computer could make genotype comparisons that were impossible or impractical using manual methods. TrueAllele computer interpretation of DNA mixture evidence is sensitive, specific, precise, accurate and more informative than manual interpretation alternatives

  9. Identification of the Er1 resistence gene and RNase S-alleles in Malus prunifolia var. ringo rootstock

    Directory of Open Access Journals (Sweden)

    Sarah Zanon Agapito-Tenfen

    2015-02-01

    Full Text Available Woolly apple aphid (WAA; Eriosoma lanigerum Hausm. is a major insect pest that has significant economic impact on apple growers worldwide. Modern breeding technologies rely on several molecular tools to help breeders select genetic determinants for traits of interest. Consequently, there is a need for specific markers linked to the genes of interest. Apple scions and rootstocks have an additional barrier to the introduction of pest resistance genes due to the presence of self-incompatibility S-RNase alleles. The genetic characterization and early identification of these alleles can amplify the contribution of a breeding program to the selection of resistant genitors that are as compatible as possible. In this study, we identified the Er1 gene involved in the resistance to WAA in Malus prunifolia var. ringo, also known as ‘Maruba Kaido’ rootstock, and we analyzed the inheritance pattern of the WAA resistance Er1 gene in a segregant population derived from Malus pumila ‘M.9’ and ‘Maruba Kaido’ rootstocks. The self-incompatibility of S-RNase alleles S6S26 of ‘Maruba Kaido’ were also identified along with their inheritance pattern. We also confirmed the identification of the S1S3 alleles in the ‘M.9’ rootstock. To the best of our knowledge, this is the first study to characterize WAA resistance and RNase S-alleles in ‘Maruba Kaido’. Furthermore, we discuss the potential use of the genetic markers for these genes and their potential impact on apple breeding programs.

  10. Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients.

    LENUS (Irish Health Repository)

    Guda, Kishore

    2009-06-15

    Recently, germline allele-specific expression (ASE) of the gene encoding for transforming growth factor-beta type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon. Germline ASE results in a lowered expression of one of the TGFBR1 alleles (>1.5-fold), and was shown to occur in approximately 20% of informative familial and sporadic colorectal cancer (CRC) cases. In the present study, using the highly quantitative pyrosequencing technique, we estimated the frequency of ASE in TGFBR1 in a cohort of affected individuals from familial clusters of advanced colon neoplasias (cancers and adenomas with high-grade dysplasia), and also from a cohort of individuals with sporadic CRCs. Cases were considered positive for the presence of ASE if demonstrating an allelic expression ratio <0.67 or >1.5. Using RNA derived from lymphoblastoid cell lines, we find that of 46 informative Caucasian advanced colon neoplasia cases with a family history, only 2 individuals display a modest ASE, with allelic ratios of 1.65 and 1.73, respectively. Given that ASE of TGFBR1, if present, would likely be more pronounced in the colon compared with other tissues, we additionally determined the allele ratios of TGFBR1 in the RNA derived from normal-appearing colonic mucosa of sporadic CRC cases. We, however, found no evidence of ASE in any of 44 informative sporadic cases analyzed. Taken together, we find that germline ASE of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event.

  11. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    Directory of Open Access Journals (Sweden)

    Stringer Saundra L

    2006-10-01

    Full Text Available Abstract Background Loss of heterozygosity (LOH contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In addition, LOH caused by mitotic crossing over might be discernable in tissues because this event produces a pair of neighboring monochromatic cells that are different colors. Results As a step in assessing the utility of this approach, we derived primary embryonic fibroblast populations and embryonic stem cell lines from mice that carried two different fluorescent protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence activated cell sorting (FACS showed that the vast majority of cells in each line expressed the two marker proteins at similar levels, and that populations exhibited expression noise similar to that seen in bacteria and yeast. Cells with a monochromatic phenotype were present at frequencies on the order of 10-4 and appeared to be produced at a rate of approximately 10-5 variant cells per mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the expected allele at the ROSA26 locus. More than half of these clones retained heterozygosity at a locus between ROSA26 and the centromere. Other clones exhibited LOH near the centromere, but were disomic for chromosome 6. Conclusion Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by FACS. LOH at this locus was usually not accompanied by LOH near the centromere, suggesting that mitotic recombination was the major cause of ROSA26 LOH. Dichromatic mouse embryonic cells provide a novel system for studying genetic/karyotypic stability and factors

  12. Functional characteristics of the Staphylococcus aureus δ-toxin allelic variant G10S.

    Science.gov (United States)

    Cheung, Gordon Y C; Yeh, Anthony J; Kretschmer, Dorothee; Duong, Anthony C; Tuffuor, Kwame; Fu, Chih-Lung; Joo, Hwang-Soo; Diep, Binh A; Li, Min; Nakamura, Yuumi; Nunez, Gabriel; Peschel, Andreas; Otto, Michael

    2015-12-10

    Staphylococcus aureus δ-toxin is a member of the phenol-soluble modulin (PSM) peptide family. PSMs have multiple functions in staphylococcal pathogenesis; for example, they lyse red and white blood cells and trigger inflammatory responses. Compared to other PSMs, δ-toxin is usually more strongly expressed but has only moderate cytolytic capacities. The amino acid sequences of S. aureus PSMs are well conserved with two exceptions, one of which is the δ-toxin allelic variant G10S. This variant is a characteristic of the subspecies S. argenteus and S. aureus sequence types ST1 and ST59, the latter representing the most frequent cause of community-associated infections in Asia. δ-toxin G10S and strains expressing that variant from plasmids or the genome had significantly reduced cytolytic and pro-inflammatory capacities, including in a strain background with pronounced production of other PSMs. However, in murine infection models, isogenic strains expressing the two δ-toxin variants did not cause measurable differences in disease severity. Our findings indicate that the widespread G10S allelic variation of the δ-toxin locus has a significant impact on key pathogenesis mechanisms, but more potent members of the PSM peptide family may overshadow that impact in vivo.

  13. Individual risk alleles of susceptibility to schizophrenia are associated with poor clinical and social outcomes.

    Science.gov (United States)

    Sakamoto, Shinji; Takaki, Manabu; Okahisa, Yuko; Mizuki, Yutaka; Inagaki, Masatoshi; Ujike, Hiroshi; Mitsuhashi, Toshiharu; Takao, Soshi; Ikeda, Masashi; Uchitomi, Yosuke; Iwata, Nakao; Yamada, Norihito

    2016-04-01

    Many patients with schizophrenia have poor clinical and social outcomes. Some risk alleles closely related to the onset of schizophrenia have been reported to be associated with their clinical phenotypes, but the direct relationship between genetic vulnerability to schizophrenia and clinical/social outcomes of schizophrenia, as evaluated by both practical clinical scales and 'real-world' function, has not been investigated. We evaluated the clinical and social outcomes of 455 Japanese patients with schizophrenia by severity of illness according to the Clinical Global Impression-Severity Scale (CGI-S) and social outcomes by social adjustment/maladjustment at 5 years after the first visit. We examined whether 46 single nucleotide polymorphisms (SNPs) selected from a Japanese genome-wide association study of susceptibility to schizophrenia were associated with clinical and social outcomes. We also investigated the polygenic risk scores of 46 SNPs. Allele-wise association analysis detected three SNPs, including rs2623659 in the CUB and Sushi multiple domains-1 (CSMD1) gene, associated with severity of illness at end point. The severity of illness at end point was associated with treatment response, but not with the severity of illness at baseline. Three SNPs, including rs2294424 in the C6orf105 gene, were associated with social outcomes. Point estimates of odds ratios showed positive relationships between polygenic risk scores and clinical/social outcomes; however, the results were not statistically significant. Because these results are exploratory, we need to replicate them with a larger sample in a future study. PMID:26674612

  14. Focal segmental glomerulosclerosis in patients with complete deletion of one WT1 allele.

    Science.gov (United States)

    Iijima, Kazumoto; Someya, Tomonosuke; Ito, Shuichi; Nozu, Kandai; Nakanishi, Koichi; Matsuoka, Kentaro; Ohashi, Hirofumi; Nagata, Michio; Kamei, Koichi; Sasaki, Satoshi

    2012-06-01

    The renal prognosis of patients with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation syndrome (WAGR) is poor. However, the renal histology and its mechanisms are not well understood. We performed renal biopsies in 3 patients with WAGR syndrome who had heavy proteinuria. The complete deletion of one WT1 allele was detected in each patient by constitutional chromosomal deletion at 11p13 using G-banding, high-resolution G-banding, and fluorescence in situ hybridization. The patients exhibited proteinuria at the ages of 6, 10, and 6 years and were diagnosed as having focal segmental glomerulosclerosis (FSGS) at the ages of 7, 16 and 19 years, respectively. They exhibited normal or mildly declined renal function at the time of biopsy. Re-examination of a nephrectomized kidney from 1 patient revealed that some glomeruli showed segmental sclerosis, although he did not have proteinuria at the time of nephrectomy. The other 2 patients did not develop Wilms' tumor and thus did not undergo nephrectomy, chemotherapy, or radiotherapy, thereby eliminating any effect of these therapies on the renal histology. In conclusion, complete deletion of one WT1 allele may induce the development of FSGS. Our findings suggest that haploinsufficiency of the WT1 could be responsible for the development of FSGS.

  15. Sporophytic self-incompatibility in Senecio squalidus (Asteraceae): S allele dominance interactions and modifiers of cross-compatibility and selfing rates.

    Science.gov (United States)

    Brennan, A C; Tabah, D A; Harris, S A; Hiscock, S J

    2011-01-01

    Understanding genetic mechanisms of self-incompatibility (SI) and how they evolve is central to understanding the mating behaviour of most outbreeding angiosperms. Sporophytic SI (SSI) is controlled by a single multi-allelic locus, S, which is expressed in the diploid (sporophyte) plant to determine the SI phenotype of its haploid (gametophyte) pollen. This allows complex patterns of independent S allele dominance interactions in male (pollen) and female (pistil) reproductive tissues. Senecio squalidus is a useful model for studying the genetic regulation and evolution of SSI because of its population history as an alien invasive species in the UK. S. squalidus maintains a small number of S alleles (7-11) with a high frequency of dominance interactions. Some S. squalidus individuals also show partial selfing and/or greater levels of cross-compatibility than expected under SSI. We previously speculated that these might be adaptations to invasiveness. Here we describe a detailed characterization of the regulation of SSI in S. squalidus. Controlled crosses were used to determine the S allele dominance hierarchy of six S alleles and effects of modifiers on cross-compatibility and partial selfing. Complex dominance interactions among S alleles were found with at least three levels of dominance and tissue-specific codominance. Evidence for S gene modifiers that increase selfing and/or cross-compatibility was also found. These empirical findings are discussed in the context of theoretical predictions for maintenance of S allele dominance interactions, and the role of modifier loci in the evolution of SI. PMID:20372180

  16. Identifying neutral allele Sb at pollen-sterility loci in cultivated rice with Oryza rufipogon origin

    Institute of Scientific and Technical Information of China (English)

    SHI LeiGang; LIU XiangDong; LIU Bo; ZHAO XingJuan; WANG Lan; LI JinQuan; LU YongGen

    2009-01-01

    Pollen sterility is commonly found in the intra-specific hybrids of indica and japonica rice, which is one of the main constrains for the utilization of heterosis between indica and japonica. Six loci controlling the pollen sterility of F1 between indica and japonica have been identified from previous studies. Neu-tral alleles at each locus are potential to overcome the F1 pollen sterility associated with the locus. Therefore, exploitation and utilization of neutral alleles are of significant importance. The present re-search was based on fine mapping of the F_1 pollen-sterility gene Sb and the abundant genetic diversity of Oryza rufipogon Griff. indigenous to Gaozhou, Guangdong Province (referred to as Gaozhou wild rice). Crosses were made using Taichung65 (with the genotype of S_b~jS_b~j and referred to as E_1) and its near-isogenic line of F_1 pollen sterility gene Sb(with the genotype of S_b~iS_b~i, E_2) as female parents, and 12 different accessions of Gaozhou wild rice as male parents. F_1 pollen fertility was examined to identify the materials having the neutral alleles at the F_1 pollen-sterility locus. Segregation of 4 molecular markers tightly linked with the Sb locus was analyzed in the F_2 populations derived from the F_1s car-rying the neutral gene. The pollen fertility related to the 3 genotypes of the molecular markers was also checked by statistical test to determine whether it was consistent with the hypothesis. The results showed that the pollen fertility of two F_1s from one accession of Gaozhou wild rice (GZW099) with E_1 and E_2 was (89.22±1.07)% and (85.65±1.05)%, respectively. Both of them were fertile and showed no significant difference by t-test. Segregation of the 3 genotypes of the 4 molecular markers followed the expected Mendelian ratio (1:2:1) in the F_2 populations. There was no significant difference for the av-eraged pollen fertility of the plants related to the 3 genotypes, suggesting that no interaction exists between the

  17. Food viscosity as determinant for adaptive growth responses in rat intestine: long-term feeding of different hydroxyethyl celluloses.

    Science.gov (United States)

    Elsenhans, B; Caspary, W F

    2000-07-01

    Carbohydrate gelling agents can be regarded as being representative for the soluble and viscous fractions of dietary fibre. Their dietary concentration affects the consistency of the ingested food as well as the dilution of nutrients and energy. By feeding hydroxyethyl cellulose (HEC) differing in molecular mass, and thus in its viscosity properties, only the consistency of the diet was modified. Three HEC (of low (LV), medium (MV) and high viscosity (HV)) were employed in a 6-week feeding study with female rats to evaluate the effect of the viscosity on adaptive responses of intestinal growth variables. Each of the HEC was added in three increasing concentrations (8, 16, and 32%, w/w) to a fibre-free control diet to yield nine test groups besides a fibre-free and an additional, fibre-rich, cereal-based control group. Except for the highest concentration of the high viscosity product (32% HV-HEC), the dilution of the energy density of the diet was almost completely compensated by an increased food intake. With the same exception, energy utilisation was not impaired and, therefore, body-weight gains in the test groups were not significantly different from that in the control. Most other changes, e.g. increases in small intestinal length, mucosal DNA content, caecal and colonic weight, not only depended on the dietary concentration but also on the viscosity of HEC in a manner that either increasing the viscosity at a given dietary concentration or increasing the dietary concentration at a given viscosity led to the same results. These findings clearly prove the important role of the viscosity of the lumen content, as a mere physico-chemical factor, in determining adaptative growth responses in the intestinal tract of rats.

  18. Autoimmune disease classification by inverse association with SNP alleles.

    Directory of Open Access Journals (Sweden)

    Marina Sirota

    2009-12-01

    Full Text Available With multiple genome-wide association studies (GWAS performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS, ankylosing spondylitis (AS, autoimmune thyroid disease (ATD, rheumatoid arthritis (RA, Crohn's disease (CD, and type 1 diabetes (T1D, as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways.

  19. Modulation of allele leakiness and adaptive mutability in Escherichia coli

    Indian Academy of Sciences (India)

    R. Jayaraman

    2000-08-01

    It is shown that partial phenotypic suppression of two ochre mutations (argE3 and lacZU118) and an amber mutation (in argE) by sublethal concentrations of streptomycin in an rpsL+ (streptomycin-sensitive) derivative of the Escherichia coli strain AB1157 greatly enhances their adaptive mutability under selection. Streptomycin also increases adaptive mutability brought about by the ppm mutation described earlier. Inactivation of recA affects neither phenotypic suppression by streptomycin nor replication-associated mutagenesis but abolishes adaptive mutagenesis. These results indicate a causal relationship between allele leakiness and adaptive mutability.

  20. 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 drop......-out is occurring. With this discussion, we hope to improve the drop-out model, so that it can be used for practical forensic genetics and stimulate further discussions. We discuss how to estimate drop-out probabilities when using a varying number of PCR cycles and other experimental conditions....

  1. Simultaneous spectrophotometric determination of synthetic dyes in food samples after cloud point extraction using multiple response optimizations.

    Science.gov (United States)

    Heidarizadi, Elham; Tabaraki, Reza

    2016-01-01

    A sensitive cloud point extraction method for simultaneous determination of trace amounts of sunset yellow (SY), allura red (AR) and brilliant blue (BB) by spectrophotometry was developed. Experimental parameters such as Triton X-100 concentration, KCl concentration and initial pH on extraction efficiency of dyes were optimized using response surface methodology (RSM) with a Doehlert design. Experimental data were evaluated by applying RSM integrating a desirability function approach. The optimum condition for extraction efficiency of SY, AR and BB simultaneously were: Triton X-100 concentration 0.0635 mol L(-1), KCl concentration 0.11 mol L(-1) and pH 4 with maximum overall desirability D of 0.95. Correspondingly, the maximum extraction efficiency of SY, AR and BB were 100%, 92.23% and 95.69%, respectively. At optimal conditions, extraction efficiencies were 99.8%, 92.48% and 95.96% for SY, AR and BB, respectively. These values were only 0.2%, 0.25% and 0.27% different from the predicted values, suggesting that the desirability function approach with RSM was a useful technique for simultaneously dye extraction. Linear calibration curves were obtained in the range of 0.02-4 for SY, 0.025-2.5 for AR and 0.02-4 μg mL(-1) for BB under optimum condition. Detection limit based on three times the standard deviation of the blank (3Sb) was 0.009, 0.01 and 0.007 μg mL(-1) (n=10) for SY, AR and BB, respectively. The method was successfully used for the simultaneous determination of the dyes in different food samples.

  2. Experimental determination of the energy response of alanine pellets in the high dose rate 192Ir spectrum

    Science.gov (United States)

    Schaeken, B.; Cuypers, R.; Goossens, J.; Van den Weyngaert, D.; Verellen, D.

    2011-10-01

    An experimental determination of the energy correction factor for alanine/paraffin pellets in the 192Ir spectrum at varying distances from the source is presented. Alanine dosimeters were irradiated in water under full scatter conditions with a high dose rate (HDR) 192Ir source (Flexisource), using a dedicated holder. Up to six line sources (catheters) fit in a regular pattern at fixed radial distances from the holder axis, the alanine detector being placed at the centre of the holder. The HDR source was stepping every 0.5 cm within a trocar needle within ± 3.0 cm around the medial plane through the detector in order to achieve dose homogeneity within the detector volume. The energy correction factor of alanine/paraffin pellets in 192Ir relative to 60Co was experimentally determined as the inverse ratio of the dose to water measured in water around the 192Ir source to the dose to water calculated in water using the TG-43 formalism. The pellets were read out with a Bruker EMXmicro spectrometer (X-band). The amplitude of the central line in the alanine absorption spectrum from pellets irradiated within the 192Ir spectrum was directly compared with the amplitude from 60Co-irradiated pellets. The energy correction factors of Harwell pellets irradiated in the 192Ir spectrum are 1.029 ± 0.02, 1.027 ± 0.02 and 1.045 ± 0.02 at a mean weighted source-detector distance of 2.0, 2.9 and 5.3 cm, respectively. The experimentally obtained values for the energy response are 1.3% lower compared to the theoretical values for radial distances smaller than 3 cm.

  3. Determination of key environmental factors responsible for distribution patterns of fiddler crabs in a tropical mangrove ecosystem.

    Science.gov (United States)

    Mokhtari, Mohammad; Ghaffar, Mazlan Abd; Usup, Gires; Cob, Zaidi Che

    2015-01-01

    In tropical regions, different species of fiddler crabs coexist on the mangrove floor, which sometimes makes it difficult to define species-specific habitat by visual inspection. The aim of this study is to find key environmental parameters which affect the distribution of fiddler crabs and to determine the habitats in which each species was most abundant. Crabs were collected from 19 sites within the mudflats of Sepang-Lukut mangrove forest. Temperature, porewater salinity, organic matter, water content, carbon and nitrogen content, porosity, chlorophyll content, pH, redox potential, sediment texture and heavy metals were determined in each 1 m2 quadrate. Pearson correlation indicated that all sediment properties except pH and redox potential were correlated with sediment grain size. Canonical correspondence analysis (CCA) indicated that Uca paradussumieri was negatively correlated with salinity and redox potential. Sand dwelling species, Uca perplexa and Uca annulipes, were highly dependent on the abundance of 250 μm and 150 μm grain size particles in the sediment. Canonical Discriminative Analysis (CDA) indicated that variation in sediment grain size best explained where each crab species was most abundant. Moreover, U. paradussumieri commonly occupies muddy substrates of low shore, while U. forcipata lives under the shade of mangrove trees. U. annulipes and U. perplexa with the high number of spoon tipped setae on their second maxiliped are specialized to feed on the sandy sediments. U. rosea and U. triangularis are more common on muddy sediment with high sediment density. In conclusion, sediment grain size that influences most sediment properties acts as a main factor responsible for sediment heterogeneity. In this paper, the correlation between fiddler crab species and environmental parameters, as well as the interaction between sediment characteristics, was explained in order to define the important environmental factors in fiddler crab distributions.

  4. Determination of key environmental factors responsible for distribution patterns of fiddler crabs in a tropical mangrove ecosystem.

    Directory of Open Access Journals (Sweden)

    Mohammad Mokhtari

    Full Text Available In tropical regions, different species of fiddler crabs coexist on the mangrove floor, which sometimes makes it difficult to define species-specific habitat by visual inspection. The aim of this study is to find key environmental parameters which affect the distribution of fiddler crabs and to determine the habitats in which each species was most abundant. Crabs were collected from 19 sites within the mudflats of Sepang-Lukut mangrove forest. Temperature, porewater salinity, organic matter, water content, carbon and nitrogen content, porosity, chlorophyll content, pH, redox potential, sediment texture and heavy metals were determined in each 1 m2 quadrate. Pearson correlation indicated that all sediment properties except pH and redox potential were correlated with sediment grain size. Canonical correspondence analysis (CCA indicated that Uca paradussumieri was negatively correlated with salinity and redox potential. Sand dwelling species, Uca perplexa and Uca annulipes, were highly dependent on the abundance of 250 μm and 150 μm grain size particles in the sediment. Canonical Discriminative Analysis (CDA indicated that variation in sediment grain size best explained where each crab species was most abundant. Moreover, U. paradussumieri commonly occupies muddy substrates of low shore, while U. forcipata lives under the shade of mangrove trees. U. annulipes and U. perplexa with the high number of spoon tipped setae on their second maxiliped are specialized to feed on the sandy sediments. U. rosea and U. triangularis are more common on muddy sediment with high sediment density. In conclusion, sediment grain size that influences most sediment properties acts as a main factor responsible for sediment heterogeneity. In this paper, the correlation between fiddler crab species and environmental parameters, as well as the interaction between sediment characteristics, was explained in order to define the important environmental factors in fiddler crab

  5. [Male reproductive behavior in Drosophila melanogaster strains with different alleles of the flamenco gene].

    Science.gov (United States)

    Subocheva, E A; Romanova, N I; Karpova, N N; Iuneva, A O; Kim, A I

    2003-05-01

    The allelic state of gene flamenco has been determined in a number of Drosophila melanogaster strains using the ovoD test. The presence of an active copy of gypsy in these strains was detected by restriction analysis. Then male reproduction behavior was studied in the strains carrying a mutation in gene flamenco. In these experiments mating success has been experimentally estimated in groups of flies. It has been demonstrated that the presence of mutant allele flamMS decreases male mating activity irrespective of the presence or absence of mutation white. The active copy of gypsy does not affect mating activity in the absence of the mutation in gene flamenco. Individual analysis has demonstrated that that mutation flamMS results in characteristic changes in courtship: flamMS males exhibit a delay in the transition from the orientation stage to the vibration stage (the so-called vibration delay). The role of locus flamenco in the formation of male mating behavior in Drosophila is discussed. PMID:12838614

  6. Allelic structure and distribution of 103 STR loci in a Southern Tunisian population

    Indian Academy of Sciences (India)

    Abdellatif Maalej; Ahmed Rebai; Adnen Ayadi; Jomaa Jouida; Hafedh Makni; Hammadi Ayadi

    2004-04-01

    Genotypes of 103 short tandem repeat (STR) markers distributed at an average of 40 cM intervals throughout the genome were determined for 40 individuals from the village of BirEl Hfai (BEH). This village of approximately 31.000 individuals is localized in the south-west of Tunisia. The allele frequency distributions in BEH were compared with those obtained for individuals in the CEPH (Centre d’Etude du Polymorphisme Humain) data using a Kolmogorov–Smirnov two-sample test. Fourteen out of the 103 markers (13.2%) showed significant differences ($P\\lt 0.05$) in distribution between the two populations. Population heterogeneity in BEH was indicated by an excess of observed homozygosity deviations from Hardy–Weinberg equilibrium at 3 loci ($P\\lt 0.0005$). No evidence for genotypic disequilibrium was found for any of the marker pairs. This demonstrated that in spite of a high inbreeding level in the population, few markers showed evidence for a different pattern of allelic distribution compared to CEPH.

  7. Selection of Plasmodium falciparum pfmdr1 Alleles following Therapy with Artemether-Lumefantrine in an Area of Uganda where Malaria Is Highly Endemic

    OpenAIRE

    Dokomajilar, Christian; Nsobya, Samuel L.; Greenhouse, Bryan; Rosenthal, Philip J; Dorsey, Grant

    2006-01-01

    Polymorphisms in the Plasmodium falciparum pfmdr1 gene were assayed in pretreatment samples and in samples from patients reinfected following therapy with artemether-lumefantrine. The pfmdr1 alleles 86N, 184F, and 1246D significantly increased in prevalence after treatment. All samples had a single pfmdr1 copy. Treatment with artemether-lumefantrine selects for polymorphisms that may alter antimalarial drug response.

  8. Analysis of the distribution of HLA-A alleles in populations from five continents.

    Science.gov (United States)

    Middleton, D; Williams, F; Meenagh, A; Daar, A S; Gorodezky, C; Hammond, M; Nascimento, E; Briceno, I; Perez, M P

    2000-10-01

    The variation and frequency of HLA-A genotypes were established by PCR-SSOP typing in diverse geographically distributed populations: Brazilian, Colombian Kogui, Cuban, Mexican, Omani, Singapore Chinese, and South African Zulu. HLA-A allelic families with only one allele were identified for HLA-A*01, -A*23, -A*25, -A*31, -A*32, -A*36, -A*43, -A*69, -A*80; and with two alleles for HLA-A*03, -A*11, -A*26, -A*29, -A*33, -A*34, and -A*66. Greater variation was detected for HLA-A*02, -A*24, and -A*68 allele families. Colombian Kogui and Mexican Seris showed the least diversity with respect to HLA-A alleles, albeit with small numbers tested, with only four and five HLA-A alleles identified, respectively. It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation. PMID:11082518

  9. Allelic Diversity of Major Histocompatibility Complex Class II DRB Gene in Indian Cattle and Buffalo

    Directory of Open Access Journals (Sweden)

    Sachinandan De

    2011-01-01

    Full Text Available The present study was conducted to study the diversity of MHC-DRB3 alleles in Indian cattle and buffalo breeds. Previously reported BoLA-DRB exon 2 alleles of Indian Zebu cattle, Bos taurus cattle, buffalo, sheep, and goats were analyzed for the identities and divergence among various allele sequences. Comparison of predicted amino acid residues of DRB3 exon 2 alleles with similar alleles from other ruminants revealed considerable congruence in amino acid substitution pattern. These alleles showed a high degree of nucleotide and amino acid polymorphism at positions forming peptide-binding regions. A higher rate of nonsynonymous substitution was detected at the peptide-binding regions, indicating that BoLA-DRB3 allelic sequence evolution was driven by positive selection.

  10. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old

    DEFF Research Database (Denmark)

    Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas;

    2013-01-01

    . We did not find a protective effect of the APOE ε2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ε4 carriers. The APOE ε2 allele may be protective on cognitive decline among the oldest old.......Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found...... no protective effect of the APOE ε2 allele on mortality compared with the APOE ε3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ε2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes...

  11. A Study of GluK1 Kainate Receptor Polymorphisms in Down Syndrome Reveals Allelic Non-Disjunction at 1173(C/T

    Directory of Open Access Journals (Sweden)

    Debarati Ghosh

    2009-01-01

    Full Text Available Mechanisms underlying Down syndrome (DS-related mental retardation (MR remain poorly understood. In trisomic offspring, non-disjunction may result in the reduction to homozygosity of a susceptibility allele inherited from a heterozygous parent. Accordingly, we sought evidence for allelic non-disjunction in the GluK1 gene that encodes the critical kainite-binding glutamate receptor subunit-5, maps to chromosome 21q22.1 in the DS critical region and is expressed in brain regions responsible for learning and memory. Three polymorphisms of GluK1 [522(A/C rs363538; 1173(C/T rs363430 and 2705(T/C rs363504] were genotyped in 86 DS patient families by means of PCR-coupled RFLP assays and evaluated with respect to allele frequency, heterozygosity, linkage disequilibrium, stage and parental origin of allelic non-disjunction. We report that the distribution of allele frequencies is in Hardy-Weinberg equilibrium. Moderate heterozygosity (0.339 and a major allele frequency of 0.78 render the 1173(C/T marker informative. Pair-wise comparisons reveal that 522(A/C-1173(C/T [χ2 = 31.2, df = 1, p = 0.0001; D’ = 0.42] and 1173(C/T-2705(T/C [χ2 = 18.3, df = 1, p = 0.0001; D’ = 0.34] are in significant linkage disequilibrium of weak magnitude. The estimated ratio of meiosis-I to meiosis-II errors arising from allelic non-disjunction of 1173(C/T is 4:1 in maternal cases and 2:1 in paternal cases. Studies including additional markers and patient samples are warranted to further substantiate present findings.

  12. Determination of LC50 of Copper Sulfate and Lead(II Nitrate and Behavioral Responses of Grass Carp (Ctenopharyngodon idella

    Directory of Open Access Journals (Sweden)

    Hamed NEKOUBIN

    2012-12-01

    Full Text Available In the present study, grass carp (Ctenopharyngodon idella were exposed to copper and lead for 24, 48, 72 and 96 h. Experimental fishes which measured an average length of 8.2 ± 0.44 cm and weighed 4.3 ± 0.5 g. Seven groups (with three replicates of experimental fish were exposed to seven concentrations of each metal. The grass carps were kept in 21 tanks each stocked with 30 fishes were used in our experiments for each metal. The median lethal concentration (LC50 of copper to grass carp for 24, 48, 72 and 96 h were 2.422 mg/L, 2.222 mg/L, 2.006 mg/L, and 1.717 mg/L respectively. The median lethal concentration (LC50 of lead to grass carp for 24, 48, 72 and 96 h were 293.747 mg/L, 278.019 mg/L, 260.324 mg/L, and 246.455 mg/L, respectively. In addition, the behavioral changes of grass carp at different metal concentrations were determined. LC50 increased as mean exposure times decreased for both metals. Physiological responses like rapid opercular movement and frequent gulping of air was observed during the initial stages of exposure after which it became occasional. All these observations can be considered to monitor the quality of aquatic ecosystem and severity of pollution. In conclusion, copper is more toxic than lead for grass carp.

  13. Mimicking brain tissues by doping scatterers into gelatin tissue phantoms and determination of chemical species responsible for NMPPAS

    Science.gov (United States)

    Dahal, Sudhir; Cullum, Brian M.

    2012-06-01

    It has been shown that non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) has a great potential to be used as a high resolution surgical guidance technique during brain tumor surgery due to its ability of non-invasive or minimally invasive tumor differentiation. However, for experimental purposes associated with method validation, the use of real tissues is not always ideal because of issues such as availability, safety, storage, chemical doping, necessary control of size and shape, etc. To overcome these issues, tissue phantoms made from animal tissues and/or biochemical constituents, are often employed for such analyses. This work demonstrates the ability to develop and characterize gelatin based tissue phantoms with comparable optical and acoustic properties to real tissues by doping the phantoms with a scattering substance, 0.3 μm diameter Al2O3 particles. Using these phantoms, light scattering coefficients (μs) of 39 cm-1 have been generated, which are comparable to real brain tissue, thus making them a great alternative to real tissue for validation studies. In addition, this work also investigates the non-fluorescent species NAD+ found in the tissues, to evaluate its potential for being detected by NMPPAS. NMPPAS spectra of NAD+ shows a very promising beginning to determine other chemical species such as flavins, collagen, tryptophan, etc responsible for NMPPAS spectral signatures, associated with tumorogenesis.

  14. Functional Response of Tumor Vasculature to PaCO2: Determination of Total and Microvascular Blood Volume by MRI

    Directory of Open Access Journals (Sweden)

    Scott D. Packard

    2003-07-01

    Full Text Available In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6±0.1%/mm Hg CO2 whereas normal striatum increased by 1.5±0.2%/mm Hg CO2, (P < .0001, group t-test. Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed.

  15. Application of response surface methodology for determining cutting force model in turning hardened AISI H11 hot work tool steel

    Indian Academy of Sciences (India)

    B Fnides; M A Yallese; T Mabrouki; J-F Rigal

    2011-02-01

    This experimental study is conducted to determine statistical models of cutting forces in hard turning of AISI H11 hot work tool steel (∼ 50 HRC). This steel is free from tungsten on Cr–Mo–V basis, insensitive to temperature changes and having a high wear resistance. It is employed for the manufacture of highly stressed diecasting moulds and inserts with high tool life expectancy, plastic moulds subject to high stress, helicopter rotor blades and forging dies. The workpiece is machined by a mixed ceramic tool (insert CC650 of chemical composition 70%Al23+30%TiC) under dry conditions. Based on 33 full factorial design, a total of 27 tests were carried out. The range of each parameter is set at three different levels, namely low, medium and high. Mathematical models were deduced 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 process. The results indicate that the depth of cut is the dominant factor affecting cutting force components. The feed rate influences tangential cutting force more than radial and axial forces. The cutting speed affects radial force more than tangential and axial forces.

  16. Niche and Neutral Processes Together Determine Diversity Loss in Response to Fertilization in an Alpine Meadow Community.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Fertilization via nutrient deposition and agricultural inputs is one of the most important factors driving decreases in plant diversity. However, we still do not fully understand which processes (niche process or neutral process are more important in leading to decreases in plant diversity caused by fertilization. A hypothesis-based approach was used to test the relative importance of niche versus neutral processes along a fertilization gradient in an alpine meadow community on the eastern Tibetan plateau, China. Niche overlap values were calculated for species biomass, and the null model was used to generate the values of niche overlap expected at random. A linear regression modeling was used to evaluate the relationship between functional traits (specific leaf area, leaf dry matter content, and leaf total nitrogen concentration and species relative abundance. Our results demonstrated that observed niche overlap for species biomass was significantly higher than expected at lower fertilization gradients. Moreover, we also found a significantly negative correlation between species relative abundance and specific leaf area and leaf dry matter content, but a significantly positive correlation between relative abundance and leaf nitrogen concentration at lower fertilization gradients. However, these relationships were not significant at higher fertilization gradients. We concluded that community assembly is dynamic progression along the environmental gradients, and niche and neutral processes may together determine species diversity loss in response to fertilization.

  17. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    NARCIS (Netherlands)

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele wa

  18. Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response

    DEFF Research Database (Denmark)

    Moser, C; Hougen, H P; Song, Z;

    1999-01-01

    Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates...... with a poor prognosis. We speculated that a change from this Th2-like response to a Th1-like response might decrease the lung inflammation and thus improve the prognosis in CF patients. To investigate this, we infected C3H/HeN and BALB/c mice intratracheally with P. aeruginosa. In addition, we studied...... with chronic P. aeruginosa lung infection have a better disease outcome compared to the Th2-reacting BALB/c mice, indicating that a Th1 response might be beneficial in CF patients with chronic P. aeruginosa lung infection....

  19. Allele mining and enhanced genetic recombination for rice breeding.

    Science.gov (United States)

    Leung, Hei; Raghavan, Chitra; Zhou, Bo; Oliva, Ricardo; Choi, Il Ryong; Lacorte, Vanica; Jubay, Mona Liza; Cruz, Casiana Vera; Gregorio, Glenn; Singh, Rakesh Kumar; Ulat, Victor Jun; Borja, Frances Nikki; Mauleon, Ramil; Alexandrov, Nickolai N; McNally, Kenneth L; Sackville Hamilton, Ruaraidh

    2015-12-01

    Traditional rice varieties harbour a large store of genetic diversity with potential to accelerate rice improvement. For a long time, this diversity maintained in the International Rice Genebank has not been fully used because of a lack of genome information. The publication of the first reference genome of Nipponbare by the International Rice Genome Sequencing Project (IRGSP) marked the beginning of a systematic exploration and use of rice diversity for genetic research and breeding. Since then, the Nipponbare genome has served as the reference for the assembly of many additional genomes. The recently completed 3000 Rice Genomes Project together with the public database (SNP-Seek) provides a new genomic and data resource that enables the identification of useful accessions for breeding. Using disease resistance traits as case studies, we demonstrated the power of allele mining in the 3,000 genomes for extracting accessions from the GeneBank for targeted phenotyping. Although potentially useful landraces can now be identified, their use in breeding is often hindered by unfavourable linkages. Efficient breeding designs are much needed to transfer the useful diversity to breeding. Multi-parent Advanced Generation InterCross (MAGIC) is a breeding design to produce highly recombined populations. The MAGIC approach can be used to generate pre-breeding populations with increased genotypic diversity and reduced linkage drag. Allele mining combined with a multi-parent breeding design can help convert useful diversity into breeding-ready genetic resources. PMID:26606925